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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 401 - 253 of 253 Journals sorted alphabetically
Microbial Drug Resistance     Hybrid Journal   (Followers: 3)
Molecular Informatics     Hybrid Journal   (Followers: 5)
Molecular Pharmacology     Hybrid Journal   (Followers: 2)
Molekul     Open Access   (Followers: 3)
Natural Product Communications     Open Access  
Nature Reviews Drug Discovery     Full-text available via subscription   (Followers: 320)
Naunyn-Schmiedeberg's Archives of Pharmacology     Hybrid Journal  
NeuroMolecular Medicine     Hybrid Journal  
Neuropharmacology     Hybrid Journal   (Followers: 5)
Neuropsychopharmacology     Hybrid Journal   (Followers: 17)
Neuropsychopharmacology Reports     Open Access  
Nigerian Journal of Natural Products and Medicine     Full-text available via subscription  
OA Drug Design & Delivery     Open Access  
OA Medical Hypothesis     Open Access  
Obesity Facts     Open Access   (Followers: 8)
Open Pharmacoeconomics & Health Economics Journal     Open Access   (Followers: 1)
Open Pharmacology Journal     Open Access  
OpenNano     Open Access   (Followers: 1)
Orbital - The Electronic Journal of Chemistry     Open Access   (Followers: 1)
Oriental Pharmacy and Experimental Medicine     Partially Free   (Followers: 2)
Pain and Therapy     Open Access   (Followers: 3)
Particulate Science and Technology: An International Journal     Hybrid Journal   (Followers: 1)
PDA Journal of Pharmaceutical Science and Technology     Full-text available via subscription   (Followers: 34)
Pediatric Drugs     Full-text available via subscription   (Followers: 3)
Pediatric Pharmacology     Open Access   (Followers: 1)
Pharmaceutica Analytica Acta     Open Access  
Pharmaceutical Biology     Open Access  
Pharmaceutical Care-La Farmacoterapia     Open Access  
Pharmaceutical Chemistry Journal     Hybrid Journal  
Pharmaceutical Development and Technology     Hybrid Journal   (Followers: 19)
Pharmaceutical Executive     Full-text available via subscription   (Followers: 2)
Pharmaceutical Fronts     Open Access   (Followers: 10)
Pharmaceutical Historian     Open Access  
Pharmaceutical Journal     Free   (Followers: 8)
Pharmaceutical Journal of Sri Lanka     Open Access  
Pharmaceutical Medicine     Full-text available via subscription   (Followers: 4)
Pharmaceutical Nanotechnology     Hybrid Journal  
Pharmaceutical Patent Analyst     Full-text available via subscription   (Followers: 3)
Pharmaceutical Research     Hybrid Journal   (Followers: 93)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 15)
Pharmaceutical Technology     Full-text available via subscription   (Followers: 7)
Pharmaceuticals     Open Access   (Followers: 4)
Pharmacia     Open Access  
Pharmaciana     Open Access  
PharmacoEconomics     Full-text available via subscription   (Followers: 26)
PharmacoEconomics & Outcomes News     Full-text available via subscription   (Followers: 3)
PharmacoEconomics German Research Articles     Full-text available via subscription  
PharmacoEconomics Spanish Research Articles     Hybrid Journal   (Followers: 1)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 33)
Pharmacogenetics and Genomics     Hybrid Journal   (Followers: 1)
Pharmacogenomics     Hybrid Journal   (Followers: 7)
Pharmacogenomics and Personalized Medicine     Open Access   (Followers: 2)
Pharmacogenomics Journal     Hybrid Journal   (Followers: 5)
Pharmacognosy Communications     Partially Free  
Pharmacognosy Magazine     Open Access   (Followers: 2)
Pharmacognosy Research     Open Access   (Followers: 2)
Pharmacological Reports     Hybrid Journal  
Pharmacological Research     Hybrid Journal   (Followers: 1)
Pharmacological Research - Modern Chinese Medicine     Open Access  
Pharmacological Reviews     Hybrid Journal   (Followers: 2)
Pharmacology     Full-text available via subscription  
Pharmacology & Therapeutics     Hybrid Journal   (Followers: 3)
Pharmacology & Pharmacy     Open Access   (Followers: 1)
Pharmacology Biochemistry and Behavior     Hybrid Journal   (Followers: 2)
Pharmacology Research & Perspectives     Open Access  
Pharmacon : Jurnal Farmasi Indonesia     Open Access  
Pharmacopsychiatry     Hybrid Journal   (Followers: 3)
Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 39)
Pharmactuel     Open Access   (Followers: 1)
Pharmacy     Open Access   (Followers: 4)
Pharmacy & Pharmacology     Open Access   (Followers: 1)
Pharmacy Education     Full-text available via subscription   (Followers: 11)
Pharmacy Practice (Internet)     Open Access   (Followers: 8)
Pharmakon : Arzneimittel in Wissenschaft und Praxis     Full-text available via subscription   (Followers: 1)
PharmaNutrition     Hybrid Journal   (Followers: 3)
PharmaTutor     Open Access  
Pharmazeutische Industrie     Full-text available via subscription   (Followers: 9)
Pharmazeutische Zeitung     Full-text available via subscription   (Followers: 11)
Pharmazie in Unserer Zeit (Pharmuz)     Hybrid Journal   (Followers: 10)
Physiology International     Full-text available via subscription   (Followers: 3)
Plant Products Research Journal     Full-text available via subscription  
Planta Medica     Hybrid Journal   (Followers: 4)
Planta Medica International Open     Open Access  
Prescriber     Hybrid Journal   (Followers: 9)
Progress in Neuro-Psychopharmacology and Biological Psychiatry     Hybrid Journal   (Followers: 8)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Psychopharmacology     Hybrid Journal   (Followers: 15)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
PZ Prisma : Materialien zur Fort- und Weiterbildung     Full-text available via subscription  
Redox Report     Open Access  
Regulatory Mechanisms in Biosystems     Open Access   (Followers: 1)
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 41)
Research & Reviews : A Journal of Drug Design & Discovery     Full-text available via subscription  
Research & Reviews : A Journal of Pharmaceutical Science     Full-text available via subscription  
Research & Reviews : A Journal of Pharmacognosy     Full-text available via subscription  
Research & Reviews : A Journal of Pharmacology     Full-text available via subscription   (Followers: 1)
Research in Pharmaceutical Sciences     Open Access   (Followers: 3)
Research in Social and Administrative Pharmacy     Hybrid Journal   (Followers: 3)
Research Journal of Pharmacognosy     Open Access  
Research Results in Pharmacology     Open Access  
Reviews of Physiology, Biochemistry and Pharmacology     Hybrid Journal   (Followers: 4)
Reviews on Clinical Pharmacology and Drug Therapy     Full-text available via subscription  
Revista Colombiana de Ciencias Químico-Farmacéuticas     Open Access  
Revista Cubana de Plantas Medicinales     Open Access   (Followers: 1)
Revista de Ciências Farmacêuticas Básica e Aplicada     Open Access  
Revista Mexicana de Ciencias Farmaceuticas     Open Access  
Revue de Médecine et de Pharmacie     Full-text available via subscription  
Safety and Risk of Pharmacotherapy     Open Access   (Followers: 1)
Saudi Pharmaceutical Journal     Open Access  
Scandinavian Journal of Clinical and Laboratory Investigation     Hybrid Journal   (Followers: 7)
Scientia Pharmaceutica     Open Access  
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Seminars in Oncology Nursing     Full-text available via subscription   (Followers: 10)
Separation Science plus (SSC plus)     Hybrid Journal  
Side Effects of Drugs Annual     Full-text available via subscription   (Followers: 2)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 6)
Substance Abuse : Research and Treatment     Open Access   (Followers: 5)
Suchttherapie     Hybrid Journal   (Followers: 1)
Sustainable Chemistry and Pharmacy     Full-text available via subscription   (Followers: 1)
Synfacts     Hybrid Journal   (Followers: 5)
SynOpen     Open Access  
The Botulinum J.     Hybrid Journal  
The Brown University Psychopharmacology Update     Hybrid Journal   (Followers: 2)
The Medical Letter     Full-text available via subscription   (Followers: 18)
The Pink Sheet     Full-text available via subscription   (Followers: 14)
The Pink Sheet Daily     Full-text available via subscription   (Followers: 4)
Therapeutic Advances in Drug Safety     Open Access   (Followers: 3)
Therapeutic Advances in Psychopharmacology     Open Access   (Followers: 4)
Therapeutic Advances in Vaccines     Hybrid Journal   (Followers: 1)
Therapeutic Drug Monitoring     Hybrid Journal   (Followers: 3)
Therapeutic Innovation & Regulatory Science     Hybrid Journal   (Followers: 7)
Thérapie     Full-text available via subscription   (Followers: 1)
TheScientist     Free   (Followers: 5)
Toxicological & Environmental Chemistry     Hybrid Journal   (Followers: 2)
Toxicological Research     Hybrid Journal  
Toxicological Sciences     Hybrid Journal   (Followers: 11)
Toxicology     Hybrid Journal   (Followers: 18)
Toxicology and Applied Pharmacology     Hybrid Journal   (Followers: 24)
Toxicology and Industrial Health     Hybrid Journal   (Followers: 6)
Toxicology in Vitro     Hybrid Journal   (Followers: 11)
Toxicology International     Full-text available via subscription   (Followers: 5)
Toxicology Letters     Hybrid Journal   (Followers: 15)
Toxicology Mechanisms and Methods     Hybrid Journal   (Followers: 7)
Toxicology Research     Partially Free   (Followers: 8)
Toxicon     Hybrid Journal   (Followers: 5)
Toxicon : X     Open Access  
Toxin Reviews     Hybrid Journal  
Translational Psychiatry     Open Access   (Followers: 15)
Trends in Peptide and Protein Sciences     Open Access  
Trends in Pharmacological Sciences     Full-text available via subscription   (Followers: 19)
Tropical Journal of Pharmaceutical Research     Open Access  
Ukrainian Biopharmaceutical Journal     Open Access  
Vascular Pharmacology     Hybrid Journal   (Followers: 2)
World Mycotoxin Journal     Hybrid Journal   (Followers: 3)
Yakugaku Zasshi     Open Access   (Followers: 1)
Zeitschrift für Phytotherapie     Hybrid Journal   (Followers: 1)
Актуальні питання фармацевтичної та медичної науки та практики     Open Access  
Фармацевтичний часопис     Open Access  

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

  This is an Open Access Journal Open Access journal
ISSN (Print) 2079-6382
Published by MDPI Homepage  [84 journals]
  • Antibiotics, Vol. 11, Pages 1005: Potential Pharmacokinetic Effect of
           Chicken Xenobiotic Receptor Activator on Sulfadiazine: Involvement of
           P-glycoprotein Induction

    • Authors: Mei Li, Ziyong Xu, Wang Lu, Liping Wang, Yujuan Zhang
      First page: 1005
      Abstract: Studies on pharmacokinetic drug–drug interactions have highlighted the importance of P-glycoprotein (P-gp) because of its involvement in substrate drug transport. This study aimed to investigate the role of chicken xenobiotic receptor (CXR) in the regulation of P-gp and its influences on pharmacokinetics of P-gp substrate sulfadiazine. ALAS1 and CYP2C45, the prototypical target genes of CXR, were used as a positive indicator for CXR activation in this study. Results show that ABCB1 gene expression was upregulated, and transporter activity was increased when exposed to the CXR activator metyrapone. Using ectopic expression techniques and RNA interference to manipulate the cellular CXR status, we confirmed that ABCB1 gene regulation depends on CXR. In vivo experiments showed that metyrapone induced ABCB1 in the liver, kidney, duodenum, jejunum and ileum of chickens. In addition, metyrapone significantly changed the pharmacokinetic behavior of orally administered sulfadiazine, with a Cmax (8.01 vs. 9.61 μg/mL, p < 0.05) and AUC0-t (31.46 vs. 45.59 h·mg/L, p < 0.01), as well as a higher T1/2λ (2.42 vs.1.67 h, p < 0.05), Cl/F (0.62 vs. 0.43 L/h/kg, p < 0.01) and Vz/F (2.16 vs.1.03 L/kg, p < 0.01). Together, our data suggest that CXR is involved in the regulation of P-gp, and, consequently, the CXR activator can affect, at least in part, the pharmacokinetic behavior of orally administered sulfadiazine.
      Citation: Antibiotics
      PubDate: 2022-07-26
      DOI: 10.3390/antibiotics11081005
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1007: Ceftazidime/Avibactam in
           Ventilator-Associated Pneumonia Due to Difficult-to-Treat Non-Fermenter
           Gram-Negative Bacteria in COVID-19 Patients: A Case Series and Review of
           the Literature

    • Authors: Giulia Jole Burastero, Gabriella Orlando, Antonella Santoro, Marianna Menozzi, Erica Franceschini, Andrea Bedini, Adriana Cervo, Matteo Faltoni, Erica Bacca, Emanuela Biagioni, Irene Coloretti, Gabriele Melegari, Jessica Maccieri, Stefano Busani, Elisabetta Bertellini, Massimo Girardis, Giulia Ferrarini, Laura Rofrano, Mario Sarti, Cristina Mussini, Marianna Meschiari
      First page: 1007
      Abstract: Ventilator-associated pneumonia (VAP) in critically ill patients with COVID-19 represents a very huge global threat due to a higher incidence rate compared to non-COVID-19 patients and almost 50% of the 30-day mortality rate. Pseudomonas aeruginosa was the first pathogen involved but uncommon non-fermenter gram-negative organisms such as Burkholderia cepacea and Stenotrophomonas maltophilia have emerged as other potential etiological causes. Against carbapenem-resistant gram-negative microorganisms, Ceftazidime/avibactam (CZA) is considered a first-line option, even more so in case of a ceftolozane/tazobactam resistance or shortage. The aim of this report was to describe our experience with CZA in a case series of COVID-19 patients hospitalized in the ICU with VAP due to difficult-to-treat (DTT) P. aeruginosa, Burkholderia cepacea, and Stenotrophomonas maltophilia and to compare it with data published in the literature. A total of 23 patients were treated from February 2020 to March 2022: 19/23 (82%) VAPs were caused by Pseudomonas spp. (16/19 DTT), 2 by Burkholderia cepacea, and 6 by Stenotrophomonas maltophilia; 12/23 (52.1%) were polymicrobial. Septic shock was diagnosed in 65.2% of the patients and VAP occurred after a median of 29 days from ICU admission. CZA was prescribed as a combination regimen in 86% of the cases, with either fosfomycin or inhaled amikacin or cotrimoxazole. Microbiological eradication was achieved in 52.3% of the cases and the 30-day overall mortality rate was 14/23 (60.8%). Despite the high mortality of critically ill COVID-19 patients, CZA, especially in combination therapy, could represent a valid treatment option for VAP due to DTT non-fermenter gram-negative bacteria, including uncommon pathogens such as Burkholderia cepacea and Stenotrophomonas maltophilia.
      Citation: Antibiotics
      PubDate: 2022-07-26
      DOI: 10.3390/antibiotics11081007
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1008: The Impact of Point-of-Care Blood
           C-Reactive Protein Testing on Prescribing Antibiotics in Out-of-Hours
           Primary Care: A Mixed Methods Evaluation

    • Authors: Sharon Dixon, Thomas R. Fanshawe, Lazaro Mwandigha, George Edwards, Philip J. Turner, Margaret Glogowska, Marjorie M. Gillespie, Duncan Blair, Gail N. Hayward
      First page: 1008
      Abstract: Improving prescribing antibiotics appropriately for respiratory infections in primary care is an antimicrobial stewardship priority. There is limited evidence to support interventions to reduce prescribing antibiotics in out-of-hours (OOH) primary care. Herein, we report a service innovation where point-of-care C-Reactive Protein (CRP) machines were introduced to three out-of-hours primary care clinical bases in England from August 2018–December 2019, which were compared with four control bases that did not have point-of-care CRP testing. We undertook a mixed-method evaluation, including a comparative interrupted time series analysis to compare monthly antibiotic prescription rates between bases with CRP machines and those without, an analysis of the number of and reasons for the tests performed, and qualitative interviews with clinicians. Antibiotic prescription rates declined during follow-up, but with no clear difference between the two groups of out-of-hours practices. A single base contributed 217 of the 248 CRP tests performed. Clinicians reported that the tests supported decision making and communication about not prescribing antibiotics, where having ‘objective’ numbers were helpful in navigating non-prescribing decisions and highlighted the challenges of training a fluctuant staff group and practical concerns about using the CRP machine. Service improvements to reduce prescribing antibiotics in out-of-hours primary care need to be developed with an understanding of the needs and context of this service.
      Citation: Antibiotics
      PubDate: 2022-07-26
      DOI: 10.3390/antibiotics11081008
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1009: Current and Potential Therapeutic
           Options for Infections Caused by Difficult-to-Treat and Pandrug Resistant
           Gram-Negative Bacteria in Critically Ill Patients

    • Authors: Helen Giamarellou, Ilias Karaiskos
      First page: 1009
      Abstract: Carbapenem resistance in Gram-negative bacteria has come into sight as a serious global threat. Carbapenem-resistant Gram-negative pathogens and their main representatives Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are ranked in the highest priority category for new treatments. The worrisome phenomenon of the recent years is the presence of difficult-to-treat resistance (DTR) and pandrug-resistant (PDR) Gram-negative bacteria, characterized as non-susceptible to all conventional antimicrobial agents. DTR and PDR Gram-negative infections are linked with high mortality and associated with nosocomial infections, mainly in critically ill and ICU patients. Therapeutic options for infections caused by DTR and PDR Gram-negative organisms are extremely limited and are based on case reports and series. Herein, the current available knowledge regarding treatment of DTR and PDR infections is discussed. A focal point of the review focuses on salvage treatment, synergistic combinations (double and triple combinations), as well as increased exposure regimen adapted to the MIC of the pathogen. The most available data regarding novel antimicrobials, including novel β-lactam-β-lactamase inhibitor combinations, cefiderocol, and eravacycline as potential agents against DTR and PDR Gram-negative strains in critically ill patients are thoroughly presented.
      Citation: Antibiotics
      PubDate: 2022-07-26
      DOI: 10.3390/antibiotics11081009
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1010: Tuning the Biological Activity of
           Camphorimine Complexes through Metal Selection

    • Authors: Joana P. Costa, Teresa Pinheiro, Maria S. Martins, M. Fernanda N. N. Carvalho, Joana R. Feliciano, Jorge H. Leitão, Rafaela A. L. Silva, Joana F. Guerreiro, Luís M. C. Alves, Inês Custódio, João Cruz, Fernanda Marques
      First page: 1010
      Abstract: The cytotoxic activity of four sets of camphorimine complexes based on the Cu(I), Cu(II), Ag(I), and Au(I) metal sites were assessed against the cisplatin-sensitive A2780 and OVCAR3 ovarian cancer cells. The results showed that the gold complexes were ca. one order of magnitude more active than the silver complexes, which in turn were ca. one order of magnitude more active than the copper complexes. An important finding was that the cytotoxic activity of the Ag(I) and Au(I) camphorimine complexes was higher than that of cisplatin. Another relevant aspect was that the camphorimine complexes did not interact significantly with DNA, in contrast with cisplatin. The cytotoxic activity of the camphorimine complexes displayed a direct relationship with the cellular uptake by OVCAR3 cells, as ascertained by PIXE (particle-induced X-ray emission). The levels of ROS (reactive oxygen species) formation exhibited an inverse relationship with the reduction potentials for the complexes with the same metal, as assessed by cyclic voltammetry. In order to gain insight into the toxicity of the complexes, their cytotoxicity toward nontumoral cells (HDF and V79 fibroblasts) was evaluated. The in vivo cytotoxicity of complex 5 using the nematode Caenorhabditis elegans was also assessed. The silver camphorimine complexes displayed the highest selectivity coefficients (activity vs. toxicity).
      Citation: Antibiotics
      PubDate: 2022-07-27
      DOI: 10.3390/antibiotics11081010
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1011: Genomics of Staphylococcus aureus
           Strains Isolated from Infectious and Non-Infectious Ocular Conditions

    • Authors: Madeeha Afzal, Ajay Kumar Vijay, Fiona Stapleton, Mark D. P. Willcox
      First page: 1011
      Abstract: Staphylococcus aureus is a major cause of ocular infectious (corneal infection or microbial keratitis (MK) and conjunctivitis) and non-infectious corneal infiltrative events (niCIE). Despite the significant morbidity associated with these conditions, there is very little data about specific virulence factors associated with the pathogenicity of ocular isolates. A set of 25 S. aureus infectious and niCIEs strains isolated from USA and Australia were selected for whole genome sequencing. Sequence types and clonal complexes of S. aureus strains were identified by using multi-locus sequence type (MLST). The presence or absence of 128 virulence genes was determined by using the virulence finder database (VFDB). Differences between infectious (MK + conjunctivitis) and niCIE isolates from USA and Australia for possession of virulence genes were assessed using the chi-square test. The most common sequence types found among ocular isolates were ST5, ST8 while the clonal complexes were CC30 and CC1. Virulence genes involved in adhesion (ebh, clfA, clfB, cna, sdrD, sdrE), immune evasion (chp, esaD, esaE, esxB, esxC, esxD), and serine protease enzymes (splA, splD, splE, splF) were more commonly observed in infectious strains (MK + conjunctivitis) than niCIE strains (p = 0.004). Toxin genes were present in half of infectious (49%, 25/51) and niCIE (51%, 26/51) strains. USA infectious isolates were significantly more likely to possess splC, yent1, set9, set11, set36, set38, set40, lukF-PV, and lukS-PV (p < 0.05) than Australian infectious isolates. MK USA strains were more likely to possesses yent1, set9, set11 than USA conjunctivitis strains (p = 0.04). Conversely USA conjunctivitis strains were more likely to possess set36 set38, set40, lukF-PV, lukS-PV (p = 0.03) than MK USA strains. The ocular strain set was then compared to 10 fully sequenced non-ocular S. aureus strains to identify differences between ocular and non-ocular isolates. Ocular isolates were significantly more likely to possess cna (p = 0.03), icaR (p = 0.01), sea (p = 0.001), set16 (p = 0.01), and set19 (p = 0.03). In contrast non-ocular isolates were more likely to possess icaD (p = 0.007), lukF-PV, lukS-PV (p = 0.01), selq (p = 0.01), set30 (p = 0.01), set32 (p = 0.02), and set36 (p = 0.02). The clones ST5, ST8, CC30, and CC1 among ocular isolates generally reflect circulating non-ocular pathogenic S. aureus strains. The higher rates of genes in infectious and ocular isolates suggest a potential role of these virulence factors in ocular diseases.
      Citation: Antibiotics
      PubDate: 2022-07-27
      DOI: 10.3390/antibiotics11081011
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1012: A Global Bibliometric Analysis on
           Antibiotic-Resistant Active Pulmonary Tuberculosis Over the Last 25 Years

