Subjects -> MEDICAL SCIENCES (Total: 8196 journals)
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MEDICAL SCIENCES (2241 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 3562 Journals sorted alphabetically
16 de Abril     Open Access   (Followers: 1)
3D Printing in Medicine     Open Access   (Followers: 5)
4 open     Open Access  
AADE in Practice     Hybrid Journal   (Followers: 2)
AAS Open Research     Open Access  
ABCS Health Sciences     Open Access   (Followers: 3)
Abia State University Medical Students' Association Journal     Full-text available via subscription   (Followers: 1)
AboutOpen     Open Access  
ACIMED     Open Access  
ACM Transactions on Computing for Healthcare     Hybrid Journal  
ACS Medicinal Chemistry Letters     Hybrid Journal   (Followers: 41)
Acta Bio Medica     Open Access   (Followers: 1)
Acta Bioethica     Open Access  
Acta Bioquimica Clinica Latinoamericana     Open Access   (Followers: 1)
Acta Herediana     Open Access  
Acta Marisiensis - Seria Medica     Open Access  
Acta Medica (Hradec Králové)     Open Access  
Acta Medica Bulgarica     Open Access  
Acta Medica Colombiana     Open Access   (Followers: 1)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Medica Indonesiana     Open Access  
Acta Medica International     Open Access  
Acta Medica Iranica     Open Access  
Acta medica Lituanica     Open Access  
Acta Medica Martiniana     Open Access  
Acta Medica Peruana     Open Access   (Followers: 1)
Acta Scientiarum. Health Sciences     Open Access   (Followers: 2)
Acupuncture & Electro-Therapeutics Research     Full-text available via subscription   (Followers: 3)
Acupuncture and Herbal Medicine     Open Access   (Followers: 8)
Addiction Science & Clinical Practice     Open Access   (Followers: 9)
Addictive Behaviors Reports     Open Access   (Followers: 8)
Adıyaman Üniversitesi Sağlık Bilimleri Dergisi / Health Sciences Journal of Adıyaman University     Open Access  
Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi     Open Access  
Advanced Health Care Technologies     Open Access   (Followers: 12)
Advanced Journal of Professional Practice     Open Access   (Followers: 3)
Advanced NanoBiomed Research     Open Access   (Followers: 1)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 4)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Advances in Bioscience and Clinical Medicine     Open Access   (Followers: 6)
Advances in Cell and Gene Therapy     Hybrid Journal   (Followers: 1)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 23)
Advances in Clinical Radiology     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 7)
Advances in Medical Education and Practice     Open Access   (Followers: 29)
Advances in Medical Sciences     Hybrid Journal   (Followers: 7)
Advances in Medicine     Open Access   (Followers: 3)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 3)
Advances in Parkinson's Disease     Open Access   (Followers: 2)
Advances in Preventive Medicine     Open Access   (Followers: 6)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18)
Advances in Regenerative Medicine     Open Access   (Followers: 3)
Advances in Therapy     Hybrid Journal   (Followers: 5)
Advances in Traditional Medicine     Hybrid Journal   (Followers: 3)
Advances in Virus Research     Full-text available via subscription   (Followers: 7)
Advances in Wound Care     Hybrid Journal   (Followers: 15)
Aerospace Medicine and Human Performance     Full-text available via subscription   (Followers: 25)
African Health Sciences     Open Access   (Followers: 6)
African Journal of Biomedical Research     Open Access  
African Journal of Clinical and Experimental Microbiology     Open Access  
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
African Journal of Medical and Health Sciences     Open Access  
Afrimedic Journal     Open Access   (Followers: 3)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 10)
Airway     Open Access   (Followers: 4)
AJOB Empirical Bioethics     Hybrid Journal   (Followers: 3)
AJSP: Reviews & Reports     Hybrid Journal  
Aktuelle Ernährungsmedizin     Hybrid Journal   (Followers: 3)
AkupunkturPraxis     Full-text available via subscription   (Followers: 7)
Al-Azhar Assiut Medical Journal     Open Access   (Followers: 1)
Al-Qadisiah Medical Journal     Open Access  
Alerta : Revista Científica del Instituto Nacional de Salud     Open Access  
Alexandria Journal of Medicine     Open Access  
Allgemeine Homöopathische Zeitung     Hybrid Journal   (Followers: 1)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 1)
American Journal of Biomedical Engineering     Open Access   (Followers: 10)
American Journal of Biomedical Research     Open Access   (Followers: 2)
American Journal of Biomedicine     Full-text available via subscription  
American Journal of Chinese Medicine, The     Hybrid Journal   (Followers: 2)
American Journal of Clinical Medicine Research     Open Access   (Followers: 5)
American Journal of Family Therapy     Hybrid Journal   (Followers: 6)
American Journal of Law & Medicine     Full-text available via subscription   (Followers: 10)
American Journal of Lifestyle Medicine     Hybrid Journal   (Followers: 5)
American Journal of Managed Care     Full-text available via subscription   (Followers: 13)
American Journal of Medical Case Reports     Open Access  
American Journal of Medical Sciences and Medicine     Open Access   (Followers: 2)
American Journal of Medicine     Hybrid Journal   (Followers: 44)
American Journal of Medicine and Medical Sciences     Open Access   (Followers: 1)
American Journal of Medicine Open     Open Access   (Followers: 8)
American Journal of Medicine Studies     Open Access   (Followers: 3)
American Journal of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American Journal of the Medical Sciences     Hybrid Journal   (Followers: 11)
American Journal on Addictions     Hybrid Journal   (Followers: 11)
American medical news     Free   (Followers: 3)
Amrita Journal of Medicine     Open Access   (Followers: 4)
Amyloid: The Journal of Protein Folding Disorders     Hybrid Journal   (Followers: 6)
Anales de la Facultad de Medicina     Open Access  
Anales de la Facultad de Medicina, Universidad de la República, Uruguay     Open Access  
Anales del Sistema Sanitario de Navarra     Open Access   (Followers: 1)
Analgesia & Resuscitation : Current Research     Hybrid Journal   (Followers: 5)
Anatolian Clinic the Journal of Medical Sciences     Open Access  
Anatomica Medical Journal     Open Access  
Anatomical Science International     Hybrid Journal   (Followers: 3)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1)
Anatomy     Open Access   (Followers: 3)
Anatomy Research International     Open Access   (Followers: 4)
Androgens : Clinical Research and Therapeutics     Open Access  
Angewandte Nuklearmedizin     Full-text available via subscription   (Followers: 7)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 1)
Animal Diseases     Open Access   (Followers: 1)
Annales de Pathologie     Full-text available via subscription  
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 2)
Annals of 3D Printed Medicine     Open Access  
Annals of African Medicine     Open Access   (Followers: 2)
Annals of Anatomy - Anatomischer Anzeiger     Hybrid Journal   (Followers: 2)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18)
Annals of Biomedical Sciences     Full-text available via subscription   (Followers: 3)
Annals of Clinical and Medical Case Reports     Open Access  
Annals of Clinical Hypertension     Open Access  
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 9)
Annals of Family Medicine     Open Access   (Followers: 14)
Annals of Health Research     Open Access   (Followers: 2)
Annals of Ibadan Postgraduate Medicine     Open Access  
Annals of Medical and Health Sciences Research     Open Access   (Followers: 5)
Annals of Medicine     Hybrid Journal   (Followers: 11)
Annals of Medicine and Surgery     Open Access   (Followers: 7)
Annals of Medicine and Surgery Case Reports     Open Access   (Followers: 1)
Annals of Medicine and Surgery Protocols     Open Access  
Annals of Microbiology     Open Access   (Followers: 9)
Annals of Musculoskeletal Medicine     Open Access  
Annals of Rehabilitation Medicine     Open Access   (Followers: 1)
Annals of Saudi Medicine     Open Access  
Annals of the College of Medicine, Mosul     Open Access  
Annals of the National Academy of Medical Sciences (India)     Open Access  
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5)
Annals of The Royal College of Surgeons of England     Full-text available via subscription   (Followers: 3)
Annals of the RussianAacademy of Medical Sciences     Open Access  
Annals of Vascular Surgery - Brief Reports and Innovations     Full-text available via subscription  
Annual Reports in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Annual Reports on NMR Spectroscopy     Full-text available via subscription   (Followers: 4)
Annual Review of Medicine     Full-text available via subscription   (Followers: 16)
Anthropological Review     Open Access   (Followers: 27)
Anthropologie et santé     Open Access   (Followers: 4)
Antibiotics     Open Access   (Followers: 11)
Antibodies     Open Access   (Followers: 3)
Antibody Reports     Open Access  
Antibody Therapeutics     Open Access  
Anuradhapura Medical Journal     Open Access  
Anwer Khan Modern Medical College Journal     Open Access  
Apmis     Hybrid Journal   (Followers: 1)
Apparence(s)     Open Access   (Followers: 1)
Applied Clinical Informatics     Hybrid Journal   (Followers: 4)
Applied Medical Informatics     Open Access   (Followers: 11)
Arab Journal of Nephrology and Transplantation     Open Access   (Followers: 2)
Arabian Journal of Scientific Research / المجلة العربية للبحث العلمي     Open Access  
Archive of Biomedical Science and Engineering     Open Access  
Archive of Clinical Medicine     Open Access   (Followers: 1)
Archives Medical Review Journal / Arşiv Kaynak Tarama Dergisi     Open Access  
Archives of Asthma, Allergy and Immunology     Open Access   (Followers: 1)
Archives of Clinical Hypertension     Open Access  
Archives of Medical and Biomedical Research     Open Access   (Followers: 2)
Archives of Medical Laboratory Sciences     Open Access  
Archives of Medicine and Health Sciences     Open Access   (Followers: 5)
Archives of Organ Transplantation     Open Access  
Archives of Preventive Medicine     Open Access   (Followers: 1)
Archives of Pulmonology and Respiratory Care     Open Access  
Archives of Renal Diseases and Management     Open Access  
Archives of Trauma Research     Open Access   (Followers: 4)
Arquivos de Medicina     Open Access  
Ars Medica : Revista de Ciencias Médicas     Open Access  
ARS Medica Tomitana     Open Access  
Art Therapy: Journal of the American Art Therapy Association     Hybrid Journal   (Followers: 14)
Arterial Hypertension     Open Access  
Artificial Intelligence in Medicine     Hybrid Journal   (Followers: 19)
Artificial Organs     Hybrid Journal   (Followers: 1)
ASA Monitor     Full-text available via subscription   (Followers: 7)
Asia Pacific Journal of Clinical Nutrition     Full-text available via subscription   (Followers: 10)
Asian Bioethics Review     Full-text available via subscription   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 4)
Asian Journal of Health     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 3)
Asian Journal of Medical and Pharmaceutical Researches     Open Access  
Asian Journal of Medical Sciences     Open Access   (Followers: 2)
Asian Journal of Medicine and Health     Open Access   (Followers: 1)
Asian Journal of Population Sciences     Open Access   (Followers: 6)
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access  
Asian Journal of Scientific Research     Open Access   (Followers: 2)
Asian Journal of Social Health and Behavior     Open Access   (Followers: 4)
Asian Journal of Transfusion Science     Open Access  
Asian Medicine     Hybrid Journal   (Followers: 5)
Asian Pacific Journal of Health Sciences     Open Access   (Followers: 2)
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Atención Primaria     Open Access   (Followers: 2)
Atención Primaria Práctica     Open Access  
Atti della Accademia Peloritana dei Pericolanti - Classe di Scienze Medico-Biologiche     Open Access  
Auris Nasus Larynx     Full-text available via subscription  
Australasian Journal of Ultrasound in Medicine (AJUM)     Hybrid Journal   (Followers: 2)
Australian Family Physician     Full-text available via subscription   (Followers: 3)
Australian Journal of Medical Science     Full-text available via subscription   (Followers: 4)
Autopsy and Case Reports     Open Access  

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Journal Cover
Journal Prestige (SJR): 1.063
Citation Impact (citeScore): 3
Number of Followers: 11  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2079-6382
Published by MDPI Homepage  [84 journals]
  • Antibiotics, Vol. 11, Pages 830: Virulence Profiling, Multidrug Resistance
           and Molecular Mechanisms of Campylobacter Strains from Chicken Carcasses
           in Tunisia

    • Authors: Awatef Béjaoui, Manel Gharbi, Sarra Bitri, Dorsaf Nasraoui, Wassim Ben Aziza, Kais Ghedira, Maryem Rfaik, Linda Marzougui, Abdeljelil Ghram, Abderrazek Maaroufi
      First page: 830
      Abstract: Antibiotic resistance in foodborne pathogens is an emergent global health concern. The objectives of this study were to assess antimicrobial resistance (AMR) in Campylobacter isolates from chicken carcasses and to investigate the AMR molecular mechanisms as well as the presence of virulence determinants. The study was performed on 257 samples collected from abattoirs and retail shops in northeastern Tunisia. Forty-eight Campylobacter isolates were recovered and identified as C. jejuni (n = 33) and C. coli (n = 15). Antibiotic resistance was tested against eight antibiotics and high resistance rates were observed against tetracycline (100%), erythromycin (97.9%), ciprofloxacin (73%), nalidixic acid (85.4%), ampicillin (83.3%), amoxicillin/clavulanic acid (22.9%), chloramphenicol (75%), and gentamicin (27.1%). All isolates were multidrug-resistant, and 22 resistance patterns were found. All isolates were screened for AMR genes (tet(O), tet(A), tet(B), tet(L), cmeB, ermB, blaOXA-61, and aphA-3), and for point mutations in gyrA (C257T substitution) and 23SrRNA (A2075G/A2074C) genes. All screened AMR genes, as well as the C257T and the A2075G mutations, were detected. The virulence genotypes were also determined, and all isolates carried the motility (flaA) and invasion (cadF) genes. Most of them also harbored the cdtA, cdtB, and cdtC genes, encoding the Campylobacter toxin. The screening of the cgtB and the wlaN genes, involved in Guillain-Barré Syndrome expression, revealed the presence of the cgtB in 21.2% of C. jejuni strains, whereas none of them carried the wlaN gene. Our findings highlight the emergence of Campylobacter strains simultaneously harboring several virulence and AMR determinants, which emphasizes the risk of transmission of MDR strains to humans via the food chain. Hence, controlling the dissemination of foodborne pathogens “from the farm to the fork” as well as restricting the use of antimicrobials in husbandry are mandatory to prevent the risk for consumers and to mitigate the dissemination of MDR pathogens.
      Citation: Antibiotics
      PubDate: 2022-06-21
      DOI: 10.3390/antibiotics11070830
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 831: Antitubercular, Cytotoxicity, and
           Computational Target Validation of Dihydroquinazolinone Derivatives

    • Authors: Katharigatta N. Venugopala, Nizar A. Al-Shar’i, Lina A. Dahabiyeh, Wafa Hourani, Pran Kishore Deb, Melendhran Pillay, Bashaer Abu-Irmaileh, Yasser Bustanji, Sandeep Chandrashekharappa, Christophe Tratrat, Mahesh Attimarad, Anroop B. Nair, Nagaraja Sreeharsha, Pottathil Shinu, Michelyne Haroun, Mahmoud Kandeel, Abdulmalek Ahmed Balgoname, Rashmi Venugopala, Mohamed A. Morsy
      First page: 831
      Abstract: A series of 2,3-dihydroquinazolin-4(1H)-one derivatives (3a–3m) was screened for in vitro whole-cell antitubercular activity against the tubercular strain H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 3l and 3m with di-substituted aryl moiety (halogens) attached to the 2-position of the scaffold showed a minimum inhibitory concentration (MIC) of 2 µg/mL against the MTB strain H37Rv. Compound 3k with an imidazole ring at the 2-position of the dihydroquinazolin-4(1H)-one also showed significant inhibitory action against both the susceptible strain H37Rv and MDR strains with MIC values of 4 and 16 µg/mL, respectively. The computational results revealed the mycobacterial pyridoxal-5′-phosphate (PLP)-dependent aminotransferase (BioA) enzyme as the potential target for the tested compounds. In vitro, ADMET calculations and cytotoxicity studies against the normal human dermal fibroblast cells indicated the safety and tolerability of the test compounds 3k–3m. Thus, compounds 3k–3m warrant further optimization to develop novel BioA inhibitors for the treatment of drug-sensitive H37Rv and drug-resistant MTB.
      Citation: Antibiotics
      PubDate: 2022-06-21
      DOI: 10.3390/antibiotics11070831
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 832: Spread of Multidrug-Resistant

    • Authors: Silvia Di Lodovico, Teresa Fasciana, Mara Di Giulio, Luigina Cellini, Anna Giammanco, Gian Maria Rossolini, Alberto Antonelli
      First page: 832
      Abstract: Multidrug-resistant organisms (MDRO) are bacteria that exhibit acquired resistance to multiple antibiotics, reducing the efficacy of antimicrobial therapies [...]
      Citation: Antibiotics
      PubDate: 2022-06-21
      DOI: 10.3390/antibiotics11070832
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 833: Characterization of Diarreaghenic
           Escherichia coli Strains Isolated from Healthy Donors, including a Triple
           Hybrid Strain

    • Authors: Evelyn Méndez-Moreno, Liliana Caporal-Hernandez, Pablo A. Mendez-Pfeiffer, Yessica Enciso-Martinez, Rafael De la Rosa López, Dora Valencia, Margarita M. P. Arenas-Hernández, Manuel G. Ballesteros-Monrreal, Edwin Barrios-Villa
      First page: 833
      Abstract: Escherichia coli is a well-recognized inhabitant of the animal and human gut. Its presence represents an essential component of the microbiome. There are six pathogenic variants of E. coli associated with diarrheal processes, known as pathotypes. These harbor genetic determinants that allow them to be classified as such. In this work, we report the presence of diarrheagenic pathotypes of E. coli strains isolated from healthy donors. Ninety E. coli strains were analyzed, of which forty-six (51%) harbored virulence markers specifics for diarrheagenic pathotypes, including four hybrids (one of them with genetic determinants of three DEC pathotypes). We also identified phylogenetic groups with a higher prevalence of B2 (45.6%) and A (17.8%). In addition, resistance to sulfonamides (100%), and aminoglycosides (100%) was found in 100% of the strains, with a lower prevalence of resistance to cefotaxime (13.3%), ceftriaxone (12.2%), fosfomycin (10%), and meropenem (0%). All analyzed strains were classified as multidrug resistant. Virulence genes were also investigated, which led us to propose three new virotypes. Among the virulence traits observed, the ability to form biofilms stands out, which was superior to that of the E. coli and Staphylococcus aureus strains used as positive controls.
      Citation: Antibiotics
      PubDate: 2022-06-21
      DOI: 10.3390/antibiotics11070833
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 834: Antimicrobial Activity of Biogenic Silver
           Nanoparticles from Syzygium aromaticum against the Five Most Common
           Microorganisms in the Oral Cavity

    • Authors: Erika Alejandra Jardón-Romero, Edith Lara-Carrillo, María G. González-Pedroza, Víctor Sánchez-Mendieta, Elías Nahum Salmerón-Valdés, Víctor Hugo Toral-Rizo, Oscar F. Olea-Mejía, Saraí López-González, Raúl A. Morales-Luckie
      First page: 834
      Abstract: Syzygium aromaticum (clove) has been used as a dental analgesic, an anesthetic, and a bioreducing and capping agent in the formation of metallic nanoparticles. The main objective of this study was to evaluate the antimicrobial effect in oral microorganisms of biogenic silver nanoparticles (AgNPs) formed with aqueous extract of clove through an ecofriendly method “green synthesis”. The obtained AgNPs were characterized by UV-Vis (ultraviolet-visible spectroscopy), SEM-EDS (scanning electron microscopy–energy dispersive X-ray spectroscopy), TEM (transmission electron microscopy), and ζ potential, while its antimicrobial effect was corroborated against oral Gram-positive and Gram-negative microorganisms, as well as yeast that is commonly present in the oral cavity. The AgNPs showed absorption at 400–500 nm in the UV-Vis spectrum, had an average size of 4–16 nm as observed by the high-resolution transmission electron microscopy (HR-TEM), and were of a crystalline nature and quasi-spherical form. The antimicrobial susceptibility test showed inhibition zones of 2–4 mm in diameter. Our results suggest that AgNPs synthesized with clove can be used as effective growth inhibitors in several oral microorganisms.
      Citation: Antibiotics
      PubDate: 2022-06-21
      DOI: 10.3390/antibiotics11070834
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 835: Molecular Characterization of
           Carbapenem-Resistant Acinetobacter baumannii Isolated from Intensive Care
           Unit Patients in Jordanian Hospitals

    • Authors: Suhaila A. Al-Sheboul, Salam Z. Al-Moghrabi, Yasemin Shboul, Farah Atawneh, Ahmed H. Sharie, Laila F. Nimri
      First page: 835
      Abstract: Acinetobacter baumannii is a common cause of healthcare-associated infections (HAI) worldwide, mostly occurring in intensive care units (ICUs). Extended-spectrum beta lactamases (ESBL)-positive A. baumannii strains have emerged as highly resistant to most currently used antimicrobial agents, including carbapenems. The most common mechanism for carbapenem resistance in this species is β-lactamase-mediated resistance. Carbapenem-hydrolyzing class D oxacillinases are widespread among multidrug-resistant (MDR) A. baumannii strains. The present study was conducted to determine the presence and distribution of blaOXA genes among multidrug-resistant A. baumannii isolated from ICU patients and genes encoding insertion sequence (IS-1) in these isolates. Additionally, the plasmid DNA profiles of these isolates were determined. A total of 120 clinical isolates of A. baumannii from various ICU clinical specimens of four main Jordanian hospitals were collected. Bacterial isolate identification was confirmed by biochemical testing and antibiotic sensitivity was then assessed. PCR amplification and automated sequencing were carried out to detect the presence of blaOXA-51, blaOXA-23, blaOXA-24, and blaOXA-58 genes, and ISAba1 insertion sequence. Out of the 120 A. baumannii isolates, 95% of the isolates were resistant to three or more classes of the antibiotics tested and were identified as MDR. The most frequent resistance of the isolates was against piperacillin (96.7%), cephalosporins (97.5%), and β-lactam/β-lactamase inhibitor combinations antibiotics (95.8%). There were 24 (20%) ESBL-producing isolates. A co-existence of blaOXA-51 gene and ISAba1 in all the 24 ESBL-producing isolates was determined. In addition, in the 24 ESBL-producing isolates, 21 (87.5%) carried blaOXA-51 and blaOXA-23 genes, 1 (4.2%) carried blaOXA-51 and blaOXA-24, but all were negative for the blaOXA-58 gene. Plasmid DNA profile A and profile B were the most common (29%) in ESBL-positive MDR A. baumannii isolates while plasmid DNA profile A was the most common in the ESBL-negative isolates. In conclusion, there was an increase in prevalence of MDR-A. baumannii in ICU wards in Jordanian hospitals, especially those having an ESBL phenotype. Thus, identification of ESBL genes is necessary for the surveillance of their transmission in hospitals.
      Citation: Antibiotics
      PubDate: 2022-06-21
      DOI: 10.3390/antibiotics11070835
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 836: Regional Variations in Outpatient
           Antibiotic Prescribing in Germany: A Small Area Analysis Based on Claims

    • Authors: Oliver Scholle, Marieke Asendorf, Christoph Buck, Susann Grill, Christopher Jones, Bianca Kollhorst, Oliver Riedel, Benjamin Schüz, Ulrike Haug
      First page: 836
      Abstract: A comprehensive small area description of regional variations in outpatient antibiotic prescribing in Germany is lacking. Using the German Pharmacoepidemiological Research Database (GePaRD), a claims database covering ~20% of the German population, we determined the age- and sex-standardized prescription rates of antibiotics (number of outpatient prescriptions per 1000 persons/year). We calculated these prescription rates overall and on the level of 401 German districts for the calendar years 2010 and 2018. In 2018, the standardized prescription rate of antibiotics in the total study population was 23% lower than in 2010 (442 vs. 575 per 1000 persons/year). Among 0–17-year-olds, prescription rates across districts ranged from 312 to 1205 in 2010 and from 188 to 710 in 2018 per 1000 persons/year; among adults (≥18 years), they ranged from 388 to 841 in 2010 and from 300 to 693 in 2018 per 1000 persons/year. Despite the overall decline in outpatient antibiotic prescribing between 2010 and 2018, regional variations at the district level remained high in all age groups in Germany. Identifying reasons that explain the persistently high prescription rates in certain regions will be helpful in designing effective and tailored measures to further improve antibiotic stewardship in these regions.
      Citation: Antibiotics
      PubDate: 2022-06-22
      DOI: 10.3390/antibiotics11070836
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 837: Association between Augmented Renal
           Clearance and Inadequate Vancomycin Pharmacokinetic/Pharmacodynamic
           Targets in Chinese Adult Patients: A Prospective Observational Study

