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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 24)
AAPS Open     Open Access   (Followers: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
AboutOpen     Open Access  
ACS Pharmacology & Translational Science     Hybrid Journal   (Followers: 3)
Acta Pharmaceutica     Open Access   (Followers: 4)
Acta Pharmaceutica Indonesia     Open Access  
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Pharmacologica Sinica     Hybrid Journal   (Followers: 3)
Acta Physiologica Hungarica     Full-text available via subscription  
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 4)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 93)
Advanced Herbal Medicine     Open Access   (Followers: 8)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Advances in Pharmacoepidemiology & Drug Safety     Open Access   (Followers: 2)
Advances in Pharmacological and Pharmaceutical Sciences     Open Access   (Followers: 9)
Advances in Pharmacology     Full-text available via subscription   (Followers: 17)
Advances in Pharmacology and Pharmacy     Open Access   (Followers: 5)
Advances in Traditional Medicine     Hybrid Journal   (Followers: 3)
Adverse Drug Reaction Bulletin     Full-text available via subscription   (Followers: 5)
AJP : The Australian Journal of Pharmacy     Full-text available via subscription   (Followers: 8)
Alternatives to Laboratory Animals     Full-text available via subscription   (Followers: 9)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 20)
American Journal of Drug Discovery and Development     Open Access   (Followers: 3)
American Journal of Health-System Pharmacy     Full-text available via subscription   (Followers: 54)
American Journal of Pharmacological Sciences     Open Access   (Followers: 1)
American Journal of Pharmacology and Toxicology     Open Access   (Followers: 23)
American Journal of Therapeutics     Hybrid Journal   (Followers: 13)
Analytical Methods     Hybrid Journal   (Followers: 8)
Annales Pharmaceutiques Francaises     Full-text available via subscription  
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 56)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 36)
Anti-Infective Agents     Hybrid Journal   (Followers: 5)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 5)
Antibiotics     Open Access   (Followers: 11)
Antibody Therapeutics     Open Access  
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 1)
Antiviral Research     Hybrid Journal   (Followers: 8)
Applied Clinical Trials     Full-text available via subscription   (Followers: 7)
Archiv der Pharmazie     Hybrid Journal   (Followers: 2)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Pharmacal Research     Full-text available via subscription   (Followers: 2)
Archives of Pharmacy and Pharmaceutical Sciences     Open Access   (Followers: 1)
Archives of Razi Institute     Open Access  
Archivos Venezolanos de Farmacología y Terapéutica     Open Access  
Ars Pharmaceutica     Open Access  
Asian Journal of Medical and Pharmaceutical Researches     Open Access  
Asian Journal of Pharmaceutical Research and Health Care     Open Access   (Followers: 2)
Asian Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
Asian Journal of Pharmaceutics     Open Access   (Followers: 1)
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access  
ASSAY and Drug Development Technologies     Hybrid Journal   (Followers: 3)
Australian Journal of Herbal Medicine     Full-text available via subscription   (Followers: 4)
Australian Pharmacist     Full-text available via subscription   (Followers: 7)
Autonomic & Autacoid Pharmacology     Hybrid Journal  
Avicenna Journal of Phytomedicine     Open Access   (Followers: 1)
Bangladesh Journal of Pharmacology     Open Access  
Bangladesh Journal of Physiology and Pharmacology     Open Access  
Bangladesh Pharmaceutical Journal     Full-text available via subscription  
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 14)
Behavioural Pharmacology     Hybrid Journal   (Followers: 2)
Bioanalysis     Full-text available via subscription   (Followers: 11)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
BioDrugs     Full-text available via subscription   (Followers: 8)
Biological & Pharmaceutical Bulletin     Full-text available via subscription   (Followers: 3)
Biomarkers in Drug Development     Partially Free   (Followers: 2)
Biomaterials     Hybrid Journal   (Followers: 55)
Biomedical and Environmental Sciences     Full-text available via subscription   (Followers: 1)
Biomedicine & Pharmacotherapy     Full-text available via subscription   (Followers: 2)
Biometrical Journal     Hybrid Journal   (Followers: 9)
Biopharm International     Full-text available via subscription   (Followers: 20)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10)
BMC Pharmacology     Open Access   (Followers: 2)
BMC Pharmacology & Toxicology     Open Access   (Followers: 8)
Brazilian Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
British Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 30)
British Journal of Pharmacology     Hybrid Journal   (Followers: 17)
British Journal of Pharmacy (BJPharm)     Open Access   (Followers: 2)
Bulletin of Faculty of Pharmacy, Cairo University     Open Access   (Followers: 2)
CADTH Technology Overviews     Free  
Canadian Journal of Pain     Open Access   (Followers: 3)
Canadian Journal of Physiology and Pharmacology     Hybrid Journal   (Followers: 2)
Canadian Pharmacists Journal / Revue des Pharmaciens du Canada     Hybrid Journal   (Followers: 3)
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal  
Cancer Chemotherapy and Pharmacology     Hybrid Journal   (Followers: 4)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 14)
Cardiovascular Therapeutics     Open Access   (Followers: 3)
Cephalalgia Reports     Open Access  
Chemical and Pharmaceutical Bulletin     Full-text available via subscription   (Followers: 1)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
ChemMedChem     Hybrid Journal   (Followers: 9)
Chemotherapy     Full-text available via subscription   (Followers: 3)
Chinese Herbal Medicines     Full-text available via subscription   (Followers: 1)
Chinese Journal of Pharmaceutical Analysis     Full-text available via subscription  
Ciencia e Investigación     Open Access  
Ciência Equatorial     Open Access  
Clinical and Experimental Pharmacology and Physiology     Hybrid Journal   (Followers: 7)
Clinical and Translational Science     Open Access   (Followers: 4)
Clinical Complementary Medicine and Pharmacology     Open Access  
Clinical Drug Investigation     Full-text available via subscription   (Followers: 8)
Clinical Medicine Insights : Therapeutics     Open Access  
Clinical Neuropharmacology     Hybrid Journal   (Followers: 2)
Clinical Pharmacist     Partially Free   (Followers: 12)
Clinical Pharmacokinetics     Full-text available via subscription   (Followers: 28)
Clinical Pharmacology & Therapeutics     Hybrid Journal   (Followers: 45)
Clinical Pharmacology in Drug Development     Hybrid Journal   (Followers: 4)
Clinical Pharmacology: Advances and Applications     Open Access   (Followers: 6)
Clinical Research and Regulatory Affairs     Hybrid Journal   (Followers: 12)
Clinical Therapeutics     Hybrid Journal   (Followers: 34)
Clinical Toxicology     Hybrid Journal   (Followers: 18)
Clinical Trials     Hybrid Journal   (Followers: 18)
CNS Drug Reviews     Open Access   (Followers: 4)
CNS Drugs     Full-text available via subscription   (Followers: 10)
Combination Products in Therapy     Open Access  
Consultant Pharmacist     Full-text available via subscription   (Followers: 2)
Consumer Drugs     Full-text available via subscription  
Contract Pharma     Full-text available via subscription  
Cosmetics     Open Access   (Followers: 4)
CPT : Pharmacometrics & Systems Pharmacology     Open Access   (Followers: 11)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 16)
Critical Reviews in Therapeutic Drug Carrier Systems     Full-text available via subscription   (Followers: 5)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 25)
Current Bioactive Compounds     Hybrid Journal  
Current Cancer Therapy Reviews     Hybrid Journal   (Followers: 5)
Current Clinical Pharmacology     Hybrid Journal   (Followers: 4)
Current Drug Delivery     Hybrid Journal   (Followers: 6)
Current Drug Discovery Technologies     Hybrid Journal   (Followers: 6)
Current Drug Metabolism     Hybrid Journal   (Followers: 5)
Current Drug Safety     Hybrid Journal   (Followers: 8)
Current Drug Targets     Hybrid Journal   (Followers: 5)
Current Drug Therapy     Hybrid Journal   (Followers: 3)
Current Enzyme Inhibition     Hybrid Journal   (Followers: 1)
Current Issues in Pharmacy and Medical Sciences     Open Access   (Followers: 2)
Current Medical Science     Hybrid Journal  
Current Medicinal Chemistry     Hybrid Journal   (Followers: 13)
Current Molecular Pharmacology     Hybrid Journal  
Current Nanoscience     Hybrid Journal  
Current Neuropharmacology     Hybrid Journal   (Followers: 1)
Current Opinion in Pharmacology     Hybrid Journal   (Followers: 9)
Current Pharmaceutical Analysis     Hybrid Journal   (Followers: 1)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 10)
Current Pharmaceutical Design     Hybrid Journal   (Followers: 11)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Current Pharmacology Reports     Hybrid Journal  
Current Protocols in Pharmacology     Hybrid Journal  
Current Radiopharmaceuticals     Hybrid Journal   (Followers: 1)
Current Research in Drug Discovery     Open Access   (Followers: 2)
Current Research in Pharmacology and Drug Discovery     Open Access   (Followers: 1)
Current Therapeutic Research     Open Access   (Followers: 6)
Current trends in Biotechnology and Pharmacy     Open Access   (Followers: 8)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 4)
Dhaka University Journal of Pharmaceutical Sciences     Open Access  
Die Pharmazie - An International Journal of Pharmaceutical Sciences     Full-text available via subscription   (Followers: 5)
Dose-Response     Open Access  
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 13)
Drug and Therapeutics Bulletin     Hybrid Journal   (Followers: 8)
Drug Delivery     Open Access   (Followers: 8)
Drug Delivery and Translational Research     Hybrid Journal   (Followers: 2)
Drug Design, Development and Therapy     Open Access   (Followers: 3)
Drug Development and Industrial Pharmacy     Hybrid Journal   (Followers: 29)
Drug Development Research     Hybrid Journal   (Followers: 11)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 12)
Drug Metabolism and Disposition     Hybrid Journal   (Followers: 13)
Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 6)
Drug Metabolism Letters     Hybrid Journal   (Followers: 3)
Drug Metabolism Reviews     Hybrid Journal   (Followers: 8)
Drug Research     Hybrid Journal   (Followers: 3)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
Drug Safety     Full-text available via subscription   (Followers: 79)
Drug Safety - Case Reports     Open Access   (Followers: 2)
Drug Target Insights     Open Access  
Drug, Healthcare and Patient Safety     Open Access   (Followers: 10)
Drugs     Full-text available via subscription   (Followers: 123)
Drugs & Aging     Full-text available via subscription   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 9)
Drugs : Real World Outcomes     Hybrid Journal   (Followers: 1)
Drugs and Therapy Studies     Open Access  
Drugs in R & D     Full-text available via subscription   (Followers: 2)
Drugs of the Future     Full-text available via subscription   (Followers: 8)
East and Central African Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
Egyptian Pharmaceutical Journal     Open Access  
EJNMMI Radiopharmacy and Chemistry     Open Access  
EMC - Cosmetologia Medica e Medicina degli Inestetismi Cutanei     Full-text available via subscription  
Emerging Trends in Drugs, Addictions, and Health     Open Access  
Environmental Toxicology and Pharmacology     Hybrid Journal   (Followers: 9)
Epilepsy Research     Hybrid Journal   (Followers: 7)
Ethiopian Pharmaceutical Journal     Full-text available via subscription   (Followers: 1)
EUREKA : Health Sciences     Open Access  
European Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 14)
European Journal of Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 8)
European Journal of Hospital Pharmacy : Science and Practice (EJHP)     Hybrid Journal   (Followers: 5)
European Journal of Medicinal Plants     Open Access   (Followers: 2)
European Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 84)
European Journal of Pharmaceutics and Biopharmaceutics     Hybrid Journal   (Followers: 34)
European Journal of Pharmacology     Hybrid Journal   (Followers: 8)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 9)
European Review for Medical and Pharmacological Sciences     Full-text available via subscription   (Followers: 1)
Experimental and Clinical Psychopharmacology     Full-text available via subscription   (Followers: 7)
Expert Opinion on Drug Delivery     Hybrid Journal   (Followers: 17)
Expert Opinion on Drug Discovery     Hybrid Journal   (Followers: 18)