    • Authors: Md Asiful Islam, Shoumik Kundu, Tengku Muhammad Hanis, Khalid Hajissa, Kamarul Imran Musa
      First page: 1012
      Abstract: Background: Tuberculosis (TB) is still a leading global cause of mortality and an increasingly crucial problem in fighting TB is antibiotic resistance. We aimed to conduct a bibliometric analysis on the articles of the past 25 years on antibiotic-resistant active pulmonary TB. Methods: Appropriate keywords were combined using the Boolean and wildcard operators and searched in Scopus database for articles published between 1996 and 2020 in English language. For all the bibliometric analyses, the Bibliometrix package in RStudio and Biblioshiny web apps were used. We identified the publication and citation trends, topmost cited documents, most productive authors, countries and institutions and most influential journals and funding agencies. We constructed collaborative networks of countries and co-citations. In addition, we developed a Three-Fields plot and a Thematic Map to explore different publication themes. Results: We included 7024 articles (88.9% research articles) and a persistently increasing publication and citation trends were evident throughout the past 25 years. Boehme 2010 was the most cited paper (1609 times cited), Stefan Niemann was the most productive author (86 papers), and ‘International Journal of Tuberculosis and Lung Disease’ was the leading journal. Centers for Disease Control and Prevention was the top contributing institution (3.7% papers) and both US- and UK-based funders were leading. The most productive countries were the USA, India, the UK, South Africa, and China and most of the collaborations took place between the USA, the UK, and South Africa. Conclusion: Undoubtedly, researchers and funders from the USA dominated followed by the UK in most of the fields in antibiotic-resistant TB research. The outcomes of antibiotic-resistant TB research would be more productive and translational if researchers from low- or middle-income countries (especially from Africa, South America and Asia) with high research productivity and TB burden could be in collaboration with high-income countries exhibiting low TB burden.
      Citation: Antibiotics
      PubDate: 2022-07-27
      DOI: 10.3390/antibiotics11081012
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1013: Genomic Analysis of Antibiotics
           Resistance in Pathogens

    • Authors: Teresa Nogueira
      First page: 1013
      Abstract: The emergence of antibiotic-resistant pathogens currently represents a serious threat to public health and the economy worldwide [...]
      Citation: Antibiotics
      PubDate: 2022-07-28
      DOI: 10.3390/antibiotics11081013
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1014: Interactions between Medical
           Plant-Derived Bioactive Compounds: Focus on Antimicrobial Combination

    • Authors: Natalia Vaou, Elisavet Stavropoulou, Chrysoula (Chrysa) Voidarou, Zacharias Tsakris, Georgios Rozos, Christina Tsigalou, Eugenia Bezirtzoglou
      First page: 1014
      Abstract: It is accepted that the medicinal use of complex mixtures of plant-derived bioactive compounds is more effective than purified bioactive compounds due to beneficial combination interactions. However, synergy and antagonism are very difficult to study in a meticulous fashion since most established methods were designed to reduce the complexity of mixtures and identify single bioactive compounds. This study represents a critical review of the current scientific literature on the combined effects of plant-derived extracts/bioactive compounds. A particular emphasis is provided on the identification of antimicrobial synergistic or antagonistic combinations using recent metabolomics methods and elucidation of approaches identifying potential mechanisms that underlie their interactions. Proven examples of synergistic/antagonistic antimicrobial activity of bioactive compounds are also discussed. The focus is also put on the current challenges, difficulties, and problems that need to be overcome and future perspectives surrounding combination effects. The utilization of bioactive compounds from medicinal plant extracts as appropriate antimicrobials is important and needs to be facilitated by means of new metabolomics technologies to discover the most effective combinations among them. Understanding the nature of the interactions between medicinal plant-derived bioactive compounds will result in the development of new combination antimicrobial therapies.
      Citation: Antibiotics
      PubDate: 2022-07-28
      DOI: 10.3390/antibiotics11081014
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1015: Is It Possible to Eradicate
           Carbapenem-Resistant Acinetobacter baumannii (CRAB) from Endemic

    • Authors: Filippo Medioli, Erica Bacca, Matteo Faltoni, Giulia Jole Burastero, Sara Volpi, Marianna Menozzi, Gabriella Orlando, Andrea Bedini, Erica Franceschini, Cristina Mussini, Marianna Meschiari
      First page: 1015
      Abstract: Background: Despite the global efforts to antagonize carbapenem-resistant Acinetobacter baumannii (CRAB) spreading, it remains an emerging threat with a related mortality exceeding 40% among critically ill patients. The purpose of this review is to provide evidence concerning the best infection prevention and control (IPC) strategies to fight CRAB spreading in endemic hospitals. Methods: The study was a critical review of the literature aiming to evaluate all available studies reporting IPC measures to control CRAB in ICU and outside ICU in both epidemic and endemic settings in the past 10 years. Results: Among the 12 included studies, the majority consisted of research reports of outbreaks mostly occurred in ICUs. The reported mortality reached 50%. Wide variability was observed related to the frequency of application of recommended CRAB IPC measures among the studies: environmental disinfection (100%); contact precautions (83%); cohorting staff and patients (75%); genotyping (66%); daily chlorhexidine baths (58%); active rectal screening (50%); closing or stopping admissions to the ward (33%). Conclusions: Despite effective control of CRAB spreading during the outbreaks, the IPC measures reported were heterogeneous and highly dependent on the different setting as well as on the structural characteristics of the wards. Reinforced ‘search and destroy’ strategies both on the environment and on the patient, proved to be the most effective measures for permanently eliminating CRAB spreading.
      Citation: Antibiotics
      PubDate: 2022-07-28
      DOI: 10.3390/antibiotics11081015
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1016: COVID-19 Secondary Infections in ICU
           Patients and Prevention Control Measures: A Preliminary Prospective
           Multicenter Study

    • Authors: Sergio Ruiz-Santana, María-Luisa Mora-Quintero, Pedro Saavedra, Raquel Montiel-González, Catalina Sánchez-Ramírez, Guillermo Pérez-Acosta, Mar Martín-Velasco, Cristóbal Rodríguez-Mata, José-Manuel Lorenzo-García, Dácil Parrilla-Toribio, Tanya Carrillo-García, Juan-Carlos Martín-González
      First page: 1016
      Abstract: The incidence of secondary infections in critically ill coronavirus disease 2019 (COVID-19) patients is worrisome. We investigated whether selective digestive decontamination (SDD) added to infection control measures during an intensive care unit (ICU) stay modified these infection rates. Methods: A retrospective observational cohort study was carried out in four ICUs in Spain. All consecutive ventilated patients with a SARS-CoV-2 infection engaged in national infection control programs between 1 March and 10 December 2020 were investigated. Patients were grouped into two cohorts according to the site of ICU admission. Secondary relevant infections were included. Infection densities corresponding to ventilator-associated pneumonia (VAP), catheter bacteremia, secondary bacteremia, and multi-resistant germs were obtained as the number of events per 1000 days of exposure and were compared between SDD and non-SDD groups using Poisson regression. Factors that had an independent association with mortality were identified using multidimensional logistic analysis. Results: There were 108 patients in the SDD cohort and 157 in the non-SDD cohort. Patients in the SDD cohort showed significantly lower rates (p < 0.001) of VAP (1.9 vs. 9.3 events per 1000 ventilation days) and MDR infections (0.57 vs. 2.28 events per 1000 ICU days) and a non-significant reduction in secondary bacteremia (0.6 vs. 1.41 events per 1000 ICU days) compared with those in the non-SDD cohort. Infections caused by MDR pathogens occurred in 5 patients in the SDD cohort and 21 patients in the non-SDD cohort (p = 0.006). Differences in mortality according to SDD were not found. Conclusion: The implementation of SDD in infection control programs significantly reduced the incidence of VAP and MDR infections in critically ill SARS-CoV-2 infected patients.
      Citation: Antibiotics
      PubDate: 2022-07-28
      DOI: 10.3390/antibiotics11081016
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1017: Antioxidant and Antimicrobial Properties
           of Helichrysum italicum (Roth) G. Don Hydrosol

    • Authors: Katja Bezek, Katja Kramberger, Darja Barlič-Maganja
      First page: 1017
      Abstract: (1) Background: According to the emergence and spread of antibiotic resistance, there is an urge for new promising substances. The purpose of the study was to test the antioxidant, cytotoxic and antimicrobial properties of the Helichrysum italicum (Roth) G. Don essential oil (EO) and hydrosol. (2) Methods: The antioxidant potential was determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. The cytotoxicity for human skin and intestinal cells was tested using primary and immortalized cell line models. The minimum inhibitory concentration (MIC) of hydrosol was then determined for six bacterial strains covering four commonly reported food pathogens. Further on, the hydrosol at a concentration of 1/8 MIC was used to test the antiadhesive effect by the crystal violet (CV) staining method. (3) Results: the EO showed a 100-times higher antioxidant and 180- to 25.000-times higher cytotoxic activity, when compared to hydrosol. Nevertheless, all bacterial strains, with the exception of Staphylococcus aureus, were sensitive to hydrosol in the range of 12.5 % (V/V) for Campylobacter jejuni, to MIC values of 100 % (V/V) for Escherichia coli and Pseudomonas aeruginosa. The antiadhesive potential of hydrosol was also shown. (4) Conclusions: Even though hydrosols are a by-product of the EO distillation process, they possess valuable biological activities.
      Citation: Antibiotics
      PubDate: 2022-07-28
      DOI: 10.3390/antibiotics11081017
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1018: Impact of the COVID-19 Pandemic on
           Antibiotic Prescribing by Dentists in Galicia, Spain: A Quasi-Experimental

    • Authors: Almudena Rodríguez-Fernández, Olalla Vázquez-Cancela, María Piñeiro-Lamas, Adolfo Figueiras, Maruxa Zapata-Cachafeiro
      First page: 1018
      Abstract: Background: Antibiotic resistance is one of the most pressing public health problems. Health authorities, patients, and health professionals, including dentists, are all involved in its development. COVID-19 pandemic restrictions on dental care may have had repercussions on antibiotic prescribing by dentists. The aim of this study was to assess the impact of the COVID-19 pandemic on antibiotic prescribing by dentists, and to review antibiotic consumption according to the WHO Access, Watch, Reserve classification. We conducted a natural, before-and-after, quasi-experimental study, using antibiotic prescription data covering the period from January 2017 to May 2021. A segmented regression analysis with interrupted time series data was used to analyse the differences between the numbers of defined daily doses (DDD) of antibiotics prescribed monthly. The outcomes showed an immediate significant decrease in overall antibiotic prescribing by primary-care dentists during lockdown, followed by a non-significant upward trend for the next year. This same pattern was, likewise, observed for Access and Watch antibiotics. COVID-19 pandemic restrictions on dental care influenced the prescription of antibiotics. During confinement, an initial decrease was observed, this trend changed when in person consultations were recovered. It might be beneficial to analyse the prescription of antibiotics using the WHO AWaRe classification, in order to monitor their appropriate use.
      Citation: Antibiotics
      PubDate: 2022-07-29
      DOI: 10.3390/antibiotics11081018
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1019: Arctic Psychrotolerant Pseudomonas sp.
           B14-6 Exhibits Temperature-Dependent Susceptibility to Aminoglycosides

    • Authors: Minjeong Kang, Tae-Rim Choi, Soyeon Ahn, Hee Young Heo, Hyerim Kim, Hye Soo Lee, Yoo Kyung Lee, Hwang-Soo Joo, Philip S. Yune, Wooseong Kim, Yung-Hun Yang
      First page: 1019
      Abstract: Bacteria can evade antibiotics by acquiring resistance genes, as well as switching to a non-growing dormant state without accompanying genetic modification. Bacteria in this quiescent state are called persisters, and this non-inheritable ability to withstand multiple antibiotics is referred to as antibiotic tolerance. Although all bacteria are considered to be able to form antibiotic-tolerant persisters, the antibiotic tolerance of extremophilic bacteria is poorly understood. Previously, we identified the psychrotolerant bacterium Pseudomonas sp. B14-6 from the glacier foreland of Midtre Lovénbreen in High Arctic Svalbard. Herein, we investigated the resistance and tolerance of Pseudomonas sp. B14-6 against aminoglycosides at various temperatures. This bacterium was resistant to streptomycin and susceptible to apramycin, gentamicin, kanamycin, and tobramycin. The two putative aminoglycoside phosphotransferase genes aph1 and aph2 were the most likely contributors to streptomycin resistance. Notably, unlike the mesophilic Pseudomonas aeruginosa PA14, this cold-adapted bacterium demonstrated reduced susceptibility to all tested aminoglycosides in a temperature-dependent manner. Pseudomonas sp. B14-6 at a lower temperature formed the persister cells that shows tolerance to the 100-fold minimum inhibitory concentration (MIC) of gentamicin, as well as the partially tolerant cells that withstand 25-fold MIC gentamicin. The temperature-dependent gentamicin tolerance appears to result from reduced metabolic activity. Lastly, the partially tolerant Pseudomonas sp. B14-6 cells could slowly proliferate under the bactericidal concentrations of aminoglycosides. Our results demonstrate that Pseudomonas sp. B14-6 has a characteristic ability to form cells with a range of tolerance, which appears to be inversely proportional to its growth rate.
      Citation: Antibiotics
      PubDate: 2022-07-29
      DOI: 10.3390/antibiotics11081019
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1020: Effects of Enrofloxacin on the Epiphytic
           Algal Communities Growing on the Leaf Surface of Vallisneria natans

    • Authors: Qi Chen, Luqi Jin, Yuan Zhong, Gaohua Ji
      First page: 1020
      Abstract: Enrofloxacin (ENR) is a member of quinolones, which are extensively used in livestock farming and aquaculture to fight various bacterial diseases, but its residues are partially transferred to surface water and affect the local aquatic ecosystem. There are many studies on the effect of ENR on the growth of a single aquatic species, but few on the level of the aquatic community. Epiphytic algae, which are organisms attached to the surface of submerged plants, play an important role in the absorption of nitrogen and phosphorus in the ecological purification pond which are mainly constructed by submerged plants, and are commonly used in aquaculture effluent treatment. Enrofloxacin (ENR) is frequently detected in aquaculture ponds and possibly discharged into the purification pond, thus imposing stress on the pond ecosystem. Here, we performed a microcosm experiment to evaluate the short-term effects of pulsed ENR in different concentrations on the epiphytic algal communities growing on Vallisneria natans. Our results showed an overall pattern of “low-dose-promotion and high-dose-inhibition”, which means under low and median ENR concentrations, the epiphytic algal biomass was promoted, while under high ENR concentrations, the biomass was inhibited. This pattern was mainly attributed to the high tolerance of filamentous green algae and yellow-green algae to ENR. Very low concentrations of ENR also favored the growth of diatoms and cyanobacteria. These results demonstrate a significant alteration of epiphytic algal communities by ENR and also spark further research on the potential use of filamentous green algae for the removal of ENR in contaminated waters because of its high tolerance.
      Citation: Antibiotics
      PubDate: 2022-07-29
      DOI: 10.3390/antibiotics11081020
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1021: The Monitoring of Mycoplasma
           gallisepticum Minimum Inhibitory Concentrations during the Last Decade
           (2010–2020) Seems to Reveal a Comeback of Susceptibility to
           Macrolides, Tiamulin, and Lincomycin

    • Authors: Marco Bottinelli, Michele Gastaldelli, Micaela Picchi, Arianna Dall’Ora, Lorena Cristovao Borges, Ana Sofía Ramírez, Andrea Matucci, Salvatore Catania
      First page: 1021
      Abstract: Mycoplasma gallisepticum (Mg) is a highly contagious avian pathogen responsible for significant economic losses for the poultry industry. In some circumstances, antimicrobial treatment is useful to contain clinical signs of Mg infection in birds. However, antimicrobial resistance emergence is now common among animal pathogens, becoming a worldwide health concern. The collection of minimum inhibitory concentration (MIC) data is fundamental for an appropriate antimicrobial use and for fighting antimicrobial resistance emergence. However, MIC data can only be generated in specialized laboratories, and therefore they are not regularly available. MICs of 67 non-vaccine-derived Mg isolates collected in Italy between 2010 and 2020 were obtained. Although 79.1% of the Mg isolates showed enrofloxacin MICs ≥ 8 µg/mL, a statistically significant trend toward low MICs of erythromycin, tylosin, tilmicosin, spiramycin, tiamulin, and lincomycin was observed, indicating a comeback to susceptibility of Mg toward these drugs. Doxycycline proved to be slightly more effective than oxytetracycline. The present study shows that Mg changed its susceptibility toward many of the drugs most commonly used for its containment over a ten-year period.
      Citation: Antibiotics
      PubDate: 2022-07-29
      DOI: 10.3390/antibiotics11081021
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1022: Advances in Integrated Antimicrobial
           Resistance Surveillance and Control Strategies in Asia-Pacific Economic
           Cooperation Economies: Assessment of a Multiyear Building Capacity Project

    • Authors: Javiera Cornejo, Gabriela Asenjo, Sebastian Zavala, Lucas Venegas, Nicolás Galarce, Juan Carlos Hormazábal, Constanza Vergara-E, Lisette Lapierre
      First page: 1022
      Abstract: Antimicrobial resistance (AMR) is a growing global health concern for both animal and public health, and collaborative strategies are needed to combat the threat. The level of awareness and funding for policies focused on reducing AMR varies between countries. The aim of this study was to compare the integrated surveillance systems for AMR in high and low–middle economies of the Asia-Pacific Economic Cooperation and determine whether there was any improvement from 2015 to 2018. We conducted a survey with a group of 21 countries at different development levels. Associations between the economic development level and the questions of AMR awareness and funding were established using Fisher’s exact test. Improvements were identified where countries established public policies for integrated surveillance of AMR. High economies showed greater advancement in several topics related to AMR than low–middle economies. The survey revealed that there is a better understanding surrounding the implications of the emergence of AMR in human medicine than in veterinary medicine, agriculture, and food production. Our results show that countries enhanced overall AMR surveillance over the 4-year-period; however, more research is needed concerning these advances, especially in low–middle economies and the food production sector.
      Citation: Antibiotics
      PubDate: 2022-07-29
      DOI: 10.3390/antibiotics11081022
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1023: Susceptibility of Meropenem-Resistant
           and/or Carbapenemase-Producing Clinical Isolates of Enterobacterales
           (Enterobacteriaceae) and Pseudomonas aeruginosa to Ceftazidime-Avibactam
           and Ceftolozane-Tazobactam as Assessed by In Vitro Testing Methods

    • Authors: Venere Cortazzo, Brunella Posteraro, Giulia Menchinelli, Flora Marzia Liotti, Tiziana D’Inzeo, Barbara Fiori, Francesco Luzzaro, Maurizio Sanguinetti, Teresa Spanu
      First page: 1023
      Abstract: This study aimed to assess the comparability of in vitro susceptibility testing methods to ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T). Meropenem-resistant and/or carbapenemase-producing clinical isolates of Enterobacterales (Enterobacteriaceae) and Pseudomonas aeruginosa were tested by both bioMérieux ETEST and VITEK-2 AST-N397 card and compared with a Micronaut AST-system broth microdilution (BMD) method. CZA and C/T MICs were interpreted using EUCAST breakpoints. Of the 153 Enterobacteriaceae isolates, 55.6% and 0.0% (VITEK 2) and 56.9% and 0.0% (ETEST and BMD) were susceptible to CZA and C/T, respectively. Of 52 P. aeruginosa isolates, 50.0% and 40.4% (VITEK 2, ETEST, and BMD) were susceptible to CZA and C/T, respectively. The essential agreement (EA) was 96.1% (197/205; VITEK 2 versus BMD) and 95.6% (196/205; ETEST versus BMD) for CZA testing, whereas EA was 98.0% (201/205; VITEK 2 versus BMD) and 96.6% (198/205; ETEST versus BMD) for C/T testing. The categorical agreement (CA) was 98.0% (201/205; VITEK 2 versus BMD) and 100% (ETEST versus BMD) for CZA testing, whereas CA was 100% (VITEK 2 versus BMD) and 100% (ETEST versus BMD) for C/T testing. Categorical errors regarded four Enterobacteriaceae isolates. VITEK 2 and ETEST yielded equivalent CZA and C/T susceptibility testing results, compared to the BMD method, in such a clinical context.
      Citation: Antibiotics
      PubDate: 2022-07-29
      DOI: 10.3390/antibiotics11081023
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1024: Study the Effect of Conjugate Novel
           Ultra-Short Antimicrobial Peptide with Silver Nanoparticles against
           Methicillin Resistant S. aureus and ESBL E. coli

