Subjects -> MEDICAL SCIENCES (Total: 8697 journals)
    - ALLERGOLOGY AND IMMUNOLOGY (220 journals)
    - ANAESTHESIOLOGY (121 journals)
    - CARDIOVASCULAR DISEASES (338 journals)
    - CHIROPRACTIC, HOMEOPATHY, OSTEOPATHY (21 journals)
    - COMMUNICABLE DISEASES, EPIDEMIOLOGY (235 journals)
    - DENTISTRY (294 journals)
    - DERMATOLOGY AND VENEREOLOGY (163 journals)
    - EMERGENCY AND INTENSIVE CRITICAL CARE (124 journals)
    - ENDOCRINOLOGY (151 journals)
    - FORENSIC SCIENCES (42 journals)
    - GASTROENTEROLOGY AND HEPATOLOGY (189 journals)
    - GERONTOLOGY AND GERIATRICS (138 journals)
    - HEMATOLOGY (158 journals)
    - HYPNOSIS (4 journals)
    - INTERNAL MEDICINE (178 journals)
    - LABORATORY AND EXPERIMENTAL MEDICINE (99 journals)
    - MEDICAL GENETICS (58 journals)
    - MEDICAL SCIENCES (2419 journals)
    - NURSES AND NURSING (371 journals)
    - OBSTETRICS AND GYNECOLOGY (208 journals)
    - ONCOLOGY (386 journals)
    - OPHTHALMOLOGY AND OPTOMETRY (141 journals)
    - ORTHOPEDICS AND TRAUMATOLOGY (170 journals)
    - OTORHINOLARYNGOLOGY (83 journals)
    - PATHOLOGY (100 journals)
    - PEDIATRICS (275 journals)
    - PHYSICAL MEDICINE AND REHABILITATION (159 journals)
    - PSYCHIATRY AND NEUROLOGY (834 journals)
    - RADIOLOGY AND NUCLEAR MEDICINE (192 journals)
    - RESPIRATORY DISEASES (105 journals)
    - RHEUMATOLOGY (79 journals)
    - SPORTS MEDICINE (81 journals)
    - SURGERY (406 journals)
    - UROLOGY, NEPHROLOGY AND ANDROLOGY (155 journals)

MEDICAL SCIENCES (2419 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 3562 Journals sorted alphabetically
16 de Abril     Open Access   (Followers: 3)
3D Printing in Medicine     Open Access   (Followers: 5)
4 open     Open Access  
AADE in Practice     Hybrid Journal   (Followers: 6)
AAS Open Research     Open Access   (Followers: 2)
ABCS Health Sciences     Open Access   (Followers: 8)
Abia State University Medical Students' Association Journal     Full-text available via subscription   (Followers: 3)
AboutOpen     Open Access  
ACIMED     Open Access   (Followers: 1)
ACS Medicinal Chemistry Letters     Hybrid Journal   (Followers: 50)
Acta Bio Medica     Full-text available via subscription   (Followers: 2)
Acta Bioethica     Open Access  
Acta Bioquimica Clinica Latinoamericana     Open Access   (Followers: 1)
Acta Científica Estudiantil     Open Access  
Acta Facultatis Medicae Naissensis     Open Access   (Followers: 1)
Acta Herediana     Open Access  
Acta Informatica Medica     Open Access   (Followers: 2)
Acta Medica (Hradec Králové)     Open Access  
Acta Medica Bulgarica     Open Access  
Acta Medica Colombiana     Open Access   (Followers: 1)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Medica Indonesiana     Open Access  
Acta Medica International     Open Access  
Acta medica Lituanica     Open Access   (Followers: 1)
Acta Medica Marisiensis     Open Access   (Followers: 1)
Acta Medica Martiniana     Open Access  
Acta Medica Nagasakiensia     Open Access   (Followers: 1)
Acta Medica Peruana     Open Access   (Followers: 2)
Acta Médica Portuguesa     Open Access  
Acta Medica Saliniana     Open Access  
Acta Scientiarum. Health Sciences     Open Access   (Followers: 3)
Acupuncture & Electro-Therapeutics Research     Full-text available via subscription   (Followers: 8)
Acupuncture and Natural Medicine     Open Access  
Addiction Science & Clinical Practice     Open Access   (Followers: 9)
Addictive Behaviors Reports     Open Access   (Followers: 9)
Adıyaman Üniversitesi Sağlık Bilimleri Dergisi / Health Sciences Journal of Adıyaman University     Open Access   (Followers: 1)
Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi     Open Access   (Followers: 1)
Advanced Biomedical Research     Open Access  
Advanced Health Care Technologies     Open Access   (Followers: 10)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 9)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Advances in Bioscience and Clinical Medicine     Open Access   (Followers: 7)
Advances in Cell and Gene Therapy     Hybrid Journal   (Followers: 1)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 27)
Advances in Clinical Radiology     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 11)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Medical Education and Practice     Open Access   (Followers: 32)
Advances in Medical Ethics     Open Access   (Followers: 5)
Advances in Medical Research     Open Access   (Followers: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 10)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Medicine     Open Access   (Followers: 3)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5)
Advances in Molecular Oncology     Open Access   (Followers: 2)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7)
Advances in Parkinson's Disease     Open Access   (Followers: 2)
Advances in Phytomedicine     Full-text available via subscription   (Followers: 1)
Advances in Preventive Medicine     Open Access   (Followers: 6)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 21)
Advances in Regenerative Medicine     Open Access   (Followers: 4)
Advances in Skeletal Muscle Function Assessment     Open Access  
Advances in Therapy     Hybrid Journal   (Followers: 5)
Advances in Traditional Medicine     Hybrid Journal   (Followers: 8)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 6)
Advances in Wound Care     Hybrid Journal   (Followers: 14)
Aerospace Medicine and Human Performance     Full-text available via subscription   (Followers: 13)
African Health Sciences     Open Access   (Followers: 5)
African Journal of Biomedical Research     Open Access   (Followers: 1)
African Journal of Clinical and Experimental Microbiology     Open Access   (Followers: 4)
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
African Journal of Medical and Health Sciences     Open Access   (Followers: 3)
African Journal of Thoracic and Critical Care Medicine     Open Access  
African Journal of Trauma     Open Access   (Followers: 1)
Afrimedic Journal     Open Access   (Followers: 3)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 9)
AJOB Empirical Bioethics     Hybrid Journal   (Followers: 3)
AJSP: Reviews & Reports     Hybrid Journal   (Followers: 1)
Aktuelle Ernährungsmedizin     Hybrid Journal   (Followers: 6)
Al-Azhar Assiut Medical Journal     Open Access   (Followers: 2)
Al-Qadisiah Medical Journal     Open Access   (Followers: 1)
Alerta : Revista Científica del Instituto Nacional de Salud     Open Access  
Alexandria Journal of Medicine     Open Access   (Followers: 1)
Allgemeine Homöopathische Zeitung     Hybrid Journal   (Followers: 3)
Alpha Omegan     Full-text available via subscription  
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 2)
Althea Medical Journal     Open Access   (Followers: 2)
American Journal of Biomedical Engineering     Open Access   (Followers: 15)
American Journal of Biomedical Research     Open Access   (Followers: 2)
American Journal of Biomedicine     Full-text available via subscription   (Followers: 7)
American Journal of Chinese Medicine, The     Hybrid Journal   (Followers: 4)
American Journal of Clinical Medicine Research     Open Access   (Followers: 8)
American Journal of Family Therapy     Hybrid Journal   (Followers: 10)
American Journal of Law & Medicine     Full-text available via subscription   (Followers: 12)
American Journal of Lifestyle Medicine     Hybrid Journal   (Followers: 7)
American Journal of Managed Care     Full-text available via subscription   (Followers: 13)
American Journal of Medical Case Reports     Open Access   (Followers: 3)
American Journal of Medical Sciences and Medicine     Open Access   (Followers: 5)
American Journal of Medicine     Hybrid Journal   (Followers: 50)
American Journal of Medicine and Medical Sciences     Open Access   (Followers: 1)
American Journal of Medicine Studies     Open Access   (Followers: 3)
American Journal of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American Journal of the Medical Sciences     Hybrid Journal   (Followers: 12)
American Journal on Addictions     Hybrid Journal   (Followers: 11)
American medical news     Free   (Followers: 3)
American Medical Writers Association Journal     Full-text available via subscription   (Followers: 6)
Amyloid: The Journal of Protein Folding Disorders     Hybrid Journal   (Followers: 5)
Anales de la Facultad de Medicina     Open Access  
Anales de la Facultad de Medicina, Universidad de la República, Uruguay     Open Access  
Anales del Sistema Sanitario de Navarra     Open Access   (Followers: 1)
Analgesia & Resuscitation : Current Research     Hybrid Journal   (Followers: 7)
Anatolian Clinic the Journal of Medical Sciences     Open Access  
Anatomica Medical Journal     Open Access  
Anatomical Science International     Hybrid Journal   (Followers: 3)
Anatomical Sciences Education     Hybrid Journal   (Followers: 2)
Anatomy     Open Access   (Followers: 3)
Anatomy Research International     Open Access   (Followers: 4)
Androgens : Clinical Research and Therapeutics     Open Access   (Followers: 1)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3)
Ankara Medical Journal     Open Access   (Followers: 2)
Ankara Üniversitesi Tıp Fakültesi Mecmuası     Open Access  
Annales de Pathologie     Full-text available via subscription  
Annales des Sciences de la Santé     Open Access  
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annals of African Medicine     Open Access   (Followers: 2)
Annals of Anatomy - Anatomischer Anzeiger     Hybrid Journal   (Followers: 3)
Annals of Bioanthropology     Open Access   (Followers: 5)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 19)
Annals of Biomedical Sciences     Full-text available via subscription   (Followers: 4)
Annals of Clinical Hypertension     Open Access  
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 15)
Annals of Family Medicine     Open Access   (Followers: 18)
Annals of Health Research     Open Access   (Followers: 1)
Annals of Ibadan Postgraduate Medicine     Open Access  
Annals of Medical and Health Sciences Research     Open Access   (Followers: 7)
Annals of Medicine     Hybrid Journal   (Followers: 12)
Annals of Medicine and Surgery     Open Access   (Followers: 7)
Annals of Medicine and Surgery Case Reports     Open Access   (Followers: 1)
Annals of Medicine and Surgery Protocols     Open Access   (Followers: 1)
Annals of Microbiology     Hybrid Journal   (Followers: 13)
Annals of Musculoskeletal Medicine     Open Access   (Followers: 2)
Annals of Nigerian Medicine     Open Access   (Followers: 1)
Annals of Rehabilitation Medicine     Open Access   (Followers: 1)
Annals of Saudi Medicine     Open Access  
Annals of the College of Medicine, Mosul     Open Access   (Followers: 1)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5)
Annals of The Royal College of Surgeons of England     Full-text available via subscription   (Followers: 3)
Annals of the RussianAacademy of Medical Sciences     Open Access   (Followers: 1)
Annual Reports in Medicinal Chemistry     Full-text available via subscription   (Followers: 7)
Annual Reports on NMR Spectroscopy     Full-text available via subscription   (Followers: 5)
Annual Review of Medicine     Full-text available via subscription   (Followers: 18)
Anthropological Review     Open Access   (Followers: 25)
Anthropologie et santé     Open Access   (Followers: 5)
Antibiotics     Open Access   (Followers: 9)
Antibodies     Open Access   (Followers: 2)
Antibody Reports     Open Access   (Followers: 1)
Antibody Technology Journal     Open Access   (Followers: 1)
Antibody Therapeutics     Open Access   (Followers: 1)
Anuradhapura Medical Journal     Open Access  
Anwer Khan Modern Medical College Journal     Open Access   (Followers: 2)
Apmis     Hybrid Journal   (Followers: 2)
Apparence(s)     Open Access   (Followers: 1)
Applied Clinical Informatics     Hybrid Journal   (Followers: 5)
Applied Clinical Research, Clinical Trials and Regulatory Affairs     Hybrid Journal   (Followers: 2)
Applied Medical Informatics     Open Access   (Followers: 14)
Arab Journal of Nephrology and Transplantation     Open Access   (Followers: 1)
Arabian Journal of Scientific Research / المجلة العربية للبحث العلمي     Open Access   (Followers: 1)
Archive of Biomedical Science and Engineering     Open Access   (Followers: 1)
Archive of Clinical Medicine     Open Access   (Followers: 1)
Archive of Community Health     Open Access   (Followers: 1)
Archives Medical Review Journal / Arşiv Kaynak Tarama Dergisi     Open Access  
Archives of Asthma, Allergy and Immunology     Open Access  
Archives of Clinical Hypertension     Open Access   (Followers: 2)
Archives of Medical and Biomedical Research     Open Access   (Followers: 3)
Archives of Medical Laboratory Sciences     Open Access   (Followers: 1)
Archives of Medicine and Health Sciences     Open Access   (Followers: 5)
Archives of Medicine and Surgery     Open Access   (Followers: 1)
Archives of Organ Transplantation     Open Access   (Followers: 2)
Archives of Preventive Medicine     Open Access   (Followers: 3)
Archives of Pulmonology and Respiratory Care     Open Access   (Followers: 2)
Archives of Renal Diseases and Management     Open Access   (Followers: 2)
Archives of Trauma Research     Open Access   (Followers: 4)
Archivos de Medicina (Manizales)     Open Access   (Followers: 1)
ArgoSpine News & Journal     Hybrid Journal  
Arquivos Brasileiros de Oftalmologia     Open Access   (Followers: 1)
Arquivos de Ciências da Saúde     Open Access  
Arquivos de Medicina     Open Access   (Followers: 1)
Ars Medica : Revista de Ciencias Médicas     Open Access  
ARS Medica Tomitana     Open Access   (Followers: 1)
Art Therapy: Journal of the American Art Therapy Association     Hybrid Journal   (Followers: 19)
Arterial Hypertension     Open Access   (Followers: 1)
Artificial Intelligence in Medicine     Hybrid Journal   (Followers: 20)
Artificial Organs     Hybrid Journal   (Followers: 1)
ASHA Leader     Open Access   (Followers: 6)
Asia Pacific Family Medicine Journal     Open Access   (Followers: 4)
Asia Pacific Journal of Clinical Nutrition     Full-text available via subscription   (Followers: 13)
Asia Pacific Journal of Clinical Trials : Nervous System Diseases     Open Access   (Followers: 1)

        1 2 3 4 5 6 7 8 | Last

Similar Journals
Journal Cover
Antibiotics
Journal Prestige (SJR): 1.063
Citation Impact (citeScore): 3
Number of Followers: 9  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2079-6382
Published by MDPI Homepage  [231 journals]
  • Antibiotics, Vol. 9, Pages 624: Prevalence and Antibiotic Resistance of
           ESKAPE Pathogens Isolated in the Emergency Department of a Tertiary Care
           Teaching Hospital in Hungary: A 5-Year Retrospective Survey

    • Authors: Ria Benkő, Márió Gajdács, Mária Matuz, Gabriella Bodó, Andrea Lázár, Edit Hajdú, Erika Papfalvi, Peter Hannauer, Péter Erdélyi, Zoltán Pető
      First page: 624
      Abstract: Antibiotic treatments initiated on Emergency Departments (ED) are empirical. Therefore, knowledge of local susceptibility patterns is important. Despite this, data on expected pathogens and their resistance profile are scarce from EDs internationally. The study aim was to assess the epidemiology and resistance patterns of bacterial isolates from a tertiary-care ED over 5 years, focusing on ESKAPE bacteria (including the Enterobacterales group). After removal of duplicates, n = 6887 individual bacterial isolates were recovered, out of which n = 4974 (72.22%) were ESKAPE isolates. E. coli was the most frequent isolate (2193, 44.1%), followed by the Klebsiella genus (664; 13.4%). The third most frequent isolate was S. aureus (561, 11.3%). In total, multi-drug resistance (MDR) was present in 23.8% and was most prevalent in A. baumanii (65.5%), P. mirabilis (42.7%), and K. pneumoniae (32.6%). MRSA was isolated in 19.6%, while ESBL-producing Enterobacterales in 17.7%, and these were associated with remarkably higher resistance to other antibacterials as well. Difficult-to-treat resistance (DTR) was detected in 0.5%. The frequent isolation of some ESKAPE bacteria and the detected considerable acquired resistance among ED patients raise concern. The revealed data identified problematic pathogens and will guide us to set up the optimal empiric antibiotic protocol for clinicians.
      Citation: Antibiotics
      PubDate: 2020-09-19
      DOI: 10.3390/antibiotics9090624
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 625: Figainin 1, a Novel Amphibian Skin Peptide
           with Antimicrobial and Antiproliferative Properties

    • Authors: Carlos José Correia Santana, Ana Carolina Martins Magalhães, Agenor C. M. dos Santos Júnior, Carlos André Ornelas Ricart, Beatriz D. Lima, Alice da Cunha Morales Álvares, Sonia Maria de Freitas, Osmindo Rodrigues Pires, Wagner Fontes, Mariana S. Castro
      First page: 625
      Abstract: Amphibian skin secretions are abundant in bioactive compounds, especially antimicrobial peptides. These molecules are generally cationic and rich in hydrophobic amino acids, have an amphipathic structure and adopt an α-helical conformation when in contact with microorganisms membranes. In this work, we purified and characterized Figainin 1, a novel antimicrobial and antiproliferative peptide from the cutaneous secretion of the frog Boana raniceps. Figainin 1 is a cationic peptide with eighteen amino acid residues—rich in leucine and isoleucine, with an amidated C-terminus—and adopts an α-helical conformation in the presence of trifluoroethanol (TFE). It displayed activity against Gram-negative and especially Gram-positive bacteria, with MIC values ranging from 2 to 16 µM, and showed an IC50 value of 15.9 µM against epimastigote forms of T. cruzi; however, Figanin 1 did not show activity against Candida species. This peptide also showed cytolytic effects against human erythrocytes with an HC50 of 10 µM, in addition to antiproliferative activity against cancer cells and murine fibroblasts, with IC50 values ranging from 10.5 to 13.7 µM. Despite its adverse effects on noncancerous cells, Figainin 1 exhibits interesting properties for the development of new anticancer agents and anti-infective drugs against pathogenic microorganisms.
      Citation: Antibiotics
      PubDate: 2020-09-21
      DOI: 10.3390/antibiotics9090625
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 626: Clinical Significance of
           Carbapenem-Tolerant Pseudomonas aeruginosa Isolated in the Respiratory
           Tract

    • Authors: Momoyo Azuma, Keiji Murakami, Rina Murata, Keiko Kataoka, Hideki Fujii, Yoichiro Miyake, Yasuhiko Nishioka
      First page: 626
      Abstract: We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the correlation between clinical outcomes and antibiotic tolerance. This study aims to clarify the effect of antibiotic tolerance on clinical outcomes of respiratory tract infection caused by Pseudomonas aeuginosa (P. aeruginosa). We examined a total of 63 strains isolated from sputum samples of different patients and conducted a retrospective survey with the medical records of 37 patients with imipenem-sensitive P. aeruginosa infections. Among them, we selected 15 patients with respiratory infections, and they were divided into high-tolerance minimal bactericidal concentration for adherent bacteria (MBCAD)/minimal inhibitory concentration for adherent bacteria (MICAD) ≥ 32 (n = 9) group and low-tolerance MBCAD/MICAD ≤ 16 (n = 6) group for further investigations. The findings indicated that the high-tolerance group consisted of many cases requiring hospitalization. Chest computed tomography findings showed that the disease was more extensive in the high-tolerance group compared to the low-tolerance group. Regarding the bacterial phenotypic characterization, the high-tolerance group significantly upregulated the production of the virulence factors compared to the low-tolerance group. Our study provided evidence that carbapenem tolerance level is a potent prognostic marker of P. aeruginosa infections, and carbapenem tolerance could be a potential target for new antimicrobial agents to inhibit the progression of persistent P. aeruginosa infections.
      Citation: Antibiotics
      PubDate: 2020-09-21
      DOI: 10.3390/antibiotics9090626
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 627: Broad-Spectrum Antimicrobial Activity and
           Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed
           Derivative of Dermaseptin Truncates

    • Authors: Yu Zai, Yuan Ying, Zhuming Ye, Mei Zhou, Chengbang Ma, Zhanzhong Shi, Xiaoling Chen, Xinping Xi, Tianbao Chen, Lei Wang
      First page: 627
      Abstract: DMPC-10A (ALWKKLLKK-Cha-NH2) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala1 and Trp3 remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens.
      Citation: Antibiotics
      PubDate: 2020-09-21
      DOI: 10.3390/antibiotics9090627
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 628: Antibacterial Activity of Essential Oils
           and Trametes versicolor Extract against Clavibacter michiganensis subsp.
           michiganensis and Ralstonia solanacearum for Seed Treatment and
           Development of a Rapid In Vivo Assay

    • Authors: Laura Orzali, Maria Teresa Valente, Valeria Scala, Stefania Loreti, Nicoletta Pucci
      First page: 628
      Abstract: Clavibacter michiganensis subsp. michiganensis (Smith) Davis et al. (Cmm) and Ralstonia solanacearum Yabuuchi et al. (Smith) (Rs) are important seed-borne bacterial pathogens of tomato (Solanum lycopersicum) listed as A2 pests in the EPPO (European and Mediterranean Plant Protection Organization) region. At present, there are few strategies to control these pathogens, and seed control with eco-compatible approaches is widely encouraged. In this work, the essential oils (EOs) of oregano (Origanum vulgare), garlic (Allium sativum), basil (Ocimum basilicum), cinnamon (Cinnamomum zeylanicum), clove buds (Syzygium aromaticum), thyme (Thymus vulgaris), and Trametes versicolor extract (Tve) were tested in vitro for their antimicrobial activity against Cmm and Rs (broth microdilution method). The tested EOs and the Tve extract caused a significant inhibition of bacterial growth, with very promising MBC (minimum bactericidal concentration) and MIC90 (minimum inhibitory concentration causing a 90% growth inhibition) values. Moreover, an in vivo germination test showed no major reduction in seed germination when the substances were applied as seed treatment. A rapid molecular screening method has been developed, through real-time PCR, for the specific quantification of Cmm in the presence of a vegetable matrix to test in vivo the antimicrobial efficacy of oregano and cinnamon oil on seed treatment without resorting to whole plant essays, which are time- and space-consuming.
      Citation: Antibiotics
      PubDate: 2020-09-21
      DOI: 10.3390/antibiotics9090628
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 629: Exploration of Chemical Diversity and
           Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the
           OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular
           Modelling