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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 850: Bacterial Colonization Incidence before
           and after Indwelling Double-J Ureteral Stents

    • Authors: Sholpan Kaliyeva, Natalya Simokhina, Alyona Lavrinenko, Gulzira Zhussupova, Serik Zhunusov, Polina Semenikhina, Yuliya Bikbatyrova, Berik Yelmagambetov, Zhanna Myasnikova
      First page: 850
      Abstract: The upper urinary tract stenting allows to restore the ureteral patency in various situations. However, one of the main disadvantages of stenting is bacterial contamination, which can be a source of persistent infections that hardly respond to antibiotic therapy. The aim of this study was to investigate the local spectrum of bacterial pathogens and their susceptibility to antibiotics in order to optimize antibacterial therapy after upper urinary tract stenting. A prospective observational study was conducted in which 140 urine samples were examined (70 before stenting and 70 after stenting). Bacterial growth was detected in 37 patients (52.8%) before stenting and in 43 patients (61.4%) after stenting. E. coli (13 (28.8%)) and Streptococcus spp. (8 (17.6%)) strains were more commonly detected before stenting; P. aeruginosa (15 (31.2%)) and E. coli (8 (16.6%)) were usually revealed after stenting. The proportion of P. aeruginosa strains after stenting grew from 4.4% up to 31.2%. E. coli strains were resistant to ampicillin (92.3% before and 100% after stenting). Three strains of E. coli (23.1%) and six strains of P. aeruginosa (40%) were multidrug-resistant. Determination of the bacterial sensitivity to antibiotics and identification of antibiotic-resistant forms of bacteria is a factor in reducing the risk of complications and optimizing antibiotic therapy during the upper urinary tract stenting.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070850
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 851: Ventilator-Associated Pneumonia Due to
           MRSA vs. MSSA: What Should Guide Empiric Therapy'

    • Authors: Marta Colaneri, Domenico Di Carlo, Alessandro Amatu, Lea Nadia Marvulli, Marta Corbella, Greta Petazzoni, Patrizia Cambieri, Alba Muzzi, Claudio Bandi, Angela Di Matteo, Paolo Sacchi, Francesco Mojoli, Raffaele Bruno
      First page: 851
      Abstract: The guidelines on ventilator-associated pneumonia (VAP) recommend an empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) according to its prevalence rate. Considering the MRSA and MSSA VAP prevalence over the last 9 years in our tertiary care hospital, we assessed the clinical value of the MRSA nasal-swab screening in either predicting or ruling out MRSA VAP. We extracted the data of 1461 patients with positive bronchoalveolar lavage (BAL). Regarding the MRSA nasal-swab screening, 170 patients were positive for MRSA or MSSA. Overall, MRSA had a high prevalence in our ICU. Despite the COVID-19 pandemic, there was a significant downward trend in MRSA prevalence, while MSSA remained steady over time. Having VAP due to MRSA did not have any impact on LOS and mortality. Finally, the MRSA nasal-swab testing demonstrated a very high negative predictive value for MRSA VAP. Our results suggested the potential value of a patient-centered approach to improve antibiotic stewardship.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070851
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 852: Antimicrobial-Resistant Enterococcus spp.
           in Wild Avifauna from Central Italy