    • Authors: Rula M. Darwish, Ali H. Salama
      First page: 1024
      Abstract: Background: Bacterial resistance is a challenging limitation in infection treatment. This work evaluates the potential antibacterial activity of conjugation of Tryasine peptide with silver nanoparticles against selected pathogens. Materials and Methods: The peptide Tryasine was produced using three subunits of tryptophan and three lysine amino acids, then its purity was determined by reverse-phase high-performance liquid chromatography. The peptide was confirmed using mass spectrometry and electrospray ionization mass spectrometry. Silver nanoparticles conjugate with Tryasine was synthesized by adding Tryasine-silver nitrate solution in the presence of the reducing agent sodium borohydride. The presence of Tryasine-silver nanoparticles was indicated by the yellow-brown color and was further confirmed through ultraviolet-visible spectrophotometry. The minimum inhibitory and minimum bactericidal concentrations for Tryasine nanoparticles were determined against Staphylococcus aureus, Escherichia coli, methicillin resistant Staphylococcus aureus, and ESBL Escherichia coli using the microdilution method. Toxicity for nanoparticles conjugated with Tryasine was determined using erythrocyte hemolytic assay. Results: Tryasine alone was effective (MIC around 100 and 200 μM) against standard and resistant strains of bacteria used. However, Tryasine-silver nanoparticles were more effective with MICs ranging from 30 to 100 μM depending on the bacterial strain used. Tryasine-silver nanoparticles at concentration of 100 μM only caused 1% hemolysis on human erythrocytes after 30 min of incubation. Conclusions: The findings indicate that Tryasine-silver nanoparticles had good antibacterial activity against pathogenic strains of Gram-positive and Gram-negative bacteria. Additionally, the conjugate showed low hemolytic activity and cytotoxicity. Therefore, conjugation of Tryasine with silver nanoparticles is a promising treatment candidate for bacterial infection with low toxicity.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081024
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1025: Status of Microbiota in Odontogenic
           Inflammatory Lesions and Dental Surgery Procedures Performed on an
           Outpatient Basis

    • Authors: Tadeusz Morawiec, Joanna Śmieszek-Wilczewska, Mateusz Bogacz, Magdalena Jędrusik-Pawłowska, Anna Bubiłek-Bogacz, Anna Mertas
      First page: 1025
      Abstract: Inflammations of the facial part of the skull are most commonly caused by a bacterial infection. They are a frequently occurring pathological process, which results from a rich bacterial flora of the oral cavity, as well as diseased teeth and periodontal tissues. These inflammations have a primarily mixed character with the prevalence of anaerobic bacteria. Gangrene of the dental pulp is the most common odontogenic cause. In the case of inflammations of oral tissues an early and corrective treatment results in quick recovery. The purpose of this work was to assess the efficiency of empirical antibiotic therapy applied in patients with inflammations of oral tissues on the basis of a drug susceptibility profile of bacteria isolated from material extracted from inflammatory lesions. The research material consisted of smears collected from patients with existing acute inflammations in the oral cavity. The smear was collected from the bottom of the lesion after its prior surgical treatment and pus evacuation, and again, 7 days after surgery. In patients with acute odontogenic inflammations the recommended first-line therapy are extended-spectrum penicillins, characterized by a low risk of side effects and strong antimicrobial activity. In the study group, both clindamycin and amoxicillin exhibited high efficiency in treating acute odontogenic inflammatory lesions in the oral cavity.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081025
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1026: Synthesis and Biological Evaluation of
           Novel Fusidic Acid Derivatives as Two-in-One Agent with Potent
           Antibacterial and Anti-Inflammatory Activity

    • Authors: Borong Tu, Nana Cao, Bingjie Zhang, Wende Zheng, Jiahao Li, Xiaowen Tang, Kaize Su, Jinxuan Li, Zhen Zhang, Zhenping Yan, Dongli Li, Xi Zheng, Kun Zhang, Weiqian David Hong, Panpan Wu
      First page: 1026
      Abstract: Fusidic acid (FA), a narrow-spectrum antibiotics, is highly sensitive to various Gram-positive cocci associated with skin infections. It has outstanding antibacterial effects against certain Gram-positive bacteria whilst no cross-resistance with other antibiotics. Two series of FA derivatives were synthesized and their antibacterial activities were tested. A new aromatic side-chain analog, FA-15 exhibited good antibacterial activity with MIC values in the range of 0.781–1.563 µM against three strains of Staphylococcus spp. Furthermore, through the assessment by the kinetic assay, similar characteristics of bacteriostasis by FA and its aromatic derivatives were observed. In addition, anti-inflammatory activities of FA and its aromatic derivatives were evaluated by using a 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse ear edema model. The results also indicated that FA and its aromatic derivatives effectively reduced TPA-induced ear edema in a dose-dependent manner. Following, multiform computerized simulation, including homology modeling, molecular docking, molecular dynamic simulation and QSAR was conducted to clarify the mechanism and regularity of activities. Overall, the present work gave vital clues about structural modifications and has profound significance in deeply scouting for bioactive potentials of FA and its derivatives.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081026
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1027: Antimicrobial Stewardship at Transitions
           of Care to Outpatient Settings: Synopsis and Strategies

    • Authors: Elaine Liu, Kristin E. Linder, Joseph L. Kuti
      First page: 1027
      Abstract: Inappropriate antibiotic use and associated consequences, including pathogen resistance and Clostridioides difficile infection, continue to serve as significant threats in the United States, with increasing incidence in the community setting. While much attention has been granted towards antimicrobial stewardship in acute care settings, the transition to the outpatient setting represents a significant yet overlooked area to target optimized antimicrobial utilization. In this article, we highlight notable areas for improved practices and present an interventional approach to stewardship tactics with a framework of disease, drug, dose, and duration. In doing so, we review current evidence regarding stewardship strategies at transitional settings, including diagnostic guidance, technological clinical support, and behavioral and educational approaches for both providers and patients.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081027
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1028: Assessment of the Impact of a
           Meningitis/Encephalitis Panel on Hospital Length of Stay: A Systematic
           Review and Meta-Analysis

    • Authors: Kyle D. Hueth, Philippe Thompson-Leduc, Todor I. Totev, Katherine Milbers, Tristan T. Timbrook, Noam Kirson, Rodrigo Hasbun
      First page: 1028
      Abstract: Meningitis and encephalitis are central nervous system infections with considerable morbidity and mortality. The BioFire® FilmArray® Meningitis/Encephalitis Panel (multiplex ME panel) can identify pathogens rapidly potentially aiding in targeted therapy and curtail antimicrobial exposure. This systematic review and meta-analysis synthesized the literature on the association between the multiplex ME panel and length of hospital stay (LOS), length of acyclovir therapy, and days with antibiotics. MEDLINE and EMBASE were searched. Only studies presenting novel data were retained. Random-effects meta-analyses were performed to assess the impact of the multiplex ME panel on outcomes. Of 169 retrieved publications, 13 met the criteria for inclusion. Patients tested with the multiplex ME panel had a reduction in the average LOS (mean difference [MD] [95% CI]: −1.20 days [−1.96, −0.44], n=11 studies). Use of the multiplex ME panel was also associated with a reduction in the length of acyclovir therapy (MD [95% CI]: −1.14 days [−1.78, −0.50], n=7 studies) and a nonsignificant reduction in the average number of days with antibiotics (MD [95% CI]: −1.01 days [−2.39, 0.37], n=6 studies). The rapidity of pathogen identification contributes to an overall reduced LOS, reductions in the duration of empiric antiviral utilization, and a nonsignificant reduction in antibiotic therapy.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081028
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1029: Evaluation of Recombinant Bovine
           Interleukin-8 (rbIL-8) as a Treatment for Chronic Intramammary Infection
           in Dairy Cows

    • Authors: Phillip M. G. Peixoto, Lais L. Cunha, Leonardo Barbosa, Wilson Coelho, Giorgia Podico, Rodrigo C. Bicalho, Igor F. Canisso, Fabio S. Lima
      First page: 1029
      Abstract: Mastitis is one of the main contributors to antimicrobial resistance in livestock, so alternative therapies are being investigated to address it. The present study assessed the capability of recombinant bovine interleukin-8 (rbIL-8) to improve neutrophil function in the mammary gland and resolve chronic high somatic cell count (SCC) in Holstein cows. Multiparous cows (n = 8) with more than 300,000 SCC per mL were allocated to one of two intramammary infusions: saline (10 mL of saline solution) or rbIL-8 (1.57 mg/mL of recombinant bovine IL-8 diluted in 9 mL of saline). In addition, there was an untreated control group (n = 2, SCC < 300,000 SCC/mL). Milk samples were collected post-treatment at 0, 4, 8, 12, 24, 48, and 144 h to quantify milk SCC, haptoglobin, and IgG concentrations. Neutrophil’s phagocytosis in milk and blood was evaluated via flow cytometry at 0, 24, and 48 h. The log of SCC did not differ between the infused groups (p = 0.369). Neutrophils presented a similar log of cells with high fluorescence for propidium-iodide (PI) and dihydrorhodamine (DHR) in milk (p = 0.412) and blood samples (p = 0.766) in both infused groups. Intramammary infusion of 1.57 mg/mL of rbIL-8 did not improve neutrophils response and failed to resolve chronic high SCC.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081029
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1030: Characterization of blaNDM-5-and
           blaCTX-M-199-Producing ST167 Escherichia coli Isolated from Shared Bikes

    • Authors: Qiyan Chen, Zhiyu Zou, Chang Cai, Hui Li, Yang Wang, Lei Lei, Bing Shao
      First page: 1030
      Abstract: Shared bikes as a public transport provide convenience for short-distance travel. Whilst they also act as a potential vector for antimicrobial resistant (AR) bacteria and antimicrobial resistance genes (ARGs). However, the understanding of the whole genome sequence of AR strains and ARGs-carrying plasmids collected from shared bikes is still lacking. Here, we used the HiSeq platform to sequence and analyze 24 Escherichia coli isolated from shared bikes around Metro Stations in Beijing. The isolates from shared bikes showed 14 STs and various genotypes. Two blaNDM-5 and blaCTX-M-199-producing ST167 E. coli have 16 resistance genes, four plasmid types and show >95% of similarities in core genomes compared with the ST167 E. coli strains from different origins. The blaNDM-5- or blaCTX-M-199-carrying plasmids sequencing by Nanopore were compared to plasmids with blaNDM-5- or blaCTX-M-199 originated from humans and animals. These two ST167 E. coli show high similarities in core genomes and the plasmid profiles with strains from hospital inpatients and farm animals. Our study indicated that ST167 E. coli is retained in diverse environments and carried with various plasmids. The analysis of strains such as ST167 can provide useful information for preventing or controlling the spread of AR bacteria between animals, humans and environments.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081030
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1031: Genomic Characterization of
           International High-Risk Clone ST410 Escherichia coli Co-Harboring
           ESBL-Encoding Genes and blaNDM-5 on IncFIA/IncFIB/IncFII/IncQ1

    • Authors: Nelly M. Mohamed, Azza S. Zakaria, Eva A. Edward
      First page: 1031
      Abstract: The accelerated dispersion of multidrug-resistant (MDR) Escherichia coli due to the production of extended-spectrum β-lactamases (ESBLs) or AmpC enzymes has been noted in Egypt, presenting a serious treatment challenge. In this study, we investigate the prevalence of ESBLs and AmpC enzymes among 48 E. coli isolates collected from patients with urinary tract infections admitted to a teaching hospital in Alexandria. Phenotypic and genotypic methods of detection are conducted. Isolates producing both enzymes are tested for the mobilization of their genes by a broth mating experiment. Whole genome sequencing (WGS) is performed for isolate EC13655. The results indicate that 80% of the isolates are MDR, among which 52% and 13% were ESBL and AmpC producers, respectively. Conjugation experiments fail to show the mobilization of blaCMY-2 in EC13655, which was chosen for WGS. In silico analysis reveals that the isolate belongs to a ST410-H24Rx high-risk clone. It coharbors the ESBL-encoding genes blaCTX-M-15, blaTEM-1, and blaOXA-1 on an IncFIA/IncFIB/IncFII/IncQ1 multireplicon plasmid. The chromosomal location of blaCMY-2 is detected with a flanking upstream copy of ISEcp1. This chromosomal integration of blaCMY-2 establishes the stable maintenance of the gene and thus, necessitates an imperative local surveillance to reduce further spread of such strains in different clinical settings.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081031
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1032: Antibiotic Resistance Risk with Oral
           Tetracycline Treatment of Acne Vulgaris

    • Authors: Madisen A. Swallow, Ryan Fan, Jeffrey M. Cohen, Christopher G. Bunick
      First page: 1032
      Abstract: Almost 1 billion people worldwide have acne, and oral tetracyclines, including doxycycline and minocycline, are effective and frequently prescribed treatments for acne. However, there is growing concern for the development of antibiotic resistance with such widespread utilization by dermatologists. Additionally, tetracyclines are known to have various potential side effects, including gut dysbiosis, gastrointestinal upset, photosensitivity, dizziness, and vertigo. However, in 2018 a novel narrow-spectrum tetracycline, sarecycline, was Food and Drug Administration-approved to treat moderate-to-severe acne vulgaris in patients 9-years-old and above. Sarecycline was designed to target Cutibacterium acnes, the pathogenic bacterium in acne vulgaris, which may reduce the risk of resistance. This paper examines the growing concerns of antibiotic resistance due to oral tetracycline usage in the treatment of acne vulgaris, with a focus on the promising third-generation, narrow-spectrum tetracycline, sarecycline.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081032
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1033: Treatment Heterogeneity in Pseudomonas
           aeruginosa Pneumonia

    • Authors: Aisling R. Caffrey, Haley J. Appaneal, J. Xin Liao, Emily C. Piehl, Vrishali Lopes, Laura A. Puzniak
      First page: 1033
      Abstract: We have previously identified substantial antibiotic treatment heterogeneity, even among organism-specific and site-specific infections with treatment guidelines. Therefore, we sought to quantify the extent of treatment heterogeneity among patients hospitalized with P. aeruginosa pneumonia in the national Veterans Affairs Healthcare System from Jan-2015 to Apr-2018. Daily antibiotic exposures were mapped from three days prior to culture collection until discharge. Heterogeneity was defined as unique patterns of antibiotic treatment (drug and duration) not shared by any other patient. Our study included 5300 patients, of whom 87.5% had unique patterns of antibiotic drug and duration. Among patients receiving any initial antibiotic/s with a change to at least one anti-pseudomonal antibiotic (n = 3530, 66.6%) heterogeneity was 97.2%, while heterogeneity was 91.5% in those changing from any initial antibiotic/s to only anti-pseudomonal antibiotics (n = 576, 10.9%). When assessing heterogeneity of anti-pseudomonal antibiotic classes, irrespective of other antibiotic/s received (n = 4542, 85.7%), 50.5% had unique patterns of antibiotic class and duration, with median time to first change of three days, and a median of two changes. Real-world evidence is needed to inform the development of treatment pathways and antibiotic stewardship initiatives based on clinical outcome data, which is currently lacking in the presence of such treatment heterogeneity.
      Citation: Antibiotics
      PubDate: 2022-07-30
      DOI: 10.3390/antibiotics11081033
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1034: Tetracycline, Macrolide and Lincosamide
           Resistance in Streptococcus canis Strains from Companion Animals and Its
           Genetic Determinants

    • Authors: Ilona Stefańska, Ewelina Kwiecień, Magdalena Kizerwetter-Świda, Dorota Chrobak-Chmiel, Magdalena Rzewuska
      First page: 1034
      Abstract: Growing antimicrobial resistance (AMR) in companion-animal pathogens, including Streptococcus canis (S. canis), is a significant concern for pet treatment as well for public health. Despite the importance of S. canis in veterinary and human medicine, studies concerning the AMR of this bacterium are still scarce. A total of 65 S. canis strains, isolated from dogs and cats, were assessed to test for susceptibility to six clinically relevant antimicrobials via a microdilution method. The prevalence of the selected acquired-resistance genes was also investigated via PCR. High MIC50 and MIC90 values (≥128 μg/mL) were noted for tetracycline, erythromycin and clindamycin. Only a few strains were resistant to the tested beta-lactams (6.2%). Tetracycline resistance was found in 66.2% of the strains. Resistance to erythromycin and clindamycin (ML resistance) was found in 55.4% of the strains. Strains with a phenotype showing concurrent resistance to tetracycline and ML were predominant (53.8%). AMR in the tested S. canis strains was associated with a variety of acquired and potentially transferable genes. Tetracycline resistance was conferred by tet(O) (40.0%), tet(M) (9.2%), and tet(T) (1.5%), which is reported for the first time in S. canis. In most cases, the tet(M) gene was detected in relation to the conjugative transposon Tn916. The MLSB phenotype was confirmed in the strains harboring erm(B) (43.1%) and erm(TR) (7.7%). To conclude, a high rate of S. canis strains occurring in dogs and cats displayed resistance to antimicrobials important for treatment; moreover, they are a potential reservoirs of various resistance determinants. Therefore, AMR in these pathogens should be continuously monitored, especially regarding the One Health concept.
      Citation: Antibiotics
      PubDate: 2022-07-31
      DOI: 10.3390/antibiotics11081034
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1035: Prevalence and Predictors of Antibiotic
           Prescriptions at Primary Healthcare Facilities in the Dodoma Region,
           Central Tanzania: A Retrospective, Cross-Sectional Study

    • Authors: Richard James Mabilika, Gabriel Shirima, Emmanuel Mpolya
      First page: 1035
      Abstract: Background: Accelerated by the misuse or overuse of antibiotics, antibiotic resistance remains a global public health threat. We report the prevalence and predictors of antibiotic prescriptions in primary healthcare facilities in Dodoma, Tanzania. Methods: This retrospective cross-sectional study by medical records review was conducted in the Dodoma region, Central Tanzania. Results: In this study, children < 5 years accounted for over 45% (474/1021) of the patients consulted. The majority, 76.3% (779/1021), of consultations had an antibiotic prescribed; amoxicillin and cotrimoxazole were the most prescribed. Over 98% (766/779) of the antibiotics prescribed were on the National Essential Medicines List, but only 45% (429/779) of the antibiotic prescriptions adhered to the Standard Treatment Guidelines. The prescribing of antibiotics by clinical officers was almost 2.55 times higher than that among medical doctors (Odds Ratio (OR) = 2.546; 95% Confidence Interval (CI): 1.359, 4.769; p = 0.0035). Patients with pneumonia and upper respiratory tract infection were 15.9 (OR = 15.928; 95% CI: 2.151, 17.973; p = 0.0067) and 2 (OR = 2.064; 95% CI: 1.184, 3.600; p = 0.0106) times more likely to be prescribed antibiotics, respectively. Conclusions: We, therefore, report high rates of antibiotic prescriptions, poor adherence to standard treatment guidelines and high levels of antibiotic prescribing practices among prescribers with a diploma in clinical medicine.
      Citation: Antibiotics
      PubDate: 2022-07-31
      DOI: 10.3390/antibiotics11081035
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1036: Model-Informed Translation of In Vitro
           Effects of Short-, Prolonged- and Continuous-Infusion Meropenem against
           Pseudomonas aeruginosa to Clinical Settings

    • Authors: Iris K. Minichmayr, Suzanne Kappetein, Margreke J. E. Brill, Lena E. Friberg
      First page: 1036
      Abstract: Pharmacokinetic-pharmacodynamic (PKPD) models have met increasing interest as tools to identify potential efficacious antibiotic dosing regimens in vitro and in vivo. We sought to investigate the impact of diversely shaped clinical pharmacokinetic profiles of meropenem on the growth/killing patterns of Pseudomonas aeruginosa (ARU552, MIC = 16 mg/L) over time using a semi-mechanistic PKPD model and a PK/PD index-based approach. Bacterial growth/killing were driven by the PK profiles of six patient populations (infected adults, burns, critically ill, neurosurgery, obese patients) given varied pathogen features (e.g. EC50, growth rate, inoculum), patient characteristics (e.g. creatinine clearance), and ten dosing regimens (including two dose levels and 0.5-h, 3-h and continuous-infusion regimens). Conclusions regarding the most favourable dosing regimen depended on the assessment of (i) the total bacterial load or fT>MIC (time that unbound concentrations exceed the minimum inhibitory concentration); (ii) the median or P0.95 profile of the population; and (iii) 8 h or 24 h time points. Continuous infusion plus loading dose as well as 3-h infusions (3-h infusions: e.g. for scenarios associated with low meropenem concentrations, P0.95 profiles, and MIC ≥ 16 mg/L) appeared superior to standard 0.5-h infusions at 24 h. The developed platform can serve to identify promising strategies of efficacious dosing for clinical trials.
      Citation: Antibiotics
      PubDate: 2022-08-01
      DOI: 10.3390/antibiotics11081036
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1037: A Proof of Concept of the Usefulness of
           a TDM-Guided Strategy for Optimizing Pharmacokinetic/Pharmacodynamic
           Target of Continuous Infusion Ampicillin-Based Regimens in a Case Series
           of Patients with Enterococcal Bloodstream Infections and/or Endocarditis