    • Authors: Noha M. Gamaleldin, Walid Bakeer, Ahmed M. Sayed, Yara I. Shamikh, Ahmed O. El-Gendy, Hossam M. Hassan, Hannes Horn, Usama Ramadan Abdelmohsen, Wael N. Hozzein
      First page: 629
      Abstract: In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coral Sarcophyton glaucum in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera Micromonospora, Streptomyces, and Nocardiopsis; out of them, Micromonospora sp. UR17 was putatively characterized as a new species. In order to explore the chemical diversity of these actinobacteria as far as possible, they were subjected to a series of fermentation experiments under altering conditions, that is, solid and liquid fermentation along with co-fermentation with a mycolic acid-containing strain, namely Nocardia sp. UR23. Each treatment was found to affect these actinomycetes differently in terms of biological activity (i.e., antitrypanosomal activity) and chemical profiles evidenced by LC-HRES-MS-based metabolomics and multivariate analysis. Thereafter, orthogonal projections to latent structures discriminant analysis (OPLS-DA) suggested a number of metabolites to be associated with the antitrypanosomal activity of the active extracts. The subsequent in silico screenings (neural networking-based and docking-based) further supported the OPLS-DA results and prioritized desferrioxamine B (3), bafilomycin D (10), and bafilomycin A1 (11) as possible antitrypanosomal agents. Our approach in this study can be applied as a primary step in the exploration of bioactive natural products, particularly those from actinomycetes.
      Citation: Antibiotics
      PubDate: 2020-09-22
      DOI: 10.3390/antibiotics9090629
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 630: Current Antibiotic Resistance Trends of
           Uropathogens in Central Europe: Survey from a Tertiary Hospital Urology
           Department 2011–2019

    • Authors: Jan Hrbacek, Pavel Cermak, Roman Zachoval
      First page: 630
      Abstract: Monitoring of pathogen resistance profiles is necessary to guide empirical antibiotic therapy before culture and sensitivity results become available. The aim of this study was to describe current antibiotic resistance patterns of five most frequent causative uropathogens in a Department of Urology of a tertiary referral centre in Central Europe over a period of nine years. The Hospital Department of Clinical Microbiology database was used to extract data on all positive urine samples from inpatients in the Department of Urology between 2011 and 2019. Numbers of susceptible and resistant isolates per year were calculated for five most frequent uropathogens: Escherichia coli, Enterococcus spp., Klebsiella spp., Pseudomonas aeruginosa, and Proteus spp. Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin, colistin, and vancomycin. High resistance rates of Gram-negative uropathogens were demonstrated to most common antimicrobials, with statistically significant increasing or decreasing trends in some cases. No carbapenem-resistant Enterobacteriaceae were isolated. Vancomycin-resistant Enterococcus spp. strains were rare in our population.
      Citation: Antibiotics
      PubDate: 2020-09-22
      DOI: 10.3390/antibiotics9090630
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 631: Antimicrobial Resistance, an Update from
           the Ward: Increased Incidence of New Potential Pathogens and Site of
           Infection-Specific Antibacterial Resistances

    • Authors: Irene Stefanini, Martina Boni, Paola Silvaplana, Paola Lovera, Stefania Pelassa, Giuseppe De Renzi, Barbara Mognetti
      First page: 631
      Abstract: In order to monitor the spread of antimicrobial resistance, the European Union requires hospitals to be equipped with infection control centers. With this aim, we analyzed 1583 bacterial strains isolated from samples of different origin from patients with community-onset and nosocomial infections in a public tertiary University Hospital on the outskirts of Turin, Italy. Statistical analyses of the isolates (source, type) and their antimicrobial resistance (AMR) were performed. The survey revealed infections associated with bacterial species considered as not-commensal and not-pathogenic, hence potentially emerging as new threats for human health. Conversely to the general observation of nosocomial strains being more resistant to antibiotics compared to community-acquired strains, nosocomial strains isolated in this study were more resistant only to 1/42 tested antibiotics (tetracycline). By adopting an ecological approach, we observed that blood infections are associated with the broadest range of species compared to infections affecting other areas and we obtained clear indications on the antibiotics that should be preferred in the treatment of infections at specific body sites. Future investigations carried out on a larger geographical scale will clarify whether these indications are limited to the geographical region investigated over this study, or whether the same trends are visible at national or international level.
      Citation: Antibiotics
      PubDate: 2020-09-22
      DOI: 10.3390/antibiotics9090631
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 632: Treatment of Bloodstream Infections Due to
           Gram-Negative Bacteria with Difficult-to-Treat Resistance

    • Authors: Matteo Bassetti, Antonio Vena, Chiara Sepulcri, Daniele Roberto Giacobbe, Maddalena Peghin
      First page: 632
      Abstract: The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii.
      Citation: Antibiotics
      PubDate: 2020-09-22
      DOI: 10.3390/antibiotics9090632
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 633: Repurposing Disulfiram (Tetraethylthiuram
           Disulfide) as a Potential Drug Candidate against Borrelia burgdorferi In
           Vitro and In Vivo

    • Authors: Hari-Hara S. K. Potula, Jahanbanoo Shahryari, Mohammed Inayathullah, Andrey Victorovich Malkovskiy, Kwang-Min Kim, Jayakumar Rajadas
      First page: 633
      Abstract: Lyme disease caused by the Borrelia burgdorferi (Bb or B. burgdorferi) is the most common vector-borne, multi-systemic disease in the USA. Although most Lyme disease patients can be cured with a course of the first line of antibiotic treatment, some patients are intolerant to currently available antibiotics, necessitating the development of more effective therapeutics. We previously found several drugs, including disulfiram, that exhibited effective activity against B. burgdorferi. In the current study, we evaluated the potential of repurposing the FDA-approved drug, disulfiram for its borreliacidal activity. Our results indicate disulfiram has excellent borreliacidal activity against both the log and stationary phase B. burgdorferi sensu stricto B31 MI. Treatment of mice with disulfiram eliminated the B. burgdorferi sensu stricto B31 MI completely from the hearts and urinary bladder by day 28 post infection. Moreover, disulfiram-treated mice showed reduced expressions of inflammatory markers, and thus they were protected from histopathology and cardiac organ damage. Furthermore, disulfiram-treated mice showed significantly lower amounts of total antibody titers (IgM and IgG) at day 21 and total IgG2b at day 28 post infection. FACS analysis of lymph nodes revealed a decrease in the percentage of CD19+ B cells and an increase in total percentage of CD3+ T cells, CD3+ CD4+ T helpers, and naive and effector memory cells in disulfiram-treated mice. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic for treating Lyme disease.
      Citation: Antibiotics
      PubDate: 2020-09-22
      DOI: 10.3390/antibiotics9090633
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 634: Comparison of Three Endodontic Irrigant
           Regimens against Dual-Species Interkingdom Biofilms: Considerations for
           Maintaining the Status Quo

    • Authors: Om Alkhir Alshanta, Saeed Alqahtani, Suror Shaban, Khawlah Albashaireh, William McLean, Gordon Ramage
      First page: 634
      Abstract: Endodontic infections are often interkingdom biofilms, though current clinical management rarely considers this phenomenon. This study aimed to evaluate new and standard endodontic antimicrobial regimens against simple and complex Candida albicans and Enterococcus faecalis mono- and dual-species biofilms. C. albicans and E. faecalis mono- and dual-species biofilms were grown upon Thermanox™ coverslips and treated for 5 min with 3% NaOCl, 3% NaOCl followed by 17% EDTA, or 9% HEDP dissolved in 3% NaOCl. The number of cells remaining immediately after treatment at 0 h and after 72 h of regrowth were assessed using real-time quantitative PCR. All three treatment arms showed a similar positive antimicrobial effect on C. albicans and E. faecalis in both mono- and dual-species biofilms following initial treatment, resulting in ≥98% reduction in colony forming equivalent (CFE). Regardless of species or biofilm type (mono- or dual- species), the antimicrobial effect of NaOCl:HEDP mixture was comparable to that of NaOCl alone, with both showing significant regrowth after 72 h, whereas sequential treatment with NaOCl and EDTA consistently prevented significant regrowth. Our data suggest that sequential irrigation with NaOCl and EDTA remains the antimicrobial strategy of choice as it significantly reduces biofilm persistence and regrowth in our experimental dual-species biofilm conditions.
      Citation: Antibiotics
      PubDate: 2020-09-22
      DOI: 10.3390/antibiotics9090634
      Issue No: Vol. 9, No. 9 (2020)
       
  • Antibiotics, Vol. 9, Pages 635: Progress Overview of Bacterial
           Two-Component Regulatory Systems as Potential Targets for Antimicrobial
           Chemotherapy

    • Authors: Hidetada Hirakawa, Jun Kurushima, Yusuke Hashimoto, Haruyoshi Tomita
      First page: 635
      Abstract: Bacteria adapt to changes in their environment using a mechanism known as the two-component regulatory system (TCS) (also called “two-component signal transduction system” or “two-component system”). It comprises a pair of at least two proteins, namely the sensor kinase and the response regulator. The former senses external stimuli while the latter alters the expression profile of bacterial genes for survival and adaptation. Although the first TCS was discovered and characterized in a non-pathogenic laboratory strain of Escherichia coli, it has been recognized that all bacteria, including pathogens, use this mechanism. Some TCSs are essential for cell growth and fitness, while others are associated with the induction of virulence and drug resistance/tolerance. Therefore, the TCS is proposed as a potential target for antimicrobial chemotherapy. This concept is based on the inhibition of bacterial growth with the substances acting like conventional antibiotics in some cases. Alternatively, TCS targeting may reduce the burden of bacterial virulence and drug resistance/tolerance, without causing cell death. Therefore, this approach may aid in the development of antimicrobial therapeutic strategies for refractory infections caused by multi-drug resistant (MDR) pathogens. Herein, we review the progress of TCS inhibitors based on natural and synthetic compounds.
      Citation: Antibiotics
      PubDate: 2020-09-23
      DOI: 10.3390/antibiotics9100635
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 636: Developing a Sustainable Antimicrobial
           Stewardship (AMS) Programme in Ghana: Replicating the Scottish Triad Model
           of Information, Education and Quality Improvement

    • Authors: Jacqueline Sneddon, Daniel Afriyie, Israel Sefah, Alison Cockburn, Frances Kerr, Lucie Byrne-Davis, Elaine Cameron
      First page: 636
      Abstract: (1) Background: Our aim was to develop robust and reliable systems for antimicrobial stewardship (AMS) in Keta Municipal Hospital and Ghana Police Hospital. Objectives were to build capacity through training staff in each hospital, establish AMS teams, collect data on antibiotic use and support local quality improvement initiatives. (2) Methods: The Scottish team visited Ghana hospitals on three occasions and the Ghanaian partners paid one visit to Scotland. Regular virtual meetings and email communication were used between visits to review progress and agree on actions. (3) Results: Multi-professional AMS teams established and met monthly with formal minutes and action plans; point prevalence surveys (PPS) carried out and data collected informed a training session; 60 staff participated in training delivered by the Scottish team and Ghanaian team cascaded training to over 100 staff; evaluation of training impact demonstrated significant positive change in knowledge of antimicrobial resistance (AMR) and appropriate antibiotic use as well as improved participant attitudes and behaviours towards AMR, their role in AMS, and confidence in using the Ghana Standard Treatment Guidelines and antimicrobial app. (4) Conclusions: Key objectives were achieved and a sustainable model for AMS established in both hospitals.
      Citation: Antibiotics
      PubDate: 2020-09-23
      DOI: 10.3390/antibiotics9100636
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 637: Anti-Biofilm Inhibitory Synergistic
           Effects of Combinations of Essential Oils and Antibiotics

    • Authors: Antonio Rosato, Sabina Sblano, Lara Salvagno, Alessia Carocci, Maria Lisa Clodoveo, Filomena Corbo, Giuseppe Fracchiolla
      First page: 637
      Abstract: In recent years, the increase of bacteria antibiotic- resistance has been a severe problem for public health. A useful solution could be to join some phytochemicals naturally present in essential oils (EOs) to the existing antibiotics, with the aim to increase their efficacy in therapies. According to in vitro studies, EOs and their components could show such effects. Among them, we studied the activity of Cinnammonum zeylanicum, Mentha piperita, Origanum vulgare, and Thymus vulgaris EOs on bacterial biofilm and their synergism when used in association with some common antibiotics such as norfloxacin, oxacillin, and gentamicin. The chemical composition of EOs was determined using gas chromatography (GC) coupled with mass spectrometry (MS) techniques. The EOs drug efficacy was evaluated on four different strains of Gram-positive bacteria forming biofilms. The synergistic effects were tested through the chequerboard microdilution method. The association EOs-antibiotics showed a strong destruction of the biofilm growth of the four bacterial species considered. The interaction of norfloxacin with EOs was the most effective in all the tested combinations against the strains object of this study. These preliminary results suggest the formulation of a new generation of antimicrobial agents based on a combination of antimicrobial compounds with different origin.
      Citation: Antibiotics
      PubDate: 2020-09-24
      DOI: 10.3390/antibiotics9100637
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 638: A Cluster of Candida auris Blood Stream
           Infections in a Tertiary Care Hospital in Oman from 2016 to 2019

    • Authors: Jalila Mohsin, Sanjeewani Weerakoon, Sarah Ahmed, Ynze Puts, Zainab Al Balushi, Jacques F. Meis, Abdullah M.S. Al-Hatmi
      First page: 638
      Abstract: (1) Background: Candida auris has been reported as emerging yeast pathogen that can cause invasive bloodstream infections in healthcare settings. It is associated with high mortality rates and resistance to multiple classes of antifungal drugs and is difficult to identify with standard laboratory methods. (2) Methods: We conducted a retrospective review of epidemiological, clinical, and microbiological records for 23 C. auris fungemia cases at the Royal Hospital, a tertiary care facility in Oman, between 2016 and 2018. Demographic data, risk factors associated with mortality, microbiology investigation and treatment regimens are described. Yeasts were identified by MALDI-TOF. (3) Results: We identified 23 patients with C. auris fungemia. All positive samples from patients were confirmed as C. auris using MALDI-TOF, and ITS-rDNA sequencing. Microsatellite genotyping showed that the Omani isolates belong to the South Asian clade I. The majority of patients had multiple underlying illnesses and other risk factors that have been associated with fungemia. All isolates were non-susceptible to fluconazole. Isolates from all patients were sensitive to echinocandins and these were used as first line therapy. (4) Conclusions: Candida auris affects adults and children with a variety of risk factors including central venous catheters and overuse of antibiotics. Infections occur in both immunocompromised and immunocompetent individuals. Mortality was high in this series, and the organism can be transmitted in healthcare settings. Programs for raising awareness in Oman hospitals are warranted. Caspofungin remains 1st line therapy as MICs are still low despite its wide use.
      Citation: Antibiotics
      PubDate: 2020-09-24
      DOI: 10.3390/antibiotics9100638
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 639: Determination of Drug Efflux Pump
           Efficiency in Drug-Resistant Bacteria Using MALDI-TOF MS

    • Authors: Wen-Jung Lu, Hsuan-Ju Lin, Pang-Hung Hsu, Hong-Ting Victor Lin
      First page: 639
      Abstract: Multidrug efflux pumps play an essential role in antibiotic resistance. The conventional methods, including minimum inhibitory concentration and fluorescent assays, to monitor transporter efflux activity might have some drawbacks, such as indirect evidence or interference from color molecules. In this study, MALDI-TOF MS use was explored for monitoring drug efflux by a multidrug transporter, and the results were compared for validation with the data from conventional methods. Minimum inhibitory concentration was used first to evaluate the activity of Escherichia coli drug transporter AcrB, and this analysis showed that the E. coli overexpressing AcrB exhibited elevated resistance to various antibiotics and dyes. Fluorescence-based studies indicated that AcrB in E. coli could decrease the accumulation of intracellular dyes and display various efflux rate constants for different dyes, suggesting AcrB’s efflux activity. The MALDI-TOF MS analysis parameters were optimized to maintain a detection accuracy for AcrB’s substrates; furthermore, the MS data showed that E. coli overexpressing AcrB led to increased ions abundancy of various dyes and drugs in the extracellular space at different rates over time, illustrating continuous substrate efflux by AcrB. This study concluded that MALDI-TOF MS is a reliable method that can rapidly determine the drug pump efflux activity for various substrates.
      Citation: Antibiotics
      PubDate: 2020-09-24
      DOI: 10.3390/antibiotics9100639
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 640: Ceftolozane/Tazobactam and
           Ceftazidime/Avibactam for Multidrug-Resistant Gram-Negative Infections in
           Immunocompetent Patients: A Single-Center Retrospective Study

    • Authors: Rosario Cultrera, Marco Libanore, Agostino Barozzi, Erica d’Anchera, Letizia Romanini, Fabio Fabbian, Francesco De Motoli, Brunella Quarta, Armando Stefanati, Niccolò Bolognesi, Giovanni Gabutti
      First page: 640
      Abstract: Complicated infections from multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a serious problem presenting many challenges. Resistance to many classes of antibiotics reduces the probability of an adequate empirical treatment, with unfavorable consequences, increasing morbidity and mortality. Readily available patient medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. There are few literature data that report real-life experiences in the use of ceftolozane/tazobactam and ceftazidime/avibactam, with particular reference to microbiological cure. Some studies reported experiences for the treatment of MDR-GNB infections in patients with hematological malignancies or specifically in Pseudomonas aeruginosa infections. We report our clinical single-center experience regarding the real-life use of ceftolozane/tazobactam and ceftazidime/avibactam to treat serious and complicated infections due to MDR-GNB and carbapenem-resistant Enterobacterales (CRE), with particular regard given to intra-abdominal and urinary tract infections and sepsis.
      Citation: Antibiotics
      PubDate: 2020-09-24
      DOI: 10.3390/antibiotics9100640
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 641: Endophytic Streptomyces laurentii Mediated
           Green Synthesis of Ag-NPs with Antibacterial and Anticancer Properties for
           Developing Functional Textile Fabric Properties

    • Authors: Ahmed M. Eid, Amr Fouda, Gniewko Niedbała, Saad El-Din Hassan, Salem S. Salem, Abdullah M. Abdo, Helal F. Hetta, Tharwat I. Shaheen
      First page: 641
      Abstract: Improvement of the medical textile industry has received more attention recently, especially with widespread of microbial and viral infections. Medical textiles with new properties, such as bacterial pathogens self-cleaning, have been explored with nanotechnology. In this study, an endophytic actinomycetes strain of Streptomyces laurentii R-1 was isolated from the roots of the medicinal plant Achillea fragrantissima. This is used as a catalyst for the mediated biosynthesis of silver nanoparticles (Ag-NPs) for applications in the textile industry. The biosynthesized Ag-NPs were characterized using UV-vis spectroscopy, Fourier transform infrared (FT-IR), transmission electron microscopy (TEM), and X-ray Diffraction (XRD), which confirmed the successful formation of crystalline, spherical metal nanoparticles. The biosynthesized Ag-NPs exhibited broad-spectrum antibacterial activity. Our data elucidated that the biosynthesized Ag-NPs had a highly cytotoxic effect against the cancerous caco-2 cell line. The selected safe dose of Ag-NPs for loading on cotton fabrics was 100 ppm, regarding their antibacterial activity and safe cytotoxic efficacy. Interestingly, scanning electron microscope connected with energy dispersive X-ray spectroscopy (SEM-EDX) of loaded cotton fabrics demonstrated the smooth distribution of Ag-NPs on treated fabrics. The obtained results highlighted the broad-spectrum activity of nano-finished fabrics against pathogenic bacteria, even after 5 and 10 washing cycles. This study contributes a suitable guide for the performance of green synthesized NPs for utilization in different biotechnological sectors.
      Citation: Antibiotics
      PubDate: 2020-09-24
      DOI: 10.3390/antibiotics9100641
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 642: Macroalgae as a Source of Valuable
           Antimicrobial Compounds: Extraction and Applications

    • Authors: Aurora Silva, Sofia A. Silva, M. Carpena, P. Garcia-Oliveira, P. Gullón, M. Fátima Barroso, M.A. Prieto, J. Simal-Gandara
      First page: 642
      Abstract: In the last few decades, attention on new natural antimicrobial compounds has arisen due to a change in consumer preferences and the increase in the number of resistant microorganisms. Macroalgae play a special role in the pursuit of new active molecules as they have been traditionally consumed and are known for their chemical and nutritional composition and their biological properties, including antimicrobial activity. Among the bioactive molecules of algae, proteins and peptides, polysaccharides, polyphenols, polyunsaturated fatty acids and pigments can be highlighted. However, for the complete obtaining and incorporation of these molecules, it is essential to achieve easy, profitable and sustainable recovery of these compounds. For this purpose, novel liquid–liquid and solid–liquid extraction techniques have been studied, such as supercritical, ultrasound, microwave, enzymatic, high pressure, accelerated solvent and intensity pulsed electric fields extraction techniques. Moreover, different applications have been proposed for these compounds, such as preservatives in the food or cosmetic industries, as antibiotics in the pharmaceutical industry, as antibiofilm, antifouling, coating in active packaging, prebiotics or in nanoparticles. This review presents the main antimicrobial potential of macroalgae, their specific bioactive compounds and novel green extraction technologies to efficiently extract them, with emphasis on the antibacterial and antifungal data and their applications.
      Citation: Antibiotics
      PubDate: 2020-09-25
      DOI: 10.3390/antibiotics9100642
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 643: Antibiotic Consumption Patterns in
           European Countries May Be Associated with the Incidence of Major
           Carcinomas