    • Authors: Jinjin Zhao, Yaxin Fan, Minjie Yang, Xiaoyu Liang, Jufang Wu, Yuancheng Chen, Beining Guo, Huifang Zhang, Ruilan Wang, Fengying Zhang, Jingqing Hang, Huayin Li, Jing Zhang
      First page: 837
      Abstract: This study aimed to examine the risk factors of augmented renal clearance (ARC) and the association between ARC and vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices in Chinese adult patients. A prospective, observational, multicenter study was conducted, and 414 adult patients undergoing vancomycin therapeutic drug monitoring (TDM) were enrolled. Clinical and PK/PD data were compared between ARC and non-ARC groups. Independent risk factors were examined using a multivariate logistic regression analysis. The ARC and augmented renal clearance in trauma intensive care (ARCTIC) scoring systems were evaluated. Eighty-eight of the enrolled patients (88/414, 21.3%) had ARC before vancomycin therapy. Patients with ARC were more likely to have subtherapeutic vancomycin PK/PD indices, including trough concentration (p = 0.003) and 24 h area under the concentration–time curve (AUC24) to minimal inhibitory concentration (MIC) ratio (p < 0.001). Male sex (OR = 2.588), age < 50 years (OR = 2.713), overweight (OR = 2.072), receiving mechanical ventilation (OR = 1.785), enteral nutrition (OR = 2.317), neutrophil percentage (OR = 0.975), and cardiovascular diseases (OR = 0.281) were significantly associated with ARC. In conclusion, ARC is associated with subtherapeutic vancomycin trough concentration and AUC24/MIC; therefore, higher than routine doses may be needed. Risk factors and ARC risk scoring systems are valuable for early identification.
      Citation: Antibiotics
      PubDate: 2022-06-22
      DOI: 10.3390/antibiotics11070837
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 838: Fecal Microbiota Transplantation in
           Decompensated Cirrhosis: A Systematic Review on Safety and Efficacy

    • Authors: Annie S. Hong, Kyaw Min Tun, Jenny M. Hong, Kavita Batra, Gordon Ohning
      First page: 838
      Abstract: Background and Aims: Due to increasing knowledge of the “gut–liver axis”, there has been growing interest regarding the use of fecal microbiota transplant in the management of chronic liver disease. There are limited data available and current guidelines are mostly based on expert opinions. We aim to perform the first systematic review investigating safety and efficacy of fecal microbiota transplant particularly among high-risk decompensated cirrhosis patient populations. Methods: Literature search was performed using variations of the keywords “fecal microbiota transplant” and “cirrhosis” on PubMed/Medline from inception to 3 October 2021. The resulting 116 articles were independently screened by two authors. In total, 5 qualifying studies, including 2 randomized control trials and 3 retrospective case series, were found to meet established eligibility criteria and have adequate quality of evidence to be included in this review. Results: Of the total 58 qualifying patients, there were 2 deaths post fecal microbiota transplant, 1 of which could not rule out being related (1.7%). Among the remaining 56 participants, 8 serious adverse events were reported, of which 2 could not rule out being related (3.6%). The success rate of fecal microbiota transplantation in treating recurrent Clostridioides difficile infection among patients with decompensated cirrhosis was 77.8%. The success rate when used as investigational treatment for hepatic encephalopathy was 86.7%, with multiple studies reporting clinically significant improvement in encephalopathy testing scores. Conclusions: We found a marginally higher rate of deaths and serious adverse events from fecal microbiota transplant in our patient population compared with the average immunocompetent population, where it was previously found to have 0 deaths and SAE rate of 2.83%. The efficacy when used for recurrent C.difficile infection was 77.8% and 87% in the decompensated cirrhotic and general populations, respectively. Studies on efficacy in novel treatment of hepatic encephalopathy have been promising. This study concludes that fecal microbiota transplant use in decompensated cirrhosis patients should be used with caution and preferably be limited to research purposes until better data are available.
      Citation: Antibiotics
      PubDate: 2022-06-23
      DOI: 10.3390/antibiotics11070838
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 839: Benefits of Combined
           Phage–Antibiotic Therapy for the Control of Antibiotic-Resistant
           Bacteria: A Literature Review

    • Authors: Kevin Diallo, Alain Dublanchet
      First page: 839
      Abstract: With the increase in bacterial resistance to antibiotics, more and more therapeutic failures are being reported worldwide. The market for antibiotics is now broken due to the high cost of developing new molecules. A promising solution to bacterial resistance is combined phage–antibiotic therapy, a century-old method that can potentiate existing antibiotics by prolonging or even restoring their activity against specific bacteria. The aim of this literature review was to provide an overview of different phage–antibiotic combinations and to describe the possible mechanisms of phage–antibiotic synergy.
      Citation: Antibiotics
      PubDate: 2022-06-22
      DOI: 10.3390/antibiotics11070839
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 840: The Optimal Permeation of Cyclic
           Boronates to Cross the Outer Membrane via the Porin Pathway

    • Authors: Gian Marco Tuveri, Matteo Ceccarelli, Alessandro Pira, Igor V. Bodrenko
      First page: 840
      Abstract: We investigated the diffusion of three cyclic boronates formulated as beta-lactamase inhibitors through the porin OmpF to evaluate their potential to cross OM via the porin pathway. The three nonbeta-lactam molecules diffuse through the porin eyelet region with the same mechanism observed for beta-lactam molecules and diazobicyclooctan derivatives, with the electric dipole moment aligned with the transversal electric field. In particular, the BOH group can interact with both the basic ladder and the acidic loop L3, which is characteristic of the size-constricted region of this class of porins. On one hand, we confirm that the transport of small molecules through enterobacter porins has a common general mechanism; on the other, the class of cyclic boronate molecules does not seem to have particular difficulties in diffusing through enterobacter porins, thus representing a good scaffold for new anti-infectives targeting Gram-negative bacteria research.
      Citation: Antibiotics
      PubDate: 2022-06-23
      DOI: 10.3390/antibiotics11070840
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 841: Acetylome and Succinylome Profiling of
           Edwardsiella tarda Reveals Key Roles of Both Lysine Acylations in
           Bacterial Antibiotic Resistance

    • Authors: Yuying Fu, Lishan Zhang, Huanhuan Song, Junyan Liao, Li Lin, Wenjia Jiang, Xiaoyun Wu, Guibin Wang
      First page: 841
      Abstract: The antibiotic resistance of Edwardsiella tarda is becoming increasingly prevalent, and thus novel antimicrobial strategies are being sought. Lysine acylation has been demonstrated to play an important role in bacterial physiological functions, while its role in bacterial antibiotic resistance remains largely unclear. In this study, we investigated the lysine acetylation and succinylation profiles of E. tarda strain EIB202 using affinity antibody purification combined with LC-MS/MS. A total of 1511 lysine-acetylation sites were identified on 589 proteins, and 2346 lysine-succinylation sites were further identified on 692 proteins of this pathogen. Further bioinformatic analysis showed that both post-translational modifications (PTMs) were enriched in the tricarboxylic acid (TCA) cycle, pyruvate metabolism, biosynthesis, and carbon metabolism. In addition, 948 peptides of 437 proteins had overlapping associations with multiple metabolic pathways. Moreover, both acetylation and succinylation were found in many antimicrobial resistance (AMR) proteins, suggesting their potentially vital roles in antibiotic resistance. In general, our work provides insights into the acetylome and succinylome features responsible for the antibiotic resistance mechanism of E. tarda, and the results may facilitate future investigations into the pathogenesis of this bacterium.
      Citation: Antibiotics
      PubDate: 2022-06-23
      DOI: 10.3390/antibiotics11070841
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 842: Self-Medication as an Important Risk
           Factor for Antibiotic Resistance: A Multi-Institutional Survey among

    • Authors: Shah Zeb, Mariam Mushtaq, Muneeb Ahmad, Waqas Saleem, Ali A. Rabaan, Bibi Salma Zahid Naqvi, Mohammed Garout, Mohammed Aljeldah, Basim R. Al Shammari, Nehad J. Al Faraj, Nisreen A. Al-Zaki, Mona J. Al Marshood, Thuria Y. Al Saffar, Khadija A. Alsultan, Shamsah H. Al-Ahmed, Jeehan H. Alestad, Muhammad Naveed, Naveed Ahmed
      First page: 842
      Abstract: Self-medication is an important issue, especially in developing countries. Self-medication is the concept in which individuals use medicine to ease and manage their minor illnesses. The current survey was designed to conduct interviews at different universities based on the availability of the students from August 2021 to October 2021 in Hazara region of Khyber Pakhtunkhwa (KPK), Pakistan. Overall, 1250 questionnaires were distributed to students from various departments. Students of microbiology (n = 305, 24.4%) and agriculture 236 (n = 18.8%) were the most elevated members in this study, while other participants were from medical lab technology (n = 118, 9.4%), chemistry (n = 103, 8.2%), food science (n = 92, 7.3%), business administration (n = 83, 6.6%), sociology (n = 78, 6.2%), math/physics (n = 6, 14.8%), Pak study (n = 58, 4.6%), English (n = 47, 3.7%), and psychology (n = 19, 1.5%). Students working towards their Bachelor numbered (n = 913, 73.0%), Master (minor) numbered (n = 80, 6.4%), Master (major) numbered (n = 221, 17.6%), and Doctorate numbered (n = 36, 2.8%). The age group of participants was majorly 20–25 years (61.0%), while others belonged to the age groups 25–30 years (20.6%), 30–35 years (9.8%), and 35–40 years (8.4%). The mean and standard deviation of daily practices of self-medication were observed (M = 416.667, SD = 1,026,108.667) and p = 0.002. The mean and standard deviation of daily practices of antibiotic knowledge was (M = 431.5, SD = 1,615,917) and p = 0.002. Antimicrobial agents were leading over others with 631 (50.4%), followed by anti-inflammatory with 331 (26.4%), multivitamins with 142 (11.3%), gynecological purpose with 59 (4.7%), and analgesic with 72 (5.7%), while the lowest frequency rate was observed against herbal remedies with 15 (1.2%). The results of the current study concluded that students practiced self-medication for reasons such as convenience to obtain these medications from cheap sources and to avoid the fee of a physician. They searched for the medicine on social media platforms and purchased it blindly from the pharmacy without any prescription from a physician.
      Citation: Antibiotics
      PubDate: 2022-06-23
      DOI: 10.3390/antibiotics11070842
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 843: Emerging Antibiotic Resistance Patterns
           Affect Visual Outcome Treating Acute Endophthalmitis

    • Authors: Xia-Ni Wu, Yi-Hsing Chen, Lazha Sharief, Ahmed Al-Janabi, Nura Al Qassimi, Sue Lightman, Oren Tomkins-Netzer
      First page: 843
      Abstract: Background: Examining the effect of antibiotic resistance, use of intravitreal antibiotics and systemic corticosteroids on visual outcome of eyes with acute endophthalmitis. Methods: We included 226 eyes with acute endophthalmitis, treated using a standardized protocol. Visual outcome up to 12 months was assessed related to biopsy results, antibiotics resistance and treatment regimens. Results: Vitreous biopsies were more likely to be culture-positive (41.1%) than anterior chamber biopsies (21.6%, p < 0.0001). Antibiotic resistance for amikacin was found in 19 eyes (24.7%), vancomycin in 29 eyes (31.5%) and moxiflocacin in 14 eyes (16.1%). At presentation 91.53% of eyes had BCVA < 20/40, reducing by 1 month to 69.94% (p < 0.0001) and remaining stable at 12 months. There was no difference in visual outcome for those receiving early systemic corticosteroids. Endophthalmitis following cataract surgery (OR 1.66, 1.04–2.66 95% CI, p = 0.03) and receiving intravitreal vancomycin (OR 3.15, 1.18–8.42 95% CI, p = 0.02) were associated with a greater chance of final BCVA ≥ 20/40. Conclusion: Using vitreous taps with intravitreal antibiotics, despite an increase in resistance to both vancomycin and moxifloxacin, results in a final BCVA > 20/200 in half of eyes and ≥20/40 in a third. Early treatment with intravitreal antibiotics should not be delayed.
      Citation: Antibiotics
      PubDate: 2022-06-23
      DOI: 10.3390/antibiotics11070843
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 844: Antimicrobial Susceptibility Profiles and
           Molecular Characterisation of Staphylococcus aureus from Pigs and Workers
           at Farms and Abattoirs in Zambia

    • Authors: Mulemba Tillika Samutela, Bruno Stephen July Phiri, Edgar Simulundu, Geoffrey Kwenda, Ladslav Moonga, Eugene C. Bwalya, Walter Muleya, Therese Nyirahabimana, Kaunda Yamba, Henson Kainga, Simegnew Adugna Kallu, Innocent Mwape, Andrew Frey, Matthew Bates, Hideaki Higashi, Bernard Mudenda Hang'ombe
      First page: 844
      Abstract: Pigs have been shown to be a reservoir for recently emerging livestock-associated Staphylococcus aureus (LA-SA), including methicillin resistant strains in many countries worldwide. However, there is sparse information about LA-SA strains circulating in Zambia. This study investigated the prevalence, phenotypic and genotypic characteristics of S. aureus from pigs and workers at farms and abattoirs handling pigs in Lusaka Province of Zambia. A total of 492 nasal pig swabs, 53 hand and 53 nasal human swabs were collected from farms and abattoirs in selected districts. Standard microbiological methods were used to isolate and determine antimicrobial susceptibility patterns of S. aureus. Polymerase Chain Reaction was used to confirm the species identity and detect antimicrobial resistance and virulence genes of isolates, whereas genetic diversity was evaluated using spa typing. Overall prevalence of S. aureus was 33.1%, 37.8% for pigs and 11.8% for humans. The isolates were resistant to several antibiotics with resistance ranging from 18% to 98% but were all susceptible to vancomycin. Typical LA-SA spa types were detected. The presence of plasmid mediated resistance genes such as tetM (12.8%), other resistance determinants and immune evasion cluster genes among the isolates is of great public health concern. Thus, continuous surveillance of S. aureus using a “One health” approach is warranted to monitor S.aureus infections and spread of antimicrobial resistance.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070844
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 845: A Universal LC-MS/MS Method for
           Simultaneous Detection of Antibiotic Residues in Animal and Environmental

    • Authors: Chak-Lun Chan, Hogan Kok-Fung Wai, Peng Wu, Siu-Wai Lai, Olivia Sinn-Kay Chan, Hein M. Tun
      First page: 845
      Abstract: Detecting and monitoring the usage of antibiotics is a critical aspect of efforts to combat antimicrobial resistance. Antibiotic residue testing with existing LC-MS/MS methods is limited in detection range. Current methods also lack the capacity to detect multiple antibiotic residues in different samples simultaneously. In this study, we demonstrate a methodology that permits simultaneous extraction and detection of antibiotic residues in animal and environmental samples. A total of 30 different antibiotics from 13 classes could be qualitatively detected with our methodology. Further study to reduce analytes’ matrix effect would allow for quantification of antibiotic residues.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070845
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 846: Stemming the Rise of Antibiotic Use for
           Community-Acquired Acute Respiratory Infections during COVID-19 Pandemic

    • Authors: Shena Y. C. Lim, Yvonne P. Zhou, Daphne Yii, De Zhi Chin, Kai Chee Hung, Lai Wei Lee, Jia Le Lim, Li Wen Loo, Narendran Koomanan, Nathalie Grace Chua, Yixin Liew, Benjamin P. Z. Cherng, Siew Yee Thien, Winnie H. L. Lee, Andrea L. H. Kwa, Shimin J. Chung
      First page: 846
      Abstract: At the start of the COVID-19 pandemic, there was an increase in the use of antibiotics for the treatment of community-acquired respiratory tract infection (CA-ARI) in patients admitted for suspected or confirmed COVID-19, raising concerns for misuse. These antibiotics are not under the usual purview of the antimicrobial stewardship unit (ASU). Serum procalcitonin, a biomarker to distinguish viral from bacterial infections, can be used to guide antibiotic recommendations in suspected lower respiratory tract infection. We modified our stewardship approach, and used a procalcitonin-guided strategy to identify “high yield” interventions for audits in patients admitted with CA-ARI. With this approach, there was an increase in the proportion of patients with antibiotics discontinued within 4 days (16.5% vs. 34.9%, p < 0.001), and the overall duration of antibiotic therapy was significantly shorter [7 (6–8) vs. 6 (3–8) days, p < 0.001]. There was a significant decrease in patients with intravenous-to-oral switch of antibiotics to “complete the course” (45.3% vs. 34.4%, p < 0.05). Of the patients who had antibiotics discontinued, none were restarted on antibiotics within 48 h, and there was no-30-day readmission or 30-day mortality attributed to respiratory infection. This study illustrates the importance of the antimicrobial stewardship during the pandemic and the need for ASU to remain attuned to prescriber’s practices, and adapt accordingly to address antibiotic misuse to curb antimicrobial resistance.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070846
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 847: Antibiotic (Mis)Use in COVID-19 Patients
           before and after Admission to a Tertiary Hospital in Serbia

    • Authors: Aleksa Despotović, Aleksandra Barać, Teodora Cucanić, Ksenija Cucanić, Goran Stevanović
      First page: 847
      Abstract: Antimicrobial resistance (AMR) is a global concern, and antibiotic use has risen throughout the COVID-19 pandemic. Up to 75% of COVID-19 patients are treated with antibiotics despite little evidence for their use. A retrospective study from 6 March 2020 (the start of the pandemic in Serbia) to 31 December 2021 was conducted at the Clinic for Infectious and Tropical Diseases, University Clinical Centre of Serbia. In total, 523 patients with a microbiological diagnosis of COVID-19 were included. Patient data were analysed, including antibiotic use before and after admission. Pre-admission use of antibiotics for COVID-19 treatment was documented in more than half of patients (58.1%), of which a third (34.1%) used more than one antibiotic. Macrolides, cephalosporins, and fluoroquinolones were mainly used, most frequently among patients aged between 31–45 years (75.2%). Prior antibiotic use was associated with a longer duration of illness at admission (8.8 vs. 5.7, p < 0.001), oxygen therapy upon admission (27.6% vs. 16.0%, p = 0.002), and a lower vaccination rate (60.7% vs. 50.7%, p = 0.04). When hospitalised, 72.1% of patients received antibiotics, primarily cephalosporins (71.9%). Significant efforts are needed to reduce antibiotic use in the community and improve prescribing rates by healthcare professionals.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070847
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 848: The Array of Antibacterial Action of
           Protocatechuic Acid Ethyl Ester and Erythromycin on Staphylococcal Strains

    • Authors: Maria Miklasińska-Majdanik, Małgorzata Kępa, Monika Kulczak, Maciej Ochwat, Tomasz J. Wąsik
      First page: 848
      Abstract: The spread of antibiotic resistance among bacteria has become one of the major health problems worldwide. Methicillin-resistant staphylococcal strains are especially dangerous because they are often resistant to other antibiotics. The increasing insensitivity to macrolides, lincosamides and streptogramin B antibiotics of methicillin-resistant staphylococcal isolates has limited the use of these drugs in therapy. The combination of natural compounds and antibiotics can be considered as an alternative tool to fight multi-drug-resistant pathogen infections. The aim of the presented study was to examine the antibacterial activity of protocatechuic acid ethyl ester–erythromycin combination towards Staphylococcus aureus and Staphylococcus epidermidis strains with various resistance profiles to methicillin and macrolides, lincosamides and streptogramin B (MLSB) antibiotics. The in-vitro antibacterial potential of the above combination was investigated by minimum inhibitory concentration assays and checkerboard testing. The observed effects were strain dependent, with 8 of 12 tested staphylococcal strains showing an indifferent effect on the natural compound and erythromycin; for 2 strains, the tested combination had an additive effect, while for another 2, the effect was synergistic. Interestingly, the multi-drug-resistant strains were more sensitive to the cooperative action of the protocatechuic acid ethyl ester and the antibiotic.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070848
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 849: Review of Antimicrobial Resistance in
           Wastewater in Japan: Current Challenges and Future Perspectives

    • Authors: Hiroaki Baba, Masateru Nishiyama, Toru Watanabe, Hajime Kanamori
      First page: 849
      Abstract: Antimicrobial resistance (AMR) circulates through humans, animals, and the environments, requiring a One Health approach. Recently, urban sewage has increasingly been suggested as a hotspot for AMR even in high-income countries (HICs), where the water sanitation and hygiene infrastructure are well-developed. To understand the current status of AMR in wastewater in a HIC, we reviewed the epidemiological studies on AMR in the sewage environment in Japan from the published literature. Our review showed that a wide variety of clinically important antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs), and antimicrobial residues are present in human wastewater in Japan. Their concentrations are lower than in low- and middle-income countries (LMICs) and are further reduced by sewage treatment plants (STPs) before discharge. Nevertheless, the remaining ARB and ARGs could be an important source of AMR contamination in river water. Furthermore, hospital effluence may be an important reservoir of clinically important ARB. The high concentration of antimicrobial agents commonly prescribed in Japan may contribute to the selection and dissemination of AMR within wastewater. Our review shows the importance of both monitoring for AMR and antimicrobials in human wastewater and efforts to reduce their contamination load in wastewater.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070849
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 749: Antiamoebic Properties of Laboratory and
           Clinically Used Drugs against Naegleria fowleri and Balamuthia

    • Authors: Ruqaiyyah Siddiqui, Mohammad Ridwane Mungroo, Tengku Shahrul Anuar, Ahmad M. Alharbi, Hasan Alfahemi, Adel B. Elmoselhi, Naveed Ahmed Khan
      First page: 749
      Abstract: Naegleria fowleri and Balamuthia mandrillaris are pathogenic free-living amoebae that infect the central nervous system with over 95% mortality rates. Although several compounds have shown promise in vitro but associated side effects and/or prolonged approval processes for clinical applications have led to limited success. To overcome this, drug repurposing of marketed compounds with known mechanism of action is considered a viable approach that has potential to expedite discovery and application of anti-amoebic compounds. In fact, many of the drugs currently employed in the treatment of N. fowleri and B. mandrillaris, such as amphotericin B, fluconazole, rifampin and miltefosine, are repurposed drugs. Here, we evaluated a range of clinical and laboratory compounds including metformin, quinclorac, indaziflam, inositol, nateglinide, 2,6-DNBT, trans-cinnamic acid, terbuthylazine, acarbose, glimepiride, vildagliptin, cellulase, thaxtomin A, repaglinide and dimethyl peptidase (IV) inhibitor against N. fowleri and B. mandrillaris. Anti-amoebic assays revealed that indaziflam, nateglinide, 2,6-DNBT, terbuthylazine, acarbose and glimepiride exhibited potent amoebicidal properties against both N. fowleri and B. mandrillaris. Notably, all compounds tested showed minimal human (HaCaT) cell cytotoxicity as determined by lactate dehydrogenase release. Prospective research using animal models is warranted to determine the potential of these repurposed compounds, as well as the need for investigating the intranasal route of delivery to treat these devastating infections.
      Citation: Antibiotics
      PubDate: 2022-05-31
      DOI: 10.3390/antibiotics11060749
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 751: Resistance to Mecillinam and Nine Other
           Antibiotics for Oral Use in Escherichia coli Isolated from Urine Specimens
           of Primary Care Patients in Germany, 2019/20