    • Authors: Giulia Cagnoli, Fabrizio Bertelloni, Paolo Interrante, Renato Ceccherelli, Margherita Marzoni, Valentina Virginia Ebani
      First page: 852
      Abstract: Bacteria of the genus Enterococcus are opportunistic pathogens, part of the normal intestinal microflora of animals, able to acquire and transfer antimicrobial resistance genes. The aim of this study was to evaluate the possible role of wild avifauna as a source of antimicrobial-resistant enterococci. To assess this purpose, 103 Enterococcus spp. strains were isolated from the feces of wild birds of different species; they were tested for antimicrobial resistance against 21 molecules, vancomycin resistance, and high-level aminoglycosides resistance (HLAR). Furthermore, genes responsible for vancomycin, tetracycline, and HLAR were searched. E. faecium was the most frequently detected species (60.20% of isolates), followed by E. faecalis (34.95% of isolates). Overall, 99.02% of the isolated enterococci were classified as multidrug-resistant, with 19.41% extensively drug-resistant, and 2.91% possible pan drug-resistant strains. Most of the isolates were susceptible to amoxicillin/clavulanic acid (77.67%) and ampicillin (75.73%), with only 5.83% of isolates showing an ampicillin MIC ≥ 64 mg/L. HLAR was detected in 35.92% of isolates, mainly associated with the genes ant(6)-Ia and aac(6′)-Ie-aph(2′’)-Ia. Few strains (4.85%) were resistant to vancomycin, and the genes vanA and vanB were not detected. A percentage of 54.37% of isolates showed resistance to tetracycline; tet(M) was the most frequently detected gene in these strains. Wild birds may contribute to the spreading of antimicrobial-resistant enterococci, which can affect other animals and humans. Constant monitoring is essential to face up to the evolving antimicrobial resistance issue, and monitoring programs should include wild avifauna, too.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070852
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 853: Biosynthesized Silver Nanoparticles from
           Eruca sativa Miller Leaf Extract Exhibits Antibacterial, Antioxidant,
           Anti-Quorum-Sensing, Antibiofilm, and Anti-Metastatic Activities

    • Authors: Amir Mahgoub Awadelkareem, Eyad Al-Shammari, AbdElmoneim O. Elkhalifa, Mohd Adnan, Arif Jamal Siddiqui, Mitesh Patel, Mohammad Idreesh Khan, Khalid Mehmood, Fauzia Ashfaq, Riadh Badraoui, Syed Amir Ashraf
      First page: 853
      Abstract: Worldwide, the primary problem today is the proliferation of cancer and secondary bacterial infections caused by biofilms, as they are the principal causes of death due to the lack of effective drugs. A great deal of biological activities of silver nanoparticles (AgNPs) have made them a brilliant choice for the development of new drugs in recent years. The present study was conducted to evaluate the anticancer, antibacterial, anti-QS, and antibiofilm effects of AgNPs synthesized from Eruca sativa (E. sativa) leaf extract. The ultraviolet–visible (UV–Vis) spectra showed a peak of surface plasmon resonance at 424 nm λmax, which corresponded to AgNP formation. The Fourier transform infrared spectroscopy (FT-IR) confirmed that biological moieties are involved for the development of AgNPs. Moreover, transmission electron microscopy (TEM) analyses confirmed the spherical shape and uniform size (8.11 to 15 nm) of the AgNPs. In human lung cancer cells (A549), the anticancer potential of AgNPs was examined by the MTT [3-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, scratch assay, and invasion assay. The results indicated that AgNPs inhibit the migration of A549 cells. The synthesized AgNPs showed MIC values of 12.5 µg/mL against Chromobacterium violaceum (C. violaceum) and 25 µg/mL against Pseudomonas aeruginosa (P. aeruginosa), which demonstrated their antibacterial abilities. Biological compounds that disable the QS system are being investigated as potential strategies for preventing bacterial infections. Thus, we analyzed the potential effectiveness of synthesized AgNPs in inhibiting QS-regulated virulence factors and biofilm formation in both strains of bacteria. In C. violaceum, the synthesized AgNPs significantly inhibited both violacein (85.18% at 1/2 × MIC) and acyl homoserine lactone (78.76% at 1/2 × MIC). QS inhibitory activity was also demonstrated in P. aeruginosa at a sub-MIC concentration (1/2 × MIC) by a reduction in pyocyanin activity (68.83%), total protease (68.50%), LasA activity (63.91%), and LasB activity (56.40%). Additionally, the exopolysaccharide production was significantly reduced in both C. violaceum (65.79% at 1/2 × MIC) and P. aeruginosa (57.65% at 1/2 × MIC). The formation of biofilm was also significantly inhibited at 1/2 × MIC in C. violaceum (76.49%) and in P. aeruginosa (65.31%). Moreover, a GC–MS analysis confirmed the presence of different classes of bioactive phytochemical constituents present in the leaf extract of E. sativa. On the basis of our results, we conclude that biologically synthesized AgNPs showed numerous multifunctional properties and have the potential to be used against human cancer and bacterial biofilm-related infections.
      Citation: Antibiotics
      PubDate: 2022-06-25
      DOI: 10.3390/antibiotics11070853
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 854: Campylobacter jejuni Biofilm Control with
           Lavandin Essential Oils and By-Products

    • Authors: Dina Ramić, Janja Ogrizek, Franz Bucar, Barbka Jeršek, Miha Jeršek, Sonja Smole Možina
      First page: 854
      Abstract: The food industry is constantly struggling with one of the most prevalent biofilm-forming and food-borne pathogenic bacteria, Campylobacter jejuni. Different approaches are used to control biofilms in the food production chain, but none is fully effective. In this study, we aim to produce and determine the chemical profile of essential oils (EOs), ethanolic extracts of flowers prior to distillation (EFs), and ethanolic extracts of post-distillation waste material (EWMs) from Lavandula × intermedia ‘Bila’, ‘Budrovka’ St Nicholas and ‘Budrovka’, which were further used to reduce C. jejuni intercellular signaling, adhesion, and biofilm formation, as well as to test their antioxidant activity. Glycosides of hydroxycinnamic acids were the major constituents of both types of lavandin ethanolic extract, while linalool, linalyl acetate, 1,8-cineol, and camphor were the major compounds found in lavandin EOs. Tested EOs showed the best antibacterial activity with a minimal inhibitory concentration of 0.25 mg/mL. Lavandin EFs proved more effective in reducing C. jejuni intercellular signaling and adhesion compared to lavandin EOs and EWMs, while lavandin EOs showed a slightly better effect against biofilm formation. Interestingly, the best antioxidant activity was determined for lavandin EWMs. A positive and moderate correlation was found between the reduction of C. jejuni intercellular signaling and adhesion, as well as between adhesion and biofilm formation. These findings mean novel bacterial targets are of interest for biofilm control with alternative natural agents throughout the whole food production chain.
      Citation: Antibiotics
      PubDate: 2022-06-25
      DOI: 10.3390/antibiotics11070854
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 855: Synergistic Role of Plant Extracts and
           Essential Oils against Multidrug Resistance and Gram-Negative Bacterial
           Strains Producing Extended-Spectrum β-Lactamases