    • Authors: Milo Gatti, Sara Tedeschi, Filippo Trapani, Stefania Ramirez, Rita Mancini, Maddalena Giannella, Pierluigi Viale, Federico Pea
      First page: 1037
      Abstract: (1) Objective: To describe the usefulness of a real-time therapeutic drug monitoring (TDM)-based strategy for optimizing pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) ampicillin-based regimens in a case series of patients affected by suspected or documented enterococcal bloodstream infections (BSIs) and/or infective endocarditis (IE). (2) Methods: Patients treated with CI ampicillin-based regimens for documented or suspected enterococcal BSI/IE who underwent real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) between June 2021 and May 2022 were retrospectively assessed. Ampicillin concentrations were determined at steady state, and the free fraction (fCss) was calculated according to a plasma protein binding of 20%. The fCss/MIC ratio was selected as the PD parameter for ampicillin efficacy and was defined as optimal for values between 4 and 8. The requirement for TDM-guided ampicillin dosing adjustments was assessed. (3) Results: Data for 12 patients with documented (n = 10) or suspected (n = 2) enterococcal infections (7 with BSIs and 5 with IE) were retrieved. The ampicillin PK/PD target was optimal over time in all of the 10 documented infections. None of the enterococcal BSIs persisted. Following the first real-time TDM-based ECPA, ampicillin dosage was decreased by >50% in 11 out of 12 patients (91.7%). (4) Conclusions: CI may be helpful in attaining aggressive ampicillin PK/PD targets in patients affected by enterococcal BSIs and/or IE. Administration of CI ampicillin after loading coupled with real-time TDM-based ECPA could be a valuable strategy for managing enterococcal infections.
      Citation: Antibiotics
      PubDate: 2022-08-01
      DOI: 10.3390/antibiotics11081037
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1038: Identification of Novel Inhibitor of
           Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium
           tuberculosis from Plant-Derived Metabolites: An In Silico Study

    • Authors: Kratika Singh, Niharika Pandey, Firoz Ahmad, Tarun Kumar Upadhyay, Mohammad Hayatul Islam, Nawaf Alshammari, Mohd Saeed, Lamya Ahmed Al-Keridis, Rolee Sharma
      First page: 1038
      Abstract: Mycobacterium tuberculosis (M.tb.) enoyl-acyl carrier protein (ACP) reductase (InhA) is validated as a useful target for tuberculosis therapy and is considered an attractive enzyme to drug discovery. This study aimed to identify the novel inhibitor of the InhA enzyme, a potential target of M.tb. involved in the type II fatty acid biosynthesis pathway that controls mycobacterial cell envelope synthesis. We compiled 80 active compounds from Ruta graveolens and citrus plants belonging to the Rutaceae family for pharmacokinetics and molecular docking analyses. The chemical structures of the 80 phytochemicals and the 3D structure of the target protein were retrieved from the PubChem database and RCSB Protein Data Bank, respectively. The evaluation of druglikeness was performed based on Lipinski’s Rule of Five, while the computed phytochemical properties and molecular descriptors were used to predict the ADMET of the compounds. Amongst these, 11 pharmacokinetically-screened compounds were further examined by performing molecular docking analysis with an InhA target using AutoDock 4.2. The docking results showed that gravacridonediol, a major glycosylated natural alkaloid from Ruta graveolens, might possess a promising inhibitory potential against InhA, with a binding energy (B.E.) of −10.80 kcal/mole and inhibition constant (Ki) of 600.24 nM. These contrast those of the known inhibitor triclosan, which has a B.E. of −6.69 kcal/mole and Ki of 12.43 µM. The binding efficiency of gravacridonediol was higher than that of the well-known inhibitor triclosan against the InhA target. The present study shows that the identified natural compound gravacridonediol possesses drug-like properties and also holds promise in inhibiting InhA, a key target enzyme of M.tb.
      Citation: Antibiotics
      PubDate: 2022-08-01
      DOI: 10.3390/antibiotics11081038
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1039: Risk Factors for Community-Acquired
           Urinary Tract Infections Caused by Multidrug-Resistant Enterobacterales in

    • Authors: Kanit Assawatheptawee, Pornpit Treebupachatsakul, Taradon Luangtongkum, Pannika R. Niumsup
      First page: 1039
      Abstract: The dissemination of multidrug-resistant Enterobacterales (MDRE) in community settings is becoming a great concern. This study aimed to assess the incidence and risk factors associated with community-acquired urinary tract infections (CA-UTIs) caused by MDRE. A prospective case–control study was undertaken among patients with UTIs visiting an outpatient department in Phitsanulok Province, Thailand. Urine samples were collected and screened to include only patients with Enterobacterales infections. Risk factors were analyzed by multivariate logistic regression analysis. Of the 284 patients with CA-UTIs, 25.7% (n = 73) and 74.3% (n = 211) were positive for MDRE (case) and non-MDRE (control), respectively. Being a farmer was identified as an independent risk factor for MDRE-associated CA-UTIs (adjusted odds ratio = 3.101; 95% confidence interval = 1.272–7.564; p = 0.013). A total of 309 Enterobacterales isolates were recovered, and Escherichia coli was the most frequently detected (86.4%). The highest resistance rate was observed for ampicillin (67.0%), followed by ciprofloxacin (34.0%) and cotrimoxazole (32.7%), while resistance to third-generation cephalosporins (cefotaxime, ceftriaxone) and levofloxacin remained <20%. Resistance to ampicillin–gentamicin–cotrimoxazole was the most common pattern among MDRE isolates. Interestingly, we detected a colistin-resistant Enterobacter cloacae harboring mcr-9 (colistin MIC = 16 µg/mL). mcr-9 was transferable at high frequency (4.5 × 10−4) and resided on IncF plasmid. This study demonstrates that being a farmer is a risk factor for MDRE-associated CA-UTIs. Interestingly, this is the first report to identify mcr-9-positive E. cloacae from a Thai patient in the community.
      Citation: Antibiotics
      PubDate: 2022-08-02
      DOI: 10.3390/antibiotics11081039
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1040: Development and Characterization of
           Azithromycin-Loaded Microemulsions: A Promising Tool for the Treatment of
           Bacterial Skin Infections

    • Authors: Angela Abruzzo, Carola Parolin, Martina Rossi, Beatrice Vitali, Concettina Cappadone, Federica Bigucci
      First page: 1040
      Abstract: In recent years, the treatment of bacterial skin infections has been considered a major healthcare issue due to the growing emergence of antibiotic-resistant strains of Staphylococcus aureus. The incorporation of antibiotics in appropriate nanosystems could represent a promising strategy, able to overcome several drawbacks of the topical treatment of infections, including poor drug retention within the skin. The present work aims to develop microemulsions containing azithromycin (AZT), a broad-spectrum macrolide antibiotic. Firstly, AZT solubility in various oils, surfactants and co-surfactants was assessed to select the main components. Subsequently, microemulsions composed of vitamin E acetate, Labrasol® and Transcutol® P were prepared and characterized for their pH, viscosity, droplet size, zeta potential and ability to release the drug and to promote its retention inside porcine skin. Antimicrobial activity against S. aureus methicillin-resistant strains (MRSA) and the biocompatibility of microemulsions were evaluated. Microemulsions showed an acceptable pH and were characterized by different droplet sizes and viscosities depending on their composition. Interestingly, they provided a prolonged release of AZT and promoted its accumulation inside the skin. Finally, microemulsions retained AZT efficacy on MRSA and were not cytotoxic. Hence, the developed AZT-loaded microemulsions could be considered as useful nanocarriers for the treatment of antibiotic-resistant infections of the skin.
      Citation: Antibiotics
      PubDate: 2022-08-02
      DOI: 10.3390/antibiotics11081040
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1041: Genomic and Phenotypic Characterization
           of Cutibacterium acnes Bacteriophages Isolated from Acne Patients

    • Authors: Shukho Kim, Hyesoon Song, Jong Sook Jin, Weon Ju Lee, Jungmin Kim
      First page: 1041
      Abstract: Cutibacterium acnes is a pathogen that can cause acne vulgaris, sarcoidosis, endodontic lesions, eye infections, prosthetic joint infections, and prostate cancer. Recently, bacteriophage (phage) therapy has been developed as an alternative to antibiotics. In this study, we attempted to isolate 15 phages specific to C. acnes from 64 clinical samples obtained from patients with acne vulgaris. Furthermore, we sequenced the genomes of these three phages. Bioinformatic analysis revealed that the capsid and tape measure proteins are strongly hydrophobic. To efficiently solubilize the phage particles, we measured the adsorption rate, one-step growth curve, and phage stability using an SMT2 buffer containing Tween 20. Here, we report the genotypic and phenotypic characteristics of the novel C. acnes-specific phages.
      Citation: Antibiotics
      PubDate: 2022-08-02
      DOI: 10.3390/antibiotics11081041
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1042: Pseudomonas fluorescens Cells’
           Recovery after Exposure to BAC and DBNPA Biocides

    • Authors: Ana C. Barros, Luis F. Melo, Ana Pereira
      First page: 1042
      Abstract: A proper assessment of the effects of biocides on bacterial cells is key to the prevention of antimicrobial resistance and the implementation of suitable biocidal programmes. It is particularly relevant regarding the ability of dead-labelled cells to recover their functional processes once the biocide is removed. In the present work, we studied how Pseudomonas fluorescens cells previously exposed to different concentrations of BAC (benzalkonium chloride) and DBNPA (2,2-Dibromo-3-nitrilopropionamide) behave upon the restoration of optimum growth conditions. The following indicators were evaluated: culturability, membrane integrity, metabolic activity (resazurin), cellular energy (ATP), and cell structure and morphology (transmission electron microscopy (TEM)). The results demonstrated that cells previously labelled as ‘dead’ recovered to a greater extent in all indicators. Only cells previously exposed to BAC at 160 mg/L (concentration above the MBC) showed significant reductions on all the evaluated indicators. However, the obtained values were much higher than the ‘death’ thresholds found for the autoclaved cells. This suggests that cells exposed to this concentration take more time to rebuild their functional processes. The recovery of DBNPA-treated cells did not seem to be related to the biocide concentration. Finally, a reflection on what kind of cells were able to recover (remaining cells below the detection limit and/or dormant cells) is also presented.
      Citation: Antibiotics
      PubDate: 2022-08-02
      DOI: 10.3390/antibiotics11081042
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1043: Fingolimod Promotes Antibacterial Effect
           of Doripenem against Carbapenem-Resistant Escherichia coli

    • Authors: Hye-Won Jin, Hye-Rim Kim, Yong-Bin Eom
      First page: 1043
      Abstract: The aim of this study was to determine whether fingolimod could synergize the antibacterial activity of doripenem against carbapenem-resistant Escherichia coli (CREC) and its potential as an antibiotic adjuvant for doripenem. The E. coli used in this study had the blaKPC gene and became resistant to many classes of antibiotics, particularly carbapenems. The minimum inhibitory concentrations (MICs) of fingolimod and doripenem were determined. To investigate the synergistic action between fingolimod and doripenem, synergy checkerboard, growth curve, and time-kill analyses were performed. A motility test was also performed using a semi-solid medium to determine whether fingolimod could inhibit the motility of E. coli, one of its virulence mechanisms. The expression levels of carbapenemase-, motility-, and efflux pump-related genes suppressed by fingolimod were analyzed by quantitative polymerase chain reaction (qPCR). Our study demonstrated that the combination of fingolimod and doripenem inhibited carbapenemase, biological activity and other CREC virulence factors. This study findings suggest the potential of fingolimod as an adjuvant to prevent antibiotic resistance in CREC.
      Citation: Antibiotics
      PubDate: 2022-08-02
      DOI: 10.3390/antibiotics11081043
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1044: Effects of Sodium Hexametaphosphate and
           Fluoride on the pH and Inorganic Components of Streptococcus mutans and
           Candida albicans Biofilm after Sucrose Exposure

    • Authors: Thayse Yumi Hosida, Juliano Pelim Pessan, Thamires Priscila Cavazana, Caio Sampaio, Leonardo Antônio de Morais, Douglas Roberto Monteiro, Alberto Carlos Botazzo Delbem
      First page: 1044
      Abstract: In order to improve the anticaries effects of fluoridated products, the supplementation of these products has been considered a promising alternative for caries control. This study evaluated the effects of sodium hexametaphosphate (HMP) and/or fluoride (F) on the inorganic components and pH of Streptococcus mutans and Candida albicans dual-species biofilms. The biofilms were treated 72, 78, and 96 h after the beginning of their formation with 0.25, 0.5, or 1% HMP-containing solutions with or without F (500 ppm, as sodium fluoride). F-containing solutions (500 ppm and 1100 ppm) and artificial saliva were used as controls. The biofilms were exposed to a 20% sucrose solution after the third treatment. Along with the biofilm pH, the concentrations of F, calcium, phosphorus (P), and HMP were determined. HMP, combined with F, increased F levels and decreased P levels in the biofilm fluid compared to that of the solution with 500 ppm F. Exposure to sucrose decreased the concentrations of all ions in the biomass, except for HMP; 1% HMP, combined with F, promoted the highest pH. It can be concluded that HMP affected the inorganic composition of the biofilm and exerted a buffering effect on the biofilm pH.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081044
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1045: Genomic Analysis of Acinetobacter
           baumannii Isolates Carrying OXA-23 and OXA-58 Genes from Animals Reveals
           ST1 and ST25 as Major Clonal Lineages

    • Authors: Lisa Jacobmeyer, Torsten Semmler, Ivonne Stamm, Christa Ewers
      First page: 1045
      Abstract: Acinetobacter baumannii is increasingly being recognized as a relevant pathogen for animals with a putative zoonotic impact. This study aimed at identifying and characterizing carbapenemase-producing A. baumannii from animals. Among 503 A. baumannii, mainly isolated from dogs/cats (75.7%) between 2013 and 2018, 42 isolates from 22 veterinary clinics (VCs) harboured blaOXA-58 (n = 29) or blaOXA-23 (n = 13). The blaOXA-58 gene was located on plasmids (11.4–21.1 kb) within different genetic surroundings (patterns A–D). BlaOXA-23 was embedded in Tn2006 on the chromosome (n = 4; pattern a) or Tn2008 on plasmids (n = 9; 41.2–71.3 kb; patterns b–e). The predominant IC1-ST1P-OXA-58 (66.7%; 96.4% cgMLST complex type (CT)-1808) was disseminated among 11 VCs in Germany. Resistance islands AbaR3-like (n = 15) and AbaR10 (n = 1) have emerged among ST1-isolates since 2016. IC7-ST25P-OXA-23 isolates (21.4%) occurred in seven VCs in Germany, France and Italy and differed in their resistance gene patterns from those of OXA-58 isolates. They were separated into six CTs, basically according to their regional origin. Other STs observed were ST10, ST578 and ST602. In conclusion, OXA-23 and OXA-58 were linked with ST1 and ST25, two globally distributed lineages in humans. The suggested transmission of certain lineages within and among VCs together with the acquisition of AbaR islands hints at a successful dissemination of multidrug-resistant strains in the VC environment.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081045
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1046: Real-World Data on Antibiotic Group
           Treatment in European Livestock: Drivers, Conditions, and Alternatives

    • Authors: Julia Jerab, Wiebke Jansen, John Blackwell, Jobke van Hout, Andreas Palzer, Stephen Lister, Ilias Chantziaras, Jeroen Dewulf, Nancy De Briyne
      First page: 1046
      Abstract: Major efforts have been made by veterinary professionals to reduce the need for antibiotic use in animals. An online survey launched by the Federation of Veterinarians of Europe (FVE) aimed to gather responses from practicing veterinarians with field experience in metaphylactic livestock group treatment. Only 17% of all veterinarians (n = 183/1087, all species-specific responses merged) applied metaphylactic group treatments to 75% or more of all their treatments. Significantly less metaphylactic group treatments were reported in mixed practices (p = 0.002) and practices specialized in cattle (p < 0.001) as well as small (p = 0.007) and very small practices (p = 0.009). Gram-negative bacteria, mostly composed of Enterobacteriaceae and Pasteurellaceae, were considered by 75.3% (n = 967/1385) as the most devastating bacterial pathogens. Respondents alleged morbidity (20.1%, n = 201/998) and mortality (42.2%, n = 421/998) as major consequences for animal health and welfare if metaphylaxis would be banned. Responding veterinarians pointed towards vaccinations; improved biosecurity, including hygiene measures; and improved herd health management as the three most effective alternative measures to prevent metaphylactic treatment. However, more research is needed on how to implement appropriate alternatives in a holistic hurdle approach. Active support on a national level will be necessary for the development and application of targeted veterinary treatment guidelines for practitioners, which promote the understanding of drivers and include initiation criteria for metaphylactic group treatments in livestock.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081046
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1047: Expansion of the pRAS3 Plasmid Family in
           Aeromonas salmonicida subsp. salmonicida and Growing Evidence of
           Interspecies Connections for These Plasmids

    • Authors: Kim C. Fournier, Valérie E. Paquet, Sabrina A. Attéré, Judith Farley, Hélène Marquis, Hubert Gantelet, Christian Ravaille, Antony T. Vincent, Steve J. Charette
      First page: 1047
      Abstract: Aeromonas salmonicida subsp. salmonicida is a pathogenic bacterium responsible for furunculosis in salmonids. Following an outbreak of furunculosis, the infection can be treated with antibiotics, but it is common to observe ineffective treatment due to antibiotic resistance. This bacterium has a wide variety of plasmids responsible for this resistance. Among them, pRAS3 carries a tetracycline resistance gene. Several variants of this plasmid have been discovered over the years (pRAS3-3432 and pRAS3.1 to 3.4). During the present study, two new variants of the plasmid pRAS3 were identified (pRAS3.5 and pRAS3-3759) in strains of A. salmonicida subsp. salmonicida. Plasmid pRAS3-3759, which has been found in many strains from the same region over the past three years, has an additional genetic element identical to one found in pRAS3-3432. This genetic element was also found in Chlamydia suis, a swine pathogen. In this study, we analyzed the bacteria’s resistance to tetracycline, the number of copies of the plasmids, and the growth of the strains that carry five of the pRAS3 variants (pRAS3.3 to 3.5, pRAS3-3432, and pRAS3-3759). The results show no particular trend despite the differences between the plasmids, except for the resistance to tetracycline when analyzed in an isogenic background. Blast analysis also revealed the presence of pRAS3 plasmids in other bacterial species, which suggests that this plasmid family has widely spread. This study once again highlights the ability of A. salmonicida subsp. salmonicida to adapt to furunculosis antibiotic treatments, and the still-growing family of pRAS3 plasmids.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081047
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1048: Targeted Modification and
           Structure-Activity Study of GL-29, an Analogue of the Antimicrobial
           Peptide Palustrin-2ISb

    • Authors: Siyan Liu, Yaxian Lin, Jiachen Liu, Xiaoling Chen, Chengbang Ma, Xinping Xi, Mei Zhou, Tianbao Chen, James F. Burrows, Lei Wang
      First page: 1048
      Abstract: Antimicrobial peptides (AMPs) are considered as promising antimicrobial agents due to their potent bioactivity. Palustrin-2 peptides were previously found to exhibit broad-spectrum antimicrobial activity with low haemolytic activity. Therefore, GL-29 was used as a template for further modification and study. Firstly, the truncated analogue, GL-22, was designed to examine the function of the ‘Rana box’, which was confirmed to have no impact on antimicrobial activity. The results of antimicrobial activity assessment against seven microorganisms demonstrated GL-22 to have a broad-spectrum antimicrobial activity, but weak potency against Candida albicans (C. albicans). These data were similar to those of GL-29, but GL-22 showed much lower haemolysis and lower cytotoxicity against HaCaT cells. Moreover, GL-22 exhibited potent in vivo activity at 4 × MIC against Staphylococcus aureus (S. aureus)-infected larvae. Several short analogues, from the C-terminus and N-terminus of GL-22, were modified to identify the shortest functional motif. However, the results demonstrated that the shorter peptides did not exhibit potent antimicrobial activity, and the factors that affect the bioactive potency of these short analogues need to be further studied.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081048
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1049: Pharmacodynamics of Flucloxacillin in a
           Neutropenic Murine Thigh Infection Model: A Piece of the Puzzle towards
           Evidence-Based Dosing

    • Authors: Eveline E. Roelofsen, Brenda C. M. de Winter, Heleen van der Spek, Susan Snijders, Birgit C. P. Koch, Sanne van den Berg, Anouk E. Muller
      First page: 1049
      Abstract: For decades, flucloxacillin has been used to treat methicillin-susceptible Staphylococcus aureus (MSSA). Little is still known about its pharmacodynamics (PD). The present study aimed to determine the pharmacokinetic (PK)/PD index and the PD-index value minimally required for efficacy. MICs of 305 MSSA isolates were measured to determine the wild-type distribution. The PD of 8 S. aureus, 1 S. pyogenes, and 1 S. agalactiae isolates were evaluated in a neutropenic murine thigh infection model. Two S. aureus isolates were used in a dose-fractionation study and a dose–response analysis was performed additionally in the in vivo model. Data were analyzed with a population PK and sigmoid maximum effect model. The end of the wild-type distribution was 1 mg/L. The percentage of time the unbound concentration was above MIC (%fT > MIC) was best correlated with efficacy. For S. aureus, median %fT > 0.25 × MIC required for 1-log reduction was 15%. The value for S. pyogenes was 10%fT > MIC and for S. agalactiae 22%fT > 0.25xMIC for a 1-log reduction. The effect of flucloxacillin reached a 2-log reduction of S. aureus at 20%fT > 0.25xMIC and also for S. pyogenes and S. agalactiae, a reduction was reached. These data may serve to optimize dosing regimens currently used in humans.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081049
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1050: Nordic Vets against AMR—An
           Initiative to Share and Promote Good Practices in the Nordic–Baltic