    • Authors: Michael Kresken, Yvonne Pfeifer, Florian Wagenlehner, Guido Werner, Esther Wohlfarth, on behalf of Study Group ‘Antimicrobial Resistance‘ of the Paul Ehrlich Society for Infection Therapy
      First page: 751
      Abstract: Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Escherichia coli is by far the leading cause of community-acquired UTIs. Pivmecillinam, the oral prodrug of the penicillin derivative mecillinam (amdinocillin), was re-introduced in Germany in March 2016 for first-line treatment of acute uncomplicated cystitis. This study aimed to evaluate the prevalence of resistance to mecillinam in comparison to nine other antibiotics used for oral treatment in E. coli urine isolates after the re-introduction of pivmecillinam. A total of 460 isolates were collected at 23 laboratories of clinical microbiology between October 2019 and March 2020. Forty-six isolates (10.0%) produced an extended-spectrum β-lactamase (ESBL) of the CTX-M family. Resistance to amoxicillin (43.3%) was most widespread, followed by resistance to trimethoprim-sulfamethoxazole (27.0%), amoxicillin-clavulanic acid (18.0%), cefuroxime (11.3%), and ciprofloxacin (11.1%). Twenty-four E. coli isolates (5.2%) were resistant to mecillinam. The concentrations of mecillinam needed to inhibit 50/90% of the ESBL-producing isolates and the remaining isolates were 1/4 mg/L and 0.5/4 mg/L, respectively. The findings support the recommendation to regard pivmecillinam as a first-line option for the treatment of uncomplicated lower UTIs.
      Citation: Antibiotics
      PubDate: 2022-05-31
      DOI: 10.3390/antibiotics11060751
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 752: The In-Vitro Activity of a Cold
           Atmospheric Plasma Device Utilizing Ambient Air against Bacteria and
           Biofilms Associated with Periodontal or Peri-Implant Diseases

    • Authors: Gert Jungbauer, Leandro Favaro, Steffen Müller, Anton Sculean, Sigrun Eick
      First page: 752
      Abstract: Due to its antimicrobial and healing-promoting effects, the application of cold atmospheric plasma (CAP) appears to be a promising modality in various fields of general medicine and dentistry. The aim of the present study was to evaluate the antibacterial and anti-biofilm activity of a handheld device utilizing ambient air for plasma generation. Suspensions of 11 oral bacteria (among them Fusobacterium nucleatum, Porphyromonas gingivalis, Parvimonas micra, Streptococcus gordonii, and Tannerella forsythia) were exposed to CAP for 10, 30, 60, and 120 s. Before and after treatment, colony forming unit (CFU) counts were determined. Then, 12-species biofilms were cultured on dentin and titanium specimens, and CAP was applied for 30, 60, and 120 s before quantifying CFU counts, biofilm mass, and metabolic activity. A reduction of ≥3 log10 CFU, was found for ten out of the eleven tested species at 30 s (except for T. forsythia) and for all species at 60 s. For biofilm grown on dentin and titanium specimens, the log10 reductions were 2.43 log10 CFU/specimen and by about 4 log10 CFU/specimen after 120 s of CAP. The CAP application did not reduce the biomass significantly, the metabolic activity of the biofilms on dentin and titanium decreased by 98% and 95% after 120 s of CAP. An application of 120 s of CAP had no cytotoxic effect on gingival fibroblasts and significantly increased the adhesion of gingival fibroblasts to the titanium surface. These results are promising and underline the potential of CAP for implementation in periodontal and peri-implantitis therapy.
      Citation: Antibiotics
      PubDate: 2022-05-31
      DOI: 10.3390/antibiotics11060752
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 753: Use of Antibiotics Against Bacterial
           Infections on Dairy Sheep and Goat Farms: Patterns of Usage and
           Associations with Health Management and Human Resources

    • Authors: Daphne T. Lianou, George C. Fthenakis
      First page: 753
      Abstract: The objectives of the study were (a) to describe the patterns of antibiotic usage against four major clinical problems and (b) to evaluate factors that were associated with their use on small ruminant farms. Sheep and goat farmers mostly administered the antibiotics to animals at the dose prescribed (80.4%) and observed the necessary withdrawal period (98.7%), but fewer farmers (22.3%) weighed the animals to calculate their bodyweight before antibiotic administration. For the treatment of clinical mastitis, oxytetracycline, penicillin and streptomycin were the antibiotics used more frequently; 2.03 different antibiotics were used per sheep flock and 2.06 per goat herd, most frequently administered in injectable forms (88.8% of farms). In cases of abortion, oxytetracycline was administered more frequently; 1.12 different antibiotics were used per sheep flock and 1.03 per goat herd. In 94 farms (21.2%), routine administration of antibiotics was performed to newborns; oxytetracycline and ampicillin were administered more often. For the treatment of pneumonia in newborns, oxytetracycline, penicillin and tulathromycin were used more frequently; 1.33 antibiotics were used per sheep flock and 1.29 per goat herd. For the treatment of diarrhoea in lambs and kids, oxytetracycline, amoxicillin and penicillin were the antibiotics used more frequently; 1.34 antibiotics were used per sheep flock and 1.59 per goat herd. Results of multivariable analyses indicated 16 variables associated with the various outcomes for usage of antibiotics for the treatment of the above clinical problems. Of these, 11 variables were associated with the farmers: education of farmers was significant for three outcomes; the age, the experience, the professional involvement and farming family tradition of farmers and the daily period spent at the farm were each significant for one outcome.
      Citation: Antibiotics
      PubDate: 2022-05-31
      DOI: 10.3390/antibiotics11060753
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 754: Antibacterial and Anti-Inflammatory
           Properties of a Novel Antimicrobial Peptide Derived from LL-37

    • Authors: Haiwei Zhuo, Xi Zhang, Maogen Li, Qian Zhang, Yonglan Wang
      First page: 754
      Abstract: Peri-implantitis is a pathological condition involving tissues around dental implants that are characterized by inflammation of the peri-implant mucosa and progressive loss of supporting bone. We found that the antimicrobial peptide KR-12-3 (KRIVKWIKKFLR) derived from LL-37 had antibacterial properties against Streptococcus gordonii. The purpose of this study was to evaluate its antibacterial and anti-inflammatory activities and its underlying mechanisms. We evaluated the antibacterial activities of antimicrobial peptides in planktonic and biofilm states by measuring their minimum inhibitory concentration, minimum bactericidal concentration, and biofilm susceptibility. The effects of antimicrobial peptides on the production of IL-6 and IL-8 in LPS-stimulated RAW264.7 cells were detected by enzyme-linked immunosorbent assay and other experiments, and their toxicity to MC3T3-E1 cells was also studied. While maintaining low cytotoxicity, KR-12-3 exhibited growth inhibitory effects on S. gordonii in planktonic and biofilm states. Lower concentrations of KR-12-3 treatment reduced the production of inflammatory cytokines in LPS-stimulated RAW264.8 cells. The mechanisms underlying the inhibition of biofilm formation and anti-inflammatory effects have been associated with the low expression of related genes. KR-12-3 may be used to develop an antibacterial, anti-infective, and anti-inflammatory drugs for peri-implantitis.
      Citation: Antibiotics
      PubDate: 2022-06-01
      DOI: 10.3390/antibiotics11060754
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 755: Antimicrobial Resistance Research
           Collaborations in Asia: Challenges and Opportunities to Equitable

    • Authors: Pami Shrestha, Shiying He, Helena Legido-Quigley
      First page: 755
      Abstract: Antimicrobial Resistance is recognized as a major threat to global health security. The WHO Southeast Asia region is dubbed a “global hub for AMR emergence”, as it runs the highest risk for AMR emergence among all WHO regions in Asia. Hence, there is a need for Asia-centric, collaborative AMR research aligned with the true needs and priorities of the region. This study aimed to identify and understand the challenges and opportunities for such collaborative endeavors to enhance equitable partnerships. This qualitative study adopted an interpretative approach involving a thematic analysis of 15 semi-structured interviews with AMR experts conducting research in the region. The study identified several factors influencing research collaborations, such as the multi-dimensional nature of AMR, limited or lack of funds, different AMR research priorities in Asian countries, absence of Asia-centric AMR leadership, lack of trust and, unequal power relationships between researchers, and the negative impact of the COVID-19 pandemic in research collaborations. It also identified some opportunities, such as the willingness of researchers to collaborate, the formation of a few networks, and the prioritization by many academics of the One Health paradigm for framing AMR research. Participants reported that the initiation of stronger cross-discipline and cross-country networks, the development of Asia-centric AMR leadership, flexible research agendas with shared priorities, transparent and transferable funds, and support to enhance research capacity in LMICs could assist in developing more equitable collaborative research in Asia.
      Citation: Antibiotics
      PubDate: 2022-06-01
      DOI: 10.3390/antibiotics11060755
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 756: Comparison and Advanced Antimicrobial
           Strategies of Silver and Copper Nanodrug-Loaded Glass Ionomer Cement
           against Dental Caries Microbes

    • Authors: Amal Adnan Ashour, Mohammed Fareed Felemban, Nayef H. Felemban, Enas T. Enan, Sakeenabi Basha, Mohamed M. Hassan, Sanaa M. F. Gad El-Rab
      First page: 756
      Abstract: Caries lesions during cement repairs are a severe issue, and developing a unique antimicrobial restorative biomaterial can help to reduce necrotic lesion recurrence. As a result, Thymus vulgaris extract was used to biosynthesize copper nanoparticles (TVE-CuNPs) exhibiting different characteristics (TVE). Along with TVE-CuNPs, commercial silver nanoparticles (AgNPs) and metronidazole were combined with glass ionomer cement (GIC) to test its antibacterial efficacy and compressive strength. FTIR, XRD, UV-Vis spectrophotometry, and TEM were applied to characterize the TVE-CuNPs. Additionally, AgNPs and TVE-CuNPs were also combined with metronidazole and GIC. The modified GIC samples were divided into six groups, where groups 1 and 2 included conventional GIC and GIC with 1.5% metromidazole, respectively; group 3 had GIC with 0.5% TVE-CuNPs, while group 4 had 0.5% TVE-CuNPs with metronidazole in 1.5%; group 5 had GIC with 0.5% AgNPs, and group 6 had 0.5% AgNPs with metronidazole at 1.5%. An antimicrobial test was performed against Staphylococcus aureus (S. aureus) and Streptococcus mutans (S. mutans) by the disc diffusion method and the modified direct contact test (MDCT). GIC groups 4 and 6 demonstrated a greater antimicrobial efficiency against the two tested strains than the other groups. In GIC groups 4 and 6, the combination of GIC with two antimicrobial agents, 1.5% metronidazole and 0.5% TVE-CuNPs or AgNPs, enhanced the antimicrobial efficiency when compared to that of the other groups with or without a single agent. GIC group specimens combined with nanosilver and nanocopper had similar mean compressive strengths when compared to the other GIC groups. Finally, the better antimicrobial efficacy of GIC boosted by metronidazole and the tested nanoparticles against the tested strains may be relevant for the future creation of more efficient and modified restorations to reduce dental caries lesions.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060756
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 757: Treatment of Pediatric Helicobacter
           pylori Infection

    • Authors: Hung-Hsiang Lai, Ming-Wei Lai
      First page: 757
      Abstract: Helicobacter pylori infection can cause gastritis, gastric or duodenal ulcers, mucosa-associated lymphoid tissue lymphoma, gastric cancer, and extra-gastrointestinal manifestations. Ideal treatment should be guided by antibiotic susceptibility testing. However, this is not feasible in many regions, so the treatment generally relies on clinical experience and regional culture sensitivity profiles. We aimed to integrate the treatment of pediatric H. pylori infection through a systematic literature review. Databases including PubMed, Cochrane Library, EMBASE, and Scholar were searched using terms containing (Helicobacter OR Helicobacter pylori OR H. pylori) AND (child OR pediatric) for all relevant manuscripts and guidelines, published from January 2011 to December 2021. The eradication rate for pediatric H. pylori infection was not satisfactory using triple therapy, sequential therapy, concomitant therapy, bismuth-based quadruple therapy, or adjuvant therapy with probiotics as the first-line therapy. Most therapies could not achieve the recommended eradication rate of >90%, which may be attributed to varying regional antibiotic resistance and possible poor children’s compliance. More studies are required to establish a best practice for pediatric H. pylori infection treatment.
      Citation: Antibiotics
      PubDate: 2022-06-01
      DOI: 10.3390/antibiotics11060757
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 758: Evaluation of a Meropenem and
           Piperacillin Monitoring Program in Intensive Care Unit Patients Calls for
           the Regular Assessment of Empirical Targets and Easy-to-Use Dosing
           Decision Tools

    • Authors: Ferdinand Anton Weinelt, Miriam Songa Stegemann, Anja Theloe, Frieder Pfäfflin, Stephan Achterberg, Franz Weber, Lucas Dübel, Agata Mikolajewska, Alexander Uhrig, Peggy Kiessling, Wilhelm Huisinga, Robin Michelet, Stefanie Hennig, Charlotte Kloft
      First page: 758
      Abstract: The drug concentrations targeted in meropenem and piperacillin/tazobactam therapy also depend on the susceptibility of the pathogen. Yet, the pathogen is often unknown, and antibiotic therapy is guided by empirical targets. To reliably achieve the targeted concentrations, dosing needs to be adjusted for renal function. We aimed to evaluate a meropenem and piperacillin/tazobactam monitoring program in intensive care unit (ICU) patients by assessing (i) the adequacy of locally selected empirical targets, (ii) if dosing is adequately adjusted for renal function and individual target, and (iii) if dosing is adjusted in target attainment (TA) failure. In a prospective, observational clinical trial of drug concentrations, relevant patient characteristics and microbiological data (pathogen, minimum inhibitory concentration (MIC)) for patients receiving meropenem or piperacillin/tazobactam treatment were collected. If the MIC value was available, a target range of 1–5 × MIC was selected for minimum drug concentrations of both drugs. If the MIC value was not available, 8–40 mg/L and 16–80 mg/L were selected as empirical target ranges for meropenem and piperacillin, respectively. A total of 356 meropenem and 216 piperacillin samples were collected from 108 and 96 ICU patients, respectively. The vast majority of observed MIC values was lower than the empirical target (meropenem: 90.0%, piperacillin: 93.9%), suggesting empirical target value reductions. TA was found to be low (meropenem: 35.7%, piperacillin 50.5%) with the lowest TA for severely impaired renal function (meropenem: 13.9%, piperacillin: 29.2%), and observed drug concentrations did not significantly differ between patients with different targets, indicating dosing was not adequately adjusted for renal function or target. Dosing adjustments were rare for both drugs (meropenem: 6.13%, piperacillin: 4.78%) and for meropenem irrespective of TA, revealing that concentration monitoring alone was insufficient to guide dosing adjustment. Empirical targets should regularly be assessed and adjusted based on local susceptibility data. To improve TA, scientific knowledge should be translated into easy-to-use dosing strategies guiding antibiotic dosing.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060758
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 759: Proteomic Comparison of Ivermectin
           Sensitive and Resistant Staphylococcus aureus Clinical Isolates Reveals
           Key Efflux Pumps as Possible Resistance Determinants

    • Authors: Shoaib Ashraf, Débora Parrine, Muhammad Bilal, Umer Chaudhry, Mark Lefsrud, Xin Zhao
      First page: 759
      Abstract: Ivermectin (IVM) is a versatile drug used against many microorganisms. Staphylococcus aureus is one of the most devastating microorganisms. IVM sensitive and resistant S. aureus strains were recently reported. However, the underlying molecular mechanisms of resistance are unknown. Clinical isolates of S. aureus were used for determination of the sensitivities against IVM by growth curve analysis and time-kill kinetics. Then, proteomic, and biochemical approaches were applied to investigate the possible mechanisms of resistance. Proteomic results showed a total of 1849 proteins in the dataset for both strains, 425 unique proteins in strain O9 (IVM sensitive), and 354 unique proteins in strain O20 (IVM resistant). Eight proteins with transport functions were differentially expressed in the IVM resistant strain. Among them, three efflux pumps (mepA, emrB, and swrC) were confirmed by qPCR. The IVM resistant S. aureus may overexpress these proteins as a key resistance determinant. Further experiments are required to confirm the exact mechanistic relationship. Nevertheless, the possibility of blocking these transporters to reverse or delay the onset of resistance and reduce selection pressure is potentially appealing.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060759
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 760: Impact of Pharmacist-Led Implementation
           of a Community Hospital-Based Outpatient Parenteral Antimicrobial Therapy
           on Clinical Outcomes in Thailand

    • Authors: Teeranuch Thomnoi, Virunya Komenkul, Abhisit Prawang, Wichai Santimaleeworagun
      First page: 760
      Abstract: Few studies have analyzed community hospital-based parenteral anti-infective therapy (CohPAT). We aimed to assess the clinical impact of a pharmacist-led implementation of a clinical practice guideline (CPG) for CohPAT, and to determine the pharmacist’s role in CohPAT medication management. The prospective-period patients (post-implementation group) were compared with the historical control-period patients (pre-implementation group) for receiving a continuous antimicrobial parenteral injection. A CPG was used for laboratory testing for efficacy and safety, the monitoring of adverse drug events during admission, microbiology results coordination, and dosage adjustment. For any antimicrobial drug-related problems, the pharmacist consulted with the clinicians. Over 14 months, 50 participants were included in each group. In the pre-implementation period, 7 (14%) and 4 (8%) out of 50 patients received an inappropriate dosage and nonlaboratory monitoring for dose adjustment, respectively. The patients received the proper dosage of antimicrobial agents, which increased significantly from 78% pre- to 100% post-implementation (p = 0.000). The pharmacist’s interventions during the prospective-period were completely accepted by the clinicians, and significantly greater laboratory monitoring complying with CPG was given to the postimplementation group than the pre-implementation group (100% vs. 60%; p = 0.000). Significantly less patients with unfavorable outcomes (failure or in-hospital mortality) were observed in the post-implementation than in the pre-implementation (6% vs. 26%; p = 0.006) group. For the logistic regression analysis, lower respiratory infection (adjusted OR, aOR 3.68; 95%CI 1.13–12.06) and the post-implementation period (aOR 0.21; 95%CI 0.06–0.83) were significant risk factors that were associated with unfavorable outcomes. Given the better clinical outcomes and the improved quality of septic patient care observed after implementation, pharmacist-led implementation should be adopted in healthcare settings.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060760
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 761: Enhanced Photocatalytic Degradation of
           Tetracycline and Oxytetracycline Antibiotics by BiVO4 Photocatalyst under
           Visible Light and Solar Light Irradiation

    • Authors: Khuanjit Hemavibool, Theepakorn Sansenya, Suwat Nanan
      First page: 761
      Abstract: The efficient degradation of a toxic antibiotic from an aqueous solution is essential for environmental protection. Our research aimed to fabricate a bismuth vanadate (BiVO4) catalyst via a facile hydrothermal method. The prepared catalyst exhibited a monoclinic phase with a band gap energy of 2.33 eV, indicating the excellent visible-light-active properties of a semiconductor. The photocatalytic performance of the synthesized BiVO4 catalyst was studied by determining the removal of tetracycline (TC) and oxytetracycline (OTC) antibiotics. After 240 min, under sunlight conditions, a high performance of 72% and 83% degradation of TC and OTC, respectively, was achieved. The photocatalytic degradation of the antibiotics correlates well with a first-order reaction, with a high rate constant of 0.0102 min−1. Photogenerated electrons and holes played an important role in the removal of the pollutant. After photocatalytic study, the structural stability of the prepared bismuth vanadate photocatalyst was confirmed. The photocatalyst provided a promising performance even after five successive runs. The result indicates the excellent cycling ability of the sample. The present work demonstrates a promising route for the preparation of a BiVO4 catalyst for the complete removal of toxic antibiotics in aqueous solutions.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060761
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 762: Mortality in Thai Nursing Homes Based on
           Antimicrobial-Resistant Enterobacterales Carriage and COVID-19 Lockdown
           Timing: A Prospective Cohort Study

    • Authors: Thundon Ngamprasertchai, Muthita Vanaporn, Sant Muangnoicharoen, Wirichada Pan-ngum, Narisa Ruenroengbun, Pittaya Piroonamornpun, Thitiya Ponam, Chatnapa Duangdee, Phanita Chankete, Anupop Jitmuang, Visanu Thamlikitkul
      First page: 762
      Abstract: Antimicrobial-resistant Enterobacterales carriage and the coronavirus disease 2019 (COVID-19) lockdown measures may impact the incidence all-cause mortality rate among nursing home residents. To determine the all-cause mortality rate in the presence/absence of antimicrobial-resistant Enterobacterales carriage and the incidence all-cause mortality rate before and during COVID-19 pandemic lockdown, this prospective closed-cohort study was conducted at various types of nursing homes in Bangkok, Thailand, from June 2020 to December 2021. The elderly residents included 142 participants (aged ≥60 years) living in nursing homes ≥3 months, who did not have terminal illnesses. Time-to-event analyses with Cox proportional hazards models and stratified log-rank tests were used. The all-cause mortality rate was 18%, and the incidence all-cause mortality rate was 0.59/1000 person-days in residents who had antimicrobial-resistant Enterobacterales carriage at baseline. Meanwhile, the incidence all-cause mortality rate among noncarriage was 0.17/1000 person-days. The mortality incidence rate of carriage was three times higher than residents who were noncarriage without statistical significance (HR 3.2; 95% CI 0.74, 13.83). Residents in nonprofit nursing homes had a higher mortality rate than those in for-profit nursing homes (OR 9.24; 95% CI 2.14, 39.86). The incidence mortality rate during and before lockdown were 0.62 and 0.30, respectively. Effective infection-control policies akin to hospital-based systems should be endorsed in all types of nursing homes. To limit the interruption of long-term chronic care, COVID-19 prevention should be individualized to nursing homes.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060762
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 763: Search for Indexes to Evaluate Trends in
           Antibiotic Use in the Sub-Prefectural Regions Using the National Database
           of Health Insurance Claims and Specific Health Checkups of Japan

    • Authors: Kanako Mizuno, Ryo Inose, Yuna Matsui, Mai Takata, Daisuke Yamasaki, Yoshiki Kusama, Ryuji Koizumi, Masahiro Ishikane, Masaki Tanabe, Hiroki Ohge, Norio Ohmagari, Yuichi Muraki
      First page: 763
      Abstract: The evaluation indexes of antimicrobial use (AMU) in sub-prefectural regions have not been established because these regional units are susceptible to the effects of population inflows and outflows. We defined the difference in AMU calculated each year as a new evaluation index and compared the AMU of secondary medical areas with those already reported for Japan and each prefecture. Patients/1000 inhabitants/day (PID) for oral antibiotics in 2013 and 2016 were calculated using the National Database of Health Insurance Claims and Specific Health Checkups. ΔPID was defined as the difference between the PIDs in 2013 and 2016. Differences in AMUs for Japan and prefectures that have already been published were also calculated, and the concordance rate with ΔPID in each secondary medical area was evaluated. Antibiotics and age groups with less than 50% concordance between secondary medical area and previously reported AMU changes were observed. This revealed that even at the secondary medical area level, which is more detailed than the prefectural level, the AMU changes were not consistent. Therefore, in order to appropriately promote measures against antimicrobial resistance, we suggest the necessity of not only surveying AMU at the national or prefectural levels but also examining sub-prefectural trends in AMU.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060763
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 764: Empirical Antibiotic Prescribing in Adult
           COVID-19 Inpatients over Two Years in Mexico

    • Authors: Efrén Murillo-Zamora, Xóchitl Trujillo, Miguel Huerta, Oliver Mendoza-Cano, José Guzmán-Esquivel, José Alejandro Guzmán-Solórzano, María Regina Ochoa-Castro, Alan Gabriel Ortega-Macías, Andrea Lizeth Zepeda-Anaya, Valeria Ruiz-Montes de Oca, Mónica Ríos-Silva, Agustin Lugo-Radillo
      First page: 764
      Abstract: Background and Objectives: Empirical antibiotic prescribing in patients with coronavirus disease 2019 (COVID-19) has been common even though bacterial coinfections are infrequent. The overuse of antibacterial agents may accelerate the antibiotic resistance crisis. We aimed to evaluate factors predicting empirical antibiotic prescribing to adult COVID-19 inpatients over 2 years (March 2020–February 2021) in Mexico. Materials and Methods: A cross-sectional analysis of a nationwide cohort study was conducted. Hospitalized adults due to laboratory-confirmed COVID-19 were included (n = 214,171). Odds ratios (OR) and 95% confidence intervals (CI), computed by using logistic regression models, were used to evaluate factors predicting empirical antibiotic prescribing. Results: The overall frequency of antibiotic usage was 25.3%. In multiple analysis, the highest risk of antibiotic prescription was documented among patients with pneumonia at hospital admission (OR = 2.20, 95% CI 2.16–2.25). Male patients, those with chronic comorbidities (namely obesity and chronic kidney disease) and longer interval days from symptoms onset to healthcare seeking, were also more likely to receive these drugs. We also documented that, per each elapsed week during the study period, the odds of receiving antibiotic therapy decreased by about 2% (OR = 0.98, 95% CI 0.97–0.99). Conclusion: Our study identified COVID-19 populations at increased risk of receiving empirical antibiotic therapy during the first two years of the pandemic.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060764
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 765: Persistent Coagulase-Negative
           Staphylococcal Bacteremia in Neonates: Clinical, Microbiological
           Characteristics and Changes within a Decade