    • Authors: Manzar Alam, Nilofer Bano, Taufeeq Ahmad, Amit Baran Sharangi, Tarun Kumar Upadhyay, Yasser Alraey, Nadiyah M. Alabdallah, Mohd Ahmar Rauf, Mohd Saeed
      First page: 855
      Abstract: Plants, being the significant and natural source of medication for humankind against several ailments with characteristic substances hidden on them, have been recognized for many centuries. Accessibility of various methodologies for the revelation of therapeutically characteristic items has opened new avenues to redefine plants as the best reservoirs of new structural types. The role of plant metabolites to hinder the development and movement of pathogenic microbes is cherished. Production of extended-spectrum β-lactamases is an amazing tolerance mechanism that hinders the antibacterial treatment of infections caused by Gram-negative bacteria and is a serious problem for the current antimicrobial compounds. The exploration of the invention from sources of plant metabolites gives sustenance against the concern of the development of resistant pathogens. Essential oils are volatile, natural, complex compounds described by a solid odor and are framed by aromatic plants as secondary metabolites. The bioactive properties of essential oils are commonly controlled by the characteristic compounds present in them. They have been commonly utilized for bactericidal, virucidal, fungicidal, antiparasitic, insecticidal, medicinal, and antioxidant applications. Alkaloids are plant secondary metabolites that have appeared to have strong pharmacological properties. The impact of alkaloids from Callistemon citrinus and Vernonia adoensis leaves on bacterial development and efflux pump activity was assessed on Pseudomonas aeruginosa. Plant-derived chemicals may have direct antibacterial activity and/or indirect antibacterial activity as antibiotic resistance modifying agents, increasing the efficiency of antibiotics when used in combination. The thorough screening of plant-derived bioactive chemicals as resistance-modifying agents, including those that can act synergistically with antibiotics, is a viable method to overcome bacterial resistance. The synergistic assessment studies with the plant extract/essential oil and the antibiotic compounds is essential with a target for achieving a redesigned model with sustainable effects which are appreciably noticeable in specific sites of the plants compared to the entirety of their individual parts.
      Citation: Antibiotics
      PubDate: 2022-06-26
      DOI: 10.3390/antibiotics11070855
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 856: Surgical Antimicrobial Prophylaxis in
           Neonates and Children Undergoing Neurosurgery: A RAND/UCLA Appropriateness
           Method Consensus Study

    • Authors: Susanna Esposito, Mino Zucchelli, Sonia Bianchini, Laura Nicoletti, Sara Monaco, Erika Rigotti, Laura Venditto, Cinzia Auriti, Caterina Caminiti, Elio Castagnola, Giorgio Conti, Maia De Luca, Daniele Donà, Luisa Galli, Silvia Garazzino, Stefania La Grutta, Laura Lancella, Mario Lima, Giuseppe Maglietta, Gloria Pelizzo, Nicola Petrosillo, Giorgio Piacentini, Simone Pizzi, Alessandro Simonini, Simonetta Tesoro, Elisabetta Venturini, Fabio Mosca, Annamaria Staiano, Nicola Principi, on behalf of the Peri-Operative Prophylaxis in Neonatal; Paediatric Age (POP-NeoPed) Study Group
      First page: 856
      Abstract: Pediatric neurosurgery is a highly specialized branch of surgery in which surgical site infections (SSIs) are potentially serious complications that can also adversely affect a good surgical outcome, compromising functional recovery and, in some cases, even putting the patient’s life at risk. The main aim of this consensus document is to provide clinicians with a series of recommendations on antimicrobial prophylaxis for neonates and children undergoing neurosurgery. The following scenarios were considered: (1) craniotomy or cranial/cranio-facial approach to craniosynostosis; (2) neurosurgery with a trans-nasal-trans-sphenoidal approach; (3) non-penetrating head injuries; (4) penetrating head fracture; (5) spinal surgery (extradural and intradural); (6) shunt surgery or neuroendoscopy; (7) neuroendovascular procedures. Patients undergoing neurosurgery often undergo peri-operative antibiotic prophylaxis, with different schedules, not always supported by scientific evidence. This consensus provides clear and shared indications, based on the most updated literature. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, and represents, in our opinion, the most complete and up-to-date collection of recommendations on the behavior to be held in the peri-operative setting in this type of intervention, in order to guide physicians in the management of the patient, standardize approaches and avoid abuse and misuse of antibiotics.
      Citation: Antibiotics
      PubDate: 2022-06-26
      DOI: 10.3390/antibiotics11070856
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 857: Enterococcus Virulence and Resistant
           Traits Associated with Its Permanence in the Hospital Environment

    • Authors: Catarina Geraldes, Luís Tavares, Solange Gil, Manuela Oliveira
      First page: 857
      Abstract: Enterococcus are opportunistic pathogens that have been gaining importance in the clinical setting, especially in terms of hospital-acquired infections. This problem has mainly been associated with the fact that these bacteria are able to present intrinsic and extrinsic resistance to different classes of antibiotics, with a great deal of importance being attributed to vancomycin-resistant enterococci. However, other aspects, such as the expression of different virulence factors including biofilm-forming ability, and its capacity of trading genetic information, makes this bacterial genus more capable of surviving harsh environmental conditions. All these characteristics, associated with some reports of decreased susceptibility to some biocides, all described in this literary review, allow enterococci to present a longer survival ability in the hospital environment, consequently giving them more opportunities to disseminate in these settings and be responsible for difficult-to-treat infections.
      Citation: Antibiotics
      PubDate: 2022-06-26
      DOI: 10.3390/antibiotics11070857
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 858: Evaluation of Three
           Carbapenemase-Phenotypic Detection Methods and Emergence of Diverse VIM
           and GES Variants among Pseudomonas aeruginosa Isolates in Tunisia

    • Authors: Sana Ferjani, Elaa Maamar, Asma Ferjani, Lamia Kanzari, Ilhem Boutiba Ben Boubaker
      First page: 858
      Abstract: Background: Since 2012, few reports on the molecular epidemiology of Pseudomonas aeruginosa were reported in Tunisia. Objectives: This study aimed to evaluate carbapenem-resistance determinants and molecular epidemiology and to compare the carbapenemase-phenotypic detection methods of multidrug-resistant P. aeruginosa isolates. Methods: During a period of four years (2014 to 2017), all imipenem-ceftazidime-resistant P. aeruginosa isolates were retrospectively selected at the microbial laboratory of Charles Nicolle hospital of Tunis. These isolates were examined by the modified Hodge test, modified carbapenem inactivation method (mCIM), and another mCIM, called CIMTris, and their performance was evaluated using PCR analysis as the gold standard. Results: A total of 35 isolates were recovered among patients hospitalized in different units. All strains were colistin-susceptible.All carbapenem-resistant isolates showed a high-level resistance to carbapenems. CIMTris and mCIM showed 96.15% and 46.15% sensitivity and 44.44% and 100% specificity, respectively, for detecting carbapenemase production.Conclusions: CIMTris is a promising approach for detecting carbapenemase activity in P. aeruginosa and merits further testing. Moreover, this study described the first detection of GES-5- and GES-9-producing P. aeruginosa in Tunisia as well as the co-occurrence of the blaGES-5 and blaVIM-11 carbapenemase genes in one isolate. These findings are of great concern because the rapid dissemination of MDR strains represents a major therapeutic and epidemiological threat.
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070858
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 859: Antibiotics and Infectious Respiratory

    • Authors: Francesco Di Gennaro, Gina Gualano, Fabrizio Palmieri
      First page: 859
      Abstract: Respiratory infectious diseases (rIDs) remain among the most significant causes of morbidity and mortality worldwide, and, in the era of COVID-19, they have come into major focus in the scientific world and global health approaches [...]
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070859
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 860: Editorial for Special Issue
           “Alternatives to Antibiotics: Bacteriocins and Antimicrobial