    • Authors: Susanna Sternberg-Lewerin, Sofia Boqvist, Simen Foyn Nørstebø, Thomas Grönthal, Annamari Heikinheimo, Venla Johansson, Viivi Heljanko, Paula Kurittu, Nils Fall, Ulf Magnusson, Ane Mohn Bjelland, Henning Sørum, Yngvild Wasteson
      First page: 1050
      Abstract: In the Nordic countries, antimicrobial use in animals and the prevalence of antimicrobial resistance are among the lowest in Europe. The network “Nordic Vets Against AMR” organized a meeting in 2021, with key actors including representatives from universities, veterinary authorities and veterinary organizations in Finland, Norway and Sweden. This paper reflects the most important discussions on education, research, policy and future perspectives, including the experiences of these countries. It concludes that Nordic veterinarians are well placed to lead the way in the fight against antimicrobial resistance and that the sharing of experiences can support colleagues in other countries. Veterinary education must go hand in hand with research activities and continuously updated guidelines and legislation. There is also a need for postgraduate training on antimicrobial resistance and prudent antimicrobial use. The veterinary profession must, by any means necessary, protect the efficiency of antimicrobials for the sake of animal health, animal welfare and productivity, as well as public health. While restrictive use of antimicrobials is crucial, the ability of veterinarians to use this medical tool is also important for the sake of animal welfare and global food security.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081050
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1051: Transcriptomic and Metabolomic Analysis
           of a Fusidic Acid-Selected fusA Mutant of Staphylococcus aureus

    • Authors: Sushim K. Gupta, Richard F. Pfeltz, Brian J. Wilkinson, John E. Gustafson
      First page: 1051
      Abstract: Physiological experimentation, transcriptomics, and metabolomics were engaged to compare a fusidic acid-resistant Staphylococcus aureus mutant SH10001st-2 to its parent strain SH1000. SH10001st-2 harbored a mutation (H457Y) in the gene fusA which encodes the fusidic acid target, elongation factor G, as well as mutations in a putative phage gene of unknown function. SH10001st-2 grew slower than SH1000 at three temperatures and had reduced coagulase activity, two indicators of the fitness penalty reported for fusA-mediated fusidic acid- resistance in the absence of compensatory mutations. Despite the difference in growth rates, the levels of O2 consumption and CO2 production were comparable. Transcriptomic profiling revealed 326 genes were upregulated and 287 were downregulated in SH10001st-2 compared to SH1000. Cell envelope and transport and binding protein genes were the predominant functional categories of both upregulated and downregulated genes in SH10001st-2. Genes of virulence regulators, notably the agr and kdp systems, were highly upregulated as were genes encoding capsule production. Contrary to what is expected of mid-exponential phase cells, genes encoding secreted virulence factors were generally upregulated while those for adhesion-associated virulence factors were downregulated in SH10001st-2. Metabolomic analysis showed an overall increase in metabolite pools in SH10001st-2 compared to SH1000, mostly for amino acids and sugars. Slowed growth and metabolite accumulation may be byproducts of fusA mutation-mediated protein synthesis impairment, but the overall results indicate that SH10001st-2 is compensating for the H457Y fitness penalty by repurposing its virulence machinery, in conjunction with increasing metabolite uptake capacity, in order to increase nutrient acquisition.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081051
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1052: Decreasing Incidence of Gastric Cancer
           with Increasing Time after Helicobacter pylori Treatment: A Nationwide
           Population-Based Cohort Study

    • Authors: Taewan Kim, Seung In Seo, Kyung Joo Lee, Chan Hyuk Park, Tae Jun Kim, Jinseob Kim, Woon Geon Shin
      First page: 1052
      Abstract: Background: Treatment of Helicobacter pylori (HP) has been shown to reduce the risk of gastric cancer (GC) development. However, previous studies have focused on patients at high risk of GC. This study aimed to assess the effect of HP treatment on the incidence of GC in the general population. Materials and Methods: Medical records were obtained from the Common Data Model-converted sample Cohort of the National Health Insurance Service of Korea (NHIS-CDM). The target cohort included those who had been prescribed HP treatment and the comparator cohort included those who had not. The association between HP treatment and the risk of GC development was assessed using the Cox proportional hazard model. The incidences of GC according to the period after HP treatment in different age groups were analyzed using proportional trend tests. Results: After large-scale 1:4 propensity score matching, 2735 and 5328 individuals were included in the target and comparator cohorts, respectively. During the median follow-up of 6.5 years, the GC incidence was lower in the HP treatment cohort than in the comparator cohort, but this was statistically insignificant (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.50–1.13; p-value = 0.19). This trend was also observed among the older age (≥65 years, HR: 0.87; 95% CI: 0.44–1.68; p-value = 0.69) and male cohorts (HR: 0.82; 95% CI: 0.51–1.27; p-value = 0.38). Among 58,684 individuals who were treated for HP from the whole NHIS-CDM cohort, the incidence of GC consistently decreased over time and showed a marked decrease with increasing age (p for trend < 0.05). Conclusions: In all age groups of the general population, HP treatment could be recommended to reduce the risk of GC.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081052
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1053: Incidence and Risk Factors for Blood
           Stream Infection in Mechanically Ventilated COVID-19 Patients

    • Authors: Konstantinos Mantzarlis, Konstantina Deskata, Dimitra Papaspyrou, Vassiliki Leontopoulou, Vassiliki Tsolaki, Epaminondas Zakynthinos, Demosthenes Makris
      First page: 1053
      Abstract: It is widely known that blood stream infections (BSIs) in critically ill patients may affect mortality, length of stay, or the duration of mechanical ventilation. There is scarce data regarding blood stream infections in mechanically ventilated COVID-19 patients. Preliminary studies report that the number of secondary infections in COVID-9 patients may be higher. This retrospective analysis was conducted to determine the incidence of BSI. Furthermore, risk factors, mortality, and other outcomes were analyzed. The setting was an Intensive Care Unit (ICU) at a University Hospital. Patients suffering from SARS-CoV-2 infection and requiring mechanical ventilation (MV) for >48 h were eligible. The characteristics of patients who presented BSI were compared with those of patients who did not present BSI. Eighty-four patients were included. The incidence of BSI was 57%. In most cases, multidrug-resistant pathogens were isolated. Dyslipidemia was more frequent in the BSI group (p < 0.05). Moreover, BSI-group patients had a longer ICU stay and a longer duration of both mechanical ventilation and sedation (p < 0.05). Deaths were not statistically different between the two groups (73% for BSI and 56% for the non-BSI group, p > 0.05). Compared with non-survivors, survivors had lower baseline APACHE II and SOFA scores, lower D-dimers levels, a higher baseline compliance of the respiratory system, and less frequent heart failure. They received anakinra less frequently and appropriate therapy more often (p < 0.05). The independent risk factor for mortality was the APACHE II score [1.232 (1.017 to 1.493), p = 0.033].
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081053
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1054: A Promising Antifungal and Antiamoebic
           Effect of Silver Nanorings, a Novel Type of AgNP

    • Authors: Sara González-Fernández, Victor Lozano-Iturbe, Mª Fe Menéndez, Helena Ordiales, Iván Fernández-Vega, Jesús Merayo, Fernando Vazquez, Luis M. Quirós, Carla Martín
      First page: 1054
      Abstract: Silver nanoparticles (AgNPs) play an important role in the medical field due to their potent antimicrobial activity. This, together with the constant emergence of resistance to antimicrobial drugs, means AgNPs are often investigated as an alternative to solve this problem. In this article, we analyzed the antifungal and antiamoebic effects of a recently described type of AgNP, silver nanorings (AgNRs), and compared them with other types of AgNPs. Tests of the activity of AgNPs against various fungal and amoebic species were carried out. In all cases, AgNPs showed a high biocidal effect, although with fungi this depended on the species involved. Antifungal activity was detected by the conditioning of culture media or water but this effect was not dependent on the release of Ag ions. On the other hand, the proliferation of Acanthamoeba castellanii trophozoites was reduced by silver nanorings (AgNRs) and silver nanowires (AgNWs), with AgNWs being capable of totally inhibiting the germination of A. castellanii cysts. AgNRs constitute a new type of AgNP with an antifungal and antiacanthamoebic activity. These results open the door to new and effective antimicrobial therapies as an alternative to the use of antifungals or antiamoebic drugs, thus avoiding the constant appearance of resistance and the difficulty of eradicating infections.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081054
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1055: Antibiotic Allergy De-Labeling: A
           Pathway against Antibiotic Resistance

    • Authors: Inmaculada Doña, Marina Labella, Gádor Bogas, Rocío Sáenz de Santa María, María Salas, Adriana Ariza, María José Torres
      First page: 1055
      Abstract: Antibiotics are one of the most frequently prescribed drugs. Unfortunately, they also are the most common cause for self-reported drug allergy, limiting the use of effective therapies. However, evidence shows that more than 90% of patients labeled as allergic to antibiotics are not allergic. Importantly, the label of antibiotic allergy, whether real or not, constitutes a major public health problem as it directly impacts antimicrobial stewardship: it has been associated with broad-spectrum antibiotic use, often resulting in the emergence of bacterial resistance. Therefore, an accurate diagnosis is crucial for de-labeling patients who claim to be allergic but are not really allergic. This review presents allergy methods for achieving successful antibiotic allergy de-labeling. Patient clinical history is often inaccurately reported, thus not being able to de-label most patients. In vitro testing offers a complementary approach but it shows limitations. Immunoassay for quantifying specific IgE is the most used one, although it gives low sensitivity and is limited to few betalactams. Basophil activation test is not validated and not available in all centers. Therefore, true de-labeling still relies on in vivo tests including drug provocation and/or skin tests, which are not risk-exempt and require specialized healthcare professionals for results interpretation and patient management. Moreover, differences on the pattern of antibiotic consumption cause differences in the diagnostic approach among different countries. A multidisciplinary approach is recommended to reduce the risks associated with the reported penicillin allergy label.
      Citation: Antibiotics
      PubDate: 2022-08-03
      DOI: 10.3390/antibiotics11081055
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1056: Antimicrobial Utilization among Neonates
           and Children: A Multicenter Point Prevalence Study from Leading
           Children’s Hospitals in Punjab, Pakistan

    • Authors: Zia Ul Mustafa, Amer Hayat Khan, Muhammad Salman, Syed Azhar Syed Sulaiman, Brian Godman
      First page: 1056
      Abstract: Antimicrobial resistance (AMR) compromises global health due to the associated morbidity, mortality, and costs. The inappropriate use of antimicrobial agents is a prime driver of AMR. Consequently, it is imperative to gain a greater understanding of current utilization patterns especially in high-risk groups including neonates and children. A point prevalence survey (PPS) was conducted among three tertiary care children’s hospitals in the Punjab province using the World Health Organization (WHO) methodology. Antibiotic use was documented according to the WHO AWaRe classification. Out of a total of 1576 neonates and children, 1506 were prescribed antibiotics on the day of the survey (prevalence = 95.5%), with an average of 1.9 antibiotics per patient. The majority of antibiotics were prescribed in the medical ward (75%), followed by surgical ward (12.8%). Furthermore, 56% of antibiotics were prescribed prophylactically, with most of the antibiotics (92.3%) administered via the parenteral route. The top three indications for antibiotics were respiratory tract infections (34.8%), gastrointestinal infections (15.8%), and prophylaxis for medical problems (14.3%). The three most common antibiotics prescribed were ceftriaxone (25.8%), amikacin (9.2%), and vancomycin (7.9%). Overall, 76.6% of the prescribed antibiotics were from Watch category followed by 21.6% from the Access group. There was a very high prevalence of antibiotic use among hospitalized neonates and children in this study. Urgent measures are needed to engage all the stakeholders to formulate effective ASPs in Pakistan, especially surrounding Watch antibiotics.
      Citation: Antibiotics
      PubDate: 2022-08-04
      DOI: 10.3390/antibiotics11081056
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1057: Revealing Genome-Based Biosynthetic
           Potential of Streptomyces sp. BR123 Isolated from Sunflower Rhizosphere
           with Broad Spectrum Antimicrobial Activity

    • Authors: Neelma Ashraf, Sana Zafar, Roman Makitrynskyy, Andreas Bechthold, Dieter Spiteller, Lijiang Song, Munir Ahmad Anwar, Andriy Luzhetskyy, Ali Nisar Khan, Kalsoom Akhtar, Shazia Khaliq
      First page: 1057
      Abstract: Actinomycetes, most notably the genus Streptomyces, have great importance due to their role in the discovery of new natural products, especially for finding antimicrobial secondary metabolites that are useful in the medicinal science and biotechnology industries. In the current study, a genome-based evaluation of Streptomyces sp. isolate BR123 was analyzed to determine its biosynthetic potential, based on its in vitro antimicrobial activity against a broad range of microbial pathogens, including gram-positive and gram-negative bacteria and fungi. A draft genome sequence of 8.15 Mb of Streptomyces sp. isolate BR123 was attained, containing a GC content of 72.63% and 8103 protein coding genes. Many antimicrobial, antiparasitic, and anticancerous compounds were detected by the presence of multiple biosynthetic gene clusters, which was predicted by in silico analysis. A novel metabolite with a molecular mass of 1271.7773 in positive ion mode was detected through a high-performance liquid chromatography linked with mass spectrometry (HPLC-MS) analysis. In addition, another compound, meridamycin, was also identified through a HPLC-MS analysis. The current study reveals the biosynthetic potential of Streptomyces sp. isolate BR123, with respect to the synthesis of bioactive secondary metabolites through genomic and spectrometric analysis. Moreover, the comparative genome study compared the isolate BR123 with other Streptomyces strains, which may expand the knowledge concerning the mechanism involved in novel antimicrobial metabolite synthesis.
      Citation: Antibiotics
      PubDate: 2022-08-04
      DOI: 10.3390/antibiotics11081057
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1058: Outpatient Antibiotic and Antiviral
           Utilization Patterns in Patients Tested for Respiratory Pathogens in the
           United States: A Real-World Database Study

    • Authors: Jenny Tse, Aimee M. Near, Mindy Cheng, James Karichu, Brian Lee, Susan N. Chang
      First page: 1058
      Abstract: This retrospective observational study evaluated outpatient treatment patterns among patients with molecular-based viral diagnostic testing for suspected upper respiratory tract infections in the United States. Patients with a respiratory viral test were identified from 1 August 2016 to 1 July 2019 in a large national reference laboratory database linked to IQVIA’s prescription and medical claims databases. Antibiotic and influenza antiviral treatment patterns were reported up to 7 days post-test result. Predictors of antibiotic utilization were assessed using multivariable logistic regression. Among 9561 patients included in the study, 24.6% had evidence of ≥1 filled antibiotic prescription. Antibiotic utilization was higher in patients who tested negative for all viral targets (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.17–1.50) and patients positive for non-influenza viruses (OR, 1.28; 95% CI, 1.09–1.51) compared with those influenza-positive only. Age ≥ 50 years and location outside of the northeast United States also predicted antibiotic utilization. Influenza antivirals were more common in influenza-positive patients compared with patients with other test results (32.5% vs. 3.6–9.0%). Thus, in this real-world study, antibiotic utilization was elevated in patients positive for non-influenza viruses, although antibiotics would generally not be indicated. Further research on pairing diagnostic tools with outpatient antibiotic stewardship programs is needed.
      Citation: Antibiotics
      PubDate: 2022-08-04
      DOI: 10.3390/antibiotics11081058
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1059: Evaluation of Locomotion Complexity in
           Zebrafish after Exposure to Twenty Antibiotics by Fractal Dimension and
           Entropy Analysis

    • Authors: Michael Edbert Suryanto, Chun-Chuen Yang, Gilbert Audira, Ross D. Vasquez, Marri Jmelou M. Roldan, Tzong-Rong Ger, Chung-Der Hsiao
      First page: 1059
      Abstract: Antibiotics are extensively used in aquaculture to prevent bacterial infection and the spread of diseases. Some antibiotics have a relatively longer half-life in water and may induce some adverse effects on the targeted fish species. This study analyzed the potential adverse effects of antibiotics in zebrafish at the behavioral level by a phenomic approach. We conducted three-dimensional (3D) locomotion tracking for adult zebrafish after acute exposure to twenty different antibiotics at a concentration of 100 ppb for 10 days. Their locomotor complexity was analyzed and compared by fractal dimension and permutation entropy analysis. The dimensionality reduction method was performed by combining the data gathered from behavioral endpoints alteration. Principal component and hierarchical analysis conclude that three antibiotics: amoxicillin, trimethoprim, and tylosin, displayed unique characteristics. The effects of these three antibiotics at lower concentrations (1 and 10 ppb) were observed in a follow-up study. Based on the results, these antibiotics can trigger several behavioral alterations in adult zebrafish, even in low doses. Significant changes in locomotor behavioral activity, such as total distance activity, average speed, rapid movement time, angular velocity, time in top/bottom duration, and meandering movement are highly related to neurological motor impairments, anxiety levels, and stress responses were observed. This study provides evidence based on an in vivo experiment to support the idea that the usage of some antibiotics should be carefully addressed since they can induce a significant effect of behavioral alterations in fish.
      Citation: Antibiotics
      PubDate: 2022-08-04
      DOI: 10.3390/antibiotics11081059
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1060: The Structures and Binding Modes of
           Small-Molecule Inhibitors of Pseudomonas aeruginosa Elastase LasB

    • Authors: Virgyl Camberlein, Gwenaëlle Jézéquel, Jörg Haupenthal, Anna K. H. Hirsch
      First page: 1060
      Abstract: Elastase B (LasB) is a zinc metalloprotease and a crucial virulence factor of Pseudomonas aeruginosa. As the need for new strategies to fight antimicrobial resistance (AMR) constantly rises, this protein has become a key target in the development of novel antivirulence agents. The extensive knowledge of the structure of its active site, containing two subpockets and a zinc atom, led to various structure-based medicinal chemistry programs and the optimization of several chemical classes of inhibitors. This review provides a brief reminder of the structure of the active site and a summary of the disclosed P. aeruginosa LasB inhibitors. We specifically focused on the analysis of their binding modes with a detailed representation of them, hence giving an overview of the strategies aiming at targeting LasB by small molecules.
      Citation: Antibiotics
      PubDate: 2022-08-04
      DOI: 10.3390/antibiotics11081060
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1061: Genetic Diversity and Virulence
           Profiling of Multi-Drug Resistant Escherichia coli of Human, Animal, and
           Environmental Origins

    • Authors: Asfand Yar, Muhammad Adil Choudary, Abdul Rehman, Abid Hussain, Amina Elahi, Farooq ur Rehman, Ahmed Bilal Waqar, Abdulrahman Alshammari, Metab Alharbi, Muhammad Atif Nisar, Mohsin Khurshid, Zaman Khan
      First page: 1061
      Abstract: Rapid urbanization has increased human-animal interaction and consequently enhanced the chances to acquire zoonotic diseases. The current investigation is focused to uncover the genetic diversity of multidrug-resistant E. coli strains between different ecologies (i.e., humans, livestock, and environment) at the molecular level by employing antimicrobial resistance profiling, virulence genes profiling, and microbial typing approach using ERIC PCR. Based on multiple antibiotic resistance, overall, 19 antibiotic resistance patterns (R1–R19) were observed. Most of the strains (49/60) were detected to have the combinations of stx, eaeA, and hlyA genes and considered STEC/EPEC/EHEC. A total of 18 unique genetic profiles were identified based on ERIC-PCR fingerprints and most of the strains (13) belong to P1 whereas the least number of strains were showing profiles P7 and P8-P11 (one member each profile). The calculated values for Shannon index (H) for human, animal, and environment are 1.70, 1.82, and 1.78, respectively revealing the highest genetic diversity among the E. coli strains of animal origin. The study revealed that drug-resistant pathogenic E. coli strains could be transmitted bidirectionally among the environment, humans, and animals.
      Citation: Antibiotics
      PubDate: 2022-08-04
      DOI: 10.3390/antibiotics11081061
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1062: Synthetic Antimicrobial Immunomodulatory
           Peptides: Ongoing Studies and Clinical Trials

    • Authors: Małgorzata Lesiuk, Małgorzata Paduszyńska, Katarzyna E. Greber
      First page: 1062
      Abstract: The increasingly widespread antimicrobial resistance forces the search for new antimicrobial substances capable of fighting infection. Antimicrobial peptides (AMPs) and their synthetic analogs form an extensive group of compounds of great structural diversity and multifunctionality, different modes of antimicrobial action, and considerable market potential. Some AMPs, in addition to their proven antibacterial, antifungal, and antiviral activity, also demonstrate anti-inflammatory and immunomodulatory capabilities; these are called innate defense regulator (IDR) peptides. IDR peptides stimulate or inhibit the body’s immune system, e.g., by stimulating leukocyte migration to the site of infection, driving macrophage differentiation and activation, providing chemotactic action for neutrophils, degranulation and activation of mast cells, altering chemokine and cytokine production, and even induction of angiogenesis and wound healing. Such multifunctional immunomodulatory peptide molecules are currently being investigated and developed. Exploring and utilizing IDR peptides as an indirect weapon against infectious diseases could represent a completely new strategy to cope with the issue of antimicrobial resistance.
      Citation: Antibiotics
      PubDate: 2022-08-05
      DOI: 10.3390/antibiotics11081062
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1063: Azithromycin through the Lens of the
           COVID-19 Treatment