    • Authors: Gábor Ternák, Károly Berényi, András Sümegi, Ágnes Szenczi, Barbara Fodor, Balázs Németh, István Kiss
      First page: 643
      Abstract: The possible role of the altered intestinal microbiome in the development of malignancies has been raised recently in several publications. Among external factors, antibiotics are considered to be the most important agent capable of producing dysbiosis in the gut flora, either temporally or permanently. The human microbiome has several beneficial effects in terms of maintaining appropriate human health, but its alteration has been implicated in the development of many illnesses. Our basic aim was to explore a possible relationship between the consumption of different antibiotic classes and the incidence of the most common cancer types (male, female) in European countries. A database of the average, yearly antibiotic consumption (1997–2018) has been developed and the consumption figures were compared to the eight, most frequent cancer incidence calculated for 2018 in 30 European countries. Pearson correlation has indicated different degrees of positive (supportive) and negative (inhibitor) significant associations between antibiotic consumption figures and cancer prevalence. It has been observed that certain antibiotic classes with positive correlation probably augment the incidence of certain cancer types, while others, with negative correlation, may show some inhibitory effect. The relatively higher or lower consumption pattern of different classes of antibiotics could be related to certain cancer prevalence figures in different European countries. Our results indicated that countries with relatively high consumption of narrow-spectrum penicillin (J01CE, J01CF) and tetracycline (J01A), like certain Scandinavian countries, showed a higher incidence of female colorectal cancer, female lung cancer, melanoma, breast, prostate and uterus corpus cancer. Countries with relatively higher consumption of broad-spectrum penicillin (J01CA, J01CR) and some broad-spectrum antibiotics (J01D, J01F, J01M), like Greece, Hungary, Slovakia, France, etc. showed a higher incidence rate of male lung cancer and male bladder cancer. The higher incidence rate of different cancer types showed association with the higher consumption of antibiotics with “augmenting” properties and with less consumption of antibiotics with “inhibitory” properties.
      Citation: Antibiotics
      PubDate: 2020-09-25
      DOI: 10.3390/antibiotics9100643
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 644: Preliminary Attempt to Predict Risk of
           Invasive Pulmonary Aspergillosis in Patients with Influenza: Decision
           Trees May Help'

    • Authors: Valeria Bellelli, Guido Siccardi, Livia Conte, Luigi Celani, Elena Congeduti, Cristian Borrazzo, Letizia Santinelli, Giuseppe Pietro Innocenti, Claudia Pinacchio, Giancarlo Ceccarelli, Mario Venditti, Gabriella d’Ettorre
      First page: 644
      Abstract: Invasive pulmonary aspergillosis (IPA) is typically considered a disease of immunocompromised patients, but, recently, many cases have been reported in patients without typical risk factors. The aim of our study is to develop a risk predictive model for IPA through machine learning techniques (decision trees) in patients with influenza. We conducted a retrospective observational study analyzing data regarding patients diagnosed with influenza hospitalized at the University Hospital “Umberto I” of Rome during the 2018-2019 season. We collected five IPA cases out of 77 influenza patients. Although the small sample size is a limit, the most vulnerable patients among the influenza-infected population seem to be those with evidence of lymphocytopenia and those that received corticosteroid therapy.
      Citation: Antibiotics
      PubDate: 2020-09-26
      DOI: 10.3390/antibiotics9100644
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 645: Effect of Antibiotic Susceptibility and
           CYP3A4/5 and CYP2C19 Genotype on the Outcome of Vonoprazan-Containing
           Helicobacter pylori Eradication Therapy

    • Authors: Mitsushige Sugimoto, Daiki Hira, Masaki Murata, Takashi Kawai, Tomohiro Terada
      First page: 645
      Abstract: Background: Helicobacter pylori eradication containing the potassium-competitive acid blocker, vonoprazan, achieves a higher eradication rate than therapy with proton pump inhibitors (PPIs). Because vonoprazan is mainly metabolized by CYP3A4/5, CYP genotype may affect the eradication rate. We investigated the influence of antibiotic susceptibility and CYP3A4/5 and CYP2C19 genotypes on the eradication rates. Methods: A total of 307 Japanese who were genotyped for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17, and investigated for susceptibility to antimicrobial agents, received vonoprazan-containing regimens: (1) With amoxicillin and clarithromycin as the first-line treatment; (2) with amoxicillin and metronidazole as the second-line treatment; or (3) with amoxicillin and sitafloxacin as the third-line treatment. Results: The eradication rate was 84.5% (95% confidence interval [CI]: 78.9–89.1%) using first-line, 92.6% (95% CI: 82.1–97.9%) using second-line and 87.5% (95% CI: 73.1–95.8%) using third-line treatment. Infection with clarithromycin-resistant strains was a predictive factor for failed eradication (odds ratio: 5.788, 95% CI: 1.916–17.485, p = 0.002) in multivariate analysis. No significant differences were observed in the eradication rate of regimens among CYP3A4, CYP3A5 and CYP2C19 genotypes. Conclusions: Genotyping for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17 before vonoprazan-containing eradication treatment may not be useful for predicting clinical outcomes.
      Citation: Antibiotics
      PubDate: 2020-09-26
      DOI: 10.3390/antibiotics9100645
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 646: The Prevalence of Multidrug Resistance of
           Helicobacter pylori and Its Impact on Eradication in Korea from 2017 to
           2019: A Single-Center Study

    • Authors: Jae Yong Park, Tae-Seop Shin, Ji Hyun Kim, Hong Jip Yoon, Beom Jin Kim, Jae Gyu Kim
      First page: 646
      Abstract: Antimicrobial resistance is one of the major factors determining the efficacy of Helicobacter pylori eradication therapy. This study aimed to estimate the recent prevalence of multidrug resistance of H. pylori and its impact on eradication in Korea. A total of 174 patients were prospectively enrolled at Chung-Ang University Hospital from 2017 to 2019. H. pylori strains were isolated from the gastric body and antrum. The minimum inhibitory concentrations of antibiotics were determined by the serial twofold agar dilution method. Eradication results were reviewed and analyzed in connection with antibiotic resistance. The prevalence of H. pylori infection was 51.7% (90/174). The culture success rate was 77.8% (70/90). The resistance rates for clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and moxifloxacin were 28.6% (20/70), 27.1% (19/70), 20.0% (14/70), 18.6% (13/70), 42.9% (30/70), and 42.9% (30/70), respectively. The multidrug resistance (resistance to two or more classes of antimicrobials) rate was 42.9% (30/70). Dual resistance to clarithromycin and metronidazole was confirmed in 8.6% (6/70). Eradication with a first-line treatment was successful in 75% (36/48), and those who received second-line treatment all achieved successful eradication. The rate of multidrug resistance is increasing, and standard triple therapy (STT) is no longer an acceptable first-line option for H. pylori eradication in Korea.
      Citation: Antibiotics
      PubDate: 2020-09-27
      DOI: 10.3390/antibiotics9100646
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 647: A Comparison of Colistin versus Colistin
           Plus Meropenem for the Treatment of Carbapenem-Resistant Acinetobacter
           

    • Authors: Wasan Katip, Suriyon Uitrakul, Peninnah Oberdorfer
      First page: 647
      Abstract: Carbapenem-resistant Acinetobacter baumannii (CRAB), an important nosocomial pathogen, occurs particularly in the intensive care unit (ICU). Thus, the aim of this study was to compare the efficacy and safety of documented treatment with colistin monotherapy versus colistin plus meropenem in critically ill patients with CRAB infections at Chiang Mai University Hospital (CMUH). We conducted a retrospective cohort study of critically ill patients with CRAB infections in an ICU from 2015 to 2017, who received colistin monotherapy versus colistin plus meropenem. After propensity score matching, an adjusted odds ratio (aOR) of a 30-day mortality rate in patients who received colistin plus meropenem was 0.43 compared to those who received colistin monotherapy (95% CI, 0.23–0.82, p = 0.01). aORs of clinical response and microbiological response were also higher in patients who received colistin plus meropenem (1.81, 95% CI 1.01–3.26, p = 0.048 and 2.08, 95% CI 1.11–3.91, p = 0.023, respectively). There was no significant difference in nephrotoxicity (aOR, 0.76, 95% CI, 0.43–1.36, p = 0.363) between colistin monotherapy and colistin plus meropenem. In conclusion, the addition of meropenem to colistin caused a reduction in 30-day mortality, higher clinical and microbiological responses, and did not increase nephrotoxicity compared to colistin monotherapy. Furthermore, 30-day mortality was significantly related with age, receiving vasopressor, having malignancy, and the APACHE II score.
      Citation: Antibiotics
      PubDate: 2020-09-28
      DOI: 10.3390/antibiotics9100647
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 648: A Review on Revolutionary Natural
           Biopolymer-Based Aerogels for Antibacterial Delivery

    • Authors: Esam Bashir Yahya, Fauziah Jummaat, A. A. Amirul, A. S. Adnan, N. G. Olaiya, C. K. Abdullah, Samsul Rizal, M. K. Mohamad Haafiz, H. P. S. Abdul Khalil
      First page: 648
      Abstract: A biopolymer-based aerogel has been developed to become one of the most potentially utilized materials in different biomedical applications. The biopolymer-based aerogel has unique physical, chemical, and mechanical properties and these properties are used in tissue engineering, biosensing, diagnostic, medical implant and drug delivery applications. Biocompatible and non-toxic biopolymers such as chitosan, cellulose and alginates have been used to deliver antibiotics, plants extract, essential oils and metallic nanoparticles. Antibacterial aerogels have been used in superficial and chronic wound healing as dressing sheets. This review critically analyses the utilization of biopolymer-based aerogels in antibacterial delivery. The analysis shows the relationship between their properties and their applications in the wound healing process. Furthermore, highlights of the potentials, challenges and proposition of the application of biopolymer-based aerogels is explored.
      Citation: Antibiotics
      PubDate: 2020-09-28
      DOI: 10.3390/antibiotics9100648
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 649: Benzoxazole-Based Metal Complexes to
           Reverse Multidrug Resistance in Bacteria

    • Authors: Annamária Kincses, Stefánia Szabó, Bálint Rácz, Nikoletta Szemerédi, Genki Watanabe, Ryosuke Saijo, Hiroshi Sekiya, Eiji Tamai, Joseph Molnár, Masami Kawase, Gabriella Spengler
      First page: 649
      Abstract: Bacteria often show resistance against antibiotics due to various mechanisms such as the expression of efflux pumps, biofilm formation, or bacterial quorum sensing (QS) controls. For successful therapy, the discovery of alternative agents is crucial. The objective of this study was to evaluate the efflux pump, anti-biofilm, and QS inhibiting, as well as antibacterial effects of 2-trifluoroacetonylbenzoxazole ligands (1–3) and their metal complexes (4–12) in bacteria. The ligand 2 and its Zn(II) complex 5, and furthermore the Cu(II) complex 7 of ligand 1, exerted remarkable antibacterial activity on the Staphylococcus aureus 272123 (MRSA) strain. In the minimum inhibitory concentration (MIC) reduction assay the ligand 3, the Zn(II) complex 5 of ligand 2, and the Cu(II), Ni(II), Mg(II), Fe(III) complexes (7, 8, 9, 12) of ligand 1 enhanced the antibacterial activity of ciprofloxacin in MRSA. An increased ethidium bromide accumulation was detected for ligand 3 in MRSA while the Fe(III) complex 12 of ligand 1 decreased the biofilm formation of the reference S. aureus ATCC 25923 strain. The Zn(II) and Ag(II) complexes (3 and 4) of ligand 1 and ligand 3 inhibited the QS. Based on our results, the ligands and their metal complexes could be potential alternative drugs in the treatment of infectious diseases.
      Citation: Antibiotics
      PubDate: 2020-09-28
      DOI: 10.3390/antibiotics9100649
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 650: Synthesis of
           4,4′-(4-Formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow
           Spectrum Antibiotics for the Potential Treatment of Acinetobacter
           Baumannii Infections

    • Authors: Evan Delancey, Devin Allison, Hansa Raj KC, David F. Gilmore, Todd Fite, Alexei G. Basnakian, Mohammad A. Alam
      First page: 650
      Abstract: Acinetobacter baumannii has emerged as one of the most lethal drug-resistant bacteria in recent years. We report the synthesis and antimicrobial studies of 25 new pyrazole-derived hydrazones. Some of these molecules are potent and specific inhibitors of A. baumannii strains with a minimum inhibitory concentration (MIC) value as low as 0.78 µg/mL. These compounds are non-toxic to mammalian cell lines in in vitro studies. Furthermore, one of the potent molecules has been studied for possible in vivo toxicity in the mouse model and found to be non-toxic based on the effect on 14 physiological blood markers of organ injury.
      Citation: Antibiotics
      PubDate: 2020-09-28
      DOI: 10.3390/antibiotics9100650
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 651: Acquisition Risk Factors of the SCCmec
           IX-Methicillin-Resistant Staphylococcus aureus in Swine Production
           Personnel in Chiang Mai and Lamphun Provinces, Thailand

    • Authors: Peerapat Rongsanam, Terdsak Yano, Wuttipong Yokart, Panuwat Yamsakul, Suweera Sutammeng, Ratchadaporn Udpaun, Duangporn Pichpol, Decha Tamdee, Usanee Anukool
      First page: 651
      Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) harboring the type-IX staphylococcal cassette chromosome mec (SCCmec) has been found in pigs and humans in Northern Thailand. However, knowledge of the prevalence and acquisition risk factors of this MRSA strain among swine production personnel (SPP) are needed. The nasal swab samples and data were collected from 202 voluntary SPP and 31 swine farms in Chiang Mai and Lamphun Provinces, Thailand in 2017. MRSA were screened and identified using mannitol salt agar, biochemical and antimicrobial susceptibility testing, multiplex PCR, and the SCCmec typing. The prevalence of MRSA was 7.9% (16/202) and 19.3% (6/31) among SPP and swine farms. All isolates were multidrug-resistant, and 55 of 59 isolates (93%) contained the type-IX SCCmec element. Data analysis indicated that education, working time, contact frequency, working solely with swine production, and personal hygiene were significantly related to MRSA acquisition (p < 0.05). The multivariate analysis revealed that pig farming experience, working days, and showering were good predictors for MRSA carriage among SPP (area under the curve (AUC) = 0.84). The biosecurity protocols and tetracycline use were significantly associated with MRSA detection in pig farms (p < 0.05). Hence, the active surveillance of MRSA and further development of local/national intervention for MRSA control are essential.
      Citation: Antibiotics
      PubDate: 2020-09-29
      DOI: 10.3390/antibiotics9100651
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 652: Antimicrobial Resistance in Escherichia
           coli and Resistance Genes in Coliphages from a Small Animal Clinic and in
           a Patient Dog with Chronic Urinary Tract Infection

    • Authors: Veronika Zechner, Dmitrij Sofka, Peter Paulsen, Friederike Hilbert
      First page: 652
      Abstract: Antimicrobial resistance is on the rise in certain pathogens that infect pets and their owners. This has raised concerns about the use of antibiotics and the transfer of resistance elements in small animal clinics. We sampled a surgery unit, diagnostic rooms after disinfection, and a dog with chronic urinary tract infection (UTI), in a small animal clinic in Austria, and isolated/characterized phages and Escherichia (E.) coli for antimicrobial resistance, resistance genes and transduction ability. Neither the coliphages nor E. coli were isolated in the 20 samples of the surgery units and diagnostic rooms. From the urinary tract of the dog, we recovered 57 E. coli isolates and 60 coliphages. All of the E. coli isolates were determined as resistant against nalidixic acid, 47 against ampicillin, 34 against sulfonamides, and 33 against streptomycin. No isolate held resistance against tetracycline, trimethoprim, kanamycin, or chloramphenicol. Among the 60 phages, 29 tested positive for one or more resistance gene(s) by PCR, but none was able to transduce it to a laboratory strain or to an E. coli isolated from samples. Nevertheless, six phages out of 60 were able to transduce ampicillin resistance (bla gene) after being grown on a puc19 harboring E. coli strain.
      Citation: Antibiotics
      PubDate: 2020-09-29
      DOI: 10.3390/antibiotics9100652
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 653: Hospitalization for Acute Respiratory
           Tract Infection in a Low-Antibiotic-Prescribing Setting: Cross-Sectional
           Data from General Practice

    • Authors: Christin Löffler, Attila Altiner, Annette Diener, Reinhard Berner, Gregor Feldmeier, Christian Helbig, Winfried V. Kern, Anna Köchling, Michaela Schmid, Gerhard Schön, Helmut Schröder, Karl Wegscheider, Anja Wollny
      First page: 653
      Abstract: Background: Acute respiratory tract infections (ARTI) are the main cause of inappropriate antibiotic prescribing. To date, there is limited evidence concerning whether low levels of antibiotic prescribing may impact patient safety. We investigate whether antibiotic prescribing for patients seeking primary care for ARTI correlates with the odds for hospitalization. Methods: Analysis of patient baseline data (n = 3669) within a cluster-randomized controlled trial. Adult patients suffering from ARTI in German primary care are included. The main outcome measure is acute hospitalization for respiratory infection and for any acute disease from 0 to 42 days after initial consultation. Results: Neither the antibiotic status of individual patients (OR 0.91; 95% CI: 0.49 to 1.69; p-value = 0.769) nor the physician-specific antibiotic prescription rates for ARTI (OR 1.22; 95% CI: 1.00 to 1.49; p-value = 0.054) had a significant effect on hospitalization. The following factors increased the odds for hospitalization: patient’s age, the ARTI being defined as lower respiratory tract infections (such as bronchitis) by the physician, the physician’s perception of disease severity, and being cared for within group practices (versus treated in single-handed practices). Conclusions: In a low-antibiotic-prescribing primary care setting such as Germany, lack of treatment with antibiotics for ARTI did not result in higher odds for hospitalization in an adult population.
      Citation: Antibiotics
      PubDate: 2020-09-29
      DOI: 10.3390/antibiotics9100653
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 654: Characterization and Antimicrobial
           Susceptibility of Pathogens Associated with Periodontal Abscess

    • Authors: Muhammad Irshad, Mohammad Khursheed Alam, Ahmad Alawneh, Mohammed Abdullah Alhadi, Ahmed Abdullah Alhadi, Yasser Saleh Almunajem, Fesal Farag Alanezi, Sharafi Abdullah Al Sagoor, Abdulrahman Mudaysh Bajawi, Ahmed Ali Alfawzan, Mohammad Amjad Kamal
      First page: 654
      Abstract: Knowledge of microbial composition and antimicrobials’ susceptibility to periodontal abscesses is vital for their successful treatment. The current study aims to provide a thorough overview of the clinical and microbial features of periodontal abscesses of the local community. The study was carried out at Rehman College of Dentistry, Peshawar, Pakistan between December 2019 to March 2020. Clinical measurements and microbial samples were collected from 45 subjects. Microbial samples were anaerobically cultured for the growth of selected bacterial species. E-test was used to assess the susceptibility of bacterial species grown from the patient samples to amoxicillin, azithromycin, metronidazole, and tetracycline. The majority of affected patients had preexisting chronic periodontitis. All abscesses clinically demonstrated bleeding on probing and suppuration. The periodontal abscess was most commonly associated with lower incisors and canines, followed by lower molars and then upper incisor and canine teeth. Fusobacterium spp. (73%) was the most frequently detected species followed by Prevotella intermedia/nigrescens (65%), Porphyromonas gingivalis (46%) and Aggregatibacter actinomycetemcomitans (24%). The detected clinical isolates of certain bacteria demonstrated resistance to all tested antibiotics except azithromycin. We conclude that Fusobacterium spp., P. intermedia/nigrescens, P. gingivalis, C. rectus, T. forsythia and A. actinomycetemcomitans are closely associated with periodontal abscess. Bacterial species associated with periodontal abscess demonstrated some level of antimicrobial resistance to amoxicillin, metronidazole and tetracycline while antibiotic resistance to azithromycin could not be demonstrated.
      Citation: Antibiotics
      PubDate: 2020-09-29
      DOI: 10.3390/antibiotics9100654
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 655: Aptamer-Based Detection of Ampicillin in
           Urine Samples

    • Authors: Matthew D. Simmons, Lisa M. Miller, Malin O. Sundström, Steven Johnson
      First page: 655
      Abstract: The misuse of antibiotics in health care has led to increasing levels of drug resistant infections (DRI’s) occurring in the general population. Most technologies developed for the detection of DRI’s typically focus on phenotyping or genotyping bacterial resistance rather than on the underlying cause and spread of DRI’s; namely the misuse of antibiotics. An aptameric based assay has been developed for the monitoring of ampicillin in urine samples, for use in determining optimal antibiotic dosage and monitoring patient compliance with treatment. The fluorescently labelled aptamers were shown to perform optimally at pH 7, ideal for buffered clinical urine samples, with limits of detection as low as 20.6 nM, allowing for determination of ampicillin in urine in the clinically relevant range of concentrations (100 nM to 100 µM). As the assay requires incubation for only 1 h with a small sample volume, 50 to 150 µL, the test would fit within current healthcare pathways, simplifying the adoption of the technology.
      Citation: Antibiotics
      PubDate: 2020-09-29
      DOI: 10.3390/antibiotics9100655
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 656: Exploration of the Neisseria Resistome
           Reveals Resistance Mechanisms in Commensals That May Be Acquired by N.
           gonorrhoeae through Horizontal Gene Transfer