    • Authors: Joao V. Neves
      First page: 860
      Abstract: The discovery of penicillin in 1928 by Sir Alexander Fleming, and its later introduction as an antibiotic in the early 1940s, was a gamechanger for the entire medical field [...]
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070860
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 861: Whole-Genome Sequence of
           Multidrug-Resistant Methicillin-Resistant Staphylococcus epidermidis
           Carrying Biofilm-Associated Genes and a Unique Composite of SCCmec

    • Authors: Hisham N. Altayb, Hana S. Elbadawi, Othman Baothman, Imran Kazmi, Faisal A. Alzahrani, Muhammad Shahid Nadeem, Salman Hosawi, Kamel Chaieb
      First page: 861
      Abstract: Staphylococcus epidermidis is part of the normal human flora that has recently become an important opportunistic pathogen causing nosocomial infections and tends to be multidrug-resistant. In this investigation, we aimed to study the genomic characteristics of methicillin-resistant S. epidermidis isolated from clinical specimens. Three isolates were identified using biochemical tests and evaluated for drug susceptibility. Genomic DNA sequences were obtained using Illumina, and were processed for analysis using various bioinformatics tools. The isolates showed multidrug resistance to most of the antibiotics tested in this study, and were identified with three types (III(3A), IV(2B&5), and VI(4B)) of the mobile genetic element SCCmec that carries the methicillin resistance gene (mecA) and its regulators (mecI and mecR1). A total of 11 antimicrobial resistance genes (ARGs) was identified as chromosomally mediated or in plasmids; these genes encode for proteins causing decreased susceptibility to methicillin (mecA), penicillin (blaZ), fusidic acid (fusB), fosfomycin (fosB), tetracycline (tet(K)), aminoglycosides (aadD, aac(6′)-aph(2′’)), fluoroquinolone (MFS antibiotic efflux pump), trimethoprim (dfrG), macrolide (msr(A)), and chlorhexidine (qacA)). Additionally, the 9SE strain belongs to the globally disseminated ST2, and harbors biofilm-formation genes (icaA, icaB, icaC, icaD, and IS256) with phenotypic biofilm production capability. It also harbors the fusidic acid resistance gene (fusB), which could increase the risk of device-associated healthcare infections, and 9SE has been identified as having a unique extra SCC gene (ccrB4); this new composite element of the ccr type needs more focus to better understand its role in the drug resistance mechanism.
      Citation: Antibiotics
      PubDate: 2022-06-24
      DOI: 10.3390/antibiotics11070861
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 862: Inactivation of Bacteria and Residual
           Antimicrobials in Hospital Wastewater by Ozone Treatment

    • Authors: Takashi Azuma, Miwa Katagiri, Tsuyoshi Sekizuka, Makoto Kuroda, Manabu Watanabe
      First page: 862
      Abstract: The emergence and spread of antimicrobial resistance (AMR) has become a persistent problem globally. In this study, an ozone treatment facility was established for an advanced hospital wastewater treatment in a core hospital facility in an urban area in Japan to evaluate the inactivation of antimicrobial-resistant bacteria and antimicrobials. Metagenomic DNA-seq analysis and the isolation of potential extended-spectrum β-lactamase (ESBL)-producing bacteria suggested that ozone exposure for at least 20 min is required for the adequate inactivation of DNA and ESBL-producing bacteria. Escherichia coli and Klebsiella species were markedly susceptible to 20-min ozone exposure, whereas Raoultella ornithinolytica and Pseudomonas putida were isolated even after an 80-min exposure. These ozone-resistant bacteria might play a pivotal role as AMR reservoirs in the environment. Nine antimicrobials (ampicillin, cefdinir, cefpodoxime, ciprofloxacin, levofloxacin, clarithromycin, chlortetracycline, minocycline, and vancomycin) were detected at 373 ng/L to 27 μg/L in the hospital wastewater, and these were removed (96–100% removal) after a 40-min treatment. These results facilitate a comprehensive understanding of the AMR risk posed by hospital wastewater and provides insights for devising strategies to eliminate or mitigate the burden of antimicrobial-resistant bacteria and the flow of antimicrobials into the environment. To the best of our knowledge, this is the first report on the implementation of a batch-type, plant-scale ozone treatment system in a hospital facility to execute and evaluate the inactivation of drug-resistant bacteria and antimicrobials.
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070862
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 863: Prevention of Surgical Site Infections in
           Neonates and Children: Non-Pharmacological Measures of Prevention

    • Authors: Aniello Meoli, Lorenzo Ciavola, Sofia Rahman, Marco Masetti, Tommaso Toschetti, Riccardo Morini, Giulia Dal Canto, Cinzia Auriti, Caterina Caminiti, Elio Castagnola, Giorgio Conti, Daniele Donà, Luisa Galli, Stefania La Grutta, Laura Lancella, Mario Lima, Andrea Lo Vecchio, Gloria Pelizzo, Nicola Petrosillo, Alessandro Simonini, Elisabetta Venturini, Fabio Caramelli, Gaetano Domenico Gargiulo, Enrico Sesenna, Rossella Sgarzani, Claudio Vicini, Mino Zucchelli, Fabio Mosca, Annamaria Staiano, Nicola Principi, Susanna Esposito, on behalf of the Peri-Operative Prophylaxis in Neonatal; Paediatric Age (POP-NeoPed) Study Group
      First page: 863
      Abstract: A surgical site infection (SSI) is an infection that occurs in the incision created by an invasive surgical procedure. Although most infections are treatable with antibiotics, SSIs remain a significant cause of morbidity and mortality after surgery and have a significant economic impact on health systems. Preventive measures are essential to decrease the incidence of SSIs and antibiotic abuse, but data in the literature regarding risk factors for SSIs in the pediatric age group are scarce, and current guidelines for the prevention of the risk of developing SSIs are mainly focused on the adult population. This document describes the current knowledge on risk factors for SSIs in neonates and children undergoing surgery and has the purpose of providing guidance to health care professionals for the prevention of SSIs in this population. Our aim is to consider the possible non-pharmacological measures that can be adopted to prevent SSIs. To our knowledge, this is the first study to provide recommendations based on a careful review of the available scientific evidence for the non-pharmacological prevention of SSIs in neonates and children. The specific scenarios developed are intended to guide the healthcare professional in practice to ensure standardized management of the neonatal and pediatric patients, decrease the incidence of SSIs and reduce antibiotic abuse.
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070863
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 864: Development of Wash-Durable Antimicrobial
           Cotton Fabrics by In Situ Green Synthesis of Silver Nanoparticles and
           Investigation of Their Antimicrobial Efficacy against Drug-Resistant

    • Authors: Ashu Jain, Bhani Kongkham, Hariprasad Puttaswamy, Bhupendra Singh Butola, Hitendra Kumar Malik, Anushree Malik
      First page: 864
      Abstract: An environment friendly and wash-durable silver nanoparticle treatment of cotton fabrics was carried out by in situ reduction of silver nitrate using Azadirachta indica leaf extract. The wash durability of the silver nanoparticles treatment on the cotton fabric was improved by pretreating the fabrics by mercerization and by adopting hydrothermal conditions of 120 °C temperature and 15 psi pressure for the in situ synthesis. The silver nanoparticle treated fabrics were characterized using scanning electron microscopy, colorimetric analysis and inductively coupled plasma mass spectroscopy. The coating of silver nanoparticles was seen to be dense and uniform in the scanning electron micrographs of the treated fabrics. An evaluation of the antibacterial efficacy of the silver nanoparticle treated fabric against antibiotic-resistant Gram-positive and Gram-negative strains was carried out. The antibacterial efficacy was found to be the highest against Bacillus licheniformis, showing 93.3% inhibition, whereas it was moderate against Klebsiella pneumoniae (20%) and Escherichia coli (10%). The transmittance data of a UV spectrophotometer (290–400nm) was used for measuring the UV protection factor of the silver nanoparticle treated fabrics. All the silver nanoparticle treated fabrics showed good antimicrobial and UV protection activity. The treatment was also seen to be durable against repeated laundering. This paper contributes the first report on a novel green synthesis approach integrating mercerization of cotton fabrics and in situ synthesis of nanoparticles under hydrothermal conditions using Azadirachta indica leaf extract for improved wash durability of the multifunctional fabric.
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070864
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 865: Comparative Evaluation of Vitek 2 and
           Etest versus Broth Microdilution for Ceftazidime/Avibactam and
           Ceftolozane/Tazobactam Susceptibility Testing of Enterobacterales and
           Pseudomonas aeruginosa