    • Authors: Georgia G. Kournoutou, George Dinos
      First page: 1063
      Abstract: Azithromycin has become famous in the last two years, not for its main antimicrobial effect, but for its potential use as a therapeutic agent for COVID-19 infection. Initially, there were some promising results that supported its use, but it has become clear that scientific results are insufficient to support such a positive assessment. In this review we will present all the literature data concerning the activity of azithromycin as an antimicrobial, an anti-inflammatory, or an antivirus agent. Our aim is to conclude whether its selection should remain as a valuable antivirus agent or if its use simply has an indirect therapeutic contribution due to its antimicrobial and/or immunomodulatory activity, and therefore, if its further use for COVID-19 treatment should be interrupted. This halt will prevent further antibiotic resistance expansion and will keep azithromycin as a valuable anti-infective therapeutic agent.
      Citation: Antibiotics
      PubDate: 2022-08-05
      DOI: 10.3390/antibiotics11081063
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1064: Antimicrobial Resistance Trends of
           Escherichia coli Isolates: A Three-Year Prospective Study of Poultry
           Production in Spain

    • Authors: Sandra Sevilla-Navarro, Pablo Catalá-Gregori, Jan Torres-Boncompte, Maria Teresa Orenga, Josep Garcia-Llorens, Verónica Cortés
      First page: 1064
      Abstract: Antimicrobial resistance (AMR) poses a major threat to health worldwide. Poultry products are one of the main threats, due to the transmission of antimicrobial resistance genes throughout the food chain. Escherichia coli is the main cause of mortality in the poultry industry, mainly mitigated with antibiotics, but due to the high genetic strain variability, recurrent outbreaks of multidrug resistant E. coli take place. The major challenge to tackling AMR is understanding the burden of resistance. For this reason, one of the main strategies is monitoring AMR by phenotypic characterisation. Our study aimed to monitor the resistance of E. coli strains isolated from the poultry sector over a period of three years (2019–2021) to provide information on the resistance magnitude and trends. Promising results have been found concerning the low frequency of resistance to cephalosporins, polymyxin, and fluoroquinolones. However, levels of resistance found to antimicrobials such as erythromycin (100%), tylosin (98%), or penicillin (97%) suggest the need to continue working on the limitation of use of antimicrobials in poultry to achieve the demise of MDR.
      Citation: Antibiotics
      PubDate: 2022-08-05
      DOI: 10.3390/antibiotics11081064
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1065: Transcriptional Regulator DasR Represses
           Daptomycin Production through Both Direct and Cascade Mechanisms in
           Streptomyces roseosporus

    • Authors: Qiong Chen, Jianya Zhu, Xingwang Li, Ying Wen
      First page: 1065
      Abstract: Daptomycin, produced by Streptomyces roseosporus, is a clinically important cyclic lipopeptide antibiotic used for the treatment of human infections caused by drug-resistant Gram-positive pathogens. In contrast to most Streptomyces antibiotic biosynthetic gene clusters (BGCs), daptomycin BGC has no cluster-situated regulator (CSR) genes. DasR, a GntR-family transcriptional regulator (TR) widely present in the genus, was shown to regulate antibiotic production in model species S. coelicolor by binding to promoter regions of CSR genes. New findings reported here reveal that DasR pleiotropically regulates production of daptomycin and reddish pigment, and morphological development in S. roseosporus. dasR deletion enhanced daptomycin production and morphological development, but reduced pigment production. DasR inhibited daptomycin production by directly repressing dpt structural genes and global regulatory gene adpA (whose product AdpA protein activates daptomycin production and morphological development). DasR-protected regions on dptEp and adpAp contained a 16 nt sequence similar to the consensus DasR-binding site dre in S. coelicolor. AdpA was shown to target dpt structural genes and dptR2 (which encodes a DeoR-family TR required for daptomycin production). A 10 nt sequence similar to the consensus AdpA-binding site was found on target promoter regions dptAp and dptR2p. This is the first demonstration that DasR regulates antibiotic production both directly and through a cascade mechanism. The findings expand our limited knowledge of the regulatory network underlying daptomycin production, and will facilitate methods for construction of daptomycin overproducers.
      Citation: Antibiotics
      PubDate: 2022-08-05
      DOI: 10.3390/antibiotics11081065
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1066: The Effect of Different Colistin Dosing
           Regimens on Nephrotoxicity: A Cohort Study

    • Authors: Michael Samarkos, Konstantinos Papanikolaou, Athena Sourdi, Nikolaos Paisios, Efstratios Mainas, Elisabeth Paramythiotou, Anastasia Antoniadou, Helen Sambatakou, Panayiotis Gargalianos-Kakolyris, Athanasios Skoutelis, George L. Daikos
      First page: 1066
      Abstract: (1) Background: It is not known whether different daily dosing schemes have different effects on colistin nephrotoxicity. We examined the effect of once- versus twice- or thrice-daily doses of colistin on renal function. (2) Methods: We performed a multicenter retrospective cohort study of hospitalized patients with a baseline glomerular filtration rate ≥ 50 mL/min who received intravenously the same colistin dose once (regimen A), twice (regimen B) or thrice daily (regimen C). The primary endpoint was acute kidney injury (AKI), defined as fulfilment of any of the RIFLE (Risk-Injury-Failure-Loss-End stage renal disease) criteria. (3) Results: We included 306 patients; 132 (43.1%) received regimen A, 151 (49.3%) regimen B, and 23 (7.5%) regimen C. Ninety-nine (32.4%) patients developed AKI; there was no difference between regimen A vs. B and C [45 (34.1%) vs. 54 (31.0%), p = 0.57]. In a propensity score–matched cohort, AKI was similar in patients receiving Regimen A, Regimen B, and Regimen C (31.6% vs. 33.3%, p = 0.78). On logistic regression analysis, diabetes was an independent predictor of AKI (OR = 4.59, 95% CI 2.03–10.39, p = 0.001) while eGFR > 80 mL/min (OR = 0.50, 95% CI 0.25–0.99, p = 0.048) was inversely associated with AKI. (4) Conclusions: Colistin once daily is not more nephrotoxic than the standard colistin regimens. The only independent predictor of nephrotoxicity was diabetes mellitus, while eGFR > 80 mL/min had a protective effect.
      Citation: Antibiotics
      PubDate: 2022-08-05
      DOI: 10.3390/antibiotics11081066
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1067: Actinomyces sp. Presence in the Bone
           Specimens of Patients with Osteonecrosis of the Jaw: The Histopathological
           Analysis and Clinical Implication

    • Authors: Norliwati Ibrahim, Nurul Inaas Mahamad Apandi, Syafiqah Aina Shuhardi, Roszalina Ramli
      First page: 1067
      Abstract: Medication-related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) are two similar bone pathologies in the jaw with different aetiologies. Actinomycosis is a relatively rare oral infection caused by the Gram-positive anaerobe Actinomyces sp. that normally colonizes the oral cavity. Actinomycosis is associated with the pathogenesis of both the MRONJ and ORN, as evident in our cases, and not just as a superficial contaminant. The clinical and histopathological aspects of the cases treated in our centre were also reported with a review of the literature. Clinical implication on the treatment of the cases was highlighted in view of the presence of this microorganism.
      Citation: Antibiotics
      PubDate: 2022-08-05
      DOI: 10.3390/antibiotics11081067
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1068: Fecal Carriage of Escherichia coli
           Harboring the tet(X4)-IncX1 Plasmid from a Tertiary Class-A Hospital in
           Beijing, China

    • Authors: Weishuai Zhai, Yingxin Tian, Dongyan Shao, Muchen Zhang, Jiyun Li, Huangwei Song, Chengtao Sun, Yang Wang, Dejun Liu, Ying Zhang
      First page: 1068
      Abstract: The emergence of the mobile tigecycline-resistance gene, tet(X4), poses a significant threat to public health. To investigate the prevalence and genetic characteristics of the tet(X4)-positive Escherichia coli in humans, 1101 human stool samples were collected from a tertiary class-A hospital in Beijing, China, in 2019. Eight E. coli isolates that were positive for tet(X4) were identified from clinical departments of oncology (n = 3), hepatology (n = 2), nephrology (n = 1), urology (n = 1), and general surgery (n = 1). They exhibited resistance to multiple antibiotics, including tigecycline, but remained susceptible to meropenem and polymyxin B. A phylogenetic analysis revealed that the clonal spread of four tet(X4)-positive E. coli from different periods of time or departments existed in this hospital, and three isolates were phylogenetically close to the tet(X4)-positive E. coli from animals and the environment. All tet(X4)-positive E. coli isolates contained the IncX1-plasmid replicon. Three isolates successfully transferred their tigecycline resistance to the recipient strain, C600, demonstrating that the plasmid-mediated horizontal gene transfer constitutes another critical mechanism for transmitting tet(X4). Notably, all tet(X4)-bearing plasmids identified in this study had a high similarity to several plasmids recovered from animal-derived strains. Our findings revealed the importance of both the clonal spread and horizontal gene transfer in the spread of tet(X4) within human clinics and between different sources.
      Citation: Antibiotics
      PubDate: 2022-08-06
      DOI: 10.3390/antibiotics11081068
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1069: Prevalence and Molecular
           Characterization of Extended-Spectrum β-Lactamase Producing
           Enterobacterales in Healthy Community Dogs in Israel

    • Authors: Anat Shnaiderman-Torban, Shiri Navon-Venezia, Hadar Baron, Wiessam Abu-Ahmad, Haya Arielly, Gal Zizelski Valenci, Israel Nissan, Yossi Paitan, Amir Steinman
      First page: 1069
      Abstract: Background: antimicrobial resistance is a global problem in human and veterinary medicine. We aimed to investigate the extended spectrum β-lactamase-producing Enterobacterales (ESBL-PE) gut colonization in healthy community dogs in Israel. Methods: Rectal swabs were sampled from 145 healthy dogs, enriched, plated on selective plates, sub-cultured to obtain pure cultures, and ESBL production was confirmed. Bacterial species and antibiotic susceptibility profiles were identified. WGS was performed on all of the ESBL-PE isolates and their resistomes were identified in silico. Owners’ questionnaires were collected for risk factor analysis. Results: ESBL-PE gut colonization rate was 6.2% (n = 9/145, 95% CI 2.9–11.5). Overall, ten isolates were detected (one dog had two isolates); the main species was Escherichia coli (eight isolates), belonging to diverse phylogenetic groups—B1, A and C. Two isolates were identified as Citrobacter braakii, and C. portucalensis. A phylogenetic analysis indicated that all of the isolates were genetically unrelated and sporadic. The isolates possessed diverse ESBL genes and antibiotic-resistance gene content, suggesting independent ESBL spread. In a multivariable risk factor analysis, coprophagia was identified as a risk factor for ESBL-PE gut colonization (p = 0.048, aOR = 4.408, 95% CI 1.014–19.169). Conclusions: healthy community dogs may be colonized with ESBL-PE MDR strains, some of which were previously reported in humans, that carry wide and diverse resistomes and may serve as a possible source for AMR.
      Citation: Antibiotics
      PubDate: 2022-08-07
      DOI: 10.3390/antibiotics11081069
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1070: Are the Newer Carbapenems of Any Value
           against Tuberculosis

    • Authors: Ximena Gonzalo, Francis Drobniewski
      First page: 1070
      Abstract: Our aim was to assess whether newer carbapenems with a better administration profile than meropenem (ertapenem, faropenem and tebipenem) were more effective against Mycobacterium tuberculosis including M/XDRTB and determine if there was a synergistic/antagonistic effect with amoxicillin or clavulanate (inhibitor of beta-lactamases that MTB possesses) in vitro. Whilst meropenem is given three times a day intravenously, ertapenem, though given parenterally, is given once a day, faropenem and tebipenem are given orally. Eighty-two clinical drug-sensitive and -resistant MTB strains and a laboratory strain, H37Rv, were assessed by a microdilution methodology against ertapenem, faropenem, tebipenem and meropenem with and without amoxicillin or clavulanic acid. Ertapenem showed a limited activity. The addition of amoxicillin and clavulanate did not translate into significant improvements in susceptibility. Sixty-two isolates (75.6%) exhibited susceptibility to faropenem; the addition of amoxicillin and clavulanate further reduced the MIC in some isolates. Faropenem showed a limited activity (MIC of 8 mg/L or lower) in 21 strains completely resistant to meropenem (MIC of 16 mg/L or higher). Fifteen of the meropenem-resistant strains were susceptible to tebipenem. Carbapenems’ activity has been reported extensively. However, there remains uncertainty as to which of them is most active against TB and what the testing methodology should be.
      Citation: Antibiotics
      PubDate: 2022-08-07
      DOI: 10.3390/antibiotics11081070
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1071: High Fecal Prevalence of mcr-Positive
           Escherichia coli in Veal Calves at Slaughter in France

    • Authors: Maryse Michèle Um, Véronique Dupouy, Nathalie Arpaillange, Clémence Bièche-Terrier, Frédéric Auvray, Eric Oswald, Hubert Brugère, Delphine Bibbal
      First page: 1071
      Abstract: The aim of this study was to determine the percentage of healthy veal calves carrying mcr-positive E. coli strains at the time of slaughter in France. Fecal samples were selectively screened for mcr-positive E. coli isolates using media supplemented with colistin. Screening for mcr genes was also carried out in E. coli isolates resistant to critically important antimicrobials used in human medicine recovered from the same fecal samples. Overall, 28 (16.5%) out of the 170 veal calves tested carried mcr-positive E. coli. As some calves carried several non-redundant mcr-positive strains, 41 mcr-positive E. coli were recovered. Thirty-one and seven strains were positive for mcr-1 and mcr-3 genes, respectively, while no strain was positive for the mcr-2 gene. Co-carriage of mcr-1 and mcr-3 was identified in three strains. All mcr-positive E. coli isolates, except one, were multidrug-resistant, with 56.1% being ciprofloxacin-resistant and 31.7% harboring blaCTX-M genes. All mcr-3-positive E. coli carried blaCTX-M genes, mainly blaCTX-M-55. This study highlights the high prevalence of mcr-positive E. coli strains in feces of veal calves at the time of slaughter. It also points out the multidrug (including ciprofloxacin) resistance of such strains and the co-occurrence of mcr-3 genes with blaCTX-M-55 genes.
      Citation: Antibiotics
      PubDate: 2022-08-08
      DOI: 10.3390/antibiotics11081071
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1072: Antimicrobial and Cytotoxic
           Cyathane-Xylosides from Cultures of the Basidiomycete Dentipellis fragilis

    • Authors: Winnie Chemutai Sum, Nico Mitschke, Hedda Schrey, Kathrin Wittstein, Harald Kellner, Marc Stadler, Josphat Clement Matasyoh
      First page: 1072
      Abstract: In our continued search for biologically active metabolites from cultures of rare Basidiomycota species, we found eight previously undescribed cyathane-xylosides from submerged cultures of Dentipellis fragilis, which were named dentifragilins A–H. In addition, the known cyathane derivatives striatal D and laxitextine A were isolated. All compounds were characterized by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) as well as by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Several of the compounds exhibited significant activities in standardized cell-based assays for the determination of antimicrobial and cytotoxic effects. The discovery of cyathanes in the genus Dentipellis has chemotaxonomic implications, as this class of diterpenoids has already been shown to be characteristic for mycelial cultures of the related genera Hericium and Laxitextum, which are classified as Dentipellis in the family Hericiaceae.
      Citation: Antibiotics
      PubDate: 2022-08-08
      DOI: 10.3390/antibiotics11081072
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1073: Thymol as an Adjuvant to Restore
           Antibiotic Efficacy and Reduce Antimicrobial Resistance and Virulence Gene
           Expression in Enterotoxigenic Escherichia coli Strains

    • Authors: Andrea Bonetti, Benedetta Tugnoli, Andrea Piva, Ester Grilli
      First page: 1073
      Abstract: The continuous spread of antimicrobial resistance is endangering the efficient control of enterotoxigenic Escherichia coli (ETEC), which is mainly responsible for post-weaning diarrhea onset in piglets. Thymol, the key constituent of thyme essential oil, is already used in animal nutrition for its antimicrobial action. The aim of this study was to investigate the potential adjuvant effect of thymol to re-establish antibiotic efficacy against highly resistant ETEC field strains. Secondly, we evaluated the modulation of virulence and antibiotic resistance genes. Thymol showed the capacity to control ETEC growth and, when combined with ineffective antibiotics, it increased their antimicrobial power. In particular, it showed significant effects when blended with colistin and tetracycline, suggesting that the adjuvant effects rely on the presence of complementary mechanisms of action between molecules, or the absence of resistance mechanisms that inactivate antibiotics and target sites. Furthermore, our findings demonstrate that, when added to antibiotics, thymol can help to further downregulate several virulence and antibiotic resistance genes, offering new insights on the potential mechanisms of action. Therefore, in a one-health approach, our study supports the beneficial effects of combining thymol with antibiotics to restore their efficacy, together with the possibility of targeting gene expression as a pioneering approach to manage ETEC pathogenicity.
      Citation: Antibiotics
      PubDate: 2022-08-08
      DOI: 10.3390/antibiotics11081073
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1074: Short Tryptamine-Based Peptoids as
           Potential Therapeutics for Microbial Keratitis: Structure-Function
           Correlation Studies

    • Authors: Ghayah Bahatheg, Rajesh Kuppusamy, Muhammad Yasir, David StC. Black, Mark Willcox, Naresh Kumar
      First page: 1074
      Abstract: Peptoids are peptidomimetics that have attracted considerable interest as a promising class of antimicrobials against multi-drug-resistant bacteria due to their resistance to proteolysis, bioavailability, and thermal stability compared to their corresponding peptides. Staphylococcus aureus is a significant contributor to infections worldwide and is a major pathogen in ocular infections (keratitis). S. aureus infections can be challenging to control and treat due to the development of multiple antibiotic resistance. This work describes short cationic peptoids with activity against S. aureus strains from keratitis. The peptoids were synthesized via acid amine-coupling between naphthyl-indole amine or naphthyl-phenyl amine with different amino acids to produce primary amines (series I), mono-guanidines (series II), tertiary amine salts (series III), quaternary ammonium salts (series IV), and di-guanidine (series V) peptoids. The antimicrobial activity of the peptoids was compared with ciprofloxacin, an antibiotic that is commonly used to treat keratitis. All new compounds were active against Staphylococcus aureus S.aureus 38. The most active compounds against S.aur38 were 20a and 22 with MIC = 3.9 μg mL−1 and 5.5 μg mL−1, respectively. The potency of these two active molecules was investigated against 12 S. aureus strains that were isolated from microbial keratitis. Compounds 20a and 22 were active against 12 strains with MIC = 3.2 μg mL−1 and 2.1 μg mL−1, respectively. There were two strains that were resistant to ciprofloxacin (Sa.111 and Sa.112) with MIC = 128 μg mL−1 and 256 μg mL−1, respectively. Compounds 12c and 13c were the most active against E. coli, with MIC > 12 μg mL−1. Cytoplasmic membrane permeability studies suggested that depolarization and disruption of the bacterial cell membrane could be a possible mechanism for antibacterial activity and the hemolysis studies toward horse red blood cells showed that the potent compounds are non-toxic at up to 50 μg mL−1.
      Citation: Antibiotics
      PubDate: 2022-08-08
      DOI: 10.3390/antibiotics11081074
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1075: Occurrence, Phenotypic and Molecular
           Characteristics of Extended-Spectrum Beta-Lactamase-Producing Escherichia
           coli in Healthy Turkeys in Northern Egypt

    • Authors: Amira A. Moawad, Helmut Hotzel, Hafez M. Hafez, Hazem Ramadan, Herbert Tomaso, Sascha D. Braun, Ralf Ehricht, Celia Diezel, Dominik Gary, Ines Engelmann, Islam M. Zakaria, Reem M. Reda, Samah Eid, Momtaz A. Shahien, Heinrich Neubauer, Stefan Monecke
      First page: 1075
      Abstract: Poultry is one of the most important reservoirs for zoonotic multidrug-resistant pathogens. The indiscriminate use of antimicrobials in poultry production is a leading factor for development and dissemination of antimicrobial resistance. This study aimed to describe the prevalence and antimicrobial resistance of E. coli isolated from healthy turkey flocks of different ages in Nile delta region, Egypt. In the current investigation, 250 cloacal swabs were collected from 12 turkey farms in five governorates in the northern Egypt. Collected samples were cultivated on BrillianceTM ESBL agar media supplemented with cefotaxime (100 mg/L). The E. coli isolates were identified using MALDI-TOF-MS and confirmed by a conventional PCR assay targeting 16S rRNA-DNA. The phenotypic antibiogram against 14 antimicrobial agents was determined using the broth micro-dilution method. DNA-microarray-based assay was applied for genotyping and determination of both, virulence and resistance-associated gene markers. Multiplex real-time PCR was additionally applied for all isolates for detection of the actual most relevant Carbapenemase genes. The phenotypic identification of colistin resistance was carried out using E-test. A total of 26 E. coli isolates were recovered from the cloacal samples. All isolates were defined as multidrug-resistant. Interestingly, two different E. coli strains were isolated from one sample. Both strains had different phenotypic and genotypic profiles. All isolates were phenotypically susceptible to imipenem, while resistant to penicillin, rifampicin, streptomycin, and erythromycin. None of the examined carbapenem resistance genes was detected among isolates. At least one beta-lactamase gene was identified in most of isolates, where blaTEM was the most commonly identified determinant (80.8%), in addition to blaCTX-M9 (23.1%), blaSHV (19.2%) and blaOXA-10 (15.4%). Genes associated with chloramphenicol resistance were floR (65.4%) and cmlA1 (46.2%). Tetracycline- and quinolone-resistance-associated genes tetA and qnrS were detected in (57.7%) and (50.0%) of isolates, respectively. The aminoglycoside resistance associated genes aadA1 (65.4%), aadA2 (53.8%), aphA (50.0%), strA (69.2%), and strB (65.4%), were detected among isolates. Macrolide resistance associated genes mph and mrx were also detected in (53.8%) and (34.6%). Moreover, colistin resistance associated gene mcr-9 was identified in one isolate (3.8%). The class 1 integron integrase intI1 (84.6%), transposase for the transposon tnpISEcp1 (34.6%) and OqxB -integral membrane and component of RND-type multidrug efflux pump oqxB (7.7%) were identified among the isolates. The existing high incidence of ESBL/colistin-producing E. coli identified in healthy turkeys is a major concern that demands prompt control; otherwise, such strains and their resistance determinants could be transmitted to other bacteria and, eventually, to people via the food chain.
      Citation: Antibiotics
      PubDate: 2022-08-08
      DOI: 10.3390/antibiotics11081075
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1076: Control of Healthcare-Associated
           Carbapenem-Resistant Acinetobacter baumannii by Enhancement of Infection
           Control Measures