    • Authors: Venetia Bellou, Despoina Gkentzi, Nikolaos Giormezis, Aggeliki Vervenioti, Iris Spiliopoulou, Gabriel Dimitriou
      First page: 765
      Abstract: Atypical outbreaks of persistent coagulase-negative staphylococci (CoNS) bacteremias, defined as three or more consecutive positive blood cultures with the same CoNS species, at least 48 h apart, have been reported in neonatal intensive-care units (NICUs). Our aim was to describe the profile of these cases in our NICU over a two-year period with the objective of assessing possible changes within a decade. Demographics, clinical and microbiological data were recorded for all CoNS bacteremias in our tertiary NICU during 2016–2017 and compared with the results of the same study in 2006–2007. Fifty-six cases of CoNS sepsis were recorded. Fourteen (25%) of them were persistent. There were no significant differences in demographic and clinical characteristics between cases with persistent vs. non-persistent bacteremia. Staphylococcus epidermidis was the most common species. In logistic regression analysis, biofilm production (β = 2.464, p = 0.04) was the most significant determinant for the development of persistent CoNS bacteremia. Our isolates were less likely to produce biofilm and carry ica operon as compared to those of 2006–2007. The cases of persistent CoNS sepsis have decreased within a decade, which could be attributed to the implementation of intensive infection control practices. Biofilm production remains the most important risk factor.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060765
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 766: Insights in the Development and Uses of
           Alternatives to Antibiotic Growth Promoters in Poultry and Swine

    • Authors: Md Ramim Tanver Rahman, Ismail Fliss, Eric Biron
      First page: 766
      Abstract: The overuse and misuse of antibiotics has contributed to the rise and spread of multidrug-resistant bacteria. To address this global public health threat, many countries have restricted the use of antibiotics as growth promoters and promoted the development of alternatives to antibiotics in human and veterinary medicine and animal farming. In food-animal production, acidifiers, bacteriophages, enzymes, phytochemicals, probiotics, prebiotics, and antimicrobial peptides have shown hallmarks as alternatives to antibiotics. This review reports the current state of these alternatives as growth-promoting factors for poultry and swine production and describes their mode of action. Recent findings on their usefulness and the factors that presently hinder their broader use in animal food production are identified by SWOT (strength, weakness, opportunity, and threat) analysis. The potential for resistance development as well as co- and cross-resistance with currently used antibiotics is also discussed. Using predetermined keywords, we searched specialized databases including Scopus, Web of Science, and Google Scholar. Antibiotic resistance cannot be stopped, but its spreading can certainly be hindered or delayed with the development of more alternatives with innovative modes of action and a wise and careful use of antimicrobials in a One Health approach.
      Citation: Antibiotics
      PubDate: 2022-06-02
      DOI: 10.3390/antibiotics11060766
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 767: Heteroaryl-Ethylenes as New Effective
           Agents for High Priority Gram-Positive and Gram-Negative Bacterial
           Clinical Isolates

    • Authors: Dalida Angela Bivona, Alessia Mirabile, Carmelo Bonomo, Paolo Giuseppe Bonacci, Stefano Stracquadanio, Andrea Marino, Floriana Campanile, Carmela Bonaccorso, Cosimo Gianluca Fortuna, Stefania Stefani, Nicolò Musso, Dafne Bongiorno
      First page: 767
      Abstract: The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumannii. Furthermore, an ATCC control strain was selected for all species tested. The MIC tests were performed according to the standard method. The PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0.12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4–64 mg/L) but still promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. Our study contributes to the search for new molecules that can fight bacterial infections, in particular those caused by MDR bacteria in hospitals. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.
      Citation: Antibiotics
      PubDate: 2022-06-03
      DOI: 10.3390/antibiotics11060767
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 768: Revisiting the Frequency and
           Antimicrobial Resistance Patterns of Bacteria Implicated in Community
           Urinary Tract Infections

    • Authors: Andreia Silva, Elisabeth Costa, Américo Freitas, Adelaide Almeida
      First page: 768
      Abstract: Urinary tract infections (UTIs) are one of the most common infectious diseases at the community level. The continue misuse of antimicrobials is leading to an increase in bacterial resistance, which is a worldwide problem. The objective of this work was to study the incidence and pattern of antimicrobial resistance of the main bacteria responsible for UTI in the community of central and northern Portugal, and establish an appropriate empirical treatment. The urine samples were collected in Avelab—Laboratório Médico de Análises Clínicas over a period of 5 years (2015–2019). The urine cultures were classified as positive when bacterial growth was equal to or higher than 105 CFU/mL, and only for these cases, an antimicrobial susceptibility test was performed. Of the 106,019 samples analyzed, 15,439 had a urinary infection. Urinary infections were more frequent in females (79.6%) than in males (20.4%), affecting more elderly patients (56.9%). Escherichia coli (70.1%) was the most frequent uropathogen, followed by Klebsiella pneumoniae (8.9%). The bacteria responsible for UTI varied according to the patient’s sex, with the greatest differences being observed for Enterococcus faecalis and Pseudomonas aeruginosa, these being more prevalent in men. In general, there was a growth in bacterial resistance as the age of the patients increased. The resistance of bacteria in male patients was, in most cases, statistically different (Chi-Square test, p < 0.05) from that observed for bacteria isolated from female patients, showing, in general, higher resistance in male patients. Although E. coli was the most responsible uropathogen for UTI, it was among the bacteria most susceptible to antibiotics. The isolates of K. pneumoniae, Proteus vulgaris and Enterobacter showed high resistance to the tested antimicrobials. The most common multidrug-resistant (MDR) bacteria implicated in UTI were K. pneumoniae (40.4%) and P. aeruginosa (34.7%), but E. coli, the most responsible bacteria for UTI, showed a MDR of 23.3%. When we compared our results with the results from 10 years ago for the same region, in general, an increase in bacterial resistance was observed. The results of this study confirmed that urinary tract infections are a very common illness, caused frequently by resistant uropathogens, for which the antibiotic resistance profile has varied over a short time, even within a specific region. This indicates that periodically monitoring the microbial resistance of each region is essential in order to select the best empirical antibiotic therapy against these infections, and prevent or decrease the resistance among uropathogenic strains.
      Citation: Antibiotics
      PubDate: 2022-06-03
      DOI: 10.3390/antibiotics11060768
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 769: Health Information Orientation Profiles
           and Their Association with Knowledge of Antibiotic Use in a Population
           with Good Internet Access: A Cross-Sectional Study

    • Authors: Huiling Guo, Huai Yang Lim, Angela Chow
      First page: 769
      Abstract: Background: Poor knowledge of antibiotic use drives poor antibiotic practices, but little is known about the influence of health information orientation (HIO) on knowledge of antibiotic use in the general public. Methods: We conducted a nationally-representative population-wide cross-sectional study (November 2021–January 2022), on a proportionately stratified random sample of 2004 Singapore residents aged ≥21 years. Multivariable logistic regression analysis was performed to assess the association between HIO and knowledge of antibiotic use. Results: Forty percent of respondents had low-levels of HIO (LL-HIO); they tended to be younger, not currently married, and did not have family/friends working in the healthcare sector. Respondents with LL-HIO (aOR 1.82, 95% CI 1.32–2.51, p < 0.001) were 82% more likely to have poor knowledge of antibiotic use. In particular, older adults aged ≥50 years with LL-HIO (aOR 1.81, 95% CI [1.32–2.51], p < 0.001) were much more likely to have poor knowledge than their HL-HIO counterparts. They were also less likely to use the Internet to seek health information and had poor eHealth efficacy. Conclusion: LL-HIO is independently associated with poor knowledge of antibiotic use. Educational strategies on antibiotic use should disseminate a consistent message through both online and offline platforms, involving traditional and non-traditional healthcare and non-healthcare influencers.
      Citation: Antibiotics
      PubDate: 2022-06-04
      DOI: 10.3390/antibiotics11060769
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 770: High Incidence of Acute Kidney Injury in
           Patients Treated with High-Dose Amoxicillin and Cloxacillin Combination

    • Authors: Yvon Ruch, Axel Ursenbach, François Danion, Fanny Reisz, Thierry Nai, Baptiste Hoellinger, Yves Hansmann, Nicolas Lefebvre, Jonas Martzloff
      First page: 770
      Abstract: High-dose amoxicillin and cloxacillin combination therapy is recommended for the empiric treatment of selected patients with infective endocarditis despite a low level of evidence. The main objective of this study was to evaluate the renal tolerance of high-dose intravenous amoxicillin and cloxacillin combination. We studied 27 patients treated with amoxicillin and cloxacillin (≥100 mg/kg daily) for at least 48 h. The primary endpoint was the occurrence of acute kidney injury (AKI). The median patient age was 68 ± 8 years, and 16 (59%) were male. The indication for this combination therapy was suspected or confirmed endocarditis with no bacterial identification in 22 (81%) patients. The primary endpoint occurred in 16 (59%) patients after initiating this combination therapy within an average of 4.4 ± 3.6 days. Among them, seven (26%) patients developed severe AKI, including four (15%) patients who required hemodialysis. Other risk factors for AKI were identified in all patients, including injection of iodinated contrast media in 21 (78%), acute heart failure in 18 (67%), cardiac surgery in 11 (41%), and aminoglycoside use in 9 (33%) patients. This study reports an incidence of 59% of AKI after initiating amoxicillin and cloxacillin combination therapy in a population at high renal risk.
      Citation: Antibiotics
      PubDate: 2022-06-04
      DOI: 10.3390/antibiotics11060770
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 771: Epidemiology of Candidemia and
           Fluconazole Resistance in an ICU before and during the COVID-19 Pandemic

    • Authors: Christina Routsi, Joseph Meletiadis, Efstratia Charitidou, Aikaterini Gkoufa, Stelios Kokkoris, Stavros Karageorgiou, Charalampos Giannopoulos, Despoina Koulenti, Petros Andrikogiannopoulos, Efstathia Perivolioti, Athina Argyropoulou, Ioannis Vasileiadis, Georgia Vrioni, Elizabeth Paramythiotou
      First page: 771
      Abstract: The objectives of this study were to investigate the incidence of candidemia, as well as the factors associated with Candida species distribution and fluconazole resistance, among patients admitted to the intensive care unit (ICU) during the COVID-19 pandemic, as compared to two pre-pandemic periods. All patients admitted to the ICU due to COVID-19 from March 2020 to October 2021, as well as during two pre-pandemic periods (2005–2008 and 2012–2015), who developed candidemia, were included. During the COVID-19 study period, the incidence of candidemia was 10.2%, significantly higher compared with 3.2% and 4.2% in the two pre-pandemic periods, respectively. The proportion of non-albicans Candida species increased (from 60.6% to 62.3% and 75.8%, respectively), with a predominance of C. parapsilosis. A marked increase in fluconazole resistance (from 31% to 37.7% and 48.4%, respectively) was also observed. Regarding the total patient population with candidemia (n = 205), fluconazole resistance was independently associated with ICU length of stay (LOS) before candidemia (OR 1.03; CI: 1.01–1.06, p = 0.003), whereas the presence of shock at candidemia onset was associated with C. albicans (OR 6.89; CI: 2.2–25, p = 0.001), and with fluconazole-susceptible species (OR 0.23; CI: 0.07–0.64, p = 0.006). In conclusion, substantial increases in the incidence of candidemia, in non-albicansCandida species, and in fluconazole resistance were found in patients admitted to the ICU due to COVID-19, compared to pre-pandemic periods. At candidemia onset, prolonged ICU LOS was associated with fluconazole-resistant and the presence of shock with fluconazole-susceptible species.
      Citation: Antibiotics
      PubDate: 2022-06-04
      DOI: 10.3390/antibiotics11060771
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 772: Biofilm Formation of Staphylococcus
           aureus from Pets, Livestock, and Wild Animals: Relationship with Clonal
           Lineages and Antimicrobial Resistance

    • Authors: Vanessa Silva, Elisete Correia, José Eduardo Pereira, Camino González-Machado, Rosa Capita, Carlos Alonso-Calleja, Gilberto Igrejas, Patrícia Poeta
      First page: 772
      Abstract: This study aimed to compare the biofilm formation ability of Staphylococcus aureus isolated from a wide range of animals and study the association between biofilm formation and antimicrobial resistance and genetic lineages. A total of 214 S. aureus strains isolated from pets, livestock, and wild animals were evaluated regarding their ability to form biofilms by the microtiter biofilm assay and their structure via confocal scanning laser microscopy. Statistical analysis was used to find an association between biofilm formation and antimicrobial resistance, multidrug resistance, sequence types (STs), spa and agr-types of the isolates. The antimicrobial susceptibility of 24 h-old biofilms was assessed against minimum inhibitory concentrations (MIC) and 10× MIC of amikacin and tetracycline, and the biomass reduction was measured. The metabolic activity of biofilms after antimicrobial treatment was evaluated by the XTT assay. All isolates were had the ability to form biofilms. Yet, significant differences in biofilm biomass production were detected among animal species. Multidrug resistance had a positive association with biofilm formation as well as methicillin-resistance. Significant differences were also detected among the clonal lineages of the isolates. Both tetracycline and amikacin were able to significantly reduce the biofilm mass. However, none of the antimicrobials were able to eradicate the biofilm at the maximum concentration used. Our results provide important information on the biofilm-forming capacity of animal-adapted S. aureus isolates, which may have potential implications for the development of new biofilm-targeted therapeutics.
      Citation: Antibiotics
      PubDate: 2022-06-04
      DOI: 10.3390/antibiotics11060772
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 773: pruR and PA0065 Genes Are Responsible for
           Decreasing Antibiotic Tolerance by Autoinducer Analog-1 (AIA-1) in
           Pseudomonas aeruginosa

    • Authors: Muhammad Reza Pahlevi, Keiji Murakami, Yuka Hiroshima, Akikazu Murakami, Hideki Fujii
      First page: 773
      Abstract: Pseudomonas aeruginosa infection is considered a high-risk nosocomial infection and is very difficult to eradicate because of its tolerance to antibiotic treatment. A new compound, autoinducer analog-1 (AIA-1), has been demonstrated to reduce antibiotic tolerance, but its mechanisms remain unknown. This study aimed to investigate the mechanisms of AIA-1 in the antibiotic tolerance of P. aeruginosa. A transposon mutant library was constructed using miniTn5pro, and screening was performed to isolate high tolerant mutants upon exposure to biapenem and AIA-1. We constructed a deletion mutant and complementation strain of the genes detected in transposon insertion site determination, pruR and PA0066-65-64, and performed killing assays with antibiotics and AIA-1. Gene expression upon exposure to biapenem and AIA-1 and their relationship to stress response genes were analyzed. High antibiotic tolerance was observed in Tn5-pruR and Tn5-PA0065 transposon mutants and their deletion mutants, ΔpruR and ΔPA0066-65-64. Complemented strains of pruR and PA0066-65-64 with their respective deletion mutants exhibited suppressed antibiotic tolerance. It was determined that deletion of PA0066-65-64 increased rpoS expression, and PA0066-65-64 affects antibiotic tolerance via the rpoS pathway. Additionally, antibiotics and AIA-1 were found to inhibit pruR and PA0066-65-64. This study proposed that pruR and PA0066-65-64 are members of the antibiotic tolerance suppressors.
      Citation: Antibiotics
      PubDate: 2022-06-06
      DOI: 10.3390/antibiotics11060773
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 774: Transmissibility and Persistence of the
           Plasmid-Borne Mobile Colistin Resistance Gene, mcr-1, Harbored in
           Poultry-Associated E. coli

    • Authors: Hassan Al Mana, Alreem A. Johar, Issmat I. Kassem, Nahla O. Eltai
      First page: 774
      Abstract: Colistin, a last-resort antibiotic, is used to treat infections caused by multi-drug-resistant Gram-negative bacteria. Colistin resistance can emerge by acquiring the mobile colistin gene, mcr-1, usually plasmid borne. Studies on mcr-1 and its transmissibility are limited in the Middle East and North Africa (MENA) region. Here, we investigated the occurrence of mcr-1 in 18 previously collected Escherichia coli isolates collected from chicken samples in Qatar; whole-genome sequencing was performed to determine the location (plasmid-borne and chromosomal) of mcr-1 in the isolates. Additionally, we assessed the transmissibility of plasmid-borne mcr-1 and its cost on fitness in E. coli biofilms. Our results showed that the E. coli isolates belonged to different sequence types, indicating that mcr-1 was occurring in strains with diverse genetic backgrounds. In silico analysis and transformation assays showed that all the isolates carried mcr-1 on plasmids that were mainly IncI2 types. All the mcr-1 plasmids were found to be transmissible by conjugation. In biofilms, a significant reduction in the number of CFU (≈0.055 logs CFU/mL) and colistin resistance (≈2.19 log CFU/mL) was observed; however, the reduction in resistance was significantly larger, indicating that the plasmids incur a high fitness cost. To our knowledge, this is the first study that investigates mcr-1 transmissibility and persistence in Qatar. Our findings highlight that mcr has the potential to spread colistin resistance to potentially disparate strains and niches in Qatar, posing a risk that requires intervention.
      Citation: Antibiotics
      PubDate: 2022-06-07
      DOI: 10.3390/antibiotics11060774
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 775: Identifying Targets for Antibiotic Use
           for the Management of Carbapenem-Resistant Acinetobacter baumannii (CRAb)
           in Hospitals—A Multi-Centre Nonlinear Time-Series Study

    • Authors: Zainab Said Al-Hashimy, Barbara R. Conway, Mubarak Al-Yaqoobi, Faryal Khamis, Ghalib Zahran Al Mawali, Aisha Mahad Al Maashani, Yaqoob Said Al Hadhrami, Said Salim Al Alawi, Mohammed Said Al Mamari, William J. Lattyak, Elizabeth A. Lattyak, Motasem Aldiab, Ian Gould, José-María López-Lozano, Mamoon A. Aldeyab
      First page: 775
      Abstract: Solutions are needed to inform antimicrobial stewardship (AMS) regarding balancing the access to effective antimicrobials with the need to control antimicrobial resistance. Theoretical and mathematical models suggest a non-linear relationship between antibiotic use and resistance, indicating the existence of thresholds of antibiotic use beyond which resistance would be triggered. It is anticipated that thresholds may vary across populations depending on host, environment, and organism factors. Further research is needed to evaluate thresholds in antibiotic use for a specific pathogen across different settings. The objective of this study is to identify thresholds of population antibiotic use associated with the incidence of carbapenem-resistant Acinetobacter baumannii (CRAb) across six hospital sites in Oman. The study was an ecological, multi-centre evaluation that involved collecting historical antibiotic use and CRAb incidence over the period from January 2015 to December 2019. By using non-linear time-series analysis, we identified different thresholds in the use of third-generation cephalosporins, piperacillin-tazobactam, aminoglycoside, and fluoroquinolones across participating hospitals. The identification of different thresholds emphasises the need for tailored analysis based on modelling data from each hospital. The determined thresholds can be used to set targets for each hospital AMS, providing a balance between access to these antibiotics versus controlling CRAb incidence.
      Citation: Antibiotics
      PubDate: 2022-06-07
      DOI: 10.3390/antibiotics11060775
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 776: Characterization of β-Lactamases and
           Multidrug Resistance Mechanisms in Enterobacterales from Hospital
           Effluents and Wastewater Treatment Plant

    • Authors: Christopher Mutuku, Szilvia Melegh, Krisztina Kovacs, Peter Urban, Eszter Virág, Reka Heninger, Robert Herczeg, Ágnes Sonnevend, Attila Gyenesei, Csaba Fekete, Zoltan Gazdag
      First page: 776
      Abstract: Antimicrobials in wastewater promote the emergence of antibiotic resistance, facilitated by selective pressure and transfer of resistant genes. Enteric bacteria belonging to Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Citrobacter species (n = 126) from hospital effluents and proximate wastewater treatment plant were assayed for susceptibility to four antimicrobial classes. The β-lactamase encoding genes harbored in plasmids were genotyped and the plasmids were sequenced. A multidrug resistance phenotype was found in 72% (n = 58) of E. coli isolates, 70% (n = 43) of Klebsiella species isolates, and 40% (n = 25) of Enterobacter and Citrobacter species. Moreover, 86% (n = 50) of E. coli, 77% (n = 33) of Klebsiella species, and 25% (n = 4) of Citrobacter species isolates phenotypically expressed extended spectrum β-lactamase. Regarding ESBL genes, blaCTX-M-27 and blaTEM-1 were found in E. coli, while Klebsiella species harbored blaCTX-M-15, blaCTX-M-30, or blaSHV-12. Genes coding for aminoglycoside modifying enzymes, adenylyltransferases (aadA1, aadA5), phosphotransferases (aph(6)-1d, aph(3″)-Ib), acetyltransferases (aac(3)-IIa), (aac(6)-Ib), sulfonamide/trimethoprim resistant dihydropteroate synthase (sul), dihydrofolate reductase (dfrA), and quinolone resistance protein (qnrB1) were also identified. Monitoring wastewater from human sources for acquired resistance in clinically important bacteria may provide a cheaper alternative in regions facing challenges that limit clinical surveillance.
      Citation: Antibiotics
      PubDate: 2022-06-07
      DOI: 10.3390/antibiotics11060776
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 777: Survey on Carbapenem-Resistant Bacteria

    • Authors: Silvia Bonardi, Clotilde Silvia Cabassi, Gerardo Manfreda, Antonio Parisi, Enrico Fiaccadori, Alice Sabatino, Sandro Cavirani, Cristina Bacci, Martina Rega, Costanza Spadini, Mattia Iannarelli, Cecilia Crippa, Ferdinando Ruocco, Frédérique Pasquali
      First page: 777
      Abstract: This study is focused on resistance to carbapenems and third-generation cephalosporins in Gram-negative microorganisms isolated from swine, whose transmission to humans via pork consumption cannot be excluded. In addition, the common carriage of carbapenem-resistant (CR) bacteria between humans and pigs was evaluated. Sampling involved 300 faecal samples collected from slaughtered pigs and 300 urine samples collected from 187 hospitalised patients in Parma Province (Italy). In swine, MIC testing confirmed resistance to meropenem for isolates of Pseudomonas aeruginosa and Pseudomonas oryzihabitans and resistance to cefotaxime and ceftazidime for Escherichia coli, Ewingella americana, Enterobacter agglomerans, and Citrobacter freundii. For Acinetobacter lwoffii, Aeromonas hydrofila, Burkolderia cepacia, Corynebacterium indologenes, Flavobacterium odoratum, and Stenotrophomonas maltophilia, no EUCAST MIC breakpoints were available. However, ESBL genes (blaCTXM-1, blaCTX-M-2, blaTEM-1, and blaSHV) and AmpC genes (blaCIT, blaACC, and blaEBC) were found in 38 and 16 isolates, respectively. P. aeruginosa was the only CR species shared by pigs (4/300 pigs; 1.3%) and patients (2/187; 1.1%). P. aeruginosa ST938 carrying blaPAO and blaOXA396 was detected in one pig as well as an 83-year-old patient. Although no direct epidemiological link was demonstrable, SNP calling and cgMLST showed a genetic relationship of the isolates (86 SNPs and 661 allele difference), thus suggesting possible circulation of CR bacteria between swine and humans.
      Citation: Antibiotics
      PubDate: 2022-06-07
      DOI: 10.3390/antibiotics11060777
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 778: Antimicrobial Resistance in New
           Zealand—A One Health Perspective