    • Authors: Arhodoula Papadomanolaki, Maria Siopi, Polyxeni Karakosta, Sophia Vourli, Spyros Pournaras
      First page: 865
      Abstract: Ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) are novel antibiotics with activity against multidrug-resistant Gram-negative pathogens. Nevertheless, resistance to both agents has been reported emphasizing the need for accurate and widely accessible susceptibility testing. In the present study, Vitek 2 and Etest CAZ and C/T MIC results for 100 non-repetitive clinical isolates (83 Enterobacterales and 17 P. aeruginosa, whereof 69 challenge isolates) were compared to the standard broth microdilution (BMD) method. EUCAST breakpoints were used for assessing the categorical (CA) and essential (EA) agreement between the methods along with the corresponding error rates. The Vitek 2 performance was comparable to that of BMD for testing both antimicrobial agents exceeding the ISO requirements (CA 98–99%, EA 96–100%, major errors (MEs) 0–1%, very major error (VMEs) 1%). Likewise, the Etest provided accurate results for CZA and C/T testing against Enterobacterales and P. aeruginosa, respectively (CA 100%, EA 97–100%, MEs 0%, VMEs 0%). On the contrary, EA of 85% and 6% VME rate were found for CZA Etest and P. aeruginosa. Overall, Vitek 2 measurements of CZA and C/T susceptibility correlated closely with the reference BMD, indicating that it can represent a suitable alternative to BMD for susceptibility testing of Enterobacterales and P. aeruginosa. The Etest did not fulfill the ISO performance criteria of EA and VME for CZA and P. aeruginosa. Further studies are needed to assess whether the Etest allows a reliable assessment of CZA and C/T EUCAST MICs.
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070865
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 866: Infection Sources and Klebsiella
           pneumoniae Antibiotic Susceptibilities in Endogenous Klebsiella

    • Authors: Kuan-Jen Chen, Yen-Po Chen, Yi-Hsing Chen, Laura Liu, Nan-Kai Wang, An-Ning Chao, Wei-Chi Wu, Yih-Shiou Hwang, Hung-Da Chou, Eugene Yu-Chuan Kang, Yen-Ting Chen, Ming-Hui Sun, Chi-Chun Lai
      First page: 866
      Abstract: Endogenous endophthalmitis is an uncommon intraocular infection with potentially devastating consequences on vision. Klebsiella pneumoniae is highly prevalent in East Asian countries, with an increasing incidence recently worldwide. This retrospective study investigates infection sources and antibiotic susceptibilities of K. pneumoniae in patients with endogenous K. pneumoniae endophthalmitis (EKE) in Northern Taiwan. One hundred and fifty-seven patients with EKE were reviewed between January 1996 and April 2019. Pyogenic liver abscess (120/157, 76.4%) was the most common infection source, followed by pneumonia (13, 8.3%), urinary tract infection (7, 4.5%), and intravenous drug use (4, 2.5%). Bilateral involvement was identified in 12.1% (19/157) of patients, especially in patients with pyogenic liver abscess (16/120, 13.3%), pneumonia (2/13, 15.4%), and urinary tract infection (1/7, 14.3%). The antibiotic susceptibility rates were 98.1%, 92.5%, 97.5%, 96.8%, 100%, 99.3%, and 100% for amikacin, cefuroxime, ceftazidime, ceftriaxone, carbapenems, ciprofloxacin, and levofloxacin, respectively. Four extended-spectrum β-lactamase-producing multidrug-resistant (MDR) K. pneumoniae isolates were identified. In conclusion, pyogenic liver abscess was the major infection source in EKE. In addition, K. pneumoniae was still highly susceptible to ceftazidime and amikacin, and the MDR K. pneumoniae isolates were not common in EKE.
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070866
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 867: Veterinary Practitioners’
           Standpoints and Comprehension towards Antimicrobial Use—Are There
           Opportunities for Antimicrobial Stewardship Improvement'

    • Authors: Zorana Kovačević, Jovana Vidović, Mihajlo Erdeljan, Marko Cincović, Zoran Ružić, Ivan Galić, Tijana Kukurić, Nenad Stojanac, Olga Horvat
      First page: 867
      Abstract: The main subject of the research is the assessment of the knowledge, attitudes and behaviors of veterinarians regarding the use of antibiotics (AMU) and antimicrobial resistance (AMR) through a questionnaire conducted among veterinarians in the northern region of Serbia. A total of 62 respondents completed the questionnaire, which represents a response rate of 44.3%. Male veterinarians are less likely to be in the group of veterinarians with insufficient knowledge (p < 0.05). Veterinarians engaged in mixed practice (small and large animals) (p < 0.001) and veterinarians who have over 100 patients per month (p < 0.005) are also less likely to be in the group with insufficient knowledge of antimicrobial resistance. The proportion of those with insufficient knowledge is growing among veterinarians whose source is the Internet (p < 0.01), while the proportion of those with insufficient knowledge about antimicrobial resistance is declining among veterinarians whose source of information is continuous education (p < 0.05). The majority of the respondents (n = 59, 95.2%) completely agreed that AMR is a very big issue in the global health sector right now. Unfortunately, there are crucial gaps in the knowledge and attitudes of the surveyed participants. They do not appear to be aware of the importance of AMU in veterinary medicine and its influence on overall AMR, or the crucial part that non-prescribed antibiotics have in all of it. Positively, many veterinarians use good practice AMU guidelines in their everyday practice and in line with the global trend of AMU reduction, respondents have also decreased their AMU compared to the previous year.
      Citation: Antibiotics
      PubDate: 2022-06-27
      DOI: 10.3390/antibiotics11070867
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 868: In Vitro Evaluation of Antimicrobial
           Effect of Phytobiotics Mixture on Salmonella spp. Isolated from Chicken

    • Authors: Hubert Iwiński, Karolina Wódz, Karolina Chodkowska, Tomasz Nowak, Henryk Różański
      First page: 868
      Abstract: Background: The identification of natural antibacterial agents from various sources that can act effectively against disease-causing foodborne bacteria is one of the major concerns throughout the world. In the present study, a unique phytobiotics mixture containing thymol, menthol, linalool, trans-anethole, methyl salicylate, 1,8-cineole, and p-cymene was evaluated for antibacterial activity against selected strains of Salmonella spp. Results: The phytobiotics mixture was effective against Salmonella enterica subsp. enterica serovars Enteritidis, Typhimurium, and Kentucky. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of this unique mixture for these three pathogens were 1:256. Among these three strains, one S. Kentucky presented the most extensive resistance profiles to 18 antibiotics belonging to 5 classes of antibiotics. One of S. Typhimurium presents extensive resistance profiles to 14 antibiotics belonging to 5 classes of antibiotics. Conclusions: The results suggest that the phytobiotics mixture used in the experiment can be used as a strong natural antibacterial agent against Gram-negative foodborne pathogens such as S. Typhimurium, S. Kentucky, and S. Enteritidis. This is a preliminary analysis of the effectiveness of a phytobiotic product in an in vitro model, which may be the starting point for further studies, including in vivo animal models.
      Citation: Antibiotics
      PubDate: 2022-06-28
      DOI: 10.3390/antibiotics11070868
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 869: Occurrence of Serratia marcescens
           Carrying blaIMP-26 and mcr-9 in Southern China: New Insights in the
           Evolution of Megaplasmid IMP-26