    • Authors: Shuk-Ching Wong, Pui-Hing Chau, Simon Yung-Chun So, Germaine Kit-Ming Lam, Veronica Wing-Man Chan, Lithia Lai-Ha Yuen, Christine Ho-Yan Au Yeung, Jonathan Hon-Kwan Chen, Pak-Leung Ho, Kwok-Yung Yuen, Vincent Chi-Chung Cheng
      First page: 1076
      Abstract: Antimicrobial stewardship and infection control measures are equally important in the control of antimicrobial-resistant organisms. We conducted a retrospective analysis of the incidence rate of hospital-onset carbapenem-resistant Acinetobacter baumannii (CRAB) infection (per 1000 patient days) in the Queen Mary Hospital, a 1700-bed, university-affiliated teaching hospital, from period 1 (1 January 2007 to 31 December 2013) to period 2 (1 January 2014 to 31 December 2019), where enhanced infection control measures, including directly observed hand hygiene before meal and medication rounds to conscious patients, and the priority use of single room isolation, were implemented during period 2. This study aimed to investigate the association between enhanced infection control measures and changes in the trend in the incidence rate of hospital-onset CRAB infection. Antimicrobial consumption (defined daily dose per 1000 patient days) was monitored. Interrupted time series, in particular segmented Poisson regression, was used. The hospital-onset CRAB infection increased by 21.3% per year [relative risk (RR): 1.213, 95% confidence interval (CI): 1.162–1.266, p < 0.001], whereas the consumption of the extended spectrum betalactam-betalactamase inhibitor (BLBI) combination and cephalosporins increased by 11.2% per year (RR: 1.112, 95% CI: 1.102–1.122, p < 0.001) and 4.2% per year (RR: 1.042, 95% CI: 1.028–1.056, p < 0.001), respectively, in period 1. With enhanced infection control measures, the hospital-onset CRAB infection decreased by 9.8% per year (RR: 0.902, 95% CI: 0.854–0.953, p < 0.001), whereas the consumption of the extended spectrum BLBI combination and cephalosporins increased by 3.8% per year (RR: 1.038, 95% CI: 1.033–1.044, p < 0.001) and 7.6% per year (RR: 1.076, 95% CI: 1.056–1.097, p < 0.001), respectively, in period 2. The consumption of carbapenems increased by 8.4% per year (RR: 1.84, 95% CI: 1.073–1.094, p < 0.001) in both period 1 and period 2. The control of healthcare-associated CRAB could be achieved by infection control measures with an emphasis on directly observed hand hygiene, despite an increasing trend of antimicrobial consumption.
      Citation: Antibiotics
      PubDate: 2022-08-08
      DOI: 10.3390/antibiotics11081076
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1077: Environmental Bovine Mastitis Pathogens:
           Prevalence, Antimicrobial Susceptibility, and Sensitivity to Thymus
           vulgaris L., Thymus serpyllum L., and Origanum vulgare L. Essential Oils

    • Authors: Dragana Tomanić, Biljana Božin, Nebojša Kladar, Jovan Stanojević, Ivana Čabarkapa, Nebojša Stilinović, Jelena Apić, Dragana D. Božić, Zorana Kovačević
      First page: 1077
      Abstract: Mastitis is considered to be one of the most important diseases of dairy cows in terms of health, production, and economy. Being the most common cause of antibiotic consumption in dairy cows, treatment of this disease is one of the biggest challenges in the veterinary profession as an increasing number of pathogens develop resistance to antibiotics used in the treatment. Therefore, new alternative approaches for limiting the use of antibiotics in livestock are required. For this reason, our study aimed to investigate prevalence of environmental mastitis associated bacterial strains, as well as the sensitivity of isolated strains to different antibiotics. Additionally, the therapeutic potential of three essential oils (EOs) was tested against bovine Serratia spp. and Proteus spp. mastitis pathogens, based on their chemical composition, as well as antibacterial potential. The study was carried out on 81 milk samples collected from dairy cows with mastitis. In order to determine prevalence of S. marcescens and P. mirabilis, microbiological isolation and identification were performed. Antimicrobial susceptibility testing was performed by disk diffusion method and the microdilution method was used to determine the antibacterial activity of selected EOs. In the oregano EO, a total of 23 compounds were detected, with carvacrol as a dominant component (78.94%). A total of 26 components were present in the EO of common thyme, where thymol was the most abundant compound (46.37%). Thymol also dominated (55.11%) the wild thyme EO. All tested EOs displayed antibacterial activity against all strains to different extents, while wild and common thyme EOs were the most effective. It could be concluded that the tested EOs represent promising therapeutic candidates for effective non-antibiotic treatment of mastitis.
      Citation: Antibiotics
      PubDate: 2022-08-09
      DOI: 10.3390/antibiotics11081077
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1078: Factors Influencing Disease Stability
           and Response to Tocilizumab Therapy in Severe COVID-19: A Retrospective
           Cohort Study

    • Authors: Wael Hafez, Ahmed Abdelrahman
      First page: 1078
      Abstract: (1) Background: The efficacy of tocilizumab in COVID-19 has been doubted. The study aimed to investigate factors affecting disease stability and response to tocilizumab among severe COVID-19 patients. (2) Methods: This was a cohort study of 70 severe COVID-19 patients at NMC Royal Hospital, UAE, from April to June 2020. (3) Results: Elderly patients and those with cardiovascular comorbidities had a higher risk of unstable COVID-19 (p = 0.025). Regarding tocilizumab therapy timing, compared to the critical group receiving tocilizumab, the unstable severe patients receiving tocilizumab had a significantly higher rate of improvement (86%). In contrast, the late critical subgroup showed a significantly increased mortality rate (52.9%). The risk for secondary infection and adverse events following tocilizumab was higher in the late critical group than in the unstable severe and early critical groups (p = 0.024 and p = 0.006, respectively). Therapeutic doses of anticoagulation and high-dose vitamin D were correlated with better outcomes than the prophylactic dose and the treatment dose of vitamin D (p < 0.001 and p = 0.07, respectively). (4) Conclusions: elderly patients and those with cardiovascular disease developed unstable COVID-19. Tocilizumab is a potentially effective choice against severe and critical COVID-19. Early tocilizumab administration combined with therapeutic dose anticoagulation and high vitamin D doses could improve the patients’ outcomes.
      Citation: Antibiotics
      PubDate: 2022-08-09
      DOI: 10.3390/antibiotics11081078
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1079: Antibiotic Resistance in
           Bacteria—A Review

    • Authors: Renata Urban-Chmiel, Agnieszka Marek, Dagmara Stępień-Pyśniak, Kinga Wieczorek, Marta Dec, Anna Nowaczek, Jacek Osek
      First page: 1079
      Abstract: Background: A global problem of multi-drug resistance (MDR) among bacteria is the cause of hundreds of thousands of deaths every year. In response to the significant increase of MDR bacteria, legislative measures have widely been taken to limit or eliminate the use of antibiotics, including in the form of feed additives for livestock, but also in metaphylaxis and its treatment, which was the subject of EU Regulation in 2019/6. Numerous studies have documented that bacteria use both phenotypis and gentic strategies enabling a natural defence against antibiotics and the induction of mechanisms in increasing resistance to the used antibacterial chemicals. The mechanisms presented in this review developed by the bacteria have a significant impact on reducing the ability to combat bacterial infections in humans and animals. Moreover, the high prevalence of multi-resistant strains in the environment and the ease of transmission of drug-resistance genes between the different bacterial species including commensal flora and pathogenic like foodborne pathoges (E. coli, Campylobacter spp., Enterococcus spp., Salmonella spp., Listeria spp., Staphylococcus spp.) favor the rapid spread of multi-resistance among bacteria in humans and animals. Given the global threat posed by the widespread phenomenon of multi-drug resistance among bacteria which are dangerous for humans and animals, the subject of this study is the presentation of the mechanisms of resistance in most frequent bacteria called as “foodborne pathoges” isolated from human and animals. In order to present the significance of the global problem related to multi-drug resistance among selected pathogens, especially those danger to humans, the publication also presents statistical data on the percentage range of occurrence of drug resistance among selected bacteria in various regions of the world. In addition to the phenotypic characteristics of pathogen resistance, this review also presents detailed information on the detection of drug resistance genes for specific groups of antibiotics. It should be emphasized that the manuscript also presents the results of own research i.e., Campylobacter spp., E. coli or Enetrococcus spp. This subject and the presentation of data on the risks of drug resistance among bacteria will contribute to initiating research in implementing the prevention of drug resistance and the development of alternatives for antimicrobials methods of controlling bacteria.
      Citation: Antibiotics
      PubDate: 2022-08-09
      DOI: 10.3390/antibiotics11081079
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1080: C-Locked Analogs of the Antimicrobial
           Peptide BP214

    • Authors: Ida Kristine Lysgaard Andersen, Thomas T. Thomsen, Jasmina Rashid, Thomas Rønnemoes Bobak, Alberto Oddo, Henrik Franzyk, Anders Løbner-Olesen, Paul R. Hansen
      First page: 1080
      Abstract: BP214 is an all-D antimicrobial peptide amide, kklfkkilryl, which shows an excellent activity against colistin-resistant Acinetobacter baumannii and a low hemolytic activity. The aim of the present work was to investigate how C-terminus-to-side chain macrocyclization and fatty acid modification affect the antimicrobial and hemolytic activity of this peptide. In total, 18 analogs of BP214 were synthesized using a combination of Fmoc-based solid-phase peptide synthesis and the submonomer approach. Cyclization was achieved by reacting the ε-amino group of a C-terminal lysine residue with a bromoacetylgroup attached to the Nαamino group of the N-terminal amino acid, generating a secondary amine at which the exocyclic lipopeptide tail was assembled. Three different ring sizes (i.e., 3–5 amino acid residues) of C-locked analogs combined with fatty acids of different lengths (i.e., C10–C14) were investigated. The antimicrobial activity of the analogs was tested against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The most promising compound was analog 13 (MIC = 4 µg/mL (2.4 µM) against E. coli and 36% hemolysis of red blood cells at 150 µM). In a time-kill assay, this peptide showed a significant, concentration-dependent reduction in viable E. coli cells comparable to that seen for colistin.
      Citation: Antibiotics
      PubDate: 2022-08-09
      DOI: 10.3390/antibiotics11081080
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1081: Exploring the Use of Antibiotics for
           Dental Patients in a Middle-Income Country: Interviews with Clinicians in
           Two Ghanaian Hospitals

    • Authors: Jacqueline Sneddon, Wendy Thompson, Lily N. A. Kpobi, Diana Abena Ade, Israel Abebrese Sefah, Daniel Afriyie, Joanna Goldthorpe, Rebecca Turner, Saher Nawaz, Shona Wilson, Jo Hart, Lucie Byrne-Davis
      First page: 1081
      Abstract: Background: Antimicrobial resistance is a global problem driven by the overuse of antibiotics. Dentists are responsible for about 10% of antibiotics usage across healthcare worldwide. Factors influencing dental antibiotic prescribing are numerous, with some differences in low- and middle-income countries compared with high-income countries. This study aimed to explore the antibiotic prescribing behaviour and knowledge of teams treating dental patients in two Ghanaian hospitals.. Methods: Qualitative interviews were undertaken with dentists, pharmacists, and other healthcare team members at two hospitals in urban and rural locations. Thematic and behaviour analyses using the Actor, Action, Context, Target, Time framework were undertaken. Results: Knowledge about ‘antimicrobial resistance and antibiotic stewardship’ and ‘people and places’ were identified themes. Influences on dental prescribing decisions related to the organisational context (such as the hierarchical influence of colleagues and availability of specific antibiotics in the hospital setting), clinical issues (such as therapeutic versus prophylactic indications and availability of sterile dental instruments), and patient issues such as hygiene in the home environment, delays in seeking professional help, ability to access antibiotics in the community without a prescription and patient’s ability to pay for the complete prescription. Conclusions: This work provides new evidence on behavioural factors influencing dental antibiotic prescribing, including resource constraints which affect the availability of certain antibiotics and diagnostic tests. Further research is required to fully understand their influence and inform the development of new approaches to optimising antibiotic use by dentists in Ghana and potentially other low- and middle-income countries.
      Citation: Antibiotics
      PubDate: 2022-08-09
      DOI: 10.3390/antibiotics11081081
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1082: Antimicrobial Resistance and Its Spread
           Is a Global Threat

    • Authors: Mohammed M. Aljeldah
      First page: 1082
      Abstract: Antimicrobial resistance (AMR) is a challenge to human wellbeing the world over and is one of the more serious public health concerns. AMR has the potential to emerge as a serious healthcare threat if left unchecked, and could put into motion another pandemic. This establishes the need for the establishment of global health solutions around AMR, taking into account microdata from different parts of the world. The positive influences in this regard could be establishing conducive social norms, charting individual and group behavior practices that favor global human health, and lastly, increasing collective awareness around the need for such action. Apart from being an emerging threat in the clinical space, AMR also increases treatment complexity, posing a real challenge to the existing guidelines around the management of antibiotic resistance. The attribute of resistance development has been linked to many genetic elements, some of which have complex transmission pathways between microbes. Beyond this, new mechanisms underlying the development of AMR are being discovered, making this field an important aspect of medical microbiology. Apart from the genetic aspects of AMR, other practices, including misdiagnosis, exposure to broad-spectrum antibiotics, and lack of rapid diagnosis, add to the creation of resistance. However, upgrades and innovations in DNA sequencing technologies with bioinformatics have revolutionized the diagnostic industry, aiding the real-time detection of causes of AMR and its elements, which are important to delineating control and prevention approaches to fight the threat.
      Citation: Antibiotics
      PubDate: 2022-08-09
      DOI: 10.3390/antibiotics11081082
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1083: In Vitro Study of the Interaction of
           Gentamicin with Ceftriaxone and Azithromycin against Neisseria gonorrhoeae
           Using Agar Dilution Method

    • Authors: Wenqi Xu, Qian Zhou, Jingwei Liu, Yan Zhang, Xiaoyu Zhu, Bangyong Zhu, Yueping Yin
      First page: 1083
      Abstract: The susceptibility to gentamicin of N. gonorrhoeae isolates collected in three Chinese provinces and the correlation among the MICs of gentamicin, azithromycin, and ceftriaxone were investigated in this study. The effects of combinations from those three antibiotics were also in the scope of this study to determine the efficacy of gentamicin as a combination therapeutic drug. The agar dilution method was used to measure the minimum inhibitory concentrations (MICs) of ceftriaxone, azithromycin and gentamicin on N. gonorrhoeae isolates. The synergy between these three antimicrobials were determined using the agar dilution checkerboard method. Subgroup studies were conducted to explore differences between azithromycin- and ceftriaxone-sensitive and resistant isolates. A total of 139 (36.60%) and 233 (61.30%) isolates demonstrated full susceptibility and intermediate susceptibility to gentamicin, respectively. The correlation analysis showed that the MICs of ceftriaxone and azithromycin weakly correlated with the value of gentamicin. The overall results of the three antibiotic combinations revealed indifferent effects. Combination therapy established a significant reduction on the MIC value. Most of the N. gonorrhoeae isolates tested in this study demonstrated a certain degree of susceptibility to gentamicin. Overall, antimicrobial combinations of gentamicin with ceftriaxone or azithromycin demonstrate indifferent effects.
      Citation: Antibiotics
      PubDate: 2022-08-10
      DOI: 10.3390/antibiotics11081083
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1084: Survey of the Knowledge, Attitudes and
           Practice towards Antibiotic Use among Prospective Antibiotic Prescribers
           in Serbia

    • Authors: Olga Horvat, Ana Tomas Petrović, Milica Paut Kusturica, Dragica Bukumirić, Bojana Jovančević, Zorana Kovačević
      First page: 1084
      Abstract: The complex issue of antibacterial resistance (ABR) requires actions taken with the One Health approach, involving both human and veterinarian medicine. It can spread from animals to humans through the food chain or through direct contact. Health profession students, as the future antibiotic providers, can greatly impact antibiotic-related issues in the future. The study was conducted to evaluate knowledge, attitudes and practice of future antibiotic prescribers in relation to judicious use of antibiotics. This cross-sectional, questionnaire-based study was performed on 400 students of health professions who were allowed to prescribe antibiotics of the University of Novi Sad, Serbia. Students of medicine and students of dentistry showed a significantly higher knowledge score compared to students of veterinary medicine (p = 0.001). Multivariate regression identified predictors of adequate antibiotic knowledge: being a female student (B = 0.571; p = 0.020), higher grade average (B = 1.204; p = 0.001), students of medicine (B = 0.802; p = 0.006) and dentistry (B = 0.769; p = 0.026), and students who used a complete package of antibiotics during the last infection (B = 0.974; p = 0.001) or for the period recommended by the doctor (B = 1.964; p = 0.001). Out of the total sample, self-medication was reported among 42.8% of students. The identified predictors of self-medication were: more frequent (B = 0.587; p = 0.001) and irregular (B = 0.719; p = 0.007) antibiotic use, taking antibiotics until symptoms disappeared (B = 2.142; p = 0.001) or until the bottle was finished (B = 1.010; p = 0.001) during the last infection. It seems prudent to reevaluate the educational curricula regarding antibiotic use and ABR of prospective prescribers in Serbia.
      Citation: Antibiotics
      PubDate: 2022-08-10
      DOI: 10.3390/antibiotics11081084
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1085: Design and Evaluation of Short Bovine
           Lactoferrin-Derived Antimicrobial Peptides against Multidrug-Resistant
           Enterococcus faecium

    • Authors: Biswajit Mishra, LewisOscar Felix, Anindya Basu, Sai Sundeep Kollala, Yashpal Singh Chhonker, Narchonai Ganesan, Daryl J. Murry, Eleftherios Mylonakis
      First page: 1085
      Abstract: Enterococcus faecium has become an important drug-resistant nosocomial pathogen because of widespread antibiotic abuse. We developed short and chemically simple antimicrobial peptides (AMPs) with a selective amino acid composition, fixed charge, and hydrophobicity ratio based on the core antimicrobial motif of bovine lactoferrin (LfcinB6). Among these peptides, 5L and 6L (both 12 residues long) demonstrated a narrow spectrum and high antibacterial activity against drug-resistant E. faecium isolates with a minimal inhibitory concentration (MIC) that ranged from 4–16 µg/mL. At 32 µg/mL, peptides 5L and 6L inhibited E. faecium strain C68 biofilm formation by 90% and disrupted established biofilms by 75%. At 40 µg/mL, 5L reduced 1 × 107E. faecium persister cells by 3 logs within 120 min of exposure, whereas 6L eliminated all persister cells within 60 min. At 0.5× MIC, 5L and 6L significantly downregulated the expression of a crucial biofilm gene ace by 8 folds (p = 0.02) and 4 folds (p = 0.01), respectively. At 32 µg/mL, peptides 5L and 6L both depolarized the E. faecium membrane, increased fluidity, and eventually ruptured the membrane. Physiologically, 5L (at 8 µg/mL) altered the tricarboxylic acid cycle, glutathione, and purine metabolism. Interestingly, in an ex vivo model of porcine skin infection, compared to no treatment, 5L (at 10× MIC) effectively eliminated all 1 × 106 exponential (p = 0.0045) and persister E. faecium cells (p = 0.0002). In conclusion, the study outlines a roadmap for developing narrow-spectrum selective AMPs and presents peptide 5L as a potential therapeutic candidate to be explored against E. faecium.
      Citation: Antibiotics
      PubDate: 2022-08-10
      DOI: 10.3390/antibiotics11081085
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1086: Acinetobacter baumannii
           Infection-Related Mortality in Hospitalized Patients: Risk Factors and
           Potential Targets for Clinical and Antimicrobial Stewardship Interventions

    • Authors: Diaa Alrahmany, Ahmed F. Omar, Aisha Alreesi, Gehan Harb, Islam M. Ghazi
      First page: 1086
      Abstract: Due to resistance and scarcity of treatment options, nosocomial Acinetobacter baumannii infections are associated with significant fatality rates. We investigated the factors contributing to infection-related deaths to develop tailored stewardship interventions that could reduce these high mortality rates. We reviewed the medical records of adult inpatients with A. baumannii infections over two years. Patient demographics and clinical data were collected and statistically analyzed. The study included 321 patients with positive A. baumannii microbiological cultures, with respiratory infections accounting for 58.6%, soft tissues 29.3%, bacteremia 8.6%, urine 2.1%, and others 1.4%. The study population’s median (IQR) age was 62.6 (38.9–94.9) years, and hospital stay was 20 (9.5–40) days. Statistical analysis revealed that various risk factors contribute significantly to high in-hospital all-cause mortality (44%), as well as 14-day and 28-day mortality rates. Deaths increased by a factor of 1.04 with every additional year of age (p = 0.000), admission to the critical care unit (p = 0.000, OR: 2.86), and patients admitted with an infectious diagnosis had nearly three times the mortality rate as those admitted with other diagnoses (p = 0.000, OR: 3.12). Male gender (p < 0.001, OR: 2.14), any comorbid conditions (p = 0.000, OR: 5.29), prolonged hospitalization (>7 days) (p = 0.023, OR: 1.98), and hospital acquisition of infection (p = 0.027, OR: 1.68) were among the most significant predictors of mortality. All variables were investigated for their impact on all-cause, 14-day, and 28-day mortality rates. Improving multidisciplinary infection control practices, regular disinfection of patient care equipment, and optimal intubation practice that avoids unnecessary intubation are necessary interventions to reduce infection-related mortality rates. Better antibiotic selection and de-escalation, shorter hospital stays whenever possible, prompt medical stabilization of comorbid conditions, and fewer unnecessary admissions to critical care units will all lead to improved outcomes.
      Citation: Antibiotics
      PubDate: 2022-08-10
      DOI: 10.3390/antibiotics11081086
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1087: Prevalence and Antimicrobial Resistance
           of Virulent Listeria monocytogenes and Cronobacter sakazakii in Dairy
           Cattle, the Environment, and Dried Milk with the In Vitro Application of
           Natural Alternative Control