    • Authors: Michael A. Fiore, Jordan C. Raisman, Narayan H. Wong, André O. Hudson, Crista B. Wadsworth
      First page: 656
      Abstract: Nonpathogenic Neisseria transfer mutations encoding antibiotic resistance to their pathogenic relative Neisseria gonorrhoeae. However, the resistance genotypes and subsequent phenotypes of nonpathogens within the genus have been described infrequently. Here, we characterize the minimum inhibitory concentrations (MICs) of a panel of Neisseria (n = 26)—including several commensal species—to a suite of diverse antibiotics. We furthermore use whole genome sequencing and the Comprehensive Antibiotic Resistance Database Resistance Gene Identifier (RGI) platform to predict putative resistance-encoding mutations. Resistant isolates to all tested antimicrobials including penicillin (n = 5/26), ceftriaxone (n = 2/26), cefixime (n = 3/26), tetracycline (n = 10/26), azithromycin (n = 11/26), and ciprofloxacin (n = 4/26) were found. In total, 63 distinct mutations were predicted by RGI to be involved in resistance. The presence of several mutations had clear associations with increased MIC such as DNA gyrase subunit A (gyrA) (S91F) and ciprofloxacin, tetracycline resistance protein (tetM) and 30S ribosomal protein S10 (rpsJ) (V57M) and tetracycline, and TEM-type β-lactamases and penicillin. However, mutations with strong associations to macrolide and cephalosporin resistance were not conclusive. This work serves as an initial exploration into the resistance-encoding mutations harbored by nonpathogenic Neisseria, which will ultimately aid in prospective surveillance for novel resistance mechanisms that may be rapidly acquired by N. gonorrhoeae.
      Citation: Antibiotics
      PubDate: 2020-09-30
      DOI: 10.3390/antibiotics9100656
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 657: Enterococcus faecalis Endocarditis and
           Outpatient Treatment: A Systematic Review of Current Alternatives

    • Authors: Laura Herrera-Hidalgo, Arístides de Alarcón, Luis E. López-Cortes, Rafael Luque-Márquez, Luis F. López-Cortes, Alicia Gutiérrez-Valencia, María V. Gil-Navarro
      First page: 657
      Abstract: The selection of the best alternative for Enterococcus faecalis infective endocarditis (IE) continuation treatment in the outpatient setting is still challenging. Three databases were searched, reporting antibiotic therapies against E. faecalis IE in or suitable for the outpatient setting. Articles the results of which were identified by species and treatment regimen were included. The quality of the studies was assessed accordingly with the study design. Data were extracted and synthesized narratively. In total, 18 studies were included. The treatment regimens reported were classified regarding the main antibiotic used as regimen, based on Aminoglycosides, dual β-lactam, teicoplanin, daptomycin or dalbavancin or oral therapy. The regimens based on aminoglycosides and dual β-lactam combinations are the treatment alternatives which gather more evidence regarding their efficacy. Dual β-lactam is the preferred option for high level aminoglycoside resistance strains, and for to its reduced nephrotoxicity, while its adaptation to the outpatient setting has been poorly documented. Less evidence supports the remaining alternatives, but many of them have been successfully adapted to outpatient care. Teicoplanin and dalbavancin as well as oral therapy seem promising. Our work provides an extensive examination of the potential alternatives to E. faecalis IE useful for outpatient care. However, the insufficient evidence hampers the attempt to give a general recommendation.
      Citation: Antibiotics
      PubDate: 2020-09-30
      DOI: 10.3390/antibiotics9100657
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 658: Synergistic Therapies as a Promising
           Option for the Treatment of Antibiotic-Resistant Helicobacter pylori

    • Authors: Paweł Krzyżek, Emil Paluch, Grażyna Gościniak
      First page: 658
      Abstract: Helicobacter pylori is a Gram-negative bacterium responsible for the development of gastric diseases. The issue of spreading antibiotic resistance of H. pylori and its limited therapeutic options is an important topic in modern gastroenterology. This phenomenon is greatly associated with a very narrow range of antibiotics used in standard therapies and, as a consequence, an alarmingly high detection of multidrug-resistant H. pylori strains. For this reason, scientists are increasingly focused on the search for new substances that will not only exhibit antibacterial effect against H. pylori, but also potentiate the activity of antibiotics. The aim of the current review is to present scientific reports showing newly discovered or repurposed compounds with an ability to enhance the antimicrobial activity of classically used antibiotics against H. pylori. To gain a broader context in their future application in therapies of H. pylori infections, their antimicrobial properties, such as minimal inhibitory concentrations and minimal bactericidal concentrations, dose- and time-dependent mode of action, and, if characterized, anti-biofilm and/or in vivo activity are further described. The authors of this review hope that this article will encourage the scientific community to expand research on the important issue of synergistic therapies in the context of combating H. pylori infections.
      Citation: Antibiotics
      PubDate: 2020-09-30
      DOI: 10.3390/antibiotics9100658
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 659: MeJA Elicitation of Chicory Hairy Roots
           Promotes Efficient Increase of 3,5-diCQA Accumulation, a Potent
           Antioxidant and Antibacterial Molecule

    • Authors: Guillaume Bernard, Harmony Alves Dos Alves Dos Santos, Audrey Etienne, Jennifer Samaillie, Christel Neut, Sevser Sahpaz, Jean-Louis Hilbert, David Gagneul, Nathalie Jullian, Ali Tahrioui, Sylvie Chevalier, Céline Rivière, Caroline Rambaud
      First page: 659
      Abstract: Cichorium intybus L. (Asteraceae) is an important industrial crop, as well as a medicinal plant which produces some bioactive compounds implicated in various biological effects with potential applications in human health. Particularly, roots produce hydroxycinnamic acids like 5-caffeoyquinic acid and 3,5-dicaffeoylquinic acid (di-CQA). The present investigation relates to the use of methyl jasmonate for enhancing phenolic compounds accumulation and production in hairy root cultures of C. intybus. Elicitated hairy root growth rate increased 13.3 times compared with the initial inoculum in a period of 14 days and di-CQA production represented about 12% of DW. The elicitation has also promoted the production of tricaffeoylquinic acid never described in the chicory roots and identified as 3,4,5-tricaffeoyquinic acid by means of nuclear magnetic resonance. Our study confirmed the strong anti-oxidant effect of di-CQA. Our results also confirmed globally a selectivity of action of di-CQA against Gram-positive bacteria, in particular against some strains of Staphylococcus and Streptococcus. However, a non-negligible antibacterial activity of di-CQA against Pseudomonas aeruginosa was also underlined (MIC = 0.156 mg.mL−1 against some P. aeruginosa strains). The influence of di-CQA has been explored to evaluate its impact on the physiology of P. aeruginosa. Di-CQA showed no effect on the biofilm formation and the production of extracellular pyocyanin. However, it demonstrated an effect on virulence through the production of pyoverdine with a dose-dependent manner by more than 7-fold when treated at a concentration of 128 µg·mL−1, thus suggesting a link between di-CQA and iron sequestration. This study shows that elicitated hairy root cultures of chicory can be developed for the production of di-CQA, a secondary metabolite with high antibacterial potential.
      Citation: Antibiotics
      PubDate: 2020-09-30
      DOI: 10.3390/antibiotics9100659
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 660: Characterization of Multidrug Resistance
           Patterns of Emerging Salmonella enterica Serovar Rissen along the Food
           Chain in China

    • Authors: Xuebin Xu, Silpak Biswas, Guimin Gu, Mohammed Elbediwi, Yan Li, Min Yue
      First page: 660
      Abstract: Salmonella spp. are recognized as important foodborne pathogens globally. Salmonella enterica serovar Rissen is one of the important Salmonella serovars linked with swine products in numerous countries and can transmit to humans by food chain contamination. Worldwide emerging S. Rissen is considered as one of the most common pathogens to cause human salmonellosis. The objective of this study was to determine the antimicrobial resistance properties and patterns of Salmonella Rissen isolates obtained from humans, animals, animal-derived food products, and the environment in China. Between 2016 and 2019, a total of 311 S. Rissen isolates from different provinces or province-level cities in China were included here. Bacterial isolates were characterized by serotyping and antimicrobial susceptibility testing. Minimum inhibitory concentration (MIC) values of 14 clinically relevant antimicrobials were obtained by broth microdilution method. S. Rissen isolates from humans were found dominant (67%; 208/311). S. Rissen isolates obtained from human patients were mostly found with diarrhea. Other S. Rissen isolates were acquired from food (22%; 69/311), animals (8%; 25/311), and the environment (3%; 9/311). Most of the isolates were resistant to tetracycline, trimethoprim-sulfamethoxazole, chloramphenicol, streptomycin, sulfisoxazole, and ampicillin. The S. Rissen isolates showed susceptibility against ceftriaxone, ceftiofur, gentamicin, nalidixic acid, ciprofloxacin, and azithromycin. In total, 92% of the S. Rissen isolates were multidrug-resistant and ASSuT (27%), ACT (25%), ACSSuT (22%), ACSSuTAmc (11%), and ACSSuTFox (7%) patterns were among the most prevalent antibiotic resistance patterns found in this study. The widespread dissemination of antimicrobial resistance could have emerged from misuse of antimicrobial agents in animal husbandry in China. These findings could be useful for rational antimicrobial usage against Salmonella Rissen infections.
      Citation: Antibiotics
      PubDate: 2020-09-30
      DOI: 10.3390/antibiotics9100660
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 661: Caerin 1 Antimicrobial Peptides that
           Inhibit HIV and Neisseria May Spare Protective Lactobacilli

    • Authors: Louise A. Rollins-Smith, Patricia B. Smith, Anna M. Ledeczi, Julia M. Rowe, Laura K. Reinert
      First page: 661
      Abstract: Although acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is a manageable disease for many, it is still a source of significant morbidity and economic hardship for many others. The predominant mode of transmission of HIV/AIDS is sexual intercourse, and measures to reduce transmission are needed. Previously, we showed that caerin 1 antimicrobial peptides (AMPs) originally derived from Australian amphibians inhibited in vitro transmission of HIV at relatively low concentrations and had low toxicity for T cells and an endocervical cell line. The use of AMPs as part of microbicidal formulations would expose the vaginal microbiome to these agents and cause potential harm to protective lactobacilli. Here, we tested the effects of caerin 1 peptides and their analogs on the viability of two species of common vaginal lactobacilli (Lactobacillus rhamnosus and Lactobacillus crispatus). Several candidate peptides had limited toxicity for the lactobacilli at a range of concentrations that would inhibit HIV. Three AMPs were also tested for their ability to inhibit growth of Neisseria lactamica, a close relative of the sexually transmissible Neisseria gonorrhoeae. Neisseria lactamica was significantly more sensitive to the AMPs than the lactobacilli. Thus, several candidate AMPs have the capacity to inhibit HIV and possible N. gonorrhoeae transmission at concentrations that are significantly less harmful to the resident lactobacilli.
      Citation: Antibiotics
      PubDate: 2020-09-30
      DOI: 10.3390/antibiotics9100661
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 662: Antimicrobial Resistance in Fecal
           Escherichia coli from Humans and Pigs at Farms at Different Levels of
           Intensification

    • Authors: Kamonwan Lunha, Thongpan Leangapichart, Jatesada Jiwakanon, Sunpetch Angkititrakul, Marianne Sunde, Josef D. Järhult, Gunilla Ström Hallenberg, Rachel A. Hickman, Thomas Van Boeckel, Ulf Magnusson
      First page: 662
      Abstract: The overall aim of the current study was to test the hypotheses that (i) antibiotic resistance in bacteria were more frequent in clinically health pigs in intensified company owned, medium-scale farms (MSFs) (100–500 sows) than in pigs in family-owned, small-scale farms (SSFs) (1–50 sows) and (ii) that farmers working at the MSFs were more prone to attain antibiotic resistant bacteria than farmers working at SSFs. The study was conducted in North-Eastern Thailand, comprising fecal Escherichia coli isolates from pigs, farmers working with the pigs (contact humans) and persons living in the same household as the farmer (non-contact humans) at 51 MSFs and 113 SSFs. Samples from all farms were also screened for methicillin-resistant staphylococcus aureus (MRSA), which was not detected in pig samples, but was found in one human sample. Susceptibility was tested by disc-diffusion for seven antibiotics commonly used in the study area. Resistance in pig isolates from MSFs were more frequent for chloramphenicol which (P < 0.001), trimethoprim/sulfamethoxazole (P < 0.001) and gentamicin (P < 0.05) compared with isolates from SSFs, whereas the opposite was true for tetracycline (P < 0.01). Resistance in the human isolates was lower than those in the isolates from pigs for tetracycline, trimethoprim/sulfamethoxazole and chloramphenicol (P < 0.001). The frequency of resistance in the contact human samples from SSFs and MSFs did not differ. There was no difference between isolates from contact and non-contact humans for any of the tested antibiotics. Multidrug resistance in isolates from pigs was 26%, significantly higher (P < 0.01) than the 13% from humans. The data indicate that (i) resistance to antibiotics, including those critical and highly important for human medicine, were more common in fecal E. coli from pigs at the MSFs than at the SSFs, whereas (ii) the resistance in fecal E. coli from pig farmers seemed not to be influenced by the level of intensification of the farm they were working at.
      Citation: Antibiotics
      PubDate: 2020-09-30
      DOI: 10.3390/antibiotics9100662
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 663: From Orphan Phage to a Proposed New
           Family–The Diversity of N4-Like Viruses

    • Authors: Johannes Wittmann, Dann Turner, Andrew D. Millard, Padmanabhan Mahadevan, Andrew M. Kropinski, Evelien M. Adriaenssens
      First page: 663
      Abstract: Escherichia phage N4 was isolated in 1966 in Italy and has remained a genomic orphan for a long time. It encodes an extremely large virion-associated RNA polymerase unique for bacterial viruses that became characteristic for this group. In recent years, due to new and relatively inexpensive sequencing techniques the number of publicly available phage genome sequences expanded rapidly. This revealed new members of the N4-like phage group, from 33 members in 2015 to 115 N4-like viruses in 2020. Using new technologies and methods for classification, the Bacterial and Archaeal Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV) has moved the classification and taxonomy of bacterial viruses from mere morphological approaches to genomic and proteomic methods. The analysis of 115 N4-like genomes resulted in a huge reassessment of this group and the proposal of a new family “Schitoviridae”, including eight subfamilies and numerous new genera.
      Citation: Antibiotics
      PubDate: 2020-09-30
      DOI: 10.3390/antibiotics9100663
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 664: Anthelminthic Activity of Assassin Bug
           Venom against the Blood Fluke Schistosoma mansoni

    • Authors: Miray Tonk, Andreas Vilcinskas, Christoph G. Grevelding, Simone Haeberlein
      First page: 664
      Abstract: Helminths such as the blood fluke Schistosoma mansoni represent a major global health challenge due to limited availability of drugs. Most anthelminthic drug candidates are derived from plants, whereas insect-derived compounds have received little attention. This includes venom from assassin bugs, which contains numerous bioactive compounds. Here, we investigated whether venom from the European predatory assassin bug Rhynocoris iracundus has antischistosomal activity. Venom concentrations of 10–50 µg/mL inhibited the motility and pairing of S. mansoni adult worms in vitro and their capacity to produce eggs. We used EdU-proliferation assays to measure the effect of venom against parasite stem cells, which are essential for survival and reproduction. We found that venom depleted proliferating stem cells in different tissues of the male parasite, including neoblasts in the parenchyma and gonadal stem cells. Certain insect venoms are known to lyse eukaryotic cells, thus limiting their therapeutic potential. We therefore carried out hemolytic activity assays using porcine red blood cells, revealing that the venom had no significant effect at a concentration of 43 µg/mL. The observed anthelminthic activity and absence of hemolytic side effects suggest that the components of R. iracundus venom should be investigated in more detail as potential antischistosomal leads.
      Citation: Antibiotics
      PubDate: 2020-10-01
      DOI: 10.3390/antibiotics9100664
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 665: New Antimicrobial Bioactivity against
           Multidrug-Resistant Gram-Positive Bacteria of Kinase Inhibitor IMD0354

    • Authors: Iliana E Escobar, Alexis White, Wooseong Kim, Eleftherios Mylonakis
      First page: 665
      Abstract: Multidrug-resistant pathogens pose a serious threat to human health. For decades, the antibiotic vancomycin has been a potent option when treating Gram-positive multidrug-resistant infections. Nonetheless, in recent decades, we have begun to see an increase in vancomycin-resistant bacteria. Here, we show that the nuclear factor-kappa B (NF-κB) inhibitor N-[3,5-Bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (IMD0354) was identified as a positive hit through a Caenorhabditis elegans–methicillin-resistant Staphylococcus aureus (MRSA) infection screen. IMD0354 was a potent bacteriostatic drug capable of working at a minimal inhibitory concentration (MIC) as low as 0.06 µg/mL against various vancomycin-resistant strains. Interestingly, IMD0354 showed no hemolytic activity at concentrations as high as 16 µg/mL and is minimally toxic to C. elegans in vivo with 90% survival up to 64 µg/mL. In addition, we demonstrated that IMD0354′s mechanism of action at high concentrations is membrane permeabilization. Lastly, we found that IMD0354 is able to inhibit vancomycin-resistant Staphylococcus aureus (VRSA) initial cell attachment and biofilm formation at sub-MIC levels and above. Our work highlights that the NF-κB inhibitor IMD0354 has promising potential as a lead compound and an antimicrobial therapeutic candidate capable of combating multidrug-resistant bacteria.
      Citation: Antibiotics
      PubDate: 2020-10-01
      DOI: 10.3390/antibiotics9100665
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 666: Mutually Isomeric 2- and
           4-(3-nitro-1,2,4-triazol-1-yl)pyrimidines Inspired by an Antimycobacterial
           Screening Hit: Synthesis and Biological Activity against the ESKAPE Panel
           of Pathogens

    • Authors: Sergey Chuprun, Dmitry Dar’in, Elizaveta Rogacheva, Liudmila Kraeva, Oleg Levin, Olga Manicheva, Marine Dogonadze, Tatiana Vinogradova, Olga Bakulina, Mikhail Krasavin
      First page: 666
      Abstract: Starting from the structure of antimycobacterial screening hit OTB-021 which was devoid of activity against ESKAPE pathogens, we designed, synthesized and tested two mutually isomeric series of novel simplified analogs, 2- and 4-(3-nitro-1,2,4-triazol-1-yl)pyrimidines, bearing various amino side chains. These compounds demonstrated a reverse bioactivity profile being inactive against M. tuberculosis while inhibiting the growth of all ESKAPE pathogens (with variable potency patterns) except for Gram-negative P. aeruginosa. Reduction potentials (E1/2, V) measured for selected compounds by cyclic voltammetry were tightly grouped in the −1.3–−1.1 V range for a reversible single-electron reduction. No apparent correlation between the E1/2 values and the ESKAPE minimum inhibitory concentrations was established, suggesting possible significance of other factors, besides the compounds’ reduction potential, which determine the observed antibacterial activity. Generally, more negative E1/2 values were displayed by 2-(3-nitro-1,2,4-triazol-1-yl)pyrimidines, which is in line with the frequently observed activity loss on moving the 3-nitro-1,2,4-triazol-1-yl moiety from position 4 to position 2 of the pyrimidine nucleus.
      Citation: Antibiotics
      PubDate: 2020-10-01
      DOI: 10.3390/antibiotics9100666
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 667: Promising Antibiofilm Agents: Recent
           Breakthrough against Biofilm Producing Methicillin-Resistant
           Staphylococcus aureus

    • Authors: Marwa I. Abd El-Hamid, El-sayed Y. El-Naenaeey, Toka M kandeel, Wael A. H. Hegazy, Rasha A. Mosbah, Majed S. Nassar, Muhammed A. Bakhrebah, Wesam H. Abdulaal, Nabil A. Alhakamy, Mahmoud M. Bendary
      First page: 667
      Abstract: Multidrug resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) is a superbug pathogen that causes serious diseases. One of the main reasons for the lack of the effectiveness of antibiotic therapy against infections caused by this resistant pathogen is the recalcitrant nature of MRSA biofilms, which results in an increasingly serious situation worldwide. Consequently, the development of innovative biofilm inhibitors is urgently needed to control the biofilm formation by this pathogen. In this work, we thus sought to evaluate the biofilm inhibiting ability of some promising antibiofilm agents such as zinc oxide nanoparticles (Zno NPs), proteinase K, and hamamelitannin (HAM) in managing the MRSA biofilms. Different phenotypic and genotypic methods were used to identify the biofilm producing MDR MRSA isolates and the antibiofilm/antimicrobial activities of the used promising agents. Our study demonstrated strong antibiofilm activities of ZnO NPs, proteinase K, and HAM against MRSA biofilms along with their transcriptional modulation of biofilm (intercellular adhesion A, icaA) and quorum sensing (QS) (agr) genes. Interestingly, only ZnO NPs showed a powerful antimicrobial activity against this pathogen. Collectively, we observed overall positive correlations between the biofilm production and the antimicrobial resistance/agr genotypes II and IV. Meanwhile, there was no significant correlation between the toxin genes and the biofilm production. The ZnO NPs were recommended to be used alone as potent antimicrobial and antibiofilm agents against MDR MRSA and their biofilm-associated diseases. On the other hand, proteinase-K and HAM can be co-administrated with other antimicrobial agents to manage such types of infections.
      Citation: Antibiotics
      PubDate: 2020-10-03
      DOI: 10.3390/antibiotics9100667
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 668: Antimicrobial and Antivirulence Impacts of
           Phenolics on Salmonella Enterica Serovar Typhimurium