    • Authors: Yuxia Zhong, Wanting Liu, Peibo Yuan, Ling Yang, Zhenbo Xu, Dingqiang Chen
      First page: 869
      Abstract: The spread of multidrug-resistant enterobacteria strains has posed a significant concern in public health, especially when the strain harbors metallo-beta-lactamase (MBL)-encoding and mobilized colistin resistance (mcr) genes as such genetic components potentially mediate multidrug resistance. Here we report an IncHI2/2A plasmid carrying blaIMP-26 and mcr-9 in multidrug-resistant Serratia marcescens human isolates YL4. Antimicrobial susceptibility testing was performed by the broth microdilution method. According to the results, S. marcescens YL4 was resistant to several antimicrobials, including β-lactams, fluorquinolones, sulfanilamide, glycylcycline, and aminoglycosides, except for amikacin. To investigate the plasmid further, we conducted whole-genome sequencing and sequence analysis. As shown, S. marcescens YL4 possessed a circular chromosome with 5,171,477 bp length and two plasmids, pYL4.1 (321,744 bp) and pYL4.2 (46,771 bp). Importantly, sharing high similarity with plasmids pZHZJ1 and pIMP-26, pYL4.1 has an IncHI2/2A backbone holding a variable region containing blaIMP-26, mcr-9, and two copies of blaTEM-1B. After comprehensively comparing relevant plasmids, we proposed an evolutionary pathway originating from ancestor pZHZJ1. Then, via an acquisition of the mcr-9 element and a few recombination events, this plasmid eventually evolved into pYL4.1 and pIMP-26 through two different pathways. In addition, the phage-like plasmid pYL4.2 also carried a blaTEM-1B gene. Remarkably, this study first identified a multidrug-resistant S. marcescens strain co-harboring blaIMP-26 and mcr-9 on a megaplasmid pYL4.1 and also included a proposed evolutionary pathway of epidemic megaplasmids carrying blaIMP-26.
      Citation: Antibiotics
      PubDate: 2022-06-28
      DOI: 10.3390/antibiotics11070869
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 870: In Silico Docking, Resistance Modulation
           and Biofilm Gene Expression in Multidrug-Resistant Acinetobacter baumannii
           via Cinnamic and Gallic Acids

    • Authors: Neveen A. Abdelaziz, Walid F. Elkhatib, Mahmoud M. Sherif, Mohammed A. S. Abourehab, Sara T. Al-Rashood, Wagdy M. Eldehna, Nada M. Mostafa, Nooran S. Elleboudy
      First page: 870
      Abstract: Despite the mounting global burden of antimicrobial resistance (AMR), the generation of new classes of effective antimicrobials still lags far behind. The interplay between multidrug resistance and biofilm formation in Acinetobacter baumannii has drastically narrowed the available therapeutic choices. The use of natural compounds holds promise as an alternate option for restoring the activity of existing antibiotics and attenuating virulence traits through reduced biofilm formation. This study aimed to evaluate the modulatory effect of combining cinnamic and gallic acids at ½MIC with various antibiotics against multidrug-resistant (MDR) A. baumannii clinical isolates as well as study the effect on the expression of the biofilm-associated genes (bap, csuE, ompA) via quantitative, real-time PCR. Combining cinnamic or gallic acid with imipenem, amikacin or doxycycline resulted in significant reduction of resistance (p < 0.05). On the contrary, no effect was recorded when both acids were combined with levofloxacin, and only cinnamic acid had a synergistic effect with colistin. The transcriptomic changes of biofilm-related genes in the presence of gallic acid at ½MIC were compared with untreated control samples. The fold expression values proved that gallic acid substantially down-regulated the respective genes in all five strong biofilm formers. Molecular docking studies of gallic and cinnamic acids on target genes revealed good binding affinities and verified the proposed mechanism of action. To the best of our knowledge, this is the first report on the effect of gallic acid on the expression of bap, csuE and ompA genes in A. baumannii, which may permit its use as an adjunct anti-virulence therapeutic strategy.
      Citation: Antibiotics
      PubDate: 2022-06-28
      DOI: 10.3390/antibiotics11070870
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 871: Genomic Analysis of
           Ceftazidime/Avibactam-Resistant GES-Producing Sequence Type 235
           Pseudomonas aeruginosa Isolates

    • Authors: Raúl Recio, Jennifer Villa, Sara González-Bodí, Patricia Brañas, María Ángeles Orellana, Mikel Mancheño-Losa, Jaime Lora-Tamayo, Fernando Chaves, Esther Viedma
      First page: 871
      Abstract: The emergence of ceftazidime/avibactam (CZA) resistance among Guiana extended-spectrum β-lactamase (GES)-producing Pseudomonas aeruginosa isolates has rarely been described. Herein, we analyze the phenotypic and genomic characterization of CZA resistance in different GES-producing P. aeruginosa isolates that emerged in our institution. A subset of nine CZA-resistant P. aeruginosa isolates was analyzed and compared with thirteen CZA-susceptible isolates by whole-genome sequencing (WGS). All CZA-resistant isolates belonged to the ST235 clone and O11 serotype. A variety of GES enzymes were detected: GES-20 (55.6%, 5/9), GES-5 (22.2%, 2/9), GES-1 (11.1%, 1/9), and GES-7 (11.1%, 1/9). WGS revealed the presence of two mutations within the blaGES-20 gene comprising two single-nucleotide substitutions, which caused aspartic acid/serine and leucine/premature stop codon amino acid changes at positions 165 (D165S) and 237 (L237X), respectively. No major differences in the mutational resistome (AmpC, OprD porin, and MexAB-OprM efflux pump-encoding genes) were found among CZA-resistant and CZA-susceptible isolates. None of the mutations that have been previously demonstrated to cause CZA resistance were observed. Different mutations within the blaGES-20 gene were documented in CZA-resistant GES-producing P. aeruginosa isolates belonging to the ST235 clone in our institution. Although further analysis should be performed, according to our results, other resistance mechanisms might be involved in CZA resistance.
      Citation: Antibiotics
      PubDate: 2022-06-28
      DOI: 10.3390/antibiotics11070871
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 872: Healthcare Professionals’ Knowledge
           and Beliefs on Antibiotic Prophylaxis in Cesarean Section: A Mixed-Methods
           Study in Benin

    • Authors: Angèle Modupè Dohou, Valentina Oana Buda, Severin Anagonou, Françoise Van Van Bambeke, Thierry Van Van Hees, Francis Moïse Dossou, Olivia Dalleur
      First page: 872
      Abstract: A low adherence to recommendations on antibiotic prophylaxis has been reported worldwide. Since 2009, cesarean sections have been performed under user fee exemption in Benin with a free kit containing the required supplies and antibiotics for prophylaxis. Despite the kit, the level of antibiotic prophylaxis achievement remains low. We conducted a convergent parallel design study in 2017 using a self-administered questionnaire and interviews to assess the knowledge and explore the beliefs of healthcare professionals regarding antibiotic prophylaxis in three hospitals. Of the 35 participants, 33 filled out the questionnaire. Based on the five conventional criteria of antibiotic prophylaxis, the mean level of knowledge was 3.3 out of 5, and only 15.2% scored 5 out of 5. From the verbatim of 19 interviewees, determinants such as suboptimal patient status health, low confidence in antibiotics, some disagreement with the policy, inappropriate infrastructures and limited financial resources in hospitals, poor management of the policy in the central level, and patient refusal to buy antibiotics can explain poor practices. Because of the dysfunction at these levels, the patient becomes the major determinant of adequate antibiotic prophylaxis. Policymakers have to consider these determinants for improving antibiotic prophylaxis in a way that ensures patient safety and reduces the incidence of antimicrobial resistance.
      Citation: Antibiotics
      PubDate: 2022-06-28
      DOI: 10.3390/antibiotics11070872
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 873: Mycobacterioses Induced by Mycobacterium
           abscessus: Case Studies Indicating the Importance of Molecular Analysis
           for the Identification of Antibiotic Resistance