    • Authors: Isabelle Pattis, Louise Weaver, Sara Burgess, James E. Ussher, Kristin Dyet
      First page: 778
      Abstract: Antimicrobial resistance (AMR) is an increasing global threat that affects human, animal and, often less acknowledged, environmental health. This complex issue requires a multisectoral One Health approach to address the interconnectedness of humans, animals and the natural environment. The prevalence of AMR in these reservoirs varies widely among countries and thus often requires a country-specific approach. In New Zealand (NZ), AMR and antimicrobial usage in humans are relatively well-monitored and -understood, with high human use of antimicrobials and the frequency of resistant pathogens increasing in hospitals and the community. In contrast, on average, NZ is a low user of antimicrobials in animal husbandry systems with low rates of AMR in food-producing animals. AMR in New Zealand’s environment is little understood, and the role of the natural environment in AMR transmission is unclear. Here, we aimed to provide a summary of the current knowledge on AMR in NZ, addressing all three components of the One Health triad with a particular focus on environmental AMR. We aimed to identify knowledge gaps to help develop research strategies, especially towards mitigating AMR in the environment, the often-neglected part of the One Health triad.
      Citation: Antibiotics
      PubDate: 2022-06-07
      DOI: 10.3390/antibiotics11060778
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 779: Computational Development of Inhibitors
           of Plasmid-Borne Bacterial Dihydrofolate Reductase

    • Authors: Pedro J. Silva
      First page: 779
      Abstract: Resistance to trimethoprim and other antibiotics targeting dihydrofolate reductase may arise in bacteria harboring an atypical, plasmid-encoded, homotetrameric dihydrofolate reductase, called R67 DHFR. Although developing inhibitors to this enzyme may be expected to be promising drugs to fight trimethoprim-resistant strains, there is a paucity of reports describing the development of such molecules. In this manuscript, we describe the design of promising lead compounds to target R67 DHFR. Density-functional calculations were first used to identify the modifications of the pterin core that yielded derivatives likely to bind the enzyme and not susceptible to being acted upon by it. These unreactive molecules were then docked to the active site, and the stability of the docking poses of the best candidates was analyzed through triplicate molecular dynamics simulations, and compared to the binding stability of the enzyme–substrate complex. Molecule 32 ([6-(methoxymethyl)-4-oxo-3,7-dihydro-4H-pyrano[2,3-d]pyrimidin-2-yl]methyl-guanidinium) was shown by this methodology to afford extremely stable binding towards R67 DHFR and to prevent simultaneous binding to the substrate. Additional docking and molecular dynamics simulations further showed that this candidate also binds strongly to the canonical prokaryotic dihydrofolate reductase and to human DHFR, and is therefore likely to be useful to the development of chemotherapeutic agents and of dual-acting antibiotics that target the two types of bacterial dihydrofolate reductase.
      Citation: Antibiotics
      PubDate: 2022-06-07
      DOI: 10.3390/antibiotics11060779
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 780: The Urinary Resistome of Clinically
           Healthy Companion Dogs: Potential One Health Implications

    • Authors: Tonatiuh Melgarejo, Nathan Sharp, Janina A. Krumbeck, Guangxi Wu, Young J. Kim, Annika Linde
      First page: 780
      Abstract: An interdisciplinary approach to antimicrobial resistance (AMR) is essential to effectively address what is projected to soon become a public health disaster. Veterinary medicine accounts for a majority of antimicrobial use, and mainly in support of industrial food animal production (IFAP), which has significant exposure implications for human and nonhuman animals. Companion dogs live in close proximity to humans and share environmental exposures, including food sources. This study aimed to elucidate the AMR-gene presence in microorganisms recovered from urine from clinically healthy dogs to highlight public health considerations in the context of a species-spanning framework. Urine was collected through cystocentesis from 50 companion dogs in Southern California, and microbial DNA was analyzed using next-generation sequencing. Thirteen AMR genes in urine from 48% of the dogs {n=24} were detected. The most common AMR genes were aph(3′)Ia, and ermB, which confer resistance to aminoglycosides and MLS (macrolides, lincosamides, streptogramins) antibiotics, respectively. Antibiotic-resistance profiles based on the AMR genes detected, and the intrinsic resistance profiles of bacterial species, were inferred in 24% of the samples {n=12} for 57 species, with most belonging to Streptococcus, Staphylococcus, and Corynebacterium genera. The presence of AMR genes that confer resistance to medically important antibiotics suggests that dogs may serve as reservoirs of clinically relevant resistomes, which is likely rooted in excessive IFAP antimicrobial use.
      Citation: Antibiotics
      PubDate: 2022-06-08
      DOI: 10.3390/antibiotics11060780
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 781: 18β-Glycyrrhetinic Acid Induces
           Metabolic Changes and Reduces Staphylococcus aureus Bacterial Cell-to-Cell

    • Authors: Alan J. Weaver, Timothy R. Borgogna, Galen O’Shea-Stone, Tami R. Peters, Valérie Copié, Jovanka Voyich, Martin Teintze
      First page: 781
      Abstract: The rise in bacterial resistance to common antibiotics has raised an increased need for alternative treatment strategies. The natural antibacterial product, 18β-glycyrrhetinic acid (GRA) has shown efficacy against community-associated methicillin-resistant Staphylococcus aureus (MRSA), although its interactions against planktonic and biofilm modes of growth remain poorly understood. This investigation utilized biochemical and metabolic approaches to further elucidate the effects of GRA on MRSA. Prolonged exposure of planktonic MRSA cell cultures to GRA resulted in increased production of staphyloxanthin, a pigment known to exhibit antioxidant and membrane-stabilizing functions. Then, 1D 1H NMR analyses of intracellular metabolite extracts from MRSA treated with GRA revealed significant changes in intracellular polar metabolite profiles, including increased levels of succinate and citrate, and significant reductions in several amino acids, including branch chain amino acids. These changes reflect the MRSA response to GRA exposure, including potentially altering its membrane composition, which consumes branched chain amino acids and leads to significant energy expenditure. Although GRA itself had no significant effect of biofilm viability, it seems to be an effective biofilm disruptor. This may be related to interference with cell–cell aggregation, as treatment of planktonic MRSA cultures with GRA leads to a significant reduction in micro-aggregation. The dispersive nature of GRA on MRSA biofilms may prove valuable for treatment of such infections and could be used to increase susceptibility to complementary antibiotic therapeutics.
      Citation: Antibiotics
      PubDate: 2022-06-08
      DOI: 10.3390/antibiotics11060781
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 782: Resistance Genes, Plasmids, Multilocus
           Sequence Typing (MLST), and Phenotypic Resistance of Non-Typhoidal
           Salmonella (NTS) Isolated from Slaughtered Chickens in Burkina Faso

    • Authors: Assèta Kagambèga, Elizabeth A. McMillan, Soutongnooma C. Bouda, Lari M. Hiott, Hazem Ramadan, Daniel K. Soro, Poonam Sharma, Sushim K. Gupta, Nicolas Barro, Charlene R. Jackson, Jonathan G. Frye
      First page: 782
      Abstract: The emergence of antimicrobial-resistant bacteria in developing countries increases risks to the health of both such countries’ residents and the global community due to international travel. It is consequently necessary to investigate antimicrobial-resistant pathogens in countries such as Burkina Faso, where surveillance data are not available. To study the epidemiology of antibiotic resistance in Salmonella, 102 Salmonella strains isolated from slaughtered chickens were subjected to whole-genome sequencing (WGS) to obtain information on antimicrobial resistance (AMR) genes and other genetic factors. Twenty-two different serotypes were identified using WGS, the most prevalent of which were Hato (28/102, 27.5%) and Derby (23/102, 22.5%). All strains analyzed possessed at least one and up to nine AMR genes, with the most prevalent being the non-functional aac(6′)-Iaa gene, followed by aph(6)-Id. Multi-drug resistance was found genotypically in 36.2% of the isolates for different classes of antibiotics, such as fosfomycin and β-lactams, among others. Plasmids were identified in 43.1% of isolates (44/102), and 25 plasmids were confirmed to carry AMR genes. The results show that chicken can be considered as a reservoir of antibiotic-resistant Salmonella strains. Due to the prevalence of these drug-resistant pathogens and the potential for foodborne illnesses, poultry processing and cooking should be performed with attention to prescribed safe handling methods to avoid cross-contamination with chicken products.
      Citation: Antibiotics
      PubDate: 2022-06-08
      DOI: 10.3390/antibiotics11060782
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 783: Bacterial Resistance to Antibiotics and
           Clonal Spread in COVID-19-Positive Patients on a Tertiary Hospital
           Intensive Care Unit, Czech Republic

    • Authors: Lenka Doubravská, Miroslava Htoutou Sedláková, Kateřina Fišerová, Vendula Pudová, Karel Urbánek, Jana Petrželová, Magdalena Röderová, Kateřina Langová, Kristýna Mezerová, Pavla Kučová, Karel Axmann, Milan Kolář
      First page: 783
      Abstract: This observational retrospective study aimed to analyze whether/how the spectrum of bacterial pathogens and their resistance to antibiotics changed during the worst part of the COVID-19 pandemic (1 November 2020 to 30 April 2021) among intensive care patients in University Hospital Olomouc, Czech Republic, as compared with the pre-pandemic period (1 November 2018 to 30 April 2019). A total of 789 clinically important bacterial isolates from 189 patients were cultured during the pre-COVID-19 period. The most frequent etiologic agents causing nosocomial infections were strains of Klebsiella pneumoniae (17%), Pseudomonas aeruginosa (11%), Escherichia coli (10%), coagulase-negative staphylococci (9%), Burkholderia multivorans (8%), Enterococcus faecium (6%), Enterococcus faecalis (5%), Proteus mirabilis (5%) and Staphylococcus aureus (5%). Over the comparable COVID-19 period, a total of 1500 bacterial isolates from 372 SARS-CoV-2-positive patients were assessed. While the percentage of etiological agents causing nosocomial infections increased in Enterococcus faecium (from 6% to 19%, p < 0.0001), Klebsiella variicola (from 1% to 6%, p = 0.0004) and Serratia marcescens (from 1% to 8%, p < 0.0001), there were significant decreases in Escherichia coli (from 10% to 3%, p < 0.0001), Proteus mirabilis (from 5% to 2%, p = 0.004) and Staphylococcus aureus (from 5% to 2%, p = 0.004). The study demonstrated that the changes in bacterial resistance to antibiotics are ambiguous. An increase in the frequency of ESBL-positive strains of some species (Serratia marcescens and Enterobacter cloacae) was confirmed; on the other hand, resistance decreased (Escherichia coli, Acinetobacter baumannii) or the proportion of resistant strains remained unchanged over both periods (Klebsiella pneumoniae, Enterococcus faecium). Changes in pathogen distribution and resistance were caused partly due to antibiotic selection pressure (cefotaxime consumption increased significantly in the COVID-19 period), but mainly due to clonal spread of identical bacterial isolates from patient to patient, which was confirmed by the pulse field gel electrophoresis methodology. In addition to the above shown results, the importance of infection prevention and control in healthcare facilities is discussed, not only for dealing with SARS-CoV-2 but also for limiting the spread of bacteria.
      Citation: Antibiotics
      PubDate: 2022-06-08
      DOI: 10.3390/antibiotics11060783
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 784: Application of Artificial Intelligence in
           Combating High Antimicrobial Resistance Rates

    • Authors: Ali A. Rabaan, Saad Alhumaid, Abbas Al Mutair, Mohammed Garout, Yem Abulhamayel, Muhammad A. Halwani, Jeehan H. Alestad, Ali Al Bshabshe, Tarek Sulaiman, Meshal K. AlFonaisan, Tariq Almusawi, Hawra Albayat, Mohammed Alsaeed, Mubarak Alfaresi, Sultan Alotaibi, Yousef N. Alhashem, Mohamad-Hani Temsah, Urooj Ali, Naveed Ahmed
      First page: 784
      Abstract: Artificial intelligence (AI) is a branch of science and engineering that focuses on the computational understanding of intelligent behavior. Many human professions, including clinical diagnosis and prognosis, are greatly useful from AI. Antimicrobial resistance (AMR) is among the most critical challenges facing Pakistan and the rest of the world. The rising incidence of AMR has become a significant issue, and authorities must take measures to combat the overuse and incorrect use of antibiotics in order to combat rising resistance rates. The widespread use of antibiotics in clinical practice has not only resulted in drug resistance but has also increased the threat of super-resistant bacteria emergence. As AMR rises, clinicians find it more difficult to treat many bacterial infections in a timely manner, and therapy becomes prohibitively costly for patients. To combat the rise in AMR rates, it is critical to implement an institutional antibiotic stewardship program that monitors correct antibiotic use, controls antibiotics, and generates antibiograms. Furthermore, these types of tools may aid in the treatment of patients in the event of a medical emergency in which a physician is unable to wait for bacterial culture results. AI’s applications in healthcare might be unlimited, reducing the time it takes to discover new antimicrobial drugs, improving diagnostic and treatment accuracy, and lowering expenses at the same time. The majority of suggested AI solutions for AMR are meant to supplement rather than replace a doctor’s prescription or opinion, but rather to serve as a valuable tool for making their work easier. When it comes to infectious diseases, AI has the potential to be a game-changer in the battle against antibiotic resistance. Finally, when selecting antibiotic therapy for infections, data from local antibiotic stewardship programs are critical to ensuring that these bacteria are treated quickly and effectively. Furthermore, organizations such as the World Health Organization (WHO) have underlined the necessity of selecting the appropriate antibiotic and treating for the shortest time feasible to minimize the spread of resistant and invasive resistant bacterial strains.
      Citation: Antibiotics
      PubDate: 2022-06-08
      DOI: 10.3390/antibiotics11060784
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 785: Clinical Determinants Predicting
           Clostridioides difficile Infection among Patients with Chronic Kidney

    • Authors: Łukasz Lis, Andrzej Konieczny, Michał Sroka, Anna Ciszewska, Kornelia Krakowska, Tomasz Gołębiowski, Zbigniew Hruby
      First page: 785
      Abstract: The majority of recently published studies indicate a greater incidence rate and mortality due to Clostridioides difficile infection (CDI) in patients with chronic kidney disease (CKD). The aim of this study was to assess the clinical determinants predicting CDI among hospitalized patients with CKD and refine methods of prevention. We evaluated the medical records of 279 patients treated at a nephrological department with symptoms suggesting CDI, of whom 93 tested positive for CDI. The survey showed that age, poor kidney function, high Padua prediction score (PPS) and patients’ classification of care at admission, treatment with antibiotics, and time of its duration were significantly higher or more frequent among patients who suffered CDI. Whereas BMI, Norton scale (ANSS) and serum albumin concentration were significantly lowered among CDI patients. In a multivariate analysis we proved the stage of CKD and length of antibiotics use increased the risk of CDI, whereas higher serum albumin concentration and ANSS have a protective impact.
      Citation: Antibiotics
      PubDate: 2022-06-08
      DOI: 10.3390/antibiotics11060785
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 786: Genomic Analysis of Two MDR Isolates of
           Salmonella enterica Serovar Infantis from a Spanish Hospital Bearing the
           blaCTX-M-65 Gene with or without fosA3 in pESI-like Plasmids

    • Authors: Xenia Vázquez, Javier Fernández, Jesús Rodríguez-Lozano, Jorge Calvo, Rosaura Rodicio, M. Rosario Rodicio
      First page: 786
      Abstract: Salmonella enterica serovar Infantis (S. Infantis) is a broiler-associated pathogen which ranks in the fourth position as a cause of human salmonellosis in the European Union. Here, we report a comparative genomic analysis of two clinical S. Infantis isolates recovered in Spain from children who just returned from Peru. The isolates were selected on the basis of resistance to cefotaxime, one of the antibiotics of choice for treatment of S. enterica infections. Antimicrobial susceptibility testing demonstrated that they were resistant to eight classes of antimicrobial agents: penicillins, cephalosporins, phenicols, aminoglycosides, tetracyclines, inhibitors of folate synthesis, (fluoro)quinolones and nitrofurans, and one of them was also resistant to fosfomycin. As shown by whole-genome sequence analysis, each isolate carried a pESI-like megaplasmid of ca. 300 kb harboring multiple resistance genes [blaCTX-M-65, aph(4)-Ia, aac(3)-IVa, aph(3′)-Ia, floR, dfrA14, sul1, tet(A), aadA1 ± fosA3], as well as genes for resistance to heavy metals and disinfectants (mer, ars and qacEΔ1). These genes were distributed in two complex regions, separated by DNA belonging to the plasmid backbone, and associated with a wealth of transposable elements. The two isolates had a D87Y amino acid substitution in the GyrA protein, and truncated variants of the nitroreductase genes nfsA and nsfB, accounting for chromosomally encoded resistances to nalidixic acid and nitrofurantoin, respectively. The two S. Infantis isolates were assigned to sequence type ST32 by in silico multilocus sequence typing (MLST). Phylogenetic analysis revealed that they were closely related, differing only by 12 SNPs, although they were recovered from different children two years apart. They were also genetically similar to blaCTX-M-65-positive ± fosA3 isolates obtained from humans and along the poultry production chain in the USA, South America, as well as from humans in several European countries, usually associated with a travel history to America. However, this is the first time that the S. Infantis blaCTX-M-65 ± fosA3 MDR clone has been reported in Spain.
      Citation: Antibiotics
      PubDate: 2022-06-09
      DOI: 10.3390/antibiotics11060786
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 787: Enhanced Antibacterial Activity of
           Dermaseptin through Its Immobilization on Alginate
           Nanoparticles—Effects of Menthol and Lactic Acid on Its

    • Authors: Noura Hazime, Yanath Belguesmia, Alexandre Barras, Mohamed Amiche, Rabah Boukherroub, Djamel Drider
      First page: 787
      Abstract: Dermaseptin B2 (DRS-B2) is an antimicrobial peptide secreted by Phyllomedusa bicolor, which is an Amazonian tree frog. Here, we show that the adsorption of DRS-B2 on alginate nanoparticles (Alg NPs) results in a formulation (Alg NPs + DRS-B2) with a remarkable antibacterial activity against Escherichia coli ATCC 8739 and E. coli 184 strains, which are sensitive and resistant, respectively, to colistin. The antibacterial activity, obtained with this new formulation, is higher than that obtained with DRS-B2 alone. Of note, the addition of lactic acid or menthol to this new formulation augments its antibacterial activity against the aforementioned Gram-negative bacilli. The safety of DRS-B2, and also that of the new formulation supplemented or not with a small molecule such as lactic acid or menthol has been proven on the human erythrocytes and the eukaryotic cell line types HT29 (human) and IPEC-1 (animal). Similarly, their stability was determined under the conditions mimicking the gastrointestinal tract with different conditions: pH, temperature, and the presence of digestive enzymes. Based on all the obtained data, we assume that these new formulations are promising and could be suggested, after in vivo approval and completing regulation aspects, as alternatives to antibiotics to fight infections caused by Gram-negative bacilli such as E. coli.
      Citation: Antibiotics
      PubDate: 2022-06-09
      DOI: 10.3390/antibiotics11060787
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 788: Epidemiology, Clinical Characteristics,
           Risk Factors, and Outcomes of Candidemia in a Large Tertiary Teaching

    • Authors: Jie Hou, Jin Deng, Ya Liu, Weili Zhang, Siying Wu, Quanfeng Liao, Ying Ma, Mei Kang
      First page: 788
      Abstract: The aim of this study was to investigate the current status of candidemia and evaluate the clinical characteristics, risk factors and outcomes among different species. We conducted a retrospective study by univariate and multivariate analysis between Candida albicans and non-albicans Candida (NAC) species in a Chinese national medical center from 2016 to 2020. Among the 259 episodes, C. albicans (38.6%) was the leading species, followed by C. tropicalis (24.3%), C. parapsilosis (20.5%), and C. glabrata (12.4%). Most C. albicans and C. parapsilosis were susceptible to nine tested antifungal agents, whereas C. tropicalis showed 30.2~65.9% resistance/non-wild-type to four azoles with great cross-resistance, indicating that fluconazole should not be used for empirical antifungal treatment. In multivariable models, the factor related to an increased risk of NAC was glucocorticoid exposure, whereas gastrointestinal hemorrhage and thoracoabdominal drainage catheters were associated with an increased risk in C. albicans. Subgroup analysis revealed leukemia and lymphoma, as well as glucocorticoid exposure, to be factors independently associated with C. tropicalis in comparison with C. albicans candidemia. No significant differences in 7-day mortality or 30-day mortality were observed between C. albicans and NAC. This study may provide useful information with respect to choosing empirical antifungal agents and exploring differences in molecular mechanisms.
      Citation: Antibiotics
      PubDate: 2022-06-09
      DOI: 10.3390/antibiotics11060788
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 789: Co-Infections, Secondary Infections, and
           Antimicrobial Use in Patients Hospitalized with COVID-19 during the First
           Five Waves of the Pandemic in Pakistan; Findings and Implications

    • Authors: Kiran Ramzan, Sameen Shafiq, Iqra Raees, Zia Ul Mustafa, Muhammad Salman, Amer Hayat Khan, Johanna C. Meyer, Brian Godman
      First page: 789
      Abstract: Background: COVID-19 patients are typically prescribed antibiotics empirically despite concerns. There is a need to evaluate antibiotic use among hospitalized COVID-19 patients during successive pandemic waves in Pakistan alongside co-infection rates. Methods: A retrospective review of patient records among five tertiary care hospitals during successive waves was conducted. Data were collected from confirmed COVID-19 patients during the first five waves. Results: 3221 patients were included. The majority were male (51.53%), residents from urban areas (56.35%) and aged >50 years (52.06%). Cough, fever and a sore throat were the clinical symptoms in 20.39%, 12.97% and 9.50% of patients, respectively. A total of 23.62% of COVID-19 patients presented with typically mild disease and 45.48% presented with moderate disease. A high prevalence of antibiotic prescribing (89.69%), averaging 1.66 antibiotics per patient despite there only being 1.14% bacterial co-infections and 3.14% secondary infections, was found. Antibiotic use significantly increased with increasing severity, elevated WBCs and CRP levels, a need for oxygen and admittance to the ICU; however, this decreased significantly after the second wave (p < 0.001). Commonly prescribed antibiotics were piperacillin plus an enzyme inhibitor (20.66%), azithromycin (17.37%) and meropenem (15.45%). Common pathogens were Staphylococcus aureus (24.19%) and Streptococcus pneumoniae (20.96%). The majority of the prescribed antibiotics (93.35%) were from the WHO’s “Watch” category. Conclusions: Excessive prescribing of antibiotics is still occurring among COVID-19 patients in Pakistan; however, rates are reducing. Urgent measures are needed for further reductions.
      Citation: Antibiotics
      PubDate: 2022-06-09
      DOI: 10.3390/antibiotics11060789
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 790: The Dynamics of Antimicrobial Resistance
           among Enterobacteriaceae Isolates in Russia: Results of the
           2012–2018 INFORM and ATLAS International Program Studies

    • Authors: Roman Kozlov, Alexey Kuzmenkov
      First page: 790
      Abstract: Background: The increasing prevalence of multidrug-resistant Enterobacteriaceae limits the range of active antimicrobial agents, thus worsening clinical outcomes. The objective of this study was to identify the trends in antimicrobial resistance for Enterobacteriaceae in Russia using the databases for the International Network for Optimal Resistance Monitoring (INFORM) and Antimicrobial Testing Leadership and Surveillance (ATLAS) studies between 2012 and 2018. Methods: This subanalysis was performed for 3811 non-duplicate clinical isolates of Enterobacteriaceae to evaluate the in vitro activity of the main classes of antibiotics against relevant clinical isolates from hospitalized patients with complicated infections of different anatomical locations. Results: The lowest susceptibility was observed for colistin (0%), ampicillin (16.4%), and ampicillin/sulbactam (31.1%), whereas the best susceptibility was observed for all combinations containing avibactam (>96%). Among individual antimicrobials, doripenem (3.2%), tigecycline (1.6%), and meropenem (5.9%) exhibited the lowest resistance. Important trends included the decreasing resistance of Enterobacteriaceae to glycylcyclines and the increasing resistance to aminoglycosides and carbapenems. K. pneumoniae strains were most aggressive in terms of the percentage of strains having multidrug resistance (8.3–18.3%, depending on location) and the percentage of ESBL-positive strains (44.8–86.8%). Conclusions: The current patterns and trends of antimicrobial resistance in different bacterial species should be taken into consideration for timely updating of clinical guidelines and local treatment protocols to ensure effective antimicrobial therapy.
      Citation: Antibiotics
      PubDate: 2022-06-10
      DOI: 10.3390/antibiotics11060790
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 791: Effectiveness of Educational
           Interventions for Health Workers on Antibiotic Prescribing in Outpatient
           Settings in China: A Systematic Review and Meta-Analysis