    • Authors: Zabdiel Alvarado-Martinez, Paulina Bravo, Nana-Frekua Kennedy, Mayur Krishna, Syed Hussain, Alana C. Young, Debabrata Biswas
      First page: 668
      Abstract: Salmonella enterica serovar Typhimurium (ST) remains a major infectious agent in the USA, with an increasing antibiotic resistance pattern, which requires the development of novel antimicrobials capable of controlling ST. Polyphenolic compounds found in plant extracts are strong candidates as alternative antimicrobials, particularly phenolic acids such as gallic acid (GA), protocatechuic acid (PA) and vanillic acid (VA). This study evaluates the effectiveness of these compounds in inhibiting ST growth while determining changes to the outer membrane through fluorescent dye uptake and scanning electron microscopy (SEM), in addition to measuring alterations to virulence genes with qRT-PCR. Results showed antimicrobial potential for all compounds, significantly inhibiting the detectable growth of ST. Fluorescent spectrophotometry and microscopy detected an increase in relative fluorescent intensity (RFI) and red-colored bacteria over time, suggesting membrane permeabilization. SEM revealed severe morphological defects at the polar ends of bacteria treated with GA and PA, while VA-treated bacteria were found to be mid-division. Relative gene expression showed significant downregulation in master regulator hilA and invH after GA and PA treatments, while fliC was upregulated in VA. Results suggest that GA, PA and VA have antimicrobial potential that warrants further research into their mechanism of action and the interactions that lead to ST death.
      Citation: Antibiotics
      PubDate: 2020-10-03
      DOI: 10.3390/antibiotics9100668
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 669: Genetic Variation Putatively Associated
           with Mycobacterium tuberculosis Resistance to Perchlozone, a New
           Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for
           Treatment of Multidrug-Resistant Tuberculosis

    • Authors: Igor Mokrousov, Anna Vyazovaya, Gulnora Akhmedova, Natalia Solovieva, Eugeni Turkin, Viacheslav Zhuravlev
      First page: 669
      Abstract: Perchlozone ([PCZ] 4-thioureido-iminomethylpyridinium perchlorate) is a new thiosemicarbazone approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia and some other countries. The ethA and hadABC mutations may confer PCZ resistance. At the same time, ethA mutations are known to mediate resistance to ethionamide (ETH) and prothionamide (PTH). We aimed to study the genetic variation underlying Mycobacterium tuberculosis resistance to PCZ through whole genome sequencing (WGS) of consecutive isolates recovered during long-term treatment. This prospective study included patients admitted in 2018–2019 to the regional tuberculosis dispensary, Kaliningrad, Russia, whose treatment regimen included PCZ. Multiple M. tuberculosis isolates were recovered during PCZ treatment, and the bacterial DNA was subjected to WGS followed by bioinformatics analysis. We identified mutations in the genes putatively associated with PCZ resistance, ethA, and hadA. The most frequent one was a frameshift ethA 106 GA > G (seven of nine patients) and most of the other mutations were also likely present before PCZ treatment. In one patient, a frameshift mutation ethA 702 CT > C emerged after six months of PCZ treatment. A frequent presence of cross-resistance mutations to PCZ and ETH/PTH should be taken into consideration when PCZ is included in the treatment regimen of MDR-TB patients.
      Citation: Antibiotics
      PubDate: 2020-10-03
      DOI: 10.3390/antibiotics9100669
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 670: Structural Antibiotic Surveillance and
           Stewardship via Indication-Linked Quality Indicators: Pilot in Dutch
           Primary Care

    • Authors: Alike W. van der Velden, Mieke I. van Triest, Annelot F. Schoffelen, Theo J. M. Verheij
      First page: 670
      Abstract: Insight into antibiotic prescribing quality is key to general practitioners (GPs) to improve their prescribing behavior and to national antibiotic surveillance and stewardship programs. Additionally to numbers of prescribed antibiotics, quality indicators (QIs) linked to the clinical indication for prescribing are urgently needed. The aim of this proof of concept study was to define indication-linked QIs which can be easily implemented in Dutch primary care by collaborating with data-extraction/processing companies that routinely process patient data for GP practices. An expert group of academic and practicing GPs defined indication-linked QIs for which outcomes can be derived from routine care data. QI outcomes were calculated and fed back to GPs from 44 practices, associations between QI outcomes were determined, and GPs’ opinions and suggestions with respect to the new set were captured using an online questionnaire. The new set comprises: (1) total number of prescribed antibiotics per 1000 registered patients and percentages of generally non-1st choice antibiotics; (2) prescribing percentages for episodes of upper and lower respiratory tract infection; (3) 1st choice prescribing for episodes of tonsillitis, pneumonia and cystitis in women. Large inter-practice variation in QI outcomes was found. The validity of the QI outcomes was confirmed by associations that were expected. The new set was highly appreciated by GPs and additional QIs were suggested. We conclude that it proved feasible to provide GPs with informative, indication-linked feedback of their antibiotic prescribing quality by collaborating with established data extraction/processing companies. Based on GPs’ suggestions the set will be refined and extended and used in the near future as yearly feedback with benchmarking for GPs and for national surveillance and stewardship purposes.
      Citation: Antibiotics
      PubDate: 2020-10-03
      DOI: 10.3390/antibiotics9100670
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 671: Transitioning of Helicobacter pylori
           Therapy from Trial and Error to Antimicrobial Stewardship

    • Authors: David Y. Graham
      First page: 671
      Abstract: Helicobacter pylori is the only major infection for which antimicrobial therapy is not designed using the principles of antimicrobial stewardship. Traditionally, antimicrobial therapy is a susceptibility-based therapy, achieves high cure rates, and includes surveillance programs to regularly provide updated data regarding resistance, outcomes, and treatment guidelines. Current H. pylori therapies identified by trial-and-error, and treatment recommendations and guidelines are based on comparisons among regimens that rarely take into account the prevalence or effect of resistance. The majority of patients currently treated achieve suboptimal results. A paradigm shift is required to abandon current approaches and embrace antimicrobial stewardship, and therefore reliably achieve high cure rates; develop, propagate, and update best practice guidelines; and provide surveillance of local or regional susceptibility/resistance patterns. These also require timely updates to clinicians regarding the current status of resistance, antimicrobial effectiveness, and ways to prevent antimicrobial misuse to extend the useful life of currently available antibiotics. Here, we discuss the differences among current approaches to H. pylori therapy and antimicrobial stewardship and identify what is required to achieve the transition. Conceptually, the differences are significant, and the transition will likely need to be both abrupt and complete. Recommendations for therapy during the transition period are given.
      Citation: Antibiotics
      PubDate: 2020-10-03
      DOI: 10.3390/antibiotics9100671
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 672: Is Early Monitoring Better' Impact of
           Early Vancomycin Exposure on Treatment Outcomes and Nephrotoxicity in
           Patients with Methicillin-Resistant Staphylococcus aureus Infections

    • Authors: Thanawat Chattaweelarp, Dhitiwat Changpradub, Baralee Punyawudho, Sudaluck Thunyaharn, Wichai Santimaleeworagun
      First page: 672
      Abstract: Optimal early vancomycin target exposure remains controversial. To clarify the therapeutic exposure range, we investigated the association between vancomycin exposure and treatment outcomes or nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. This retrospective study reviewed clinical data obtained from 131 patients with MRSA infections between January 2017 and September 2019. Clinical outcomes included treatment failure, 30-day mortality, microbiological failure, and acute kidney injury. We measured serum vancomycin levels after the first dose to 48 h and estimated vancomycin exposure using the Bayesian theorem. The minimum inhibitory concentration (MIC) of antimicrobial agents was determined using the broth microdilution method. Classification and Regression Tree analyses identified day 1 and 2 exposure thresholds associated with an increased risk of failure and nephrotoxicity. Treatment failure (27.9% vs. 33.3%) and 30-day mortality (26.6% vs. 31.74%) were numerically but not significantly reduced in patients with the area under the curve (AUC)24–48h/MICBMD ≥ 698. Patients with AUCss/MICBMD ≥ 679 exhibited a significantly increased risk of acute kidney injury (27.9% vs. 10.9%, p = 0.041). These findings indicate that AUCss/MICBMD ratios > 600 may cause nephrotoxicity. AUC/MICBMD at days 1 and 2 do not appear to be significantly associated with particular clinical outcomes, but further studies are needed.
      Citation: Antibiotics
      PubDate: 2020-10-04
      DOI: 10.3390/antibiotics9100672
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 673: Analysis of the Antibiotic Resistance
           Profiles in Methicillin-Sensitive S. aureus Pathotypes Isolated on a
           Commercial Rabbit Farm in Italy

    • Authors: Anna-Rita Attili, Alessandro Bellato, Patrizia Robino, Livio Galosi, Cristiano Papeschi, Giacomo Rossi, Eleonora Fileni, Martina Linardi, Vincenzo Cuteri, Francesco Chiesa, Patrizia Nebbia
      First page: 673
      Abstract: The breeding of meat rabbits is an important sector in the livestock industry in Italy. The focus of this study was to describe the antibiotic resistance profile distribution among the Methicillin-sensitive Staphylococcus aureus isolated in a rabbit farm. From 400 animals of different ages and three farm workers, 96 randomly selected strains isolated from various anatomical sites and lesions were analysed. According to spa typing and the resistance profiles towards veterinary and human antibiotics, 26 pathotypes were identified. The highest resistance was observed against Tetracyclines (92.3%) and Macrolides (80.8%), while almost all were susceptible to Penicillins, according to the limited use of β-lactams on the farm. In total, 92.3% of pathotypes were multidrug resistant (MDRs). Two MDR pathotypes belonging to the t2802 spa type were isolated from both farmers and rabbits. Age categories harboured significantly different pathotypes (p = 0.019), while no association was found between pathotypes and lesions (p = 0.128) or sampling sites (p = 0.491). The antibiotic resistance was observed to increase with the time spent in the farm environment (age category). The selective pressure exerted by antibiotic use acted by giving advantage to more resistant strains rather than by lowering susceptibility to various drug categories within strains.
      Citation: Antibiotics
      PubDate: 2020-10-05
      DOI: 10.3390/antibiotics9100673
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 674: The Antibacterial and Anti-Biofilm
           Activity of Metal Complexes Incorporating 3,6,9-Trioxaundecanedioate and
           1,10-Phenanthroline Ligands in Clinical Isolates of Pseudomonas aeruginosa
           from Irish Cystic Fibrosis Patients

    • Authors: Megan O’Shaughnessy, Pauraic McCarron, Livia Viganor, Malachy McCann, Michael Devereux, Orla Howe
      First page: 674
      Abstract: Chronic infections of Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) patients are problematic in Ireland where inherited CF is prevalent. The bacteria’s capacity to form a biofilm in its pathogenesis is highly virulent and leads to decreased susceptibility to most antibiotic treatments. Herein, we present the activity profiles of the Cu(II), Mn(II) and Ag(I) tdda-phen chelate complexes {[Cu(3,6,9-tdda)(phen)2]·3H2O·EtOH}n (Cu-tdda-phen), {[Mn(3,6,9-tdda)(phen)2]·3H2O·EtOH}n (Mn-tdda-phen) and [Ag2(3,6,9-tdda)(phen)4]·EtOH (Ag-tdda-phen) (tddaH2 = 3,6,9-trioxaundecanedioic acid; phen = 1,10-phenanthroline) towards clinical isolates of P. aeruginosa derived from Irish CF patients in comparison to two reference laboratory strains (ATCC 27853 and PAO1). The effects of the metal-tdda-phen complexes and gentamicin on planktonic growth, biofilm formation (pre-treatment) and mature biofilm (post-treatment) alone and in combination were investigated. The effects of the metal-tdda-phen complexes on the individual biofilm components; exopolysaccharide, extracellular DNA (eDNA), pyocyanin and pyoverdine are also presented. All three metal-tdda-phen complexes showed comparable and often superior activity to gentamicin in the CF strains, compared to their activities in the laboratory strains, with respect to both biofilm formation and established biofilms. Combination studies presented synergistic activity between all three complexes and gentamicin, particularly for the post-treatment of established mature biofilms, and was supported by the reduction of the individual biofilm components examined.
      Citation: Antibiotics
      PubDate: 2020-10-05
      DOI: 10.3390/antibiotics9100674
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 675: Antibiotic Resistance and Mobile Genetic
           Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type
           147 Recovered from Germany

    • Authors: Kyriaki Xanthopoulou, Alessandra Carattoli, Julia Wille, Lena M. Biehl, Holger Rohde, Fedja Farowski, Oleg Krut, Laura Villa, Claudia Feudi, Harald Seifert, Paul G. Higgins
      First page: 675
      Abstract: Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the blaOXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare.
      Citation: Antibiotics
      PubDate: 2020-10-05
      DOI: 10.3390/antibiotics9100675
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 676: Some Suggestions from PK/PD Principles to
           Contain Resistance in the Clinical Setting—Focus on ICU Patients and
           Gram-Negative Strains

    • Authors: Chiara Adembri, Andrea Novelli, Stefania Nobili
      First page: 676
      Abstract: The containment of the phenomenon of resistance towards antimicrobials is a priority, especially in preserving molecules acting against Gram-negative pathogens, which represent the isolates more frequently found in the fragile population of patients admitted to Intensive Care Units. Antimicrobial therapy aims to prevent resistance through several actions, which are collectively known as “antimicrobial stewardship”, to be taken together, including the application of pharmacokinetic/pharmacodynamic (PK/PD) principles. PK/PD application has been shown to prevent the emergence of resistance in numerous experimental studies, although a straight translation to the clinical setting is not possible. Individualized antibiotic dosing and duration should be pursued in all patients, and even more especially when treating intensive care unit (ICU) septic patients in whom optimal exposure is both difficult to achieve and necessary. In this review, we report on the available data that support the application of PK/PD parameters to contain the development of resistance and we give some practical suggestions that can help to translate the benefit of PK/PD application to the bedside.
      Citation: Antibiotics
      PubDate: 2020-10-06
      DOI: 10.3390/antibiotics9100676
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 677: Effect of Adjuvants on Oxytetracycline
           Uptake upon Foliar Application in Citrus

    • Authors: Nabil Killiny, Faraj Hijaz, Pedro Gonzalez-Blanco, Shelley E. Jones, Myrtho O. Pierre, Christopher I. Vincent
      First page: 677
      Abstract: Recently in Florida, foliar treatments using products with the antibiotics oxytetracycline and streptomycin have been approved for the treatment of citrus Huanglongbing (HLB), which is caused by the putative bacterial pathogen ‘Candidatus Liberibacter asiaticus’. Herein, we assessed the levels of oxytetracycline and ‘Ca. L. asiaticus’ titers in citrus trees upon foliar applications with and without a variety of commercial penetrant adjuvants and upon trunk injection. The level of oxytetracycline in citrus leaves was measured using an oxytetracycline ELISA kit and ‘Ca. L. asiaticus’ titer was measured using quantitative PCR. Low levels of oxytetracycline were taken up by citrus leaves after foliar sprays of oxytetracycline in water. Addition of various adjuvants to the oxytetracycline solution showed minimal effects on its uptake by citrus leaves. The level of oxytetracycline in leaves from trunk-injected trees was higher than those treated with all foliar applications. The titer of ‘Ca. L. asiaticus’ in the midrib of leaves from trees receiving oxytetracycline by foliar application was not affected after four days and thirty days of application, whereas the titer was significantly reduced in oxytetracycline-injected trees thirty days after treatment. Investigation of citrus leaves using microscopy showed that they are covered by a thick lipidized cuticle. Perforation of citrus leaf cuticle with a laser significantly increased the uptake of oxytetracycline, decreasing the titer of ‘Ca. L. asiaticus’ in citrus leaves upon foliar application. Taken together, our findings indicate that trunk injection is more efficient than foliar spray even after the use of adjuvants. Our conclusion could help in setting useful recommendations for the application of oxytetracycline in citrus to improve tree health, minimize the amount of applied antibiotic, reduce environmental exposure, and limit off-target effects.
      Citation: Antibiotics
      PubDate: 2020-10-06
      DOI: 10.3390/antibiotics9100677
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 678: Extended Spectrum β-Lactamase (ESBL)
           Producing Escherichia coli in Pigs and Pork Meat in the European Union

    • Authors: Ieva Bergšpica, Georgia Kaprou, Elena A. Alexa, Miguel Prieto, Avelino Alvarez-Ordóñez
      First page: 678
      Abstract: The aim of this article is to review the fast and worldwide distribution of ESBL enzymes and to describe the role of the pork production chain as a reservoir and transmission route of ESBL-producing Escherichia coli and ESBLs in the European Union (EU). The use of β-lactam antibiotics in swine production and the prevalence of ESBL producing E. coli in fattening pigs and pork meat across Europe is analyzed. Overall, an increasing trend in the prevalence of presumptive ESBL producing E. coli in fattening pigs in the EU has been observed in the last decade, although with major differences among countries, linked to different approaches in the use of antimicrobials in pork production within the EU. Moreover, the various dissemination pathways of these bacteria along the pork production chain are described, along with factors at farm and slaughterhouse level influencing the risk of introducing or spreading ESBL producing bacteria throughout the food chain.
      Citation: Antibiotics
      PubDate: 2020-10-07
      DOI: 10.3390/antibiotics9100678
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 679: Pimenta Oil as a Potential Treatment for
           Acinetobacter baumannii Wound Infection: In Vitro and In Vivo Bioassays in
           Relation to Its Chemical Composition

    • Authors: Maha M. Ismail, Reham Samir, Fatema R. Saber, Shaimaa R. Ahmed, Mohamed A. Farag
      First page: 679
      Abstract: Bacterial biofilm contributes to antibiotic resistance. Developing antibiofilm agents, more favored from natural origin, is a potential method for treatment of highly virulent multidrug resistant (MDR) bacterial strains; The potential of Pimenta dioica and Pimenta racemosa essential oils (E.Os) antibacterial and antibiofilm activities in relation to their chemical composition, in addition to their ability to treat Acinetobacter baumannii wound infection in mice model were investigated; P. dioica leaf E.O at 0.05 µg·mL−1 efficiently inhibited and eradicated biofilm formed by A. baumannii by 85% and 34%, respectively. Both P. diocia and P. racemosa leaf E.Os showed a bactericidal action against A. baumanii within 6h at 2.08 µg·mL−1. In addition, a significant reduction of A. baumannii microbial load in mice wound infection model was found. Furthermore, gas chromatography mass spectrometry analysis revealed qualitative and quantitative differences among P. racemosa and P. dioica leaf and berry E.Os. Monoterpene hydrocarbons, oxygenated monoterpenes, and phenolics were the major detected classes. β-Myrcene, limonene, 1,8-cineole, and eugenol were the most abundant volatiles. While, sesquiterpenes were found as minor components in Pimenta berries E.O; Our finding suggests the potential antimicrobial activity of Pimenta leaf E.O against MDR A. baumannii wound infections and their underlying mechanism and to be further tested clinically as treatment for MDR A. baumannii infections.
      Citation: Antibiotics
      PubDate: 2020-10-07
      DOI: 10.3390/antibiotics9100679
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 680: Risk Factors for Carbapenemase-Producing
           Enterobacterales Infection or Colonization in a Korean Intensive Care
           Unit: A Case–Control Study

    • Authors: Young Ah Kim, Se Ju Lee, Yoon Soo Park, Yeo Jin Lee, Jeong Hwa Yeon, Young Hee Seo, Kyungwon Lee
      First page: 680
      Abstract: The purpose of this study is to identify the factors related to the infection and/or colonization of carbapenemase-producing Enterobacterales (CPE) based on clinical and microbiological data for patients in the intensive care unit (ICU). All patients admitted to medical ICU were screened for CPE on admission and weekly, and this 1:2 case–control study included patients with CPE identified by screening or clinical cultures from 2017 to 2018. The clonal relatedness was evaluated by pulsed-field gel electrophoresis (PFGE). A total of 45 CPE patients were identified with a prevalence of 3.8%. The most frequent organism was Klebsiella pneumoniae (69%) and the carbapenemases belonged to the class A Klebsiella pneumoniae Carbapenemase (KPC-2) (87%), class B New Delhi Metallo-β-lactamase (NDM) (11%), and Imipenemase (IMP-1) (2%) strains. The PFGE profiles showed two large clustered groups of KPC-2-producing K. pneumoniae. In the multivariate analysis, pneumonia/chronic pulmonary disease, previous fluoroquinolone use, and previous use of nasogastric tube were the significant risk factors for CPE infection or colonization in ICU-admitted patients. Critical illness and underlying medical conditions such as pneumonia/chronic pulmonary disease, antimicrobial selective pressure, and the use of a medical device are identified as risk factors for CPE infection or colonization in ICU. Person to person transmission also contributed.
      Citation: Antibiotics
      PubDate: 2020-10-08
      DOI: 10.3390/antibiotics9100680
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 681: Pullulan Films Containing Rockrose
           Essential Oil for Potential Food Packaging Applications

    • Authors: Ângelo Luís, Ana Ramos, Fernanda Domingues
      First page: 681
      Abstract: Active packaging is designed to control the development of decay- and disease-causing microorganisms and is emerging as a promising technology for extending shelf-life, maintaining food safety, reducing waste, and minimizing the risks for foodborne diseases. The goal of this work was to develop and characterize bioactive pullulan-based films, containing rockrose (Cistus ladanifer) essential oil. Among other abundant compounds (camphene, bornyl acetate and trans-pinocarveol), α-pinene was identified as the major compound of rockrose essential oil (39.25%). The essential oil presented stronger antibacterial activity against Gram-positive than against Gram-negative bacteria. The antioxidant results indicate the potential of the developed films to be used to package foods susceptible to oxidation and rancification, thus improving their shelf-life. Also, this study reflects the potential of rockrose essential oil, free or incorporated in pullulan, as a promising quorum sensing inhibitor, since it was able to interrupt intercellular communication, inhibiting violacein production. Electronic microscopy images showed the antibiofilm activity of the films with rockrose essential oil that were able to influence bacterial adhesion, which may be explained by the differences in the surface free energy of the films, as also determined.
      Citation: Antibiotics
      PubDate: 2020-10-08
      DOI: 10.3390/antibiotics9100681
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 682: Combination Therapy Using
           Low-Concentration Oxacillin with Palmitic Acid and Span85 to Control
           Clinical Methicillin-Resistant Staphylococcus aureus