    • Authors: Lenka Ryskova, Radka Bolehovska, Rudolf Kukla, Michal Svarc, Alzbeta Zavrelova, Hubert Vanicek, Ivo Pavlik, Pavel Bostik
      First page: 873
      Abstract: Mycobacterioses are less frequently occurring but serious diseases. In recent years, at a global level, the incidence of mycobacterioses induced by the rapidly growing species Mycobacterium abscessus (M. a.), which is considered to be the most resistant to antibiotics and most difficult to treat, has been on the rise. Correct identification to the level of the subspecies (M. a. abscessus, M. a. massiliense, and M. a. bolletii) and determination of its sensitivity to macrolides, which are the basis of combination therapy, are of principal importance for the management of the disease. We describe five cases of mycobacterioses caused by M. a., where the sequencing of select genes was performed to identify the individual subspecies and antibiotic resistance. The analysis of the rpoB gene showed two isolates each of M. a. abscessus and M. a. massiliense and one isolate of M. a. bolletii. The complete (full length) erm(41) gene responsible for the development of inducible resistance to macrolides was demonstrated in both M. a. abscessus and M. a. bolletii isolates. A partially deleted and non-functional erm(41) gene was demonstrated in M. a. massiliense isolates. The subsequent sequencing of the full length erm(41) gene products showed, however, the mutation (T28→C) in both isolates of M. a. abscessus, causing a loss of the function and preserved sensitivity to macrolides. The antibiotic sensitivity testing confirmed that both the isolates of M. a. abscessus and M. a. massiliense were sensitive to clarithromycin even after prolonged 14-day incubation. The inducible resistance to clarithromycin was maintained only in M. a. bolletii. Thus, the sequence analysis of the erm(41) gene can reliably identify the preservation of sensitivity to macrolides and serve as an important tool in the establishment of therapeutic regimens in cases of infections with M. abscessus.
      Citation: Antibiotics
      PubDate: 2022-06-28
      DOI: 10.3390/antibiotics11070873
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 874: Elevated Mortality Risk from CRKp
           Associated with Comorbidities: Systematic Review and Meta-Analysis

    • Authors: Lucas Candido Gonçalves Barbosa, José Arthur Silva e Sousa, Graziela Picciola Bordoni, Gabriel de Oliveira Barbosa, Lilian Carla Carneiro
      First page: 874
      Abstract: Carbapenem-resistant Klebsiella pneumoniae has become a public health problem with therapeutic limitations and high mortality associated with comorbidities. Methods: This is a systematic review and meta-analysis with a search in PubMed, SciELO, and Lilacs. Ten articles were selected, considering cohort, case-control, and cross-sectional studies. Tests for proportions and relative risk of mortality were performed, considering a 5% threshold for significance. Statistical analyses were performe dusing Rstudio® software, version 4.0.2 of Ross Ihaka and Robert Genleman in Auckland, New Zealand. Results: Klebsiella pneumoniae, associated with chronic kidney disease, was responsible for 26%/258 deaths, chronic lung disease 28%/169, diabetes 31%/185, liver disease 15%/262, and heart disease 51%/262 deaths. Carbapenem-resistant Klebsiella pneumoniae associated with chronic kidney disease was responsible for 49%/83 deaths, with diabetes 29%/73, and with liver disease 33%/73 deaths. The risk of death from carbapenem-resistant Klebsiella pneumoniae was twice as high as the number of deaths associated with carbapenem-sensitive Klebsiella pneumoniae, RR = 2.07 (p < 0.00001). Conclusions: The present study showed an increase in mortality from carbapenem-resistant Klebsiella pneumoniae when associated with comorbidities.
      Citation: Antibiotics
      PubDate: 2022-06-29
      DOI: 10.3390/antibiotics11070874
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 875: mcr-1-Mediated In Vitro Inhibition of
           Plasmid Transfer Is Reversed by the Intestinal Environment

    • Authors: Xiaoman Yang, Rundong Shu, Leqi Hou, Panpan Ren, Xin Lu, Zhi Huang, Zengtao Zhong, Hui Wang
      First page: 875
      Abstract: Colistin is regarded as an antibiotic of last resort against multidrug-resistant Gram-negative bacteria, including Klebsiella pneumoniae and Escherichia coli. Colistin resistance is acquired by microorganisms via chromosome-mediated mutations or plasmid-mediated mobile colistin resistance (mcr) gene, in which the transfer of mcr is the predominant factor underlying the spread of colistin resistance. However, the factors that are responsible for the spread of the mcr gene are still unclear. In this study, we observed that mcr-1 inhibited the transfer of the pHNSHP45 backbone in liquid mating. Similar inhibitory effect of mcr-1.6 and chromosomal mutant ΔmgrB suggested that colistin resistance, acquired from either plasmid or chromosomal mutation, hindered the transfer of colistin resistance-related plasmid in vitro. Dual plasmid system further proved that co-existing plasmid transfer was reduced too. However, this inhibitory effect was reversed in vivo. Some factors in the gut, including bile salt and anaerobic conditions, could increase the transfer frequency of the mcr-1-containing plasmid. Our results demonstrated the potential risk for the spread of colistin resistance in the intestine, provide a scientific basis against the transmission of colistin resistance threat.
      Citation: Antibiotics
      PubDate: 2022-06-29
      DOI: 10.3390/antibiotics11070875
      Issue No: Vol. 11, No. 7 (2022)
  • Antibiotics, Vol. 11, Pages 876: Multi-Drug Resistance to Salmonella spp.
           When Isolated from Raw Meat Products

    • Authors: Joanna Pławińska-Czarnak, Karolina Wódz, Magdalena Kizerwetter-Świda, Janusz Bogdan, Piotr Kwieciński, Tomasz Nowak, Zuzanna Strzałkowska, Krzysztof Anusz
      First page: 876
      Abstract: Salmonella spp. is the most frequent cause of foodborne diseases, and the increasing occurrence of MDR strains is an additional and increasing problem. We collected Salmonella spp. strains isolated from meat (poultry and pork) and analysed their antibiotic susceptibility profiles and the occurrence of resistance genes. To determine the susceptibility profiles and identify MDR strains, we used two MIC methods (MICRONAUT and VITEC2 Compact) and 25 antibiotics. Phenotypic tests showed that 53.84% strains were MDR. Finally, molecular analysis strains revealed the presence of blaSHV, blaPSE-1, blaTEM, but not blaCTX-M genes. Moreover, several genes were associated with resistance to aminoglycosides, cephalosporins, fluorochinolones, sulfonamides, and tetracyclines. This suggests that further research on the prevalence of antibiotic resistance genes (ARGs) in foodborne strains is needed, especially from a One Health perspective.
      Citation: Antibiotics
      PubDate: 2022-06-29
      DOI: 10.3390/antibiotics11070876
      Issue No: Vol. 11, No. 7 (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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