    • Authors: Kunhua Zheng, Ying Xie, Lintao Dan, Meixian Mao, Jie Chen, Ran Li, Xuanding Wang, Therese Hesketh
      First page: 791
      Abstract: Educational interventions are considered an important component of antibiotic stewardship, but their effect has not been systematically evaluated in outpatient settings in China. This research aims to evaluate the effectiveness of educational interventions for health workers on antibiotic prescribing rates in Chinese outpatient settings. Eight databases were searched for relevant randomized clinical trials, non-randomized trials, controlled before–after studies and interrupted time-series studies from January 2001 to July 2021. A total of 16 studies were included in the systematic review and 12 in the meta-analysis. The results showed that educational interventions overall reduced the antibiotic prescription rate significantly (relative risk, RR 0.72, 95% confidence interval, CI 0.61 to 0.84). Subgroup analysis demonstrated that certain features of education interventions had a significant effect on antibiotic prescription rate reduction: (1) combined with compulsory administrative regulations (RR With: 0.65 vs. Without: 0.78); (2) combined with financial incentives (RR With: 0.51 vs. Without: 0.77). Educational interventions can also significantly reduce antibiotic injection rates (RR 0.83, 95% CI 0.74 to 0.94) and the inappropriate use of antibiotics (RR 0.61, 95% CI 0.51 to 0.73). The limited number of high-quality studies limits the validity and reliability of the results. More high-quality educational interventions targeting the reduction of antibiotic prescribing rates are needed.
      Citation: Antibiotics
      PubDate: 2022-06-10
      DOI: 10.3390/antibiotics11060791
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 792: Impact of the COVID-19 Pandemic on
           Inpatient Antibiotic Consumption in Switzerland

    • Authors: Olivier Friedli, Michael Gasser, Alexia Cusini, Rosamaria Fulchini, Danielle Vuichard-Gysin, Roswitha Halder Tobler, Nasstasja Wassilew, Catherine Plüss-Suard, Andreas Kronenberg
      First page: 792
      Abstract: The aim of this study was to analyze inpatient antibiotic consumption during the first 16 months of the COVID-19 pandemic in Switzerland. The entire period (January 2018–June 2021) was divided into the prepandemic period, the first and second waves, and the intermediate period. In the first year of the pandemic, total overall inpatient antibiotic consumption measured in defined daily doses (DDD) per 100 bed-days remained stable (+1.7%), with a slight increase in ICUs of +4.2%. The increase in consumption of broad-spectrum antibiotics was +12.3% overall and 17.3% in ICUs. The segmented regression model of monthly data revealed an increase in overall antibiotic consumption during the first wave but not during the second wave. In the correlation analysis performed in a subset of the data, a significant positive association was found between broad-spectrum antibiotic consumption and an increasing number of hospitalized COVID-19 patients (p = 0.018). Restricting this dataset to ICUs, we found significant positive correlations between the number of hospitalized COVID-19 patients and total antibiotic consumption (p = 0.007) and broad-spectrum antibiotic consumption (p < 0.001). In conclusion, inpatient antibiotic use during the different periods of the COVID-19 pandemic varied greatly and was predominantly notable for broad-spectrum antibiotics.
      Citation: Antibiotics
      PubDate: 2022-06-11
      DOI: 10.3390/antibiotics11060792
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 793: The Role of Gut Microbiota in the
           Skeletal Muscle Development and Fat Deposition in Pigs

    • Authors: Qi Han, Xingguo Huang, Fuyong Yan, Jie Yin, Yingping Xiao
      First page: 793
      Abstract: Pork quality is a factor increasingly considered in consumer preferences for pork. The formation mechanisms determining meat quality are complicated, including endogenous and exogenous factors. Despite a lot of research on meat quality, unexpected variation in meat quality is still a major problem in the meat industry. Currently, gut microbiota and their metabolites have attracted increased attention in the animal breeding industry, and recent research demonstrated their significance in muscle fiber development and fat deposition. The purpose of this paper is to summarize the research on the effects of gut microbiota on pig muscle and fat deposition. The factors affecting gut microbiota composition will also be discussed, including host genetics, dietary composition, antibiotics, prebiotics, and probiotics. We provide an overall understanding of the relationship between gut microbiota and meat quality in pigs, and how manipulation of gut microbiota may contribute to increasing pork quality for human consumption.
      Citation: Antibiotics
      PubDate: 2022-06-11
      DOI: 10.3390/antibiotics11060793
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 794: Nanomaterials-Based Combinatorial Therapy
           as a Strategy to Combat Antibiotic Resistance

    • Authors: Angel León-Buitimea, Cesar R. Garza-Cárdenas, María Fernanda Román-García, César Agustín Ramírez-Díaz, Martha Ulloa-Ramírez, José Rubén Morones-Ramírez
      First page: 794
      Abstract: Since the discovery of antibiotics, humanity has been able to cope with the battle against bacterial infections. However, the inappropriate use of antibiotics, the lack of innovation in therapeutic agents, and other factors have allowed the emergence of new bacterial strains resistant to multiple antibiotic treatments, causing a crisis in the health sector. Furthermore, the World Health Organization has listed a series of pathogens (ESKAPE group) that have acquired new and varied resistance to different antibiotics families. Therefore, the scientific community has prioritized designing and developing novel treatments to combat these ESKAPE pathogens and other emergent multidrug-resistant bacteria. One of the solutions is the use of combinatorial therapies. Combinatorial therapies seek to enhance the effects of individual treatments at lower doses, bringing the advantage of being, in most cases, much less harmful to patients. Among the new developments in combinatorial therapies, nanomaterials have gained significant interest. Some of the most promising nanotherapeutics include polymers, inorganic nanoparticles, and antimicrobial peptides due to their bactericidal and nanocarrier properties. Therefore, this review focuses on discussing the state-of-the-art of the most significant advances and concludes with a perspective on the future developments of nanotherapeutic combinatorial treatments that target bacterial infections.
      Citation: Antibiotics
      PubDate: 2022-06-12
      DOI: 10.3390/antibiotics11060794
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 795: Self-Medication with Antibiotics:
           Prevalence, Practices and Related Factors among the Pakistani Public

    • Authors: Adeel Aslam, Che Suraya Zin, Shazia Jamshed, Norny Syafinaz Ab Rahman, Syed Imran Ahmed, Péter Pallós, Márió Gajdács
      First page: 795
      Abstract: Self-medication with antibiotics (SMA) has become considerably common in developing countries, which is a critical factor for driving antibiotic resistance. Individuals involved in SMA generally do not have adequate knowledge regarding the appropriate use, indications and dosage of these drugs. The objective of the present study was to investigate population SMA practices, knowledge and sociodemographic factors associated with SMA in Islamabad, Pakistan. The study adopted a cross-sectional methodology and data collection was performed through an anonymous, structured and pilot-tested questionnaire, which was interview-administered. Inferential statistics and multivariate logistic regression were performed. Out of 480 participants, 55.6% (n = 267) were male with a mean age of 37.1 ± 10.1 years; the total prevalence of SMA was 32.5%. Ciprofloxacin (42.9%) was the most commonly used antibiotic to treat coughs or colds, a runny nose, flu or sore throat, diarrhea or fevers, which were relevant reasons for SMA. Findings from multivariate logistic regression showed that predictors of SMA were: male gender (95% CI: 0.383–1.005), age (95% CI: 0.317–0.953) and highest level of education (95% CI: 0.961–0.649). Despite reasonable access to healthcare facilities, people are still obtaining antibiotics without prescription, bypassing diagnostic and consultative healthcare services. Thus, the government must implement strict healthcare policies to restrict the sale of antibiotics without prescriptions, while at the same time, targeted public awareness campaigns about the proper use of antibiotics are also required.
      Citation: Antibiotics
      PubDate: 2022-06-12
      DOI: 10.3390/antibiotics11060795
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 796: Safety and Efficacy of Ivermectin for the
           Prevention and Treatment of COVID-19: A Double-Blinded Randomized
           Placebo-Controlled Study

    • Authors: Nasikarn Angkasekwinai, Pinyo Rattanaumpawan, Methee Chayakulkeeree, Pakpoom Phoompoung, Pornpan Koomanachai, Sorawit Chantarasut, Walaiporn Wangchinda, Varalak Srinonprasert, Visanu Thamlikitkul
      First page: 796
      Abstract: The safety and efficacy of ivermectin for the prevention and treatment of COVID-19 are still controversial topics. From August to November 2021, we conducted a double-blinded, randomized controlled trial at Siriraj Hospital, Thailand. Eligible participants were adults ≥ 18 years with suspected COVID-19 who underwent a SARS-CoV-2 RT-PCR test. After enrollment, the participants were randomized to receive either ivermectin (400–600 µg/kg/d) or placebo once daily for 3 days. Among 983 participants, 536 (54.5%) with a negative RT-PCR result were enrolled in the prevention study, and 447 (45.5%) with a positive RT-PCR result were enrolled in the treatment study. In the prevention study, the incidence of COVID-19 on Day 14 was similar between the ivermectin and the placebo group (4.7% vs. 5.2%; p = 0.844; Δ = −0.4%; 95% CI; −4.3–3.5%). In the treatment study, there was no significant difference between the ivermectin and placebo group for any Day 14 treatment outcome: proportion with oxygen desaturation (2.7% vs. 1.9%; p = 0.75), change in WHO score from baseline (1 [−5, 1] vs. 1 [−5, 1]; p = 0.50), and symptom resolution (76% vs. 82.2%; p = 0.13). The ivermectin group had a significantly higher proportion of transient blurred vision (5.6% vs. 0.6%; p < 0.001). Our study failed to demonstrate the efficacy of a 3-day once daily of ivermectin for the prevention and treatment of COVID-19. The given regimen of ivermectin should not be used for either prevention or treatment of COVID-19 in populations with a high rate of COVID-19 vaccination.
      Citation: Antibiotics
      PubDate: 2022-06-12
      DOI: 10.3390/antibiotics11060796
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 797: Levofloxacin Cocrystal/Salt with
           Phthalimide and Caffeic Acid as Promising Solid-State Approach to Improve
           Antimicrobial Efficiency

    • Authors: Noor Ul Islam, Muhammad Naveed Umar, Ezzat Khan, Fakhria A. Al-Joufi, Shaymaa Najm Abed, Muhammad Said, Habib Ullah, Muhammad Iftikhar, Muhammad Zahoor, Farhat Ali Khan
      First page: 797
      Abstract: To overcome the issue of multidrug resistant (MDR) microbes, the exploration of ways to improve the antimicrobial efficiency of existing antibiotics is one of the promising approaches. In search of synthons with higher efficiency, in current investigations, cocrystal and amorphous salt of levofloxacin hemihydrate (LEV) were developed with phthalimide (PTH) and caffeic acid (CFA). New materials were characterized with the help of FT-IR, Raman spectroscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Shifting, attenuation, appearance/disappearance and broadening of bands were observed in the FT-IR and Raman spectra of the materials as evidence of the required product. The PXRD diffraction pattern observed for LEV-PTH indicated cocrystal while halo diffractogram of LEV-CFA revealed amorphous nature. DSC/TG analysis confirmed the hydrated nature of the cocrystal/salt. The dissolution rate and antimicrobial activity against selected strains, K.pneumonia, E. coli and S. typhi of parent drug and the new material were compared. The zone of inhibition (ZI) observed for 5 µg LEV-PTH was 30.4 + 0.36 (K. pneumonia), 26.33 + 0.35 (E. coli) and 30.03 + 0.25 mm (S. typhi) while LEV-CFA salt (5 µg) against the same strains inhibited 33.96 ± 0.25, 31.66 ± 0.35 and 27.93 ± 0.40 mm, respectively. These novel formulations enhance the dissolution rate as well as antibacterial efficiency and are expected to be potent against MDR bacterial strains.
      Citation: Antibiotics
      PubDate: 2022-06-13
      DOI: 10.3390/antibiotics11060797
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 798: Pharmacokinetics and Pharmacodynamics of
           Colistin Methanesulfonate in Healthy Chinese Subjects after Multi-Dose

    • Authors: Yaxin Fan, Yi Li, Yuancheng Chen, Jicheng Yu, Xiaofen Liu, Wanzhen Li, Beining Guo, Xin Li, Jingjing Wang, Hailan Wu, Yu Wang, Jiali Hu, Yan Guo, Fupin Hu, Xiaoyong Xu, Guoying Cao, Jufang Wu, Yingyuan Zhang, Jing Zhang, Xiaojie Wu
      First page: 798
      Abstract: Colistin methanesulfonate (CMS) is an important treatment option for infections caused by carbapenem-resistant Gram-negative organisms (CROs). This study evaluated the pharmacokinetic/pharmacodynamic (PK/PD) profiles and safety of CMS in Chinese subjects following a recommended dosage. A total of 12 healthy Chinese subjects received CMS injections at 2.5 mg/kg once every 12 h for 7 consecutive days. The PK/PD profiles of the active form of CMS, colistin, against CROs were analyzed with the Monte Carlo simulation method. No serious adverse events were observed. The average steady-state plasma concentrations of CMS and colistin were 4.41 ± 0.75 μg/mL and 1.27 ± 0.27 μg/mL, and the steady-state exposures (AUC0–12,ss) were 52.93 ± 9.05 h·μg/mL and 15.28 ± 3.29 h·μg/mL, respectively. Colistin, at its minimum inhibitory concentration (MIC) of 0.5 μg/mL, has >90% probability to reduce CROs by ≥1 log. The PK/PD breakpoints for the ≥1 log kill were ≥MIC90 for carbapenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa, but were ≤MIC50 for carbapenem-resistant Acinetobacter baumannii. The recommended dose regimen of CMS for 7 consecutive days was safe in Chinese subjects. The systemic exposure of colistin showed a high probability of being sufficient for most CROs, but was not sufficient for some carbapenem-resistant A. baumannii.
      Citation: Antibiotics
      PubDate: 2022-06-14
      DOI: 10.3390/antibiotics11060798
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 799: Prevalence and Molecular Characteristics
           of Polymyxin-Resistant Pseudomonas aeruginosa in a Chinese Tertiary
           Teaching Hospital

    • Authors: Chenlu Xiao, Yan Zhu, Zhitao Yang, Dake Shi, Yuxing Ni, Li Hua, Jian Li
      First page: 799
      Abstract: Polymyxin-resistant Pseudomonas aeruginosa is a major threat to public health globally. We investigated the prevalence of polymyxin-resistant P. aeruginosa in a Chinese teaching hospital and determined the genetic and drug-resistant phenotypes of the resistant isolates. P. aeruginosa isolates identified by MALDI-TOF MS were collected across a 3-month period in Ruijin Hospital. Antimicrobial susceptibility was determined by a Vitek-2 Compact system with broth dilution used to determine polymyxin B (PMB) susceptibility. Polymyxin-resistant isolates were further characterized by molecular typing using PCR, multi-locus sequence typing (MLST) and whole-genome sequencing. Phylogenetic relationships were analyzed using single nucleotide polymorphism (SNP) from the whole-genome sequencing. Of 362 P. aeruginosa isolates collected, 8 (2.2%) isolates from separate patients across six wards were polymyxin-resistant (MIC range, PMB 4–16 μg/mL and colistin 4–≥16 μg/mL). Four patients received PMB treatments (intravenous, aerosolized and/or topical) and all patients survived to discharge. All polymyxin-resistant isolates were genetically related and were assigned to five different clades (Isolate 150 and Isolate 211 being the same ST823 type). Genetic variations V51I, Y345H, G68S and R155H in pmrB and L71R in pmrA were identified, which might confer polymyxin resistance in these isolates. Six of the polymyxin-resistant isolates showed reduced susceptibility to imipenem and meropenem (MIC range ≥ 16 μg/mL), while two of the eight isolates were resistant to ceftazidime. We revealed a low prevalence of polymyxin-resistant P. aeruginosa in a Chinese teaching hospital with most polymyxin-resistant isolates being multidrug-resistant. Therefore, effective infection control measures are urgently needed to prevent further spread of resistance to the last-line polymyxins.
      Citation: Antibiotics
      PubDate: 2022-06-14
      DOI: 10.3390/antibiotics11060799
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 800: Optimized Synthesis of Small and Stable
           Silver Nanoparticles Using Intracellular and Extracellular Components of
           Fungi: An Alternative for Bacterial Inhibition

    • Authors: Elvira Ivonne Murillo-Rábago, Alfredo R. Vilchis-Nestor, Karla Juarez-Moreno, Luis E. Garcia-Marin, Katrin Quester, Ernestina Castro-Longoria
      First page: 800
      Abstract: Silver nanoparticles (AgNPs) represent an excellent option to solve microbial resistance problems to traditionally used antibiotics. In this work, we report optimized protocols for the production of AgNPs using extracts and supernatants of Trichoderma harzianum and Ganoderma sessile. AgNPs were characterized using UV-Vis spectroscopy and transmission electron microscopy, and the hydrodynamic diameter and Z potential were also determined. The obtained AgNPs were slightly larger using the fungal extract, and in all cases, a quasi-spherical shape was obtained. The mean sizes of AgNPs were 9.6 and 19.1 nm for T. harzianum and 5.4 and 8.9 nm for G. sessile using supernatant and extract, respectively. The AgNPs were evaluated to determine their in vitro antibacterial effect against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) was determined, and in all cases the AgNPs showed an antimicrobial effect, with a MIC varying from 1.26–5.0 µg/mL, depending on the bacterial strain and type of nanoparticle used. Cytotoxicity analyses of AgNPs were carried out using macrophages and fibroblast cell lines. It was determined that the cell viability of fibroblasts exposed for 24 h to different concentrations of AgNPs was more than 50%, even at concentrations of up to 20 µg/mL of silver. However, macrophages were more susceptible to exposure at higher concentrations of AgNPs as their viability decreased at concentrations of 10 µg/mL. The results presented here demonstrate that small AgNPs are obtained using either supernatants or extracts of both fungal strains. A remarkable result is that very low concentrations of AgNPs were necessary for bacterial inhibition. Furthermore, AgNPs were stable for more than a year, preserving their antibacterial properties. Therefore, the reported optimized protocol using fungal supernatants or extracts may be used as a fast method for synthesizing small AgNPs with high potential to use in the clinic.
      Citation: Antibiotics
      PubDate: 2022-06-14
      DOI: 10.3390/antibiotics11060800
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 801: Antiplasmodial Cyclodecapeptides from
           Tyrothricin Share a Target with Chloroquine

    • Authors: Adrienne N.-N. Leussa, Marina Rautenbach
      First page: 801
      Abstract: Previous research found that the six major cyclodecapeptides from the tyrothricin complex, produced by Brevibacillus parabrevis, showed potent activity against chloroquine sensitive (CQS) Plasmodium falciparum. The identity of the aromatic residues in the aromatic dipeptide unit in cyclo-(D-Phe1-Pro2-(Phe3/Trp3)-D-Phe4/D-Trp4)-Asn5-Gln6-(Tyr7/Phe7/Trp7)-Val8-(Orn9/Lys9)-Leu10 was proposed to have an important role in activity. CQS and resistant (CQR) P. falciparum strains were challenged with three representative cyclodecapeptides. Our results confirmed that cyclodecapeptides from tyrothricin had significantly higher antiplasmodial activity than the analogous gramicidin S, rivaling that of CQ. However, the previously hypothesized size and hydrophobicity dependent activity for these peptides did not hold true for P. falciparum strains, other than for the CQS 3D7 strain. The Tyr7 in tyrocidine A (TrcA) with Phe3-D-Phe4 seem to be related with loss in activity correlating with CQ antagonism and resistance, indicating a shared target and/or resistance mechanism in which the phenolic groups play a role. Phe7 in phenycidine A, the second peptide containing Phe3-D-Phe4, also showed CQ antagonism. Conversely, Trp7 in tryptocidine C (TpcC) with Trp3-D-Trp4 showed improved peptide selectivity and activity towards the more resistant strains, without overt antagonism towards CQ. However, TpcC lead to similar parasite stage inhibition and parasite morphology changes than previously observed for TrcA. The disorganization of chromatin packing and neutral lipid structures, combined with amorphous hemozoin crystals, could account for halted growth in late trophozoite/early schizont stage and the nanomolar non-lytic activity of these peptides. These targets related to CQ antagonism, changes in neural lipid distribution, leading to hemozoin malformation, indicate that the tyrothricin cyclodecapeptides and CQ share a target in the malaria parasite. The differing activities of these cyclic peptides towards CQS and CQR P. falciparum strains could be due to variable target interaction in multiple modes of activity. This indicated that the cyclodecapeptide activity and parasite resistance response depended on the aromatic residues in positions 3, 4 and 7. This new insight on these natural cyclic decapeptides could also benefit the design of unique small peptidomimetics in which activity and resistance can be modulated.
      Citation: Antibiotics
      PubDate: 2022-06-14
      DOI: 10.3390/antibiotics11060801
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 802: Antifungal Susceptibility of Candida
           albicans Isolated from Tongue and Subgingival Biofilm of Periodontitis

    • Authors: Milena Radunovic, Milena Barac, Jovana Kuzmanovic Pficer, Dusan Pavlica, Aleksandar Jovanovic, Ana Pucar, Sanja Petrovic
      First page: 802
      Abstract: The subgingival biofilm, as the most complex microbial community, has been proven to be reservoir of Candida spp. The main concept of this study was to investigate if there is a difference between the sensitivity of Candida albicans (C. albicans) isolated from tongue and subgingival areas of periodontitis patients to antifungal agents. The aim of the study was to determine: (1) the distribution of different Candida species in the tongue and subgingival samples of periodontitis patients; (2) the susceptibility of Candida albicans strains from tongue and subgingival biofilm to the effects of commonly used antifungal agents: fluconazole, amphotericin B and itraconazole; (3) the correlation between the susceptibility of Candida albicans and clinical periodontal parameters. Tongue and subgingival biofilm samples of periodontitis subjects (N = 163) were examined. Susceptibility was tested when the same Candida species was isolated from both sites (17 subjects). Candida spp. were isolated in 23.3% of tongue and 21.5% of the subgingival samples. All isolates were susceptible to amphotericin B, while 64.71% of tongue and 52.94% of subgingival isolates were susceptible to fluconazole. A low frequency of itraconazole susceptibility was observed for tongue (17.64%) and subgingival isolates (11.76%). The correlations between full-mouth plaque score and Minimal Inhibitory Concentration (MIC) for tongue isolates were strongly positive for all antimycotics. Positive correlation was also observed between moderate periodontal destruction and MICs for tongue and subgingival isolates. The susceptibility of C. albicans to antifungals correlate with oral hygiene and moderate periodontal destruction. There is no difference in antifungal susceptibility between tongue and subgingival isolates.
      Citation: Antibiotics
      PubDate: 2022-06-14
      DOI: 10.3390/antibiotics11060802
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 803: COVID-19 and Fungal Diseases