    • Authors: Hun-Suk Song, Tae-Rim Choi, Shashi Kant Bhatia, Sun Mi Lee, Sol Lee Park, Hye Soo Lee, Yun-Gon Kim, Jae-Seok Kim, Wooseong Kim, Yung-Hun Yang
      First page: 682
      Abstract: The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). MRSA is difficult to kill with a single antibiotic because it has evolved to be resistant to various antibiotics by increasing the PBP2a (mecA) expression level, building up biofilm, introducing SCCmec for multidrug resistance, and changing its membrane properties. Therefore, to overcome antibiotic resistance and decrease possible genetic mutations that can lead to the acquisition of higher antibiotic resistance, drug combination therapy was applied based on previous results indicating that MRSA shows increased susceptibility to free fatty acids and surfactants. The optimal ratio of three components and the synergistic effects of possible combinations were investigated. The combinations were directly applied to clinically isolated strains, and the combination containing 15 μg/mL of oxacillin was able to control SCCmec type III and IV isolates having an oxacillin minimum inhibitory concentration (MIC) up to 1024 μg/mL; moreover, the combination with a slightly increased oxacillin concentration was able to kill SCCmec type II. Phospholipid analysis revealed that clinical strains with higher resistance contained a high portion of 12-methyltetradecanoic acid (anteiso-C15:0) and 14-methylhexadecanoic acid (anteiso-C17:0), although individual strains showed different patterns. In summary, we showed that combinatorial therapy with a low concentration of oxacillin controlled different laboratory and highly diversified clinical MRSA strains.
      Citation: Antibiotics
      PubDate: 2020-10-08
      DOI: 10.3390/antibiotics9100682
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 683: Diagnostic Value of Serum Procalcitonin in
           Patients with Convulsion in Emergency Department, an Observational Study

    • Authors: Hisashi Murakami, Hiromu Naraba, Takashi Gondo, Masaki Mochizuki, Hidehiko Nakano, Yuji Takahashi, Tomohiro Sonoo, Hideki Hashimoto, Kensuke Nakamura
      First page: 683
      Abstract: Procalcitonin (PCT), a widely used biomarker for bacterial infections, is sometimes measured in convulsion patients to distinguish bacterial infections including bacterial meningitis. However, serum PCT elevation is reported in several other conditions. This study assessed the diagnostic value of serum PCT concentrations in convulsion patients. This study examined a convulsion group: patients admitted to our critical care center during April 2018 through September 2019 via the emergency department presenting with convulsions. Randomly sampled patients admitted without convulsions were categorized as a non-convulsion group. Serum PCT analysis was performed with consideration of whether or not the patient had an infection. Diagnostic values of serum PCT for bacterial infection were evaluated for convulsion and non-convulsion patients using the positive likelihood ratio of PCT. This study found 84 patients as eligible for the convulsion group; 1:2 matched 168 control patients were selected as non-convulsion group members. The positive likelihood ratio for bacterial infection was found to be significantly lower in the convulsion group than in the control group (1.94 vs. 2.65) when setting the positive cut-off for PCT as 0.5 ng/mL. Convulsion patients had a higher PCT value. The positive likelihood ratio for patients without bacterial infection was lower.
      Citation: Antibiotics
      PubDate: 2020-10-08
      DOI: 10.3390/antibiotics9100683
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 684: The Bactericidal Activity and Spore
           Inhibition Effect of Manuka Honey against Clostridioides Difficile

    • Authors: Lillian Yu, Reynal Palafox-Rosas, Brian Luna, Rosemary C. She
      First page: 684
      Abstract: Clostridioides difficile colitis overgrowth occurs when the normal gut microbiome becomes disrupted, often due to antibiotics. Effective treatment remains elusive, due partly to the persistence of its spores in the gut. Natural substances like manuka honey offer an alternative antimicrobial mechanism of action to conventional antibiotics. We investigated the antibiotic activity of manuka honey against 20 C. difficile isolates. The minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBC) of manuka honeys of methylglyoxal (MGO) grades 30+, 100+, 250+, and 400+ were determined based on broth microdilution. Sporicidal activity was assessed in a range of honey concentrations by enumerating total viable cell and spore counts at 0–96 h after organism inoculation. The MICs of C. difficile ranged from 4% to >30% (w/v). MIC50 for the four MGO grades were similar at 10–14%. MBC results for the majority of isolates were distributed bimodally at MBC/MIC ratios ≤4 or MBC >30%. Growth kinetics in honey showed total viable cell counts remaining >105 colony-forming units (CFU)/mL at all time points, whereas spore counts remained within 1-log of baseline (102 CFU/mL) in honey but steadily increased in the drug-free control to >105 CFU/mL by 96 h. Manuka honey demonstrated variable inhibitory and bactericidal activity against C. difficile. MGO grade had no noticeable impact on overall MIC distributions or bactericidal activity. Although manuka honey could inhibit spore proliferation, it did not eradicate spores completely.
      Citation: Antibiotics
      PubDate: 2020-10-09
      DOI: 10.3390/antibiotics9100684
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 685: Rifabutin-Containing Triple Therapy
           (RHB-105) for Eradication of Helicobacter pylori: Randomized ERADICATE Hp
           Trial

    • Authors: Ira N. Kalfus, David Y. Graham, Dennis S. Riff, Raymond M. Panas
      First page: 685
      Abstract: Due to increasing resistance to commonly used antibiotics, the World Health Organization and Food and Drug Administration have advocated the development of new therapeutic regimens for Helicobacter pylori (H. pylori). This phase three, double-blind study (ERADICATE Hp) randomized (2:1) treatment-naïve adults with H. pylori infection and dyspepsia to RHB-105 (an all-in-one combination of omeprazole 40 mg, amoxicillin 1000 mg, and rifabutin 50 mg) or an identically-appearing placebo, both administered every 8 h for 14 days. The H. pylori eradication rate with RHB-105, using a modified intent-to-treat (mITT) population of subjects who received ≥1 dose of study drug and had test-of-eradication performed 28–35 days post-completion of therapy, was compared (one-sample Z-test) to a literature-derived comparator rate of 70% and success rate with physician-selected standard-of-care given to placebo failures. The mITT H. pylori eradication rate (95% CI) with RHB-105 of 89.4% (82.0–96.8%) was greater than both the literature-derived comparator rate (P < 0.001) and the standard-of-care rate of 63.0% (44.8–81.1%) (P = 0.006). Adverse events with an incidence ≥5% for RHB-105 were diarrhea (12.7%), headache (11.9%), chromaturia (9.3%), abdominal tenderness (6.8%), and dizziness (5.1%). No leukopenia was noted. RHB-105 (Talicia®) proved to be a safe and effective empiric therapy for H. pylori eradication.
      Citation: Antibiotics
      PubDate: 2020-10-09
      DOI: 10.3390/antibiotics9100685
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 686: Non-Surgical Periodontal Therapy with
           Adjunctive Amoxicillin/Metronidazole or Metronidazole When No
           Aggregatibacter actinomycetemcomitans Is Detected—A Randomized Clinical
           Trial

    • Authors: Holger F. R. Jentsch, Martin Dietrich, Sigrun Eick
      First page: 686
      Abstract: Background: The aim was to compare two different systemic antibiotics regimens adjunctive to non-surgical periodontal therapy when Aggregatibacter actinomycetemcomitans was not detected in the subgingival biofilm. Methods: A total of 58 patients with periodontitis and with no A. actinomycetemcomitans in the subgingival biofilm were treated with full-mouth subgingival instrumentation and either metronidazole (MET; n = 29) or amoxicillin/metronidazole (AMX/MET; n = 29). Probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded at baseline, as well as after three and six months. Subgingival biofilm and gingival crevicular fluid were collected and analyzed for major periodontopathogens and biomarkers. Results: PD, CAL and BOP improved at 3 and 6 months (each p < 0.001 vs. baseline) with no difference between the groups. Sites with initial PD ≥ 6 mm also improved in both groups after 3 and 6 months (p < 0.001) with a higher reduction of PD in the AMX/MET group (p < 0.05). T. forsythia was lower in the AMX/MET group after 3 months (p < 0.05). MMP-8 and IL-1β were without significant changes and differences between the groups. Conclusion: When A. actinomycetemcomitans was not detected in the subgingival biofilm, the adjunctive systemic use of amoxicillin/metronidazole results in better clinical and microbiological outcomes of non-surgical periodontal therapy when the application of systemic antibiotics is scheduled.
      Citation: Antibiotics
      PubDate: 2020-10-09
      DOI: 10.3390/antibiotics9100686
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 687: Pulmonary Sequestration Associated with
           Actinomycosis: A Case Report

    • Authors: Juan José Chaves, Fernando Polo Nieto, María Gómez-Gómez, Diana Fierro Rodríguez, Daniel García-Concha, Rafael Parra-Medina
      First page: 687
      Abstract: Background: Bronchopulmonary sequestration is a rare congenital malformation of the lower respiratory tract; it consists of a nonfunctioning mass of lung tissue that is irrigated by an anomalous systemic artery. The association with Actinomyces superinfection has not been well established. Methods: We present the case of a 35-year-old woman with a history of recurrent episodes of pneumonia. Based on radiological and histopathological examination, she was diagnosed with intralobar bronchopulmonary sequestration associated with Actinomyces infection. Promoting clinical suspicion is essential to diagnose pulmonary actinomycosis in patients with recurrent pneumonia, to improve early recognition and timely management.
      Citation: Antibiotics
      PubDate: 2020-10-09
      DOI: 10.3390/antibiotics9100687
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 688: Antibiotics in Food Chain: The
           Consequences for Antibiotic Resistance

    • Authors: Shashi B. Kumar, Shanvanth R. Arnipalli, Ouliana Ziouzenkova
      First page: 688
      Abstract: Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.
      Citation: Antibiotics
      PubDate: 2020-10-13
      DOI: 10.3390/antibiotics9100688
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 689: Staphylococcus aureus and Methicillin
           Resistant S. aureus in Nepalese Primates: Resistance to Antimicrobials,
           Virulence, and Genetic Lineages

    • Authors: Marilyn C. Roberts, Prabhu Raj Joshi, Stefan Monecke, Ralf Ehricht, Elke Müller, Darius Gawlik, Celia Diezel, Sascha D. Braun, Saroj Paudel, Mahesh Acharya, Laxman Khanal, Narayan P. Koju, Mukesh Chalise, Randall C. Kyes
      First page: 689
      Abstract: Staphylococcus aureus is a ubiquitous pathogen and colonizer in humans and animals. There are few studies on the molecular epidemiology of S. aureus in wild monkeys and apes. S. aureus carriage in rhesus macaques (Macaca mulatta) and Assam macaques (Macaca assamensis) is a species that has not previously been sampled and lives in remote environments with limited human contact. Forty Staphylococcus aureus isolates including 33 methicillin-susceptible S. aureus (MSSA) and seven methicillin-resistant S. aureus (MRSA) were characterized. Thirty-four isolates were from rhesus macaques and six isolates (five MSSA, one MRSA) were from Assam macaques. Isolates were characterized using StaphyType DNA microarrays. Five of the MRSA including one from Assam macaque were CC22 MRSA-IV (PVL+/tst+), which is a strain previously identified in Nepalese rhesus. One MRSA each were CC6 MRSA-IV and CC772 MRSA-V (PVL+). One MSSA each belonged to CC15, CC96, and CC2990. Six MRSA isolates carried the blaZ, while ten known CC isolates (seven MRSA, three MSSA) carried a variety of genes including aacA-aphD, aphA3, erm(C), mph(C), dfrA, msrA, and/or sat genes. The other 30 MSSA isolates belonged to 17 novel clonal complexes, carried no antibiotic resistance genes, lacked Panton–Valentine Leukocidin (PVL), and most examined exotoxin genes. Four clonal complexes carried egc enterotoxin genes, and four harbored edinB, which is an exfoliative toxin homologue.
      Citation: Antibiotics
      PubDate: 2020-10-13
      DOI: 10.3390/antibiotics9100689
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 690: Awareness of Appropriate Antibiotic Use in
           Primary Care for Influenza-Like Illness: Evidence of Improvement from UK
           Population-Based Surveys

    • Authors: Koen B. Pouwels, Laurence S. J. Roope, James Buchanan, Liz Morrell, Sarah Tonkin-Crine, Michele Peters, Leah F. Jones, Enrique Castro-Sánchez, Derrick W. Crook, Tim Peto, Christopher C. Butler, Julie V. Robotham, A. Sarah Walker, Sarah Wordsworth
      First page: 690
      Abstract: Influenza-like illnesses (ILI) account for a significant portion of inappropriate antibiotic use. Patient expectations for antibiotics for ILI are likely to play a substantial role in ‘unnecessary’ antibiotic consumption. This study aimed to investigate trends in awareness of appropriate antibiotic use and antimicrobial resistance (AMR). Three sequential online surveys of independent representative samples of adults in the United Kingdom investigated expectations for, and consumption of, antibiotics for ILI (May/June 2015 (n = 2064); Oct/Nov 2016 (n = 4000); Mar 2017 (n = 4000)). Respondents were asked whether they thought antibiotics were effective for ILI and about their antibiotic use. Proportions and 95% confidence intervals (CI) were calculated for each question and interactions with respondent characteristics were tested using logistic regression. Over the three surveys, the proportion of respondents who believed antibiotics would “definitely/probably” help an ILI fell from 37% (95% CI 35–39%) to 28% (95% CI 26–29%). Those who would “definitely/probably” visit a doctor in this situation fell from 48% (95% CI 46–50%) to 36% (95% CI 34–37%), while those who would request antibiotics during a consultation fell from 39% (95% CI 37–41%) to 30% (95% CI 29–32%). The percentage of respondents who found the information we provided about AMR “new/surprising” fell from 34% (95% CI 32–36%) to 28% (95% CI 26–31%). Awareness improved more among black, Asian and minority ethnic (BAME) than white people, with little other evidence of differences in improvements between subgroups. Whilst a degree of selection bias is unavoidable in online survey samples, the results suggest that awareness of AMR and appropriate antibiotic use has recently significantly improved in the United Kingdom, according to a wide range of indicators.
      Citation: Antibiotics
      PubDate: 2020-10-13
      DOI: 10.3390/antibiotics9100690
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 691: The Role of the Xylem in Oxytetracycline
           Translocation within Citrus Trees

    • Authors: Faraj Hijaz, Yasser Nehela, Fuad Al-Rimawi, Christopher I. Vincent, Nabil Killiny
      First page: 691
      Abstract: Antibiotics have been successfully used to control plant diseases for more than fifty years. Recently, oxytetracycline and streptomycin have been approved for the treatment of Huanglongbing, which is threatening the citrus industry in many regions. Because the efficiency of antibiotics in planta is highly affected by their movement and distribution, understanding the mechanism of antibiotics’ uptake and distribution could lead to a better control of plant pathogens. Herein, we investigated the movement of oxytetracycline within citrus plants. Oxytetracycline was applied by root drenching to both girdled and non-girdled citrus seedlings. In addition, oxytetracycline was applied by trunk injection to girdled and non-girdled citrus trees. After the exposure time (24 h), citrus seedlings were dissected and the levels of oxytetracycline in the different tissues were measured using an oxytetracycline ELISA kit. Upon root application (laboratory experiment), oxytetracycline was detected in the inner part of the stem (xylem-associated tissue), cortex (phloem-associated tissue), and leaves above and below the girdled area. Likewise, oxytetracycline was also detected in leaves of trunk-injected field trees (girdled and non-girdled) three days post treatment. Interestingly, cortex girdling did not affect the distribution and translocation of oxytetracycline, indicating that the xylem is the main path for oxytetracycline translocation. Taken together, our results indicate that oxytetracycline translocation mainly occurs via xylem vessels, and that movement into the phloem occurs subsequent to xylem translocation. Our findings also clearly demonstrated that upon trunk injection, only trace levels of oxytetracycline reached the roots, minimizing its therapeutic value there. Thus, our recommendation is to time tree injections to coincide with the flushing periods when the bacteria are moving into new shoots to maximize the efficiency of oxytetracycline.
      Citation: Antibiotics
      PubDate: 2020-10-13
      DOI: 10.3390/antibiotics9100691
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 692: Antimicrobial and Antibiofilm Properties
           of Graphene Oxide on Enterococcus faecalis

    • Authors: Cecilia Martini, Francesca Longo, Raffaella Castagnola, Luca Marigo, Nicola Maria Grande, Massimo Cordaro, Margherita Cacaci, Massimiliano Papi, Valentina Palmieri, Francesca Bugli, Maurizio Sanguinetti
      First page: 692
      Abstract: The aim of this study was to evaluate the antibacterial properties of graphene oxide (GO) against Enterococcus faecalis in vitro conditions and when used to coat dentin surface to prevent E. faecalis adhesion. The ATCC strain of E. faecalis 29212 has been used to perform a viability test. The pellet was suspended in ultrapure water, NaCl, PBS buffer, CaCl2 and MgCl2, Luria−Bertani broth solutions. The viability was evaluated by the colony forming unit counting method. Atomic force microscopy images and the measure of surface zeta potential variation were analyzed. Dentin discs were covered with a film of GO (n = 15) or were not treated (n = 15). Bacterial suspension was added to each sample of dentine discs and microbial counts were calculated. Statistically significant differences between two groups were assessed by a two-tailed unpaired t-test. Bacteria cell morphology was investigated with scanning electron microscopy. The highest growth inhibition was obtained in ddH2O and CaCl2 solution while, in PBS and NaCl, GO had poor antibacterial efficacy with a growth enhancing effect in the latter. GO on dentin discs demonstrated high antibacterial activity. GO film has demonstrated acceptable adhesion properties to root dentin and a role in the inhibition of bacterial film proliferation and biofilm formation.
      Citation: Antibiotics
      PubDate: 2020-10-13
      DOI: 10.3390/antibiotics9100692
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 693: Molecular Epidemiology of Carbapenemases
           in Enterobacteriales from Humans, Animals, Food and the Environment

    • Authors: Gurleen Taggar, Muhammad Attiq Rheman, Patrick Boerlin, Moussa Sory Diarra
      First page: 693
      Abstract: The Enterobacteriales order consists of seven families including Enterobacteriaceae, Erwiniaceae, Pectobacteriaceae, Yersiniaceae, Hafniaceae, Morganellaceae, and Budviciaceae and 60 genera encompassing over 250 species. The Enterobacteriaceae is currently considered as the most taxonomically diverse among all seven recognized families. The emergence of carbapenem resistance (CR) in Enterobacteriaceae caused by hydrolytic enzymes called carbapenemases has become a major concern worldwide. Carbapenem-resistant Enterobacteriaceae (CRE) isolates have been reported not only in nosocomial and community-acquired pathogens but also in food-producing animals, companion animals, and the environment. The reported carbapenemases in Enterobacteriaceae from different sources belong to the Ambler class A (blaKPC), class B (blaIMP, blaVIM, blaNDM), and class D (blaOXA-48) β-lactamases. The carbapenem encoding genes are often located on plasmids or associated with various mobile genetic elements (MGEs) like transposons and integrons, which contribute significantly to their spread. These genes are most of the time associated with other antimicrobial resistance genes such as other β-lactamases, as well as aminoglycosides and fluoroquinolones resistance genes leading to multidrug resistance phenotypes. Control strategies to prevent infections due to CRE and their dissemination in human, animal and food have become necessary. Several factors involved in the emergence of CRE have been described. This review mainly focuses on the molecular epidemiology of carbapenemases in members of Enterobacteriaceae family from humans, animals, food and the environment.
      Citation: Antibiotics
      PubDate: 2020-10-13
      DOI: 10.3390/antibiotics9100693
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 694: Impetigo Animal Models: A Review of Their
           Feasibility and Clinical Utility for Therapeutic Appraisal of
           Investigational Drug Candidates

    • Authors: Solomon Abrha, Andrew Bartholomaeus, Wubshet Tesfaye, Jackson Thomas
      First page: 694
      Abstract: Impetigo (school sores), a superficial skin infection commonly seen in children, is caused by the gram-positive bacteria Staphylococcus aureus and/or Streptococcus pyogenes. Antibiotic treatments, often topical, are used as the first-line therapy for impetigo. The efficacy of potential new antimicrobial compounds is first tested in in vitro studies and, if effective, followed by in vivo studies using animal models and/or humans. Animal models are critical means for investigating potential therapeutics and characterizing their safety profile prior to human trials. Although several reviews of animal models for skin infections have been published, there is a lack of a comprehensive review of animal models simulating impetigo for the selection of therapeutic drug candidates. This review critically examines the existing animal models for impetigo and their feasibility for testing the in vivo efficacy of topical treatments for impetigo and other superficial bacterial skin infections.
      Citation: Antibiotics
      PubDate: 2020-10-14
      DOI: 10.3390/antibiotics9100694
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 695: Synthesis and Biological Evaluation of New
           Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia
           coli Topoisomerase II Inhibitors

    • Authors: Eman M. Mohi El-Deen, Eman A. Abd El-Meguid, Eman A. Karam, Eman S. Nossier, Marwa F. Ahmed
      First page: 695
      Abstract: The growing resistance of bacteria to many antibiotics that have been in use for several decades has generated the need to discover new antibacterial agents with structural features qualifying them to overcome the resistance mechanisms. Thus, novel pyridothienopyrimidine derivatives (2a,b–a,b) were synthesized by a series of various reactions, starting with 3-aminothieno[2,3-b]pyridine-2-carboxamides (1a,b). Condensation of compounds 1a,b with cyclohexanone gave 1’H-spiro[cyclohexane-1,2’-pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidin]-4’(3’H)-ones (2a,b), which in turn were utilized to afford the target 4-substituted derivatives (3a,b–8a,b). In vitro antibacterial activity evaluations of all the new compounds (2a,b–8a,b) were performed against six strains of Gram-negative and Gram-positive bacteria. The target compounds showed significant antibacterial activity, especially against Gram-negative strains. Moreover, the compounds (2a,b; 3a,b; 4a,b; and 5a,b) that exhibited potent activity against Escherichia coli were selected to screen their inhibitory activity against Escherichia coli topoisomerase II (DNA gyrase and topoisomerase IV) enzymes. Compounds 4a and 4b showed potent dual inhibition of the two enzymes with IC50 values of 3.44 µΜ and 5.77 µΜ against DNA gyrase and 14.46 µΜ and 14.89 µΜ against topoisomerase IV, respectively. In addition, docking studies were carried out to give insight into the binding mode of the tested compounds within the E. coli DNA gyrase B active site compared with novobiocin.
      Citation: Antibiotics
      PubDate: 2020-10-14
      DOI: 10.3390/antibiotics9100695
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 696: Dalbavancin, Vancomycin and Daptomycin
           Alone and in Combination with Cefazolin against Resistant Phenotypes of
           Staphylococcus aureus in a Pharmacokinetic/Pharmacodynamic Model

    • Authors: Jacinda C. Abdul-Mutakabbir, Razieh Kebriaei, Kyle C. Stamper, Zain Sheikh, Philip T. Maassen, Katherine L. Lev, Michael J. Rybak
      First page: 696
      Abstract: The most efficacious antimicrobial therapy to aid in the successful elimination of resistant S. aureus infections is unknown. In this study, we evaluated varying phenotypes of S. aureus against dalbavancin (DAL), vancomycin (VAN), and daptomycin (DAP) alone and in combination with cefazolin (CFZ). The objective of this study was to observe whether there was a therapeutic improvement in adding a beta-lactam to a glycopeptide, lipopeptide, or a lipoglycopeptide. We completed a series of in vitro tests including minimum inhibitory concentration testing (MIC) of the antimicrobials in combination, time-kill analysis (TKA), and a 168 h (7-day) one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model on two daptomycin non-susceptible (DNS), vancomycin intermediate S. aureus strains (VISA), D712 and 6913. Results from our MIC testing demonstrated a minimum 2-fold and a maximum 32-fold reduction in MIC values for DAL, VAN, and DAP in combination with CFZ, in contrast to either agent used alone. The TKAs completed on four strains paralleled the enhanced activity demonstrated via the combination MICs. In the one-compartment PK/PD models, the combination of DAP plus CFZ or VAN plus CFZ resulted in a significant (p < 0.001) improvement in bactericidal activity and overall reduction in CFU/ml over the 7-day period. While the addition of CFZ to DAL improved time to bactericidal activity, DAL alone demonstrated equal and more sustained overall activity compared to all other treatments. The use of DAL alone, with or without CFZ and the combinations of VAN or DAP with CFZ appear to result in increased bactericidal activity against various recalcitrant S. aureus phenotypes.
      Citation: Antibiotics
      PubDate: 2020-10-14
      DOI: 10.3390/antibiotics9100696
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 697: Antiviral Effects of Lindera obtusiloba
           Leaf Extract on Murine Norovirus-1 (MNV-1), a Human Norovirus Surrogate,
           and Potential Application to Model Foods

    • Authors: Diana Solis-Sanchez, Adriana Rivera-Piza, Soyoung Lee, Jia Kim, Bomi Kim, Joo Bong Choi, Ye Won Kim, Gwang Pyo Ko, Moon Jung Song, Sung-Joon Lee
      First page: 697
      Abstract: Noroviruses are the leading cause of acute gastroenteritis and food poisoning worldwide. In this study, we investigated the anti-noroviral activity of Lindera obtusiloba leaf extract (LOLE) using murine norovirus (MNV-1), a surrogate of human norovirus. Preincubation of MNV-1 with LOLE at 4, 8, or 12 mg/mL for 1 h at 25 °C significantly reduced viral infectivity, by 51.8%, 64.1%, and 71.2%, respectively. Among LOLE single compounds, β-pinene (49.7%), α-phellandrene (26.2%), and (+)-limonene (17.0%) demonstrated significant inhibitory effects on viral infectivity after pretreatment with MNV-1, suggesting that the anti-noroviral effects of LOLE may be due to the synergetic activity of several compounds, with β-pinene as a key molecule. The inhibitory effect of LOLE was tested on the edible surfaces of lettuce, cabbage, and oysters, as well as on stainless steel. After one hour of incubation at 25°C, LOLE (12 mg/mL) pretreatment significantly reduced MNV-1 plaque formation on lettuce (76.4%), cabbage (60.0%), oyster (38.2%), and stainless-steel (62.8%). These results suggest that LOLE effectively inhibits norovirus on food and metal surfaces. In summary, LOLE, including β-pinene, may inactivate norovirus and could be used as a natural agent promoting food safety and hygiene.
      Citation: Antibiotics
      PubDate: 2020-10-14
      DOI: 10.3390/antibiotics9100697
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 698: Comparative Evaluation of qnrA, qnrB, and
           qnrS Genes in Enterobacteriaceae Ciprofloxacin-Resistant Cases, in Swine
           Units and a Hospital from Western Romania

    • Authors: Alexandru O. Doma, Roxana Popescu, Mihai Mitulețu, Delia Muntean, János Dégi, Marius V. Boldea, Isidora Radulov, Eugenia Dumitrescu, Florin Muselin, Nikola Puvača, Romeo T. Cristina
      First page: 698
      Abstract: Excessive use of antimicrobials and inadequate infection control practices has turned antimicrobial resistance (AMR) into a global, public health peril. We studied the expression of qnrA, qnrB, and qnrS plasmid in ciprofloxacin (CIP)-resistant strains of Escherichia coli in swine and humans from Romania, using the Polymerase Chain Reaction (PCR) technique. Antibiotic Susceptibility Testing (AST) for human subjects (H) on 147 samples and 53 swine (S) was ascertained as well as the isolation of bacterial DNA (E. coli) as follows: bacteriolysis, DNA-binding, rinsing, elution, amplification, and nucleic acids’ migration and U.V. visualization stages. From 24 samples of E. coli resistant to CIP collected from H subjects and 15 from S, for PCR analysis, 15 H and 12 S were used, with DNA purity of 1.8. The statistically analyzed results using the Crosstabs function (IBM SPSS Statistics-Ver. 2.1.), revealed the qnrS (417 bp) gene in 13 human subjects (52.0%), as well as in all swine samples studied. The qnrB (526 bp) gene was exposed in 9 of the human patients (36.0%) and in all swine isolates, and the qnrA (516 bp) gene was observed only in 3 of the isolates obtained from human subjects (12.0%) and was not discovered in pigs (p > 0.05). The presence of plasmids qnrA, qnrB, and qnrS in the human samples and of qnrB and qnrS in swine, facilitates the survival of pathogens despite the CIP action. The long-term use of CIP could cause a boost in the prevalence of qnr resistance genes, and resistance in the pigs destined for slaughter, a perturbing fact for public health and the human consumer.
      Citation: Antibiotics
      PubDate: 2020-10-14
      DOI: 10.3390/antibiotics9100698
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 699: The Hydric Environment: A Hub for
           Clinically Relevant Carbapenemase Encoding Genes

    • Authors: Florence Hammer-Dedet, Estelle Jumas-Bilak, Patricia Licznar-Fajardo
      First page: 699
      Abstract: Carbapenems are β-lactams antimicrobials presenting a broad activity spectrum and are considered as last-resort antibiotic. Since the 2000s, carbapenemase producing Enterobacterales (CPE) have emerged and are been quickly globally spreading. The global dissemination of carbapenemase encoding genes (CEG) within clinical relevant bacteria is attributed in part to its location onto mobile genetic elements. During the last decade, carbapenemase producing bacteria have been isolated from non-human sources including the aquatic environment. Aquatic ecosystems are particularly impacted by anthropic activities, which conduce to a bidirectional exchange between aquatic environments and human beings and therefore the aquatic environment may constitute a hub for CPE and CEG. More recently, the isolation of autochtonous aquatic bacteria carrying acquired CEG have been reported and suggest that CEG exchange by horizontal gene transfer occurred between allochtonous and autochtonous bacteria. Hence, aquatic environment plays a central role in persistence, dissemination and emergence of CEG both within environmental ecosystem and human beings, and deserves to be studied with particular attention.
      Citation: Antibiotics
      PubDate: 2020-10-15
      DOI: 10.3390/antibiotics9100699
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 700: Dalbavancin in the Treatment of Bacteremia
           and Endocarditis in People with Barriers to Standard Care

    • Authors: Leama Ajaka, Emily Heil, Sarah Schmalzle
      First page: 700
      Abstract: Introduction: Dalbavancin is an antibiotic administered by intravenous infusion weekly or bi-weekly and is currently FDA-approved only for treatment of skin and soft-tissue infections. It has shown promise, but is not considered the standard of care, for bacteremia and infective endocarditis (IE), which typically require outpatient parenteral antibiotic therapy (OPAT) for prolonged durations. People who inject drugs (PWID) with bacteremia or IE are often perceived as having barriers to OPAT and standard daily-administered antibiotics, prompting off-label use of dalbavancin in this population. Methods: A retrospective review of adult patients receiving at least one dose of dalbavancin for bacteremia or IE was conducted between 1 November 2017 and 31 October 2019. Outcomes and reasons for use of dalbavancin were recorded, including specific barriers to standard therapy. Results: Stated reasons for dalbavancin use in the 18 patients identified included active injection drug use (50%), inability to arrange standard OPAT due to patient adherence or inability to place in skilled nursing facility (SNF) (22%), risk for additional infections or other morbidity with OPAT (22%), and patient preference (6%). In 11 patients (61%) SNF placement was not attempted due to behavioral issues or patient declination. There were five patients who did not complete their intended course of treatment (28%). At 90 days, eight patients (44%) achieved a clinical or biologic cure, six (33%) failed treatment, and four (22%) were lost to follow-up. Conclusion: Dalbavancin may have a role as salvage therapy in the treatment of IE and bacteremia in PWID who have significant barriers to standard treatment.
      Citation: Antibiotics
      PubDate: 2020-10-15
      DOI: 10.3390/antibiotics9100700
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 701: Antibiogram Profiles and Risk Factors for
           Multidrug Resistance of Salmonella enterica Recovered from Village
           Chickens (Gallus gallus domesticus Linnaeus) and Other Environmental
           Sources in the Central and Southern Peninsular Malaysia

    • Authors: Saleh Mohammed Jajere, Latiffah Hassan, Zunita Zakaria, Jalila Abu, Saleha Abdul Aziz
      First page: 701
      Abstract: The emergence of multidrug resistance (MDR), including colistin resistance, among Enterobacteriaceae recovered from food animals poses a serious public health threat because of the potential transmission of these resistant variants to humans along the food chain. Village chickens or Ayam Kampung are free-range birds and are preferred by a growing number of consumers who consider these chickens to be organic and more wholesome. The current study investigates the antibiogram profiles of Salmonella isolates recovered from village chicken flocks in South-central Peninsular Malaysia. A total of 34 isolates belonging to eight serotypes isolated from village chickens were screened for resistance towards antimicrobials including colistin according to the WHO and OIE recommendations of critical antibiotics. S. Weltevreden accounted for 20.6% of total isolates, followed by serovars Typhimurium and Agona (17.6%). The majority of isolates (73.5%) demonstrated resistance to one or more antimicrobials. Eight isolates (23.5%) were resistant to ≥3 antimicrobial classes. Colistin resistance (minimum inhibitory concentrations: 4–16 mg/L) was detected among five isolates (14.7%), including S. Weltevreden, S. Albany, S. Typhimurium, and Salmonella spp. Univariable analysis of risk factors likely to influence the occurrence of MDR Salmonella revealed that the flock size, poultry production system, and use of antibiotics in the farm were not significantly (p > 0.05) associated with MDR Salmonella. The current study highlights that MDR Salmonella occur at a lower level in village chickens compared to that found in live commercial chickens. However, MDR remains a problem even among free-range chickens with minimal exposure to antibiotics.
      Citation: Antibiotics
      PubDate: 2020-10-15
      DOI: 10.3390/antibiotics9100701
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 702: Alternative Anti-Infective Treatments to
           Traditional Antibiotherapy against Staphylococcal Veterinary Pathogens

    • Authors: Álvaro Mourenza, José A. Gil, Luis M. Mateos, Michal Letek
      First page: 702
      Abstract: The genus Staphylococcus encompasses many species that may be pathogenic to both humans and farm animals. These bacteria have the potential to acquire multiple resistant traits to the antimicrobials currently used in the veterinary or medical settings. These pathogens may commonly cause zoonoses, and the infections they cause are becoming difficult to treat due to antimicrobial resistance. Therefore, the development of novel alternative treatments to traditional antibiotherapy has gained interest in recent years. Here, we reviewed the most promising therapeutic strategies developed to control staphylococcal infections in the veterinary field to overcome antibiotic resistance.
      Citation: Antibiotics
      PubDate: 2020-10-15
      DOI: 10.3390/antibiotics9100702
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 703: The Onset of Tacrolimus Biosynthesis in
           Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status

    • Authors: Sílvia D. S. Pires, Rute Oliveira, Pedro Moradas-Ferreira, Marta V. Mendes
      First page: 703
      Abstract: The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox status in the biosynthesis of tacrolimus in Streptomyces tsukubaensis has been briefly acknowledged. Here, we investigate the impact of the oxidative stress response on tacrolimus biosynthesis in S. tsukubaensis. Physiological characterization of S. tsukubaensis showed that the onset of tacrolimus biosynthesis coincided with the induction of catalase activity. In addition, tacrolimus displays antioxidant properties and thus a controlled redox environment would be beneficial for its biosynthesis. In addition, S. tsukubaensis ∆ahpC strain, a strain defective in the H2O2-scavenging enzyme AhpC, showed increased production of tacrolimus. Proteomic and transcriptomic studies revealed that the tacrolimus over-production phenotype was correlated with a metabolic rewiring leading to increased availability of tacrolimus biosynthetic precursors. Altogether, our results suggest that the carbon source, mainly used for cell growth, can trigger the production of tacrolimus by modulating the oxidative metabolism to favour a low oxidizing intracellular environment and redirecting the metabolic flux towards the increase availability of biosynthetic precursors.
      Citation: Antibiotics
      PubDate: 2020-10-15
      DOI: 10.3390/antibiotics9100703
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 704: A Qualitative Study of Pregnant Women’s
           Perspectives on Antibiotic Use for Mom and Child: Implications for
           Developing Tailored Health Education Interventions

    • Authors: Lynn Y. Chen, Elizabeth Flood-Grady, Austen Hentschel, Lauren Wright, Rahma Mkuu, Alyson Young, Magda Francois, Josef Neu, Leslie A. Parker, Elizabeth Shenkman, Janice L. Krieger, Dominick J. Lemas
      First page: 704
      Abstract: The overutilization of antibiotics during pregnancy and early life are associated with adverse health outcomes for mothers and infants. In this study, we explored pregnant women’s opinions and concerns of antibiotics and how perceptions may affect their health-related decision-making. We conducted 18 in-depth, semi-structured interviews with pregnant women and used the Health Belief Model (HBM) as a framework to analyze the data. We found that mothers generally understood the benefits of antibiotics and were aware that antibiotics are clinically effective for treating bacterial infections. Importantly, perceived barriers related to antibiotic use included concerns regarding the impact of antibiotics on breastfeeding efficacy, microbial health, and societal factors such as antimicrobial resistance. The prescription of antibiotics by a healthcare provider was a cue to action for women, as they trusted providers to recommend medications that were safe for them and their infants. Overall, mothers shared that receiving education on the effects of antibiotics would improve their self-efficacy and decision-making surrounding the use of antibiotics for treating illness. Implications for tailored perinatal health education interventions to enhance antibiotic use, knowledge, and decision-making are discussed.
      Citation: Antibiotics
      PubDate: 2020-10-15
      DOI: 10.3390/antibiotics9100704
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 705: Investigation of Outbreaks of
           Extended-Spectrum Beta-Lactamase-Producing Klebsiella Pneumoniae in Three
           Neonatal Intensive Care Units Using Whole Genome Sequencing

    • Authors: Sammy Frenk, Nadya Rakovitsky, Elizabeth Temkin, Vered Schechner, Regev Cohen, Bat Sheva Kloyzner, Mitchell J. Schwaber, Ester Solter, Shoshana Cohen, Sarit Stepansky, Yehuda Carmeli
      First page: 705
      Abstract: Infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) are on a constant rise and are a noted cause of outbreaks in neonatal intensive care units (NICUs). We used whole genome sequencing (WGS) to investigate the epidemiology of consecutive and overlapping outbreaks caused by ESBL-KP in NICUs in three hospitals in close proximity. Clonality of 43 ESBL-KP isolates from 40 patients was determined by BOX-PCR. Short-read sequencing was performed on representative isolates from each clone. The dominant clones from each NICU were sequenced using long-read sequencing. Bioinformatics methods were used to define multilocus sequence type (MLST), analyze plasmid content, resistomes, and virulence factors. In each NICU, we found a unique dominant clone (ST985, ST37, and ST35), each belonging to a distinct sequence type (ST), as well as satellite clones. A satellite strain in NICU-2 (ST35) was the dominant strain in NICU-3, where it was isolated four weeks later, suggesting transmission. NICU-1- and NICU-2-dominant strains had blaCTX-M-15 carried on a similar transposable element (Tn3-ISEcp1) but at different locations: on a plasmid and on the chromosome, respectively. We concluded that the overlapping ESBL-KP outbreaks were a combination of clonal transmission within NICUs, possible transposable element transmission between NICUs, and repeated importation of ESBL-KP from the community.
      Citation: Antibiotics
      PubDate: 2020-10-16
      DOI: 10.3390/antibiotics9100705
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 706: Design and Synthesis of Small Molecules as
           Potent Staphylococcus aureus Sortase A Inhibitors

    • Authors: Min Woo Ha, Sung Wook Yi, Seung-Mann Paek
      First page: 706
      Abstract: The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in virulence and its nonessentiality in bacterial survival, sortase A has been considered as a great target for new antibiotics. Sortase A inhibitors have emerged as promising alternative antivirulence agents against bacteria. Herein, the structural and preparative aspects of some small synthetic organic compounds that block the pathogenic action of sortase A have been described.
      Citation: Antibiotics
      PubDate: 2020-10-16
      DOI: 10.3390/antibiotics9100706
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 707: Is Antimicrobial Dosing Adjustment
           Associated with Better Outcomes in Patients with Severe Obesity and
           Bloodstream Infections' An Exploratory Study

    • Authors: Stéphanie Sirard, Claire Nour Abou Chakra, Marie-France Langlois, Julie Perron, Alex Carignan, Louis Valiquette
      First page: 707
      Abstract: The impact of adjusted treatment on clinical outcomes in patients with severe obesity is unclear. This study included adults with severe obesity admitted for bloodstream infections between 2005 and 2015. The patients were grouped according to the percentage of the appropriateness of the dosage of their antimicrobial treatment: 80–100% = good, 20–79% = moderate, and 0–19% = poor. The association between antimicrobial adjustment and a composite of unfavourable outcomes [intensive care unit stay ≥72 h, duration of sepsis >3 days, length of stay ≥7 days or all-cause 30-day mortality] was assessed using logistic regression. Of 110 included episodes, the adjustment was rated good in 47 (43%) episodes, moderate in 31 (28%), and poor in 32 (29%). Older age, Pitt bacteremia score ≥2, sepsis on day 1, and infection site were independent risk factors for unfavourable outcomes. The level of appropriateness was not associated with unfavourable outcomes. The number of antimicrobials, consultation with an infectious disease specialist, blood urea nitrogen 7–10.9 mmol/L, and hemodialysis were significantly associated with adjusted antimicrobial dosing. While the severity of the infection had a substantial impact on the measured outcomes, we did not find an association between dosing optimization and better outcomes.
      Citation: Antibiotics
      PubDate: 2020-10-16
      DOI: 10.3390/antibiotics9100707
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 708: Prevalence and Epidemiology of
           Multidrug-Resistant Pathogens in the Food Chain and the Urban Environment
           in Northwestern Germany

    • Authors: Sylvia Klees, Natalie Effelsberg, Birgit Stührenberg, Alexander Mellmann, Stefan Schwarz, Robin Köck
      First page: 708
      Abstract: The surveillance of antimicrobial resistance among humans and food-producing animals is important to monitor the zoonotic transmission of multidrug-resistant bacteria (MDRB). We assessed the prevalence of four MDRB within the meat production chain, including extended-spectrum β-lactamase (ESBL)-producing, carbapenemase-producing Enterobacterales (CPE) and colistin-resistant Enterobacterales (Col-E), as well as vancomycin-resistant enterococci (VRE). In total, 505 samples from four stages of meat production, i.e., slaughterhouses, meat-processing plants, fresh food products and the urban environment, were collected in northwestern Germany in 2018/2019 and screened for the presence of MDRB using both culture-based and PCR-based techniques. We detected genes encoding for carbapenemases in 9–56% (blaOXA-48, blaKPC, blaNDM, blaVIM) and colistin resistance-encoding mcr genes in 9–26% of the samples from all stages. Culture-based analysis found CPE and VRE only in environmental samples (11% and 7%, respectively), but Col-E and ESBL-producers in 1–7% and 12–46% of samples from all stages, respectively. Overall, our results showed that ESBL-producers and mcr-carrying Col-E were common in food-producing animals at slaughterhouses, in meat-processing plants and in food items at retail, while CPE and VRE were only found in the environment. The discrepancy between detected carbapenemase genes and isolated CPE emphasizes the need for more sensitive detection methods for CPE monitoring.
      Citation: Antibiotics
      PubDate: 2020-10-16
      DOI: 10.3390/antibiotics9100708
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 709: Antibiotic Resistance of Human Periodontal
           Pathogen Parvimonas micra Over 10 Years