    • Authors: Kyoung-Ho Oh, Seung-Hoon Lee
      First page: 803
      Abstract: Coronavirus Disease-2019 (COVID-19) can cause secondary bacterial and fungal infections by affecting the expression of pro-inflammatory markers, such as tumor necrosis alpha and certain cytokines, as well as the numbers of CD4 and CD8 cells. In particular, in the head and neck, various fungal species are naturally present, making it the main route of secondary infection. It is difficult to clearly distinguish whether secondary infection is caused by COVID-19 directly or indirectly as a result of the immunocompromised state induced by drugs used to treat the disease. However, the risk of fungal infection is high in patients with severe COVID-19, and lymphopenia is observed in most patients with the disease. Patients with COVID-19 who are immunosuppressed or have other pre-existing comorbidities are at a significantly higher risk of acquiring invasive fungal infections. In order to reduce morbidity and mortality in these patients, early diagnosis is required, and treatment with systemic antifungal drugs or surgical necrotic tissue resection is essential. Therefore, this review aimed to examine the risk of fungal infection in the head and neck of patients with COVID-19 and provide information that could reduce the risk of mortality.
      Citation: Antibiotics
      PubDate: 2022-06-15
      DOI: 10.3390/antibiotics11060803
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 804: Editorial for the Special Issue:
           “Epidemiology, Prognosis and Antimicrobial Treatment of Extensively
           Antibiotic-Resistant Bacterial Infections”

    • Authors: Stamatis Karakonstantis, Evangelos I. Kritsotakis
      First page: 804
      Abstract: The increasing consumption of broad-spectrum antimicrobials is fuelling a vicious cycle leading to extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria [...]
      Citation: Antibiotics
      PubDate: 2022-06-15
      DOI: 10.3390/antibiotics11060804
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 805: Real-World Effectiveness and Optimal
           Dosage of Favipiravir for Treatment of COVID-19: Results from a
           Multicenter Observational Study in Thailand

    • Authors: Pinyo Rattanaumpawan, Supunnee Jirajariyavej, Kanokorn Lerdlamyong, Nattawan Palavutitotai, Jatuporn Saiyarin
      First page: 805
      Abstract: Favipiravir is a broad-spectrum oral antiviral agent that shows in vitro activity against SARS-CoV-2. Presently, data on the real-world effectiveness and optimal dosage of favipiravir for treating COVID-19 are limited. We conducted a retrospective observational study of hospitalized adult patients with COVID-19 at five tertiary care hospitals in Thailand. We reviewed patient charts to obtain all necessary data. Among 247 COVID-19 patients, 63 (23.0%) received ≥1 dose of favipiravir. Of these 63 patients, 61.9% were male with a median age of 48 years (range 22–85 years), 27.0% required an O2 nasal cannula, 9.5% required non-invasive ventilation and/or high-flow O2 therapy, and 6.4% required invasive mechanical ventilation and/or ECMO. The median baseline NEWS2 score was 5 (0–16). The Day-7 clinical improvement rate [95%CI] was 66.7% [53.7–78.0%] in all patients, 92.5% [75.7–99.1%] in patients who did not require O2 supplementation, and 47.2% [0.4–64.5%] in patients who required O2 supplementation. No life-threatening adverse events were identified. The 28-day mortality rate was 4.8%. A multivariate analysis revealed three poor prognostic factors for Day-7 clinical improvement (odds ratio (95%CI); p-value): older age (0.94 (0.89–0.99); p = 0.04), a higher baseline NEWS2 score (0.64 (0.47–0.88); p = 0.006), and a lower favipiravir loading dose (≤45 mg/kg/day) (0.04 (0.005–0.4); p = 0.006). In conclusion, our study reports the promising effectiveness of favipiravir for treating COVID-19 patients. In addition to older age and a high baseline NEWS2 score, a low loading dose of favipiravir (≤45 mg/kg/day) was also identified as a poor prognostic factor for early clinical improvement. Further studies to explore the optimal dose and the optimal timing of drug initiation for favipiravir should be performed.
      Citation: Antibiotics
      PubDate: 2022-06-15
      DOI: 10.3390/antibiotics11060805
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 806: Adapting Clofazimine for Treatment of
           Cutaneous Tuberculosis by Using Self-Double-Emulsifying Drug Delivery

    • Authors: Daniélle van Staden, Richard K. Haynes, Joe M. Viljoen
      First page: 806
      Abstract: Although chemotherapeutic treatment regimens are currently available, and considerable effort has been lavished on the development of new drugs for the treatment of tuberculosis (TB), the disease remains deeply intractable and widespread. This is due not only to the nature of the life cycle and extraordinarily disseminated habitat of the causative pathogen, principally Mycobacterium tuberculosis (Mtb), in humans and the multi-drug resistance of Mtb to current drugs, but especially also to the difficulty of enabling universal treatment of individuals, immunocompromised or otherwise, in widely differing socio-economic environments. For the purpose of globally eliminating TB by 2035, the World Health Organization (WHO) introduced the “End-TB” initiative by employing interventions focusing on high impact, integrated and patient-centered approaches, such as individualized therapy. However, the extraordinary shortfall in stipulated aims, for example in actual treatment and in TB preventative treatments during the period 2018–2022, latterly and greatly exacerbated by the COVID-19 pandemic, means that even greater pressure is now placed on enhancing our scientific understanding of the disease, repurposing or repositioning old drugs and developing new drugs as well as evolving innovative treatment methods. In the specific context of multidrug resistant Mtb, it is furthermore noted that the incidence of extra-pulmonary TB (EPTB) has significantly increased. This review focusses on the potential of utilizing self-double-emulsifying drug delivery systems (SDEDDSs) as topical drug delivery systems for the dermal route of administration to aid in treatment of cutaneous TB (CTB) and other mycobacterial infections as a prelude to evaluating related systems for more effective treatment of CTB and other mycobacterial infections at large. As a starting point, we consider here the possibility of adapting the highly lipophilic riminophenazine clofazimine, with its potential for treatment of multi-drug resistant TB, for this purpose. Additionally, recently reported synergism achieved by adding clofazimine to first-line TB regimens signifies the need to consider clofazimine. Thus, the biological effects and pharmacology of clofazimine are reviewed. The potential of plant-based oils acting as emulsifiers, skin penetration enhancers as well as these materials behaving as anti-microbial components for transporting the incorporated drug are also discussed.
      Citation: Antibiotics
      PubDate: 2022-06-15
      DOI: 10.3390/antibiotics11060806
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 807: Effects of Typical Antimicrobials on
           Growth Performance, Morphology and Antimicrobial Residues of Mung Bean

    • Authors: Jing Cao, Yajie Wang, Guanzhao Wang, Pingping Ren, Yongning Wu, Qinghua He
      First page: 807
      Abstract: Antimicrobials may be used to inhibit the growth of micro-organisms in the cultivation of mung bean sprouts, but the effects on mung bean sprouts are unclear. In the present study, the growth performance, morphology, antimicrobial effect and antimicrobial residues of mung bean sprouts cultivated in typical antimicrobial solutions were investigated. A screening of antimicrobial residues in thick-bud and rootless mung bean sprouts from local markets showed that the positive ratios of chloramphenicol, enrofloxacin, and furazolidone were 2.78%, 22.22%, and 13.89%, respectively. The cultivating experiment indicated that the production of mung bean sprouts in antimicrobial groups was significantly reduced over 96 h (p < 0.05). The bud and root length of mung bean sprouts in enrofloxacin, olaquindox, doxycycline and furazolidone groups were significantly shortened (p < 0.05), which cultivated thick-bud and rootless mung bean sprouts similar to the 6-benzyl-adenine group. Furthermore, linear regression analysis showed average optical density of 450 nm in circulating water and average production had no obvious correlation in mung bean sprouts (p > 0.05). Antimicrobial residues were found in both mung bean sprouts and circulating water. These novel findings reveal that the antimicrobials could cultivate thick-bud and rootless mung bean sprouts due to their toxicity. This study also proposed a new question regarding the abuse of antimicrobials in fast-growing vegetables, which could be a potential food safety issue.
      Citation: Antibiotics
      PubDate: 2022-06-15
      DOI: 10.3390/antibiotics11060807
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 808: Prevalence and Correlates of
           Self-Medication Practices for Prevention and Treatment of COVID-19: A
           Systematic Review

    • Authors: Oluwasola Stephen Ayosanmi, Babatunde Yusuf Alli, Oluwatosin Adetolani Akingbule, Adeyemi Hakeem Alaga, Jason Perepelkin, Delbaere Marjorie, Sujit S. Sansgiry, Jeffrey Taylor
      First page: 808
      Abstract: It has been suggested that the COVID-19 pandemic led to an increase in self-medication practices across the world. Yet, there is no up-to-date synthesized evidence on the prevalence of self-medication that is attributable to the pandemic. This study aimed to conduct a systematic literature review on the prevalence and correlates of self-medication for the prevention and treatment of COVID-19 globally. The review was registered with the PROSPERO database. Searches were conducted following PRISMA guidelines, and relevant articles published between 1 April 2020 and 31 March 2022 were included. Pooled prevalence rate was conducted using the Meta package in R. A total of 14 studies from 14 countries, which represented 15,154 participants, were included. The prevalence of COVID-19-related self-medication ranged from 3.4–96%. The pooled prevalence of self-medication for this purpose was 44.9% (95% CI: 23.8%, 68.1%). Medications reported by studies for self-medication were antibiotics (79%), vitamins (64%), antimalarials (50%), herbal and natural products (50%), analgesics and antipyretics (43%), minerals and supplements (43%), cold and allergy preparations (29%), corticosteroids (14%), and antivirals (7%). The prevalence of self-medication with antibiotics is concerning. More public health education about responsible self-medication amidst the COVID-19 pandemic and future pandemics is required to mitigate the rising threat of antimicrobial resistance.
      Citation: Antibiotics
      PubDate: 2022-06-16
      DOI: 10.3390/antibiotics11060808
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 809: Epigenetic-Mediated Antimicrobial
           Resistance: Host versus Pathogen Epigenetic Alterations

    • Authors: Jibran Sualeh Muhammad, Naveed Ahmed Khan, Sutherland K. Maciver, Ahmad M. Alharbi, Hasan Alfahemi, Ruqaiyyah Siddiqui
      First page: 809
      Abstract: Since the discovery of antibiotics, humans have been benefiting from them by decreasing the morbidity and mortality associated with bacterial infections. However, in the past few decades, misuse of antibiotics has led to the emergence of bacterial infections resistant to multiple drugs, a significant health concern. Bacteria exposed to inappropriate levels of antibiotics lead to several genetic changes, enabling them to survive in the host and become more resistant. Despite the understanding and targeting of genetic-based biochemical changes in the bacteria, the increasing levels of antibiotic resistance are not under control. Many reports hint at the role of epigenetic modifications in the bacterial genome and host epigenetic reprogramming due to interaction with resistant pathogens. Epigenetic changes, such as the DNA-methylation-based regulation of bacterial mutation rates or bacteria-induced histone modification in human epithelial cells, facilitate its long-term survival. In this review article, epigenetic changes leading to the development of antibiotic resistance in clinically relevant bacteria are discussed. Additionally, recent lines of evidence focusing on human host epigenetic changes due to the human–pathogen interactions are presented. As genetic mechanisms cannot explain the transient nature of antimicrobial resistance, we believe that epigenetics may provide new frontiers in antimicrobial discovery.
      Citation: Antibiotics
      PubDate: 2022-06-16
      DOI: 10.3390/antibiotics11060809
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 810: Pattern of Antibiotic Use among
           Hospitalized Patients according to WHO Access, Watch, Reserve (AWaRe)
           Classification: Findings from a Point Prevalence Survey in Bangladesh

    • Authors: Md. Mahbubur Rashid, Zubair Akhtar, Sukanta Chowdhury, Md. Ariful Islam, Shahana Parveen, Probir Kumar Ghosh, Aninda Rahman, Zobaidul Haque Khan, Khaleda Islam, Nitish Debnath, Mahmudur Rahman, Fahmida Chowdhury
      First page: 810
      Abstract: For supporting antibiotic stewardship interventions, the World Health Organization (WHO) classified antibiotics through the AWaRe (Access, Watch, and Reserve) classification. Inappropriate use of antimicrobials among hospital-admitted patients exposes them to the vulnerability of developing resistant organisms which are difficult to treat. We aimed to describe the proportion of antibiotic use based on the WHO AWaRe classification in tertiary and secondary level hospitals in Bangladesh. A point prevalence survey (PPS) was conducted adapting the WHO PPS design in inpatients departments in 2021. Among the 1417 enrolled patients, 52% were female and 63% were from the 15–64 years age group. Nearly 78% of patients received at least one antibiotic during the survey period. Third-generation cephalosporins (44.6%), penicillins (12.3%), imidazoles (11.8%), aminoglycosides (7.2%), and macrolides (5.8%) were documented as highly used antibiotics. Overall, 64.0% of Watch, 35.6% of Access, and 0.1% of Reserve group antibiotics were used for treatment. The use of Watch group antibiotics was high in medicine wards (78.7%) and overall high use of Watch antibiotics was observed at secondary hospitals (71.5%) compared to tertiary hospitals (60.2%) (p-value of 0.000). Our PPS findings underscore the need for an urgent nationwide antibiotic stewardship program for physicians including the development and implementation of local guidelines and in-service training on antibiotic use.
      Citation: Antibiotics
      PubDate: 2022-06-16
      DOI: 10.3390/antibiotics11060810
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 811: Clonality and Persistence of
           Multiresistant Methicillin-Resistant Coagulase-Negative Staphylococci
           Isolated from the Staff of a University Veterinary Hospital

    • Authors: Joaquín Rey, María Gil, Javier Hermoso de Mendoza, Alfredo García, Gemma Gaitskell-Phillips, Carlos Bastidas-Caldes, Laura Zalama
      First page: 811
      Abstract: The aim of this study was to characterize methicillin-resistant coagulase-negative staphylococci (MRCoNS) isolates from the healthy staff of a university veterinary hospital in order to assess their importance as a reservoir of antimicrobial resistance and to determine their population structure and evolution. The study duration was over two years (2020–2021), 94 individuals were analyzed in duplicate, and 78 strains were obtained. The overall prevalence of methicillin-resistant strains detected throughout the study was 61.7%, with point prevalence values of 53.2% in 2020 and 31.5% in 2021. A total of 19.1% of the individuals analyzed were carriers throughout the study. The most frequently identified MRCoNs were Staphylococcus epidermidis (92.3%) and S. warneri (3.8%). A total of 75.6% of the isolates obtained showed the development of multi-resistance, preferentially against erythromycin, gentamicin, and tetracycline, and to a lesser extent against fusidic acid, norfloxacin, and clindamycin; these antimicrobials are frequently used in the veterinary field. Although most of the S. epidermidis isolates obtained showed wide genetic variability and low dispersion, which are characteristic of community-associated isolates, a small number of strains spread between individuals in close physical proximity and were maintained over time, forming stable clones. These clones generally maintained the same type of staphylococcal cassette chromosome mec (SCCmec) and had a similar antimicrobial resistance pattern.
      Citation: Antibiotics
      PubDate: 2022-06-16
      DOI: 10.3390/antibiotics11060811
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 812: Effect of the Symbiosis with Mycoplasma
           hominis and Candidatus Mycoplasma girerdii on Trichomonas vaginalis
           Metronidazole Susceptibility

    • Authors: Valentina Margarita, Le Chi Cao, Nicholas P. Bailey, Thuy Ha Thi Ngoc, Thi Minh Chau Ngo, Phuong Anh Ton Nu, Nicia Diaz, Daniele Dessì, Robert P. Hirt, Pier Luigi Fiori, Paola Rappelli
      First page: 812
      Abstract: Trichomoniasis, the most common non-viral sexually transmitted infection worldwide, is caused by the protozoon Trichomonas vaginalis. The 5- nitroimidazole drugs, of which metronidazole is the most prescribed, are the only effective drugs to treat trichomoniasis. Resistance against metronidazole is increasingly reported among T. vaginalis isolates. T. vaginalis can establish an endosymbiosis with two Mycoplasma species, Mycoplasma hominis and Candidatus Mycoplasma girerdii, whose presence has been demonstrated to influence several aspects of the protozoan pathobiology. The role of M. hominis in T. vaginalis resistance to metronidazole is controversial, while the influence of Ca.M. girerdii has never been investigated. In this work, we investigate the possible correlation between the presence of Ca.M. girerdii and/or M. hominis and the in vitro drug susceptibility in a large group of T. vaginalis isolated in Italy and in Vietnam. We also evaluated, via RNA-seq analysis, the expression of protozoan genes involved in metronidazole resistance in a set of syngenic T. vaginalis strains, differing only for the presence/absence of the two Mycoplasmas. Our results show that the presence of M. hominis significantly increases the sensitivity to metronidazole in T. vaginalis and affects gene expression. On the contrary, the symbiosis with Candidatus Mycoplasma girerdii seems to have no effect on metronidazole resistance in T. vaginalis.
      Citation: Antibiotics
      PubDate: 2022-06-16
      DOI: 10.3390/antibiotics11060812
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 813: Predicting In-Hospital Antibiotic Use in
           the Medical Department: Derivation and Validation Study

    • Authors: Itamar Poran, Michal Elbaz, Adi Turjeman, Maayan Huberman Samuel, Noa Eliakim-Raz, Jeries Nashashibi, Mical Paul, Leonard Leibovici
      First page: 813
      Abstract: Background: The rise of multi-drug-resistant pathogens and nosocomial infections among hospitalized patients is partially attributed to the increased use of antibiotic therapy. A prediction model for in-hospital antibiotic treatment could be valuable to target preventive strategies. Methods: This was a retrospective cohort study, including patients admitted in 2018 to medical departments and not treated with antibiotics during the first 48 h. Data available at hospital admission were used to develop a logistic model to predict the probability of antibiotic treatment during hospitalization. The performance of the model was evaluated in two independent validation cohorts. Results: In the derivation cohort, antibiotic treatment was initiated in 454 (8.1%) out of 5592 included patients. Male gender, lower functional capacity, prophylactic antibiotic treatment, medical history of atrial fibrillation, peripheral vascular disease, solid organ transplantation, chronic use of a central venous catheter, urinary catheter and nasogastric tube, albumin level, mental status and vital signs at presentation were identified as predictors for antibiotic use during hospitalization and were included in the prediction model. The area under the ROC curve (AUROC) was 0.72 (95% CI 0.70–0.75). In the highest probability group, the percentage of antibiotic treatment was 18.2% (238/1,307). In the validation cohorts, the AUROC was 0.73 (95% CI 0.68–0.77) and 0.75 (95% CI 0.72–0.78). In the highest probability group, the percentage of antibiotic treatment was 12.5% (66/526) and 20.7% (244/1179) of patients. Conclusions: Our prediction model performed well in the validation cohorts and was able to identify a subgroup of patients at high risk for antibiotic treatment.
      Citation: Antibiotics
      PubDate: 2022-06-16
      DOI: 10.3390/antibiotics11060813
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 814: Nosocomial Outbreak of Extensively
           Drug-Resistant (Polymyxin B and Carbapenem) Klebsiella pneumoniae in a
           Collapsed University Hospital Due to COVID-19 Pandemic

    • Authors: Gilberto G. Gaspar, Gustavo Tamasco, Nathália Abichabki, Ana Flavia T. Scaranello, Maria Auxiliadora-Martins, Renata Pocente, Leonardo N. Andrade, María-Eugenia Guazzaroni, Rafael Silva-Rocha, Valdes R. Bollela
      First page: 814
      Abstract: We correlated clinical, epidemiological, microbiological, and genomic data of an outbreak with polymyxin B (PB)- and carbapenem-resistant Klebsiella pneumoniae during the COVID-19 pandemic. Twenty-six PB- and carbapenem-resistant K. pneumoniae were isolated from patients in the COVID-19 ICU (Intensive Care Unit), non-COVID-19 ICU (Intensive Care Unit), clinical, or surgical ward. Bacterial identification, drug susceptibility tests, and DNA sequencing were performed, followed by in silico resistance genes identification. All isolates showed extensively drug-resistant (XDR) phenotypes. Four different sequence types (ST) were detected: ST16, ST11, ST258, and ST437. Nineteen isolates were responsible for an outbreak in the ICU in September 2020. They belong to ST258 and harbored the 42Kb IncX3plasmid (pKP98M3N42) with the same genomic pattern of two K. pneumoniae identified in 2018. Twenty-four isolates carried bla-KPC-2 gene. No plasmid-mediated colistin (mcr) resistance genes were found. Eight isolates presented mgrB gene mutation. The clonal isolates responsible for the outbreak came from patients submitted to pronation, with high mortality rates in one month. XDR-K. pneumoniae detected during the outbreak presented chromosomal resistance to PB and plasmid-acquired carbapenem resistance due to KPC production in most isolates and 42Kb IncX3(pKP98M3N42) plasmid carrying blaKPC-2 was associated with ST258 isolates. The outbreak followed the collapse of the local healthcare system with high mortality rates.
      Citation: Antibiotics
      PubDate: 2022-06-17
      DOI: 10.3390/antibiotics11060814
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 815: Editorial for the Special Issue:
           “Therapeutic Drug Monitoring of Antimicrobials”

    • Authors: Matthias Gijsen, Karel Allegaert
      First page: 815
      Abstract: A recent guideline [...]
      Citation: Antibiotics
      PubDate: 2022-06-17
      DOI: 10.3390/antibiotics11060815
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 816: Non-Antibiotic Drug Repositioning as an
           Alternative Antimicrobial Approach

    • Authors: Alexia Barbarossa, Antonio Rosato, Filomena Corbo, Maria Lisa Clodoveo, Giuseppe Fracchiolla, Antonio Carrieri, Alessia Carocci
      First page: 816
      Abstract: The worldwide scenario of antibiotic resistance and the falling number of funds for the development of novel antibiotics have led research efforts toward the study of specific cost-effective strategies aimed at discovering drugs against microbial infections. Among the potential options, drug repositioning, which has already exhibited satisfactory results in other medical fields, came out as the most promising. It consists of finding new uses for previously approved medicines and, over the years, many “repurposed drugs” displayed some encouraging in vitro and in vivo results beyond their initial application. The principal theoretical justification for reusing already existing drugs is that they have known mechanisms of action and manageable side effects. Reuse of old drugs is now considered an interesting approach to overcome the drawbacks of conventional antibiotics. The purpose of this review is to offer the reader a panoramic view of the updated studies concerning the repositioning process of different classes of non-antibiotic drugs in the antimicrobial field. Several research works reported the ability of some non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, antipsychotics, and statins to counteract the growth of harmful microorganisms, demonstrating an interesting winning mode to fight infectious diseases caused by antimicrobial resistant bacteria.
      Citation: Antibiotics
      PubDate: 2022-06-17
      DOI: 10.3390/antibiotics11060816
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 817: Ethyl Acetate Fraction of Bixa orellana
           and Its Component Ellagic Acid Exert Antibacterial and Anti-Inflammatory
           Properties against Mycobacterium abscessus subsp. massiliense

    • Authors: Roberval Nascimento Moraes-Neto, Gabrielle Guedes Coutinho, Ana Caroline Santos Ataíde, Aline de Oliveira Rezende, Camila Evangelista Carnib Nascimento, Rafaela Pontes de Albuquerque, Cláudia Quintino da Rocha, Adriana Sousa Rêgo, Maria do Socorro de Sousa Cartágenes, Ana Lúcia Abreu-Silva, Igor Victor Ferreira dos Santos, Cleydson Breno Rodrigues dos Santos, Rosane Nassar Meireles Guerra, Rachel Melo Ribeiro, Valério Monteiro-Neto, Eduardo Martins de Sousa, Rafael Cardoso Carvalho
      First page: 817
      Abstract: Mycobacterium abscessus subsp. massiliense (Mabs) causes chronic infections, which has led to the need for new antimycobacterial agents. In this study, we investigated the antimycobacterial and anti-inflammatory activities of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc). In silico analysis predicted that ElAc had low toxicity, was not mutagenic or carcinogenic, and had antimicrobial and anti-inflammatory activities. Apparently, ElAc can interact with COX2 and Dihydrofolate reductase (DHFR) enzymes, which could explain both activities. In vitro analysis showed that BoEA and ElAc exerted antimicrobial activity against Mabs (minimum inhibitory concentration of 1.56, 1.56 mg/mL and bactericidal concentration of 6.25, 3.12 mg/mL, respectively. Clarithromycin showed MIC and MBC of 1 and 6 µg/mL). Treatment with BoEA or ElAc increased survival of Tenebrio molitor larvae after lethal infection with Mabs and reduced carrageenan-induced paw edema in mice, around 40% of edema volume after the fourth hour, similarly to diclofenac. In conclusion, BoEA and ElAc exert antimicrobial effects against Mabs and have anti-inflammatory effects, making them potential sources of antimycobacterial drugs. The biological activities of ElAc may be due to its high binding affinities predicted for COX2 and DHFR enzymes.
      Citation: Antibiotics
      PubDate: 2022-06-17
      DOI: 10.3390/antibiotics11060817
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 818: Dietary Bacitracin Methylene Disalicylate
           Improves Growth Performance by Mediating the Gut Microbiota in Broilers