    • Authors: Thomas E. Rams, Jacqueline D. Sautter, Arie J. van Winkelhoff
      First page: 709
      Abstract: Changes were evaluated over 10 years in the in vitro resistance of human periodontopathic strains of Parvimonas micra to four antibiotics. Subgingival biofilms culture positive for P. micra from 300 United States adults with severe periodontitis in 2006, and from a similar group of 300 patients in 2016, were plated onto anaerobically incubated enriched Brucella blood agar alone, or supplemented with either doxycycline (4 mg/L), clindamycin (4 mg/L), amoxicillin (8 mg/L), or metronidazole (16 mg/L). P. micra growth on antibiotic-supplemented media indicated in vitro resistance to the evaluated antibiotic concentration. P. micra resistance was significantly more frequent among patients in 2016, as compared to 2006, for doxycycline (11.3% vs. 0.3% patients; 37.7-fold increase), and clindamycin (47.3% vs. 2.0% patients; 23.7-fold increase) (both p < 0.001), whereas resistance to amoxicillin (2.3% vs. 1.0% patients) and metronidazole (0% vs. 0.3% patients) remained low and statistically unchanged between the two patient groups (p-values > 0.05). No P. micra isolates in 2006 or 2016 were jointly resistant in vitro to both amoxicillin and metronidazole. The alarming increases in subgingival P. micra resistance to doxycycline and clindamycin raise serious questions about the empiric use of these antibiotics, either locally or systemically, in the treatment of United States periodontitis patients harboring subgingival P. micra.
      Citation: Antibiotics
      PubDate: 2020-10-17
      DOI: 10.3390/antibiotics9100709
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 710: Prevalence of Antibiotic-Resistant
           Pulmonary Tuberculosis in Bangladesh: A Systematic Review and
           Meta-Analysis

    • Authors: Shoumik Kundu, Mahfuza Marzan, Siew Hua Gan, Md Asiful Islam
      First page: 710
      Abstract: Resistance to anti-tuberculosis (anti-TB) antibiotics is a major public health concern for many high-TB burden countries in Asia, including Bangladesh. Therefore, to represent the overall drug-resistance pattern against TB in Bangladesh, a systematic review and meta-analysis was conducted. Databases such as PubMed, Scopus, and Google Scholar were searched to identify studies related to antibiotic-resistant TB. A total of 24 studies covering 13,336 patients with TB were secured and included. The random-effects model was used to calculate the summary estimates. The pooled prevalence of any, mono, multi, poly, and extensive anti-TB antibiotic-resistances were 45.3% [95% CI: 33.5–57.1], 14.3% [95% CI: 11.4–17.2], 22.2% [95% CI: 18.8–25.7], 7.7% [95% CI: 5.6–9.7], and 0.3% [95% CI: 0.0–1.0], respectively. Among any first and second-line anti-TB drugs, isoniazid (35.0%) and cycloserine (44.6%) resistances were the highest, followed by ethambutol (16.2%) and gatifloxacin (0.2%). Any, multi, and poly drug-resistances were higher in retreatment cases compared to the newly diagnosed cases, although mono drug-resistance tended to be higher in newly diagnosed cases (15.7%) than that in retreatment cases (12.5%). The majority (82.6%) of the included studies were of high quality, with most not exhibiting publication bias. Sensitivity analyses confirmed that all outcomes are robust and reliable. It is concluded that resistance to anti-TB drugs in Bangladesh is rampant and fast growing. Therefore, the implementation of a nationwide surveillance system to detect suspected and drug-resistant TB cases, as well as to ensure a more encompassing treatment management by national TB control program, is highly recommended.
      Citation: Antibiotics
      PubDate: 2020-10-17
      DOI: 10.3390/antibiotics9100710
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 711: Single Cell Analysis of Drug
           Susceptibility of Mycobacterium Abscessus During Macrophage Infection

    • Authors: Brzostek, Fatin, Chua, Tan, Dick, Gascoigne
      First page: 711
      Abstract: Mycobacterium abscessus is an emerging health risk to immunocompromised individuals and to people with pre-existing pulmonary conditions. As M. abscessus possesses multiple mechanisms of drug resistance, treatments of M. abscessus are of poor efficacy. Therefore, there is an urgent need for new therapeutic strategies targeting M. abscessus. We describe an experimental system for screening of compounds for their antimicrobial activity against intracellular M. abscessus using flow cytometry and imaging flow cytometry. The assay allows simultaneous analysis of multiple parameters, such as proportion of infected host cells, bacterial load per host cell from the infected population, and host cell viability. We verified the suitability of this method using two antibiotics with known activity against M. abscessus: clarithromycin and amikacin. Our analysis revealed a high degree of infection heterogeneity, which correlated with host cell size. A higher proportion of the larger host cells is infected with M. abscessus as compared to smaller host cells, and infected larger cells have higher intracellular bacterial burden than infected smaller cells. Clarithromycin treatment has a more pronounced effect on smaller host cells than on bigger host cells, suggesting that heterogeneity within the host cell population has an effect on antibiotic susceptibility of intracellular bacteria.
      Citation: Antibiotics
      PubDate: 2020-10-17
      DOI: 10.3390/antibiotics9100711
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 712: Antibacterial Use of Macroalgae Compounds
           against Foodborne Pathogens

    • Authors: Aurora Silva, Sofia A. Silva, C. Lourenço-Lopes, C. Jimenez-Lopez, M. Carpena, P. Gullón, M. Fraga-Corral, V. F. Domingues, M. Fátima Barroso, J. Simal-Gandara, M. A. Prieto
      First page: 712
      Abstract: The search for food resources is a constant in human history. Nowadays, the search for natural and safe food supplies is of foremost importance. Accordingly, there is a renewed interest in eco-friendly and natural products for substitution of synthetic additives. In addition, microbial contamination of food products during their obtaining and distribution processes is still a sanitary issue, and an important target for the food industry is to avoid food contamination and its related foodborne illnesses. These diseases are fundamentally caused by certain microorganisms listed in this review and classified according to their Gram negative or positive character. Algae have proven to possess high nutritional value and a wide variety of biological properties due to their content in active compounds. Among these capabilities, macroalgae are recognized for having antimicrobial properties. Thus, the present paper revises the actual knowledge of microbial contaminants in the food industry and proposes antimicrobial algal compounds against those pathogenic bacteria responsible for food contamination as valuable molecules for its growth inhibition. The capacity of algae extracts to inhibit some major food pathogen growth was assessed. Moreover, the main applications of these compounds in the food industry were discussed while considering their favorable effects in terms of food safety and quality control.
      Citation: Antibiotics
      PubDate: 2020-10-17
      DOI: 10.3390/antibiotics9100712
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 713: Preoperative Antibiotic Prophylaxis in
           Elective Minor Surgical Procedures among Adults in Southern Italy

    • Authors: Giorgia Della Polla, Aida Bianco, Silvia Mazzea, Francesco Napolitano, Italo Francesco Angelillo
      First page: 713
      Abstract: Little is known regarding the factors associated with surgical antibiotic prophylaxis (SAP) compliance in elective minor surgery. The purposes of this cross-sectional study were to identify the frequency of inappropriate SAP administration and to understand the characteristics associated with such inappropriateness in a sample of elective minor surgical procedures. The study was performed between May and July 2019 among a random sample of patients aged 18 years and older in seven public hospitals randomly selected in the Campania and Calabria Regions of Italy. Globally, only 45% of SAP approaches were deemed completely in accordance with the evidence-based guidelines. Patients with an ordinary admission, those who underwent local anesthesia, those receiving plastic and reconstructive and ophthalmology surgery, and those who had not received a prosthetic implant were more likely to receive an appropriate SAP approach; those receiving obstetrics, gynecological, and urological surgical procedures were less likely than those who underwent abdominal, vascular, and breast surgery. The course of antibiotic prophylaxis was not consistent with the guidelines in 48.5% procedures with one or more reasons for inappropriateness. Appropriate time of the SAP administration was more frequently observed in patients who were older, those with a Charlson comorbidity index of 0, those who did not receive a prosthetic implant, and those receiving plastic and reconstructive surgery; it was less likely in patients receiving obstetrics, gynecological, and urological surgeries compared with those who underwent abdominal, vascular, and breast surgery. Aspects of SAP that need to be improved are molecule choice, time of administration, and specific surgical procedures. Hospital managers should involve surgeons and anesthesiologists in initiatives tailored to optimize SAP prescribing.
      Citation: Antibiotics
      PubDate: 2020-10-18
      DOI: 10.3390/antibiotics9100713
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 714: Aminoglycoside Antibiotics Inhibit
           Mycobacteriophage Infection

    • Authors: Zheng Jiang, Junwei Wei, Yunxiang Liang, Nan Peng, Yingjun Li
      First page: 714
      Abstract: Antibiotic resistance is becoming the biggest threat to global health. At the same time, phage therapy is witnessing a return of interest. The therapeutic use of bacteriophages that infect and kill bacteria is a suitable strategy to combat antibiotic resistance. Furthermore, bacteriophages are increasingly used in combination with standard antibiotics against drug-resistant pathogens. Interestingly, we found that the engineered mycobacteriophage phAE159 and natural phage D29 cannot infect the Mycobacterium tuberculosis in the presence of kanamycin, hygromycin or streptomycin, but the phage infection was not affected in the presence of spectinomycin. Based on a series of studies and structural analysis of the above four aminoglycoside antibiotics, it could be speculated that the amino sugar group of aminoglycoside might selectively inhibit mycobacteriophage DNA replication. Our discovery that broad-spectrum antibiotics inhibit phage infection is of great value. This study will provide guidance for people to combine phage and antibiotics to treat M. tuberculosis.
      Citation: Antibiotics
      PubDate: 2020-10-19
      DOI: 10.3390/antibiotics9100714
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 715: Aureolic Acid Group of Agents as Potential
           Antituberculosis Drugs

    • Authors: Julia Bespyatykh, Dmitry Bespiatykh, Maja Malakhova, Ksenia Klimina, Andrey Bespyatykh, Anna Varizhuk, Anna Tevyashova, Tatiana Nikolenko, Galina Pozmogova, Elena Ilina, Egor Shitikov
      First page: 715
      Abstract: Mycobacterium tuberculosis is one of the most dangerous pathogens. Bacterial resistance to antituberculosis drugs grows each year, but searching for new drugs is a long process. Testing for available drugs to find active against mycobacteria may be a good alternative. In this work, antibiotics of the aureolic acid group were tested on a model organism Mycobacterium smegmatis. We presumed that antibiotics of this group may be potential G4 ligands. However, this was not confirmed in our analyses. We determined the antimicrobial activity of these drugs and revealed morphological changes in the cell structure upon treatment. Transcriptomic analysis documented increased expression of MSMEG_3743/soj and MSMEG_4228/ftsW, involved in cell division. Therefore, drugs may affect cell division, possibly disrupting the function of the Z-ring and the formation of a septum. Additionally, a decrease in the transcription level of several indispensable genes, such as nitrate reductase subunits (MSMEG_5137/narI and MSMEG_5139/narX) and MSMEG_3205/hisD was shown. We concluded that the mechanism of action of aureolic acid and its related compounds may be similar to that bedaquiline and disturb the NAD+/NADH balance in the cell. All of this allowed us to conclude that aureolic acid derivatives can be considered as potential antituberculosis drugs.
      Citation: Antibiotics
      PubDate: 2020-10-19
      DOI: 10.3390/antibiotics9100715
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 716: Antibacterial Property and
           Biocompatibility of Silver, Copper, and Zinc in Titanium Dioxide Layers
           Incorporated by One-Step Micro-Arc Oxidation: A Review

    • Authors: Masaya Shimabukuro
      First page: 716
      Abstract: Titanium (Ti) and its alloys are commonly used in medical devices. However, biomaterial-associated infections such as peri-implantitis and prosthetic joint infections are devastating and threatening complications for patients, dentists, and orthopedists and are easily developed on titanium surfaces. Therefore, this review focuses on the formation of biofilms on implant surfaces, which is the main cause of infections, and one-step micro-arc oxidation (MAO) as a coating technology that can be expected to prevent infections due to the implant. Many researchers have provided sufficient data to prove the efficacy of MAO for preventing the initial stages of biofilm formation on implant surfaces. Silver (Ag), copper (Cu), and zinc (Zn) are well used and are incorporated into the Ti surface by MAO. In this review, the antibacterial properties, cytotoxicity, and durability of these elements on the Ti surface incorporated by one-step MAO will be summarized. This review is aimed at enhancing the importance of the quantitative control of Ag, Cu, and Zn for their use in implant surfaces and the significance of the biodegradation behavior of these elements for the development of antibacterial properties.
      Citation: Antibiotics
      PubDate: 2020-10-20
      DOI: 10.3390/antibiotics9100716
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 717: Antibacterial and Cytotoxic Activities of
           Ten Commercially Available Essential Oils

    • Authors: Sofia Oliveira Ribeiro, Véronique Fontaine, Véronique Mathieu, Abdesselam Zhiri, Dominique Baudoux, Caroline Stévigny, Florence Souard
      First page: 717
      Abstract: There is a huge concern in the medical field concerning the emergence of bacterial resistance to antibiotics. Essential oils are a source of antibacterial compounds that can overcome this problem. Ten essential oils that are commercially available were investigated in the present study: ajowan, basil, German chamomile, Chinese cinnamon, coriander, clove, lemongrass, Spanish lavender, oregano and palmarosa. Their direct, synergistic and indirect antibacterial activities were evaluated against different human pathogenic Gram-positive and Gram-negative strains. To evaluate their possible use in clinics, the cytotoxicity of these essential oils was also tested on keratinocyte and epithelial cell lines. Except for the Chinese cinnamon, coriander and lemongrass, all other essential oils presented no cytotoxicity at 32 and 16 μg/mL. The highest indirect antibacterial activities were observed with the palmarosa and Spanish lavender in association with penicillin V. These two associations presented a 64-fold decrease against a resistant strain of Staphylococcus aureus, however, at a cytotoxic concentration. It can also be highlighted that when tested at a non-cytotoxic concentration, the activity of oregano in association with penicillin V presented an eight-fold decrease. These results show the interest to use essential oils in combination with antibiotics to reduce their concentrations inside drugs.
      Citation: Antibiotics
      PubDate: 2020-10-20
      DOI: 10.3390/antibiotics9100717
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 718: Peptidomic Analysis of Skin Secretions of
           the Caribbean Frogs Leptodactylus insularum and Leptodactylus nesiotus
           (Leptodactylidae) Identifies an Ocellatin with Broad Spectrum
           Antimicrobial Activity

    • Authors: Gervonne Barran, Jolanta Kolodziejek, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Norbert Nowotny, J. Michael Conlon, Milena Mechkarska
      First page: 718
      Abstract: Ocellatins are peptides produced in the skins of frogs belonging to the genus Leptodactylus that generally display weak antimicrobial activity against Gram-negative bacteria only. Peptidomic analysis of norepinephrine-stimulated skin secretions from Leptodactylus insularum Barbour 1906 and Leptodactylus nesiotus Heyer 1994, collected in the Icacos Peninsula, Trinidad, led to the purification and structural characterization of five ocellatin-related peptides from L. insularum (ocellatin-1I together with its (1–16) fragment, ocellatin-2I and its (1–16) fragment, and ocellatin-3I) and four ocellatins from L. nesiotus (ocellatin-1N, -2N, -3N, and -4N). While ocellatins-1I, -2I, and -1N showed a typically low antimicrobial potency against Gram-negative bacteria, ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH2) was active against an antibiotic-resistant strain of Klebsiella pneumoniae and reference strains of Escherichia coli, K. pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium (minimum inhibitory concentrations (MICs) in the range 31.25–62.5 μM), and was the only peptide active against Gram-positive Staphylococcus aureus (MIC = 31.25 μM) and Enterococcus faecium (MIC = 62.5 μM). The therapeutic potential of ocellatin-3N is limited by its moderate hemolytic activity (LC50 = 98 μM) against mouse erythrocytes. The peptide represents a template for the design of long-acting, non-toxic, and broad-spectrum antimicrobial agents for targeting multidrug-resistant pathogens.
      Citation: Antibiotics
      PubDate: 2020-10-20
      DOI: 10.3390/antibiotics9100718
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 719: Relationship between Virulence and
           Resistance among Gram-Negative Bacteria

    • Authors: Virginio Cepas, Sara M. Soto
      First page: 719
      Abstract: Bacteria present in the human body are innocuous, providing beneficial functions, some of which are necessary for correct body function. However, other bacteria are able to colonize, invade, and cause damage to different tissues, and these are categorised as pathogens. These pathogenic bacteria possess several factors that enable them to be more virulent and cause infection. Bacteria have a great capacity to adapt to different niches and environmental conditions (presence of antibiotics, iron depletion, etc.). Antibiotic pressure has favoured the emergence and spread of antibiotic-resistant bacteria worldwide. Several studies have reported the presence of a relationship (both positive and negative, and both direct and indirect) between antimicrobial resistance and virulence among bacterial pathogens. This review studies the relationship among the most important Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) taking into account two points of view: (i) the effect the acquisition of resistance has on virulence, and (ii) co-selection of resistance and virulence. The relationship between resistance and virulence among bacteria depends on the bacterial species, the specific mechanisms of resistance and virulence, the ecological niche, and the host.
      Citation: Antibiotics
      PubDate: 2020-10-20
      DOI: 10.3390/antibiotics9100719
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 720: Effect of Fosfomycin on Cyclosporine
           Nephrotoxicity

    • Authors: Juan Antonio Ortega-Trejo, Rosalba Pérez-Villalva, José M. Arreola-Guerra, Victoria Ramírez, José Sifuentes-Osornio, Norma A Bobadilla
      First page: 720
      Abstract: Fosfomycin (Fos) has emerged as a potential treatment against multidrug-resistant organisms, however, there has been little work done on its influence on calcineurin inhibitor nephrotoxicity (CIN). This study was designed to evaluate the effect of Fos in combination with cyclosporine (CsA) on CIN. Two sets of experiments were undertaken. In the first, Wistar rats received different doses of Fos: 0, 62.5, 125, 250, and 500 mg/kg. In the second, rats were divided into four groups: control, CsA 15 mg/kg s.c., CsA + fosfomycin 62.5 mg/kg (CsA + LF), and CsA + Fos 500 mg/kg (CsA + HF). CsA was administrated daily for 14 days, whereas Fos administration started on the ninth day followed by two more doses, delivered 48 h apart. The administration of different Fos doses did not alter renal function. In contrast, CsA induced arteriolopathy, hypoperfusion, a reduction in the glomerular filtration rate, and downregulation of eNOS, angiotensinogen, and AT1R mRNA levels. Lower doses of Fos did not modify CIN. Instead, the CsA + HF group exhibited greater hypoperfusion, arteriolopathy, and oxidative stress, and increased mRNA levels of pro-inflammatory cytokines. This study shows that Fos administered by itself at different doses did not cause renal injury, but when it was given repeatedly at high dosages (500 mg/kg) in combination with CsA, it increased CIN through the promotion of greater oxidative stress and renal inflammation.
      Citation: Antibiotics
      PubDate: 2020-10-21
      DOI: 10.3390/antibiotics9100720
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 721: Editorial for the Special Issue: “Phage
           Therapy: A Biological Approach to Treatment of Bacterial Infections”

    • Authors: Saija Kiljunen
      First page: 721
      Abstract: The emergence of antibiotic-resistant bacteria presents a major challenge in terms of increased morbidity, mortality, and healthcare costs [...]
      Citation: Antibiotics
      PubDate: 2020-10-21
      DOI: 10.3390/antibiotics9100721
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 722: Antibiotic Adsorption by Metal-Organic
           Framework (UiO-66): A Comprehensive Kinetic, Thermodynamic, and
           Mechanistic Study

    • Authors: Mossab K. Alsaedi, Ghada K. Alothman, Mohammed N. Alnajrani, Omar A. Alsager, Sultan A. Alshmimri, Majed A. Alharbi, Majed O. Alawad, Shahad Alhadlaq, Seetah Alharbi
      First page: 722
      Abstract: Bacterial antibiotic resistance has been deemed one of the largest modern threats to human health. One of the root causes of antibiotic resistance is the inability of traditional wastewater management techniques, such as filtration and disinfection, to completely eliminate residual antibiotics from domestic and industrial effluents. In this study, we examine the ability of UiO-66; a metal-organic framework (MOF); in removing the antibiotic Doxycycline from aqueous environments. This study’s findings suggest that UiO-66 was able to remove nearly 90% of the initial Doxycycline concentration. To correlate the isothermal data, Langmuir and Freundlich models were used. It was determined that the Langmuir model was best suited. Pseudo-first and -second order models were examined for kinetic data, where the pseudo-second order model was best suited—consistent with the maximum theoretical adsorption capacity found by the Langumir model. Thermodynamic analysis was also examined by studying UiO-66 adsorption under different temperatures. Mechanisms of adsorption were also analyzed through measuring adsorption at varying pH levels, thermogravimetric analysis (TGA), Infrared spectroscopy (IR) and Brunauer–Emmet–Teller (BET). This study also explores the possibility of recycling MOFs through exposure to gamma radiation, heat, and heating under low pressure, in order for UiO-66 to be used in multiple, consecutive cycles of Doxycycline removal.
      Citation: Antibiotics
      PubDate: 2020-10-21
      DOI: 10.3390/antibiotics9100722
      Issue No: Vol. 9, No. 10 (2020)
       
  • Antibiotics, Vol. 9, Pages 723: Helicobacter pylori Primary and Secondary
           Genotypic Resistance to Clarithromycin and Levofloxacin Detection in
           Stools: A 4-Year Scenario in Southern Italy

    • Authors: Giuseppe Losurdo, Floriana Giorgio, Maria Pricci, Bruna Girardi, Francesco Russo, Giuseppe Riezzo, Manuela Martulli, Mariano Piazzolla, Francesco Cocomazzi, Francesco Abbruzzi, Elisabetta Parente, Rosa Paolillo, Alessia Mileti, Andrea Iannone, Mariabeatrice Principi, Enzo Ierardi, Alfredo Di Leo
      First page: 723
      Abstract: Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017–2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains.
      Citation: Antibiotics
      PubDate: 2020-10-21
      DOI: 10.3390/antibiotics9100723
      Issue No: Vol. 9, No. 10 (2020)
       
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
 


Your IP address: 54.236.35.159
 
Home (Search)
API
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-