    • Authors: Jingshang Li, Yingping Xiao, Qian Fan, Hua Yang, Caimei Yang, Guolong Zhang, Shengchang Chen
      First page: 818
      Abstract: The growth performance of livestock and poultry has always been a concern. However, much work is currently focused on the selection of breeds and diets to improve the growth performance of livestock and poultry. Furthermore, numerous studies have shown that the gut microbiota is closely related to the growth performance of livestock and poultry. At present, there are many reports on the impact of antibiotic intervention on the structure of gut microbiota. However, there are few reports on the influence of antibiotic intervention on the structure of intestinal microbes and the effect of this change on growth performance. Bacitracin methylene disalicylate (BMD) intervention changes the microbial structure in the caecum of broilers at different growth stages, as shown in this study. To further reveal the potential relationship between gut microbiota changes and growth performance caused by BMD intervention, correlation analysis was used for analysis. A total of 144 1-day-old male Cobb-Vantress were randomly divided into two groups. In addition to antibiotic-free starter mash diets, starter mash diets supplemented with 55 mg/kg BMD were also used, called the CON group and the BMD group, and lasted 28 days. (1) These study results showed that adding BMD to the diet had a significant effect on the growth performance of broilers. Compared with the CON group, the body weight of the BMD group increased significantly by 11.08% and 20.13% on Days 14 and 28, respectively (p < 0.05). Similarly, at 0–14, 14–28 and 0–28 days of age, the average daily gain of the BMD group increased significantly by 12.28%, 24.49% and 20.80%, respectively. The average daily feed intake of the BMD group increased significantly by 18.28%, 27.39% and 24.97% (p < 0.05). In addition, at 0–28 days of age, the feed conversion ratio increased significantly by 5.5% (p < 0.05). (2) Alpha diversity results show that BMD intervention has an impact on gut microbiota at different growth stages. (3) The early intervention significantly affected 7 taxa by Day 14, followed by 22 taxa by Day 28, which is similar to the results in the caecal flora. Compared with the CON group, the Christensenellaceae R-7 group had the highest linear discriminant analysis (LDA) score on Day 28. In addition, Pearson’s correlation analysis showed that the Lachnospiraceae FCS020 group was significantly negatively correlated with growth performance. In general, these results indicate that dietary supplementation of BMD has an effect on broiler gut microbiota structure and growth performance. However, changes in growth performance may be caused by the gut microbiota structure.
      Citation: Antibiotics
      PubDate: 2022-06-17
      DOI: 10.3390/antibiotics11060818
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 819: Antivirulence Agent as an Adjuvant of
           β-Lactam Antibiotics in Treating Staphylococcal Infections

    • Authors: Peng Gao, Yuanxin Wei, Sherlock Shing Chiu Tai, Pradeep Halebeedu Prakash, Ho Ting Venice Iu, Yongli Li, Hin Cheung Bill Yam, Jonathan Hon Kwan Chen, Pak Leung Ho, Julian Davies, Richard Yi Tsun Kao
      First page: 819
      Abstract: Staphylococcus aureus can cause a plethora of life-threatening infections. Antibiotics have been extensively used to treat S. aureus infections. However, when antibiotics are used at sub-inhibitory concentrations, especially for β-lactam antibiotics, they may enhance staphylococcal pathogenicity and exacerbate the infection. The combination of antivirulence agents and antibiotics may be a novel approach to controlling antibiotic-induced S. aureus pathogenicity. We have illustrated that under in vitro conditions, antivirulence agent M21, when administered concurrently with ampicillin, suppressed the expression and production of virulence factors induced by ampicillin. In a mouse peritonitis model, M21 reduced bacterial load irrespective of administration of ampicillin. In a bacteremia model, combinatorial treatment consisting of ampicillin or ceftazidime and M21 increased the survival rate of mice and reduced cytokine abundance, suggesting the suppression of antibiotic-induced virulence by M21. Different from traditional antibiotic adjuvants, an antivirulence agent may not synergistically inhibit bacterial growth in vitro, but effectively benefit the host in vivo. Collectively, our findings from this study demonstrated the benefits of antivirulence–antibiotic combinatorial treatment against S. aureus infections and provide a new perspective on the development of antibiotic adjuvants.
      Citation: Antibiotics
      PubDate: 2022-06-17
      DOI: 10.3390/antibiotics11060819
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 820: A Qualitative Study on the Design and
           Implementation of the National Action Plan on Antimicrobial Resistance in
           the Philippines

    • Authors: Maria Margarita M. Lota, Alvin Qijia Chua, Karen Azupardo, Carlo Lumangaya, Katherine Ann V. Reyes, Sharon Yvette Angelina M. Villanueva, Helena Legido-Quigley, Evalyn A. Roxas
      First page: 820
      Abstract: Antimicrobial resistance (AMR) is a global public health threat that warrants urgent attention. Countries developed their national action plans (NAPs) following the launch of the Global Action Plan on AMR in 2015. The development and implementation of NAPs are often complicated due to the multifaceted nature of AMR, and studies analyzing these aspects are lacking. We analyzed the development and implementation of the Philippine NAP on AMR with guidance from an AMR governance framework. We conducted in-depth interviews with 37 participants across the One Health spectrum. The interviews were transcribed verbatim and were analyzed thematically, adopting an interpretative approach. The enabling factors for NAP implementation include (1) a high level of governmental support and involvement of relevant stakeholders, (2) the development of policies to support improved responses in infection prevention and control and antimicrobial stewardship, and (3) better engagement and advocacy by professional associations and civil society groups. The challenges include (1) a lack of resources and regulatory capacity, (2) insufficient impetus for AMR research and surveillance, and (3) limited One Health engagement. Although there has been considerable progress for human health, strengthening the involvement and representation of the animal health and environment sectors in the AMR scene must be undertaken. Developing well-defined roles within policies will be paramount to the strong implementation of AMR strategies.
      Citation: Antibiotics
      PubDate: 2022-06-17
      DOI: 10.3390/antibiotics11060820
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 821: Antimicrobial Resistance Development
           Pathways in Surface Waters and Public Health Implications

    • Authors: Joseph Kusi, Catherine Oluwalopeye Ojewole, Akinloye Emmanuel Ojewole, Isaac Nwi-Mozu
      First page: 821
      Abstract: Human health is threatened by antibiotic-resistant bacteria and their related infections, which cause thousands of human deaths every year worldwide. Surface waters are vulnerable to human activities and natural processes that facilitate the emergence and spread of antibiotic-resistant bacteria in the environment. This study evaluated the pathways and drivers of antimicrobial resistance (AR) in surface waters. We analyzed antibiotic resistance healthcare-associated infection (HAI) data reported to the CDC’s National Healthcare Safety Network to determine the number of antimicrobial-resistant pathogens and their isolates detected in healthcare facilities. Ten pathogens and their isolates associated with HAIs tested resistant to the selected antibiotics, indicating the role of healthcare facilities in antimicrobial resistance in the environment. The analyzed data and literature research revealed that healthcare facilities, wastewater, agricultural settings, food, and wildlife populations serve as the major vehicles for AR in surface waters. Antibiotic residues, heavy metals, natural processes, and climate change were identified as the drivers of antimicrobial resistance in the aquatic environment. Food and animal handlers have a higher risk of exposure to resistant pathogens through ingestion and direct contact compared with the general population. The AR threat to public health may grow as pathogens in aquatic systems adjust to antibiotic residues, contaminants, and climate change effects. The unnecessary use of antibiotics increases the risk of AR, and the public should be encouraged to practice antibiotic stewardship to decrease the risk.
      Citation: Antibiotics
      PubDate: 2022-06-18
      DOI: 10.3390/antibiotics11060821
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 822: Effect of Fluoroquinolone Use in Primary
           Care on the Development and Gradual Decay of Escherichia coli Resistance
           to Fluoroquinolones: A Matched Case-Control Study

    • Authors: Peter Konstantin Kurotschka, Chiara Fulgenzio, Roberto Da Cas, Giuseppe Traversa, Gianluigi Ferrante, Orietta Massidda, Ildikó Gágyor, Richard Aschbacher, Verena Moser, Elisabetta Pagani, Stefania Spila Alegiani, Marco Massari
      First page: 822
      Abstract: The reversibility of bacterial resistance to antibiotics is poorly understood. Therefore, the aim of this study was to determine, over a period of five years, the effect of fluoroquinolone (FQ) use in primary care on the development and gradual decay of Escherichia coli resistance to FQ. In this matched case–control study, we linked three sources of secondary data of the Health Service of the Autonomous Province of Bolzano, Italy. Cases were all those with an FQ-resistant E. coli (QREC)-positive culture from any site during a 2016 hospital stay. Data were analyzed using conditional logistic regression. A total of 409 cases were matched to 993 controls (FQ-sensitive E. coli) by the date of the first isolate. Patients taking one or more courses of FQ were at higher risk of QREC colonization/infection. The risk was highest during the first year after FQ was taken (OR 2.67, 95%CI 1.92–3.70, p < 0.0001), decreased during the second year (OR 1.54, 95%CI 1.09–2.17, p = 0.015) and became undetectable afterwards (OR 1.09, 95%CI 0.80–1.48, p = 0.997). In the first year, the risk of resistance was highest after greater cumulative exposure to FQs. Moreover, older age, male sex, longer hospital stays, chronic obstructive pulmonary disease (COPD) and diabetes mellitus were independent risk factors for QREC colonization/infection. A single FQ course significantly increases the risk of QREC colonization/infection for no less than two years. This risk is higher in cases of multiple courses, longer hospital stays, COPD and diabetes; in males; and in older patients. These findings may inform public campaigns and courses directed to prescribers to promote rational antibiotic use.
      Citation: Antibiotics
      PubDate: 2022-06-18
      DOI: 10.3390/antibiotics11060822
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 823: Patterns and Determinants of Antibiotic
           Use Behaviors among Rural Community Residents in Eastern China

    • Authors: Yanhuan Wang, Xinping Zhao, Yurong Li, Na Wang, Feng Jiang, Helen Lambert, Fei Yan, Chaowei Fu, Qingwu Jiang
      First page: 823
      Abstract: Inappropriate antibiotic use may lead to antibiotic resistance, which has become a serious global crisis. Addressing suboptimal antibiotic use in the general population can play a significant role in the fight against antimicrobial resistance. This study aims to describe antibiotic use and sources of acquisition, and to identify factors influencing antibiotic access among rural community residents in Eastern China. A cross-sectional survey was conducted from July to August 2020, and 1494 participants from two villages in Eastern China were enrolled. Information was obtained using face-to-face interviews with a structured electronic questionnaire. Chi-squared and multinominal logistic regression analysis were used to explore possible determinants. In total, 1379 participants were eligible for the analysis. In the past 12 months, nearly half the respondents had taken any antibiotic (48.4%), and this proportion varied across marital status and age group. Two thirds of them (59.9%) obtained antibiotics from medical facilities with a prescription when they last took antibiotics, while 17.7% and 22.4% chose retail pharmacies and other sources, respectively. Multinominal analysis found that a higher proportion obtained antibiotics outside medical facilities among those aged 15 to 44 years, unmarried, non-white collar workers, with more years of education, lower annual household income per capita and lower levels of antibiotic knowledge. The antibiotic use behavior of rural community residents in Eastern China remains suboptimal. Antibiotic use and access behaviors need to be further addressed. Effective antibiotic stewardship in non-medical facility sources and training programs targeted for rural Chinese is warranted in future.
      Citation: Antibiotics
      PubDate: 2022-06-18
      DOI: 10.3390/antibiotics11060823
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 824: Heparin-Binding Protein (HBP), Neutrophil
           Gelatinase-Associated Lipocalin (NGAL) and S100 Calcium-Binding Protein B
           (S100B) Can Confirm Bacterial Meningitis and Inform Adequate Antibiotic

    • Authors: Maria Obreja, Egidia Gabriela Miftode, Iulian Stoleriu, Daniela Constantinescu, Andrei Vâță, Daniela Leca, Corina Maria Cianga, Olivia Simona Dorneanu, Mariana Pavel-Tanasa, Petru Cianga
      First page: 824
      Abstract: The empirical administration of antibiotics for suspected bacterial meningitis denotes a poor bacterial stewardship. In this context, the use of biomarkers can distinguish between bacterial and viral infections before deciding treatment. Our study assesses how levels of heparin-binding protein (HBP), neutrophil gelatinase-associated lipocalin (NGAL), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) and in blood can promptly confirm bacterial etiology and the need for antibiotic treatment. The CSF and blood levels of HBP, NGAL, S100B, and NSE of 81 patients with meningitis were measured and analyzed comparatively. Statistical sensitivity, specificity, and positive and negative predictive values were evaluated. CSF levels of HBP and NGAL and the blood level of S100B in the bacterial meningitis group were significantly higher (p < 0.05). The area under curve (AUC) for predicting bacterial meningitis was excellent for the CSF level of HBP (0.808 with 93.54% sensitivity and 80.64% specificity), good for the CSF level of NGAL (0.685 with 75.00% sensitivity and 65.62% specificity), and good for the blood level of S100B (0.652 with 65.90% sensitivity and 57.14% specificity). CSF levels of HBP and NGAL, as well as the blood level of S100B, could help discriminate between bacterial and viral meningitis before considering antibiotic treatment.
      Citation: Antibiotics
      PubDate: 2022-06-19
      DOI: 10.3390/antibiotics11060824
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 825: Clinical Trial for Evaluating the
           Effectiveness and Safety of a New Dental Plaque Removal Device: Microscale
           Mist Unit

    • Authors: Hiroki Hihara, Kuniyuki Izumita, Misato Iwatsu, Tomoya Sato, Ryo Tagaino, Kenta Shobara, Yuta Shinohara, Takanori Hatakeyama, Chie Kayaba, Mariko Sato, Ayako Tokue, Tomoko Sugawara, Kanamai Ashino, Koji Ikeda, Jun Aida, Keiichi Sasaki
      First page: 825
      Abstract: This study evaluates the effectiveness and safety of a microscale mist unit (MSM-UNIT) that sprays high-speed fine water droplets to remove dental plaque adhering to the oral mucosa (tongue and palate) and tooth surface. Fifteen patients who had difficulty self-managing sufficient oral care were included in this study. Effectiveness was evaluated for at least five patients’ tongues, palate mucosas, and tooth surfaces, and safety evaluation was conducted at all three sites for all patients. Effectiveness was evaluated using the rate of degree of dental plaque removal. Safety was evaluated using a numerical rating scale (NRS) for pain and symptoms of inflammation. An operator who performed treatment and an evaluator who evaluated effectiveness and safety were designated. In addition, an image judgment committee judged effectiveness. Although evaluation of the tongue varied between the evaluators and the image judgment committee, the rates of degree for all plaque removal increased in all regions. In addition, low pain NRS results and minimal symptoms of inflammation were observed and within an acceptable range. The MSM-UNIT can be used effectively and safely for removing oral plaque not only from teeth, but also from the oral mucosa.
      Citation: Antibiotics
      PubDate: 2022-06-19
      DOI: 10.3390/antibiotics11060825
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 826: Long-Term Impact of the COVID-19 Pandemic
           on In-Hospital Antibiotic Consumption and Antibiotic Resistance: A Time
           Series Analysis (2015–2021)

    • Authors: Marianna Meschiari, Lorenzo Onorato, Erica Bacca, Gabriella Orlando, Marianna Menozzi, Erica Franceschini, Andrea Bedini, Adriana Cervo, Antonella Santoro, Mario Sarti, Claudia Venturelli, Emanuela Biagioni, Irene Coloretti, Stefano Busani, Massimo Girardis, José-María Lòpez-Lozano, Cristina Mussini
      First page: 826
      Abstract: The coronavirus disease 2019 (COVID-19)-pandemic-related overload of health systems has compromised the application of antimicrobial stewardship (AS) models and infection prevention and control (IPC) programs. We aimed to evaluate the impact of COVID-19 on antimicrobial consumption (AC) and antimicrobial resistance (AMR) in the University Hospital of Modena. A time series analysis with an autoregressive integrated moving average model was conducted from January 2015 to October 2021 to evaluate the AC in the whole hospital and the intensive care unit (ICU), the incidence density (ID) of bloodstream infections (BSIs) due to the main multidrug-resistant organisms, and of C. difficile infections (CDIs). After an initial peak during the COVID-19 period, a decrease in the trend of AC was observed, both at the hospital (CT: −1.104, p = 0.025) and ICU levels (CT: −4.47, p = 0.047), with no significant difference in the single classes. Among the Gram-negative isolates, we observed a significant increase only in the level of BSIs due to carbapenem-susceptible Pseudomonas aeruginosa (CL: 1.477, 95% CI 0.130 to 2.824, p = 0.032). Considering Gram-positive bacteria, an increase in the level of BSIs due to methicillin-resistant Staphylococcus aureus and in the trend of CDIs were observed, though they did not reach statistical significance (CL: 0.72, 95% CI −0.039 to 1.48, p = 0.062; CT: 1.43, 95% CI −0.002 to 2.863, p = 0.051; respectively). Our findings demonstrated that the increases in AMR and AC that appeared in the first COVID-19 wave may be later controlled by restoring IPC and AS programs to pre-epidemic levels. A coordinated healthcare effort is necessary to address the longer-term impact of COVID-19 on AC to avoid irreversible consequences on AMR.
      Citation: Antibiotics
      PubDate: 2022-06-20
      DOI: 10.3390/antibiotics11060826
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 827: Hospital-Wide Protocol Significantly
           Improved Appropriate Management of Patients with Staphylococcus aureus
           Bloodstream Infection

    • Authors: Kawisara Krasaewes, Saowaluck Yasri, Phadungkiat Khamnoi, Romanee Chaiwarith
      First page: 827
      Abstract: Background:Staphylococcus aureus bloodstream infection (SA-BSI) causes morbidity and mortality. We established a management protocol for patients with SA-BSI aimed at improving quality of care and patient outcomes. Methods: A retrospective pre–post intervention study was conducted at Maharaj Nakorn Chiang Mai Hospital from 1 October 2019 to 30 September 2020 in the pre-intervention period and from 1 November 2020 to 31 October 2021 in the post-intervention period. Results: Of the 169 patients enrolled, 88 were in the pre-intervention and 81 were in the post-intervention periods. There were similar demographic characteristics between the two periods. In the post-intervention period, evaluations for metastatic infections were performed more frequently, e.g., echocardiography (70.5% vs. 91.4%, p = 0.001). The appropriateness of antibiotic prescription was higher in the post-intervention period (42% vs. 81.5%, p < 0.001). The factors associated with the appropriateness of antibiotic prescription were ID consultation (OR 15.5; 95% CI = 5.9–40.8, p < 0.001), being in the post-intervention period (OR 9.4; 95% CI: 3.5–25.1, p < 0.001), and thorough investigations for metastatic infection foci (OR 7.2; 95% CI 2.1–25.2, p = 0.002). However, the 90-day mortality was not different (34.1% and 27.2% in the pre- and post-intervention periods, respectively). The factors associated with mortality from the multivariate analysis were the presence of alteration of consciousness (OR 11.24; 95% CI: 3.96–31.92, p < 0.001), having a malignancy (OR 6.64; 95% CI: 1.83–24.00, p = 0.004), hypoalbuminemia (OR 5.23; 95% CI: 1.71–16.02, p = 0.004), and having a respiratory tract infection (OR 5.07; 95% CI: 1.53–16.84, p = 0.008). Source control was the only factor that reduced the risk of death (OR 0.08; 95% CI: 0.01–0.53, p = 0.009). Conclusion: One-third of patients died. Hospital-wide protocol implementation significantly improved the quality of care. However, the mortality rate did not decrease.
      Citation: Antibiotics
      PubDate: 2022-06-20
      DOI: 10.3390/antibiotics11060827
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 828: Companion Animals as Potential Reservoirs

    • Authors: Lulu Cui, Xiaonan Zhao, Ruibo Li, Yu Han, Guijuan Hao, Guisheng Wang, Shuhong Sun
      First page: 828
      Abstract: Antibiotic resistance genes of Escherichia coli (E. coli) from companion animals were still poorly understood. Here, we investigated the extended-spectrum β-lactamases (ESBLs) resistance genes of E. coli from companion animals in Shandong, China. A total of 79 isolates (80.6%) were recovered from 98 healthy or diarrheal companion animals in 2021, among which ESBLs-producing isolates accounted for 43.0% (34/79), and more than half of ESBL E. coli (ESBL-EC) strains (n = 19) were isolated from healthy companion animals. Diarrheagenic E. coli isolates (45.6%, n = 36) were represented by enterotoxigenic (ETEC) (32.9%), enteropathogenic (EPEC) (10.1%) and enteroinvasive (EIEC) (2.6%), 20 isolates of which were from healthy pets. Among tested antibiotics, resistance to tetracycline (64.6%) was the most commonly observed, followed by doxycycline (59.5%) and ampicillin (53.2%). Notably, all isolates were susceptible to meropenem. The multidrug-resistant (MDR) rate was 49.4%, 20 isolates of which were ESBLs producers; moreover, 23.4%, 16.4% of ESBL-EC strains were resistant to 5 or more, 7 or more antibiotics, respectively. Among the 5 β-lactamase resistance genes, the most frequent gene was blaCTX-M (60.76%), followed by blaSHV (40.51%). The plasmid-mediated quinolone resistance (PMQR) gene aac(6’)-Ib-cr was detected in 35 isolates. Additionally, ESBL-associated genes (i.e., blaCTX-M, blaSHV) were found in 76.5% ESBL-EC strains, with six isolates carrying blaCTX-M and blaSHV. The marker gene of high-pathogenicity island gene irp2 (encoding iron capture systems) was the most frequency virulence gene. Our results showed that ESBL-EC were widespread in healthy or diarrhea companion animals, especially healthy pets, which may be a potential reservoir of antibiotic resistance, therefore, enhancing a risk to public and animal health.
      Citation: Antibiotics
      PubDate: 2022-06-20
      DOI: 10.3390/antibiotics11060828
      Issue No: Vol. 11, No. 6 (2022)
  • Antibiotics, Vol. 11, Pages 829: Antifungal, Antioxidant and Antibiofilm
           Activities of Essential Oils of Cymbopogon spp.

    • Authors: Wafa Rhimi, Mona A. Mohammed, Aya Attia Koraney Zarea, Grazia Greco, Maria Tempesta, Domenico Otranto, Claudia Cafarchia
      First page: 829
      Abstract: Essential oils (EOs) of Cymbopogon citratus and Cymbopogon proximus are known as sources of monoterpenes and sesquiterpenoids, although their biological activities have not been well investigated. In this study, the compositions of C. citratus and C. proximus EOs of Egyptian origin and their antifungal and antibiofilm properties against Candida spp. and Malassezia furfur were investigated. Antioxidant activities were also evaluated. GC-MS showed the presence of nine and eight constituents in C. citratus and C. proximus EOs, respectively, with geranial and neral as the major compounds of C. citratus EO and piperitone and α-terpinolene as the major compounds of C. proximus EO. Both EOs showed antifungal (MIC values ranging from 1.25 to 20 µL/ mL) and antibiofilm activities (% of reduction ranging from 27.65 ± 11.7 to 96.39 ± 2.8) against all yeast species. The antifungal and antibiofilm activities of C. citratus EO were significantly higher than those observed for C. proximus EO. M. furfur was more susceptible to both EOs than Candida spp. Both EOs exhibited the highest antioxidant activity. This study suggests that C. citratus and C. proximus EOs might be an excellent source of antifungal, antibiofilm and antioxidant drugs and might be useful for preventing Malassezia infections in both medical and veterinary medicine.
      Citation: Antibiotics
      PubDate: 2022-06-20
      DOI: 10.3390/antibiotics11060829
      Issue No: Vol. 11, No. 6 (2022)
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Heriot-Watt University
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