    • Authors: Basma Badawy, Mayada Gwida, Asmaa Sadat, Marwa EL-Toukhy, Mohamed Sayed-Ahmed, Nawazish Alam, Sarfaraz Ahmad, MD Sajid Ali, Mahmoud Elafify
      First page: 1087
      Abstract: This study aims to detect the prevalence and antimicrobial resistance of Listeria monocytogenes and Cronobacter sakazakii in three dairy households and dried milk from different suppliers, and evaluate the antimicrobial effect of rose water, rose, and orange essential oils. In total, 360 samples were collected from cattle, the environment, and dried milk (n = 30). Antimicrobial activity was evaluated with twofold microtube dilution and the time-kill method. L. monocytogenes was identified in all households (13.3%) with a prevalence in the range of 5.8–17.5%, while C. sakazakii was identified in one household (5.3%). The former and latter pathogens were highly isolated from the feces at 20% and 2.5% and bedding at 12.5% and 1.6%, respectively. L. monocytogenes was isolated only from milk at 7.5%, but C. sakazakii was not detected in either milk or dried milk. L. monocytogenes strains were screened for virulence genes (iap, hylA, and actA). All strains were positive for the iap gene, while for hlyA and actA, the percentages were (35.4% 16.6%, respectively). L. monocytogenes strains showed high resistance against sulfamethoxazole–trimethoprim (100%), followed by gentamicin, penicillin, and imipenem (95.8%, 95.8%, and 91.6%, respectively). All C. sakazakii strains were susceptible to all tested antibiotics. The bactericidal activity of orange oil was the strongest, appeared after 1 h for both pathogens, followed by rose oil and then rose water.
      Citation: Antibiotics
      PubDate: 2022-08-10
      DOI: 10.3390/antibiotics11081087
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1088: Therapeutic Options and Outcomes for the
           Treatment of Neonates and Preterms with Gram-Negative Multidrug-Resistant
           Bacteria: A Systematic Review

    • Authors: Lorenzo Chiusaroli, Cecilia Liberati, Maria Caseti, Luigi Rulli, Elisa Barbieri, Carlo Giaquinto, Daniele Donà
      First page: 1088
      Abstract: (1) Background: Infections caused by multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria represent a challenge in the neonatal population due to disease severity and limited therapeutic possibilities compared to adults. The spread of antimicrobial resistance and drug availability differ significantly worldwide. The incidence of MDR bacteria has constantly risen, causing an increase in morbidity, mortality, and healthcare costs in both high-income (HIC) and low- and middle-income countries (LMIC). Therefore, more evidence is needed to define the possible use of newer molecules and to optimize combination regimens for the oldest antimicrobials in neonates. This systematic review aims to identify and critically appraise the current antimicrobial treatment options and the relative outcomes for MDR and XDR Gram-negative bacterial infections in the neonatal population. (2) Methods: A literature search for the treatment of MDR Gram-negative bacterial infections in neonates (term and preterm) was conducted in Embase, MEDLINE, and Cochrane Library. Studies reporting data on single-patient-level outcomes related to a specific antibiotic treatment for MDR Gram-negative bacterial infection in children were included. Studies reporting data from adults and children were included if single-neonate-level information could be identified. We focused our research on four MDROs: Enterobacterales producing extended-spectrum beta-lactamase (ESBL) or carbapenemase (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii. PROSPERO registration: CRD42022346739 (3) Results: The search identified 11,740 studies (since January 2000), of which 22 fulfilled both the inclusion and exclusion criteria and were included in the analysis. Twenty of these studies were conducted in LMIC. Colistin is the main studied and used molecule to treat Gram-negative MDR bacteria for neonate patients in the last two decades, especially in LMIC, with variable evidence of efficacy. Carbapenems are still the leading antibiotics for ESBL Enterobacterales, while newer molecules (i.e., beta-lactam agents/beta-lactamase inhibitor combination) are promising across all analyzed categories, but data are few and limited to HICs. (4) Conclusions: Data about the treatment of Gram-negative MDR bacteria in the neonatal population are heterogeneous and limited mainly to older antimicrobials. Newer drugs are promising but not affordable yet for many LMICs. Therefore, strategies cannot be generalized but will differ according to the country’s epidemiology and resources. More extensive studies are needed to include new antimicrobials and optimize the combination strategies for the older ones.
      Citation: Antibiotics
      PubDate: 2022-08-10
      DOI: 10.3390/antibiotics11081088
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1089: Neonatal Early Onset Sepsis (EOS)
           Calculator plus Universal Serial Physical Examination (SPE): A Prospective
           Two-Step Implementation of a Neonatal EOS Prevention Protocol for
           Reduction of Sepsis Workup and Antibiotic Treatment

    • Authors: Francesco Cavigioli, Francesca Viaroli, Irene Daniele, Michela Paroli, Luigi Guglielmetti, Elena Esposito, Francesco Cerritelli, Gianvincenzo Zuccotti, Gianluca Lista
      First page: 1089
      Abstract: Current neonatal early-onset sepsis (EOS) guidelines lack consensus. Recent studies suggest three different options for EOS risk assessment among infants born ≥35 wks gestational age (GA), leading to different behaviors in the sepsis workup and antibiotic administration. A broad disparity in clinical practice is found in Neonatal Units, with a large number of non-infected newborns evaluated and treated for EOS. Broad spectrum antibiotics in early life may induce different short- and long-term adverse effects, longer hospitalization, and early mother-child separation. In this single-center prospective study, a total of 3002 neonates born in three periods between 2016 and 2020 were studied, and three different workup algorithms were compared: the first one was based on the categorical risk assessment; the second one was based on a Serial Physical Examination (SPE) strategy for infants with EOS risk factors; the third one associated an informatic tool (Neonatal EOS calculator) with a universal extension of the SPE strategy. The main objective of this study was to reduce the number of neonatal sepsis workups and the rate of antibiotic administration and favor rooming-in and mother–infant bonding without increasing the risk of sepsis and mortality. The combined strategy of universal SPE with the EOS Calculator showed a significant reduction of laboratory tests (from 33% to 6.6%; p < 0.01) and antibiotic treatments (from 8.5% to 1.4%; p < 0.01) in term and near-term newborns. EOS and mortality did not change significantly during the study period.
      Citation: Antibiotics
      PubDate: 2022-08-11
      DOI: 10.3390/antibiotics11081089
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1090: In Vitro Assessment of the Combination
           of Antibiotics against Some Integron-Harbouring Enterobacteriaceae from
           Environmental Sources

    • Authors: Folake Temitope Fadare, Elsiddig A. E. Elsheikh, Anthony Ifeanyin Okoh
      First page: 1090
      Abstract: One strategy for combating antimicrobial resistance in many infections is to combine antibacterial compounds to create combinations that outperform each molecule alone. In this study, we examine and study the inhibitory effect of combining two drugs belonging to different antibiotic classes to obtain a possible potentiating effect against some Enterobacteriaceae isolates harbouring integrons recovered from rivers and effluents of hospital and wastewater treatment plants in Eastern Cape Province, South Africa. These integrons could easily enable the isolates to acquire genes that confer additional resistance against conventional antibiotics. The minimum inhibitory concentration of the various antibiotics was determined using the broth microdilution, while the checkerboard method was used to determine the fractional inhibitory concentration indices (FICIs). A total of 26.3% (10/38) of the interactions were categorised as synergistic, while 73.7% (28/38) were indifferent. None of the combinations were antagonistic. The time–kill assays revealed all the synergistic interactions as bactericidal. Therefore, the combinations of gentamicin with tetracycline, ciprofloxacin, and ceftazidime against multidrug-resistant (MDR) Klebsiella pneumoniae, tetracycline–ceftazidime combination against MDR Escherichia coli, colistin combinations with ceftazidime and gentamicin, and tetracycline–gentamicin combinations against MDR Citrobacter freundii may be future therapeutic alternatives. Hence, the synergistic combinations reported in this study must be assessed further in vivo before their clinical applications.
      Citation: Antibiotics
      PubDate: 2022-08-11
      DOI: 10.3390/antibiotics11081090
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1091: A National Survey of Dispensing Practice
           and Customer Knowledge on Antibiotic Use in Vietnam and the Implications

    • Authors: Thuy Thi Phuong Nguyen, Thang Xuan Do, Hoang Anh Nguyen, Cuc Thi Thu Nguyen, Johanna Catharina Meyer, Brian Godman, Phumzile Skosana, Binh Thanh Nguyen
      First page: 1091
      Abstract: Misconceptions and pressures have increased the sales of antibiotics without a prescription across countries. There are concerns with such practices in Vietnam given rising antimicrobial resistance rates. A national survey was conducted among 360 private drugstores located in nine provinces in Vietnam. Anonymous interviews were conducted with participants selected by convenience sampling. Subsequently, multivariable logistic regression analyses were undertaken evaluating the relationship between customer characteristics and antibiotic purchases. A total of 480 out of 1626 surveyed participants purchased antibiotics, 81.7% of which did not have a prescription, involving 29 different antibiotics. In 86.4% of these, participants were prescribed antibiotics by drug sellers. Most antibiotics were sold to treat respiratory tract infections (61.4%), with the ‘Access’ antibiotics (amoxicillin and cephalexin) being the most frequently sold. Only one-fifth of participants understood that they were breaking the law by purchasing antibiotics without a prescription. Participants purchasing antibiotics without a prescription had lower awareness concerning antibiotic laws and treatment duration (p < 0.05). Under 50% agreed to having a doctors’ prescription in the future when purchasing antibiotics. Freelancer occupation (OR = 0.52, 95% CI = 0.83–0.96) and a lower educational level (OR = 0.49, 95% CI = 0.25–0.96) were factors related to purchasing antibiotics without a prescription. Overall, we recommend increasing fines and monitoring of drugs stores, greater promotion of the family doctor system as well as increasing media and educational campaigns to limit self-purchasing of antibiotics in Vietnam and reduce resistance.
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081091
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1092: Systemic Uptake of Oxytetracycline and
           Streptomycin in Huanglongbing-Affected Citrus Groves after Foliar
           Application and Trunk Injection

    • Authors: Christopher I. Vincent, Faraj Hijaz, Myrtho Pierre, Nabil Killiny
      First page: 1092
      Abstract: Huanglongbing (HLB), which is caused by the phloem-limited bacterium ‘Candidatus Liberibacter asiaticus,’ is an economically important disease of citrus in many regions of the world. Due to the significant damage caused by the HLB disease in recent years, the use of antibiotics was recommended for the therapy of this destructive disease. Products with active ingredients oxytetracycline and streptomycin have been approved for the control of the HLB via foliar application. However, previous work raised questions about the efficacy of foliar delivery of antibiotics in the field. In this study, we examined the effects of a variety of adjuvants on the uptake of oxytetracycline and streptomycin using the foliar application. We also compared the efficiency of foliar application of oxytetracycline and streptomycin with trunk injection. The ‘Ca. L. asiaticus’ titers in citrus plants were measured using quantitative PCR, and the levels of antibiotics were determined using the ELISA assay. Our results include extremely low levels of oxytetracycline and streptomycin in leaves that were covered during foliar application, indicating that neither streptomycin nor oxytetracycline was successfully systemically delivered by foliar application even after being mixed with adjuvants. Likewise, the ‘Ca. L. asiaticus’ titer0 was not affected by any of the foliar applications. High levels of streptomycin were detected in leaves that were exposed to direct foliar application, indicating that streptomycin was adsorbed or bound to citrus leaves. On the other hand, the trunk injection of oxytetracycline resulted in high levels of this antibiotic in leaves and significantly reduced the level of ‘Ca. L. asiaticus’ titer in citrus trees. Unfortunately, the trunk injection of streptomycin resulted in low levels of streptomycin in citrus leaves and did not affect the ‘Ca. L. asiaticus’ titer, indicating that streptomycin was either bound in the xylem of citrus trees or it was not applied in sufficient quantity required for the inhibition of ‘Ca. L. asiaticus.’ Taken together, our current results demonstrated that foliar application of oxytetracycline and streptomycin did not effectively deliver antibiotics in citrus despite using adjuvants. Our results also suggested that oxytetracycline could be more effective against the HLB pathogen than streptomycin, which is possibly due to differences between the two in systemic movement in citrus trees.
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081092
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1093: Impacts of Gut Microbiota on the Immune
           System and Fecal Microbiota Transplantation as a Re-Emerging Therapy for
           Autoimmune Diseases

    • Authors: Ashenafi Feyisa Beyi, Michael Wannemuehler, Paul J. Plummer
      First page: 1093
      Abstract: The enormous and diverse population of microorganisms residing in the digestive tracts of humans and animals influence the development, regulation, and function of the immune system. Recently, the understanding of the association between autoimmune diseases and gut microbiota has been improved due to the innovation of high-throughput sequencing technologies with high resolutions. Several studies have reported perturbation of gut microbiota as one of the factors playing a role in the pathogenesis of many diseases, such as inflammatory bowel disease, recurrent diarrhea due to Clostridioides difficile infections. Restoration of healthy gut microbiota by transferring fecal material from a healthy donor to a sick recipient, called fecal microbiota transplantation (FMT), has resolved or improved symptoms of autoimmune diseases. This (re)emerging therapy was approved for the treatment of drug-resistant recurrent C. difficile infections in 2013 by the U.S. Food and Drug Administration. Numerous human and animal studies have demonstrated FMT has the potential as the next generation therapy to control autoimmune and other health problems. Alas, this new therapeutic method has limitations, including the risk of transferring antibiotic-resistant pathogens or transmission of genes from donors to recipients and/or exacerbating the conditions in some patients. Therefore, continued research is needed to elucidate the mechanisms by which gut microbiota is involved in the pathogenesis of autoimmune diseases and to improve the efficacy and optimize the preparation of FMT for different disease conditions, and to tailor FMT to meet the needs in both humans and animals. The prospect of FMT therapy includes shifting from the current practice of using the whole fecal materials to the more aesthetic transfer of selective microbial consortia assembled in vitro or using their metabolic products.
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081093
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1094: New Pyrazolo-Benzimidazole Mannich Bases
           with Antimicrobial and Antibiofilm Activities

    • Authors: Christina Zalaru, Florea Dumitrascu, Constantin Draghici, Isabela Tarcomnicu, Maria Marinescu, George Mihai Nitulescu, Rodica Tatia, Lucia Moldovan, Marcela Popa, Mariana Carmen Chifiriuc
      First page: 1094
      Abstract: A new series of pyrazolo-benzimidazole hybrid Mannich bases were synthesized, characterized by 1H-NMR, 13C-NMR, IR, UV-Vis, MS, and elemental analysis. In vitro cytotoxicity of the new compounds studied on fibroblast cells showed that the newly synthesized pyrazolo-benzimidazole hybrid derivatives were noncytotoxic until the concentration of 1 μM and two compounds presented a high degree of biocompatibility. The antibacterial and antibiofilm activity of the newly synthesized compounds was assayed on Gram-positive Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Gram-negative Pseudomonas aeruginosa ATCC27853, Escherichia coli ATCC25922 strains. All synthesized compounds 5a–g are more active against all three tested bacterial strains Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Escherichia coli ATCC25922 than reference drugs (Metronidazole, Nitrofurantoin), with the exception of compounds 5d and 5g, which are less active compared to Nitrofurantoin, and all synthesized compounds 5a–g are more active against Pseudomonas aeruginosa ATCC27853 compared to reference drugs (Metronidazole, Nitrofurantoin). Compound 5f showed the best activity against Staphylococcus aureus ATCC 25923, with a MIC of 150 μg/mL and has also inhibited the biofilm formed by all the bacterial strains, having an MBIC of 310 µg/mL compared to the reference drugs (Metronidazole, Nitrofurantoin).
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081094
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1095: Cefonicid Benzathine Salt: A Convenient,
           Lean, and High-Performance Protocol to Make an Old Cephalosporin Shine

    • Authors: Marziale Comito, Riccardo Monguzzi, Silvia Tagliapietra, Giovanni Palmisano, Giancarlo Cravotto
      First page: 1095
      Abstract: Cefonicid is a second-generation cephalosporin sold under the brand name Sintocef™. It is an injectable drug obtained via a freeze-drying process and is also available for oral preparations. The high-quality standard required is very challenging to satisfy, and current production protocols are characterized by steps that are lengthy and cumbersome, making the product unattractive for the international market. Industrial R&D is constantly working on the process optimization for API synthesis, with the aim of increasing productivity and decreasing production costs and waste. We herein report a new and efficient method for the synthesis of the cefonicid benzathine salt that provides a good yield and high product stability. The double-nucleophilic and lipophilic nature of N′,N″-dibenzylethylene diacetate enables the deformylation of the OH-protected group on the mandelic moiety and also enables product crystallization to occur. We demonstrate that the formyl group in the peculiar position has high reactivity, promoting an amidation reaction that deprotects a hydroxy group and generates a new C-N bond in the reaction by-product. Several amines and OH-protected groups have been studied, but none were able to replicate the excellent results of benzathine diacetate.
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081095
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1096: Impact of the SARS-CoV-2 Virus Pandemic
           on Patients with Bronchiectasis: A Multicenter Study

    • Authors: Adrián Martínez-Vergara, Rosa Mª Girón Moreno, Casilda Olveira, María Victoria Girón, Adrián Peláez, Julio Ancochea, Grace Oscullo, Miguel Ángel Martínez-García
      First page: 1096
      Abstract: Background: Infection by SARS-CoV-2 has unquestionably had an impact on the health of patients with chronic respiratory airway diseases, such as COPD and asthma, but little information is available about its impact on patients with bronchiectasis. The objective of the present study was to analyze the effect of the SARS-CoV-2 pandemic on the state of health, characteristics, and clinical severity (including the number and severity of exacerbations) of patients with non-cystic fibrosis bronchiectasis. Methods: This study was multicenter, observational, and ambispective (with data collected before and during the SARS-CoV-2 pandemic), and included 150 patients diagnosed with non-cystic fibrosis bronchiectasis. Results: A significant drop was observed in the number and severity of the exacerbations (57% in all exacerbations and 50% in severe exacerbations) in the E-FACED and BSI multidimensional scores, in the pandemic, compared with the pre-pandemic period. There was also a drop in the percentage of sputum samples positive for pathogenic microorganisms in general (from 58% to 44.7%) and, more specifically, Pseudomonas aeruginosa (from 23.3% to 13.3%) and Haemophilus influenzae (from 21.3% to 14%). Conclusions: During the SARS-CoV-2 period, a significant reduction was observed in the exacerbations, severity, and isolations of pathogenic microorganisms in patients with bronchiectasis.
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081096
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1097: Diverse Metabolites and Pharmacological
           Effects from the Basidiomycetes Inonotus hispidus

    • Authors: Zhenxin Wang, Xilong Feng, Chengwei Liu, Jinming Gao, Jianzhao Qi
      First page: 1097
      Abstract: Inonotus hispidus mushroom is a popular edible and medicinal mushroom with a long history of use. It is well known as a medicinal fungus with various health benefits for its significant anticancer and immunomodulatory activities. Over the last 60 years, secondary metabolites derived from I. hispidus and their biological activities have been discovered and investigated. Structurally, these compounds are mainly polyphenols and triterpenoids, which have anticancer, anti-inflammatory, antioxidant, antimicrobial, and enzyme inhibitor activities. Here, the secondary metabolites derived from I. hispidus and their activities were systematically and comprehensively classified and summarized, and the biosynthetic pathway of stylylpyrones was deduced and analyzed further. This review contributes to our understanding of I. hispidus and will help with research into natural product chemistry, pharmacology, and the biosynthesis of I. hispidus metabolites. According to this review, I. hispidus could be a promising source of bioactive compounds for health promotion and the development of functional foods.
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081097
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1098: Diagnostic Value of CRP and Serum WBC
           Count during Septic Two-Stage Revision of Total Hip Arthroplasties

    • Authors: Moritz Mederake, Ulf K. Hofmann, Sebastian Benda, Philipp Schuster, Bernd Fink
      First page: 1098
      Abstract: The diagnostic value of C-reactive protein (CRP) and the serum white blood cell (WBC) count is still barely defined for decision making during septic two-stage revision surgery of hip arthroplasty. We, therefore, compared these values between stages as well as between the groups without and with reinfection in 117 patients. A total of 106 patients were reinfection-free (91%). The median follow-up was 51 months. With a ΔCRP of −10 mg/L and a ΔWBC count of −1000/µL, a significant decrease between stages (p = 0.001) could be observed. When comparing the CRP and WBC count values between groups, however, no significant difference was found at stage one, stage two and even the difference between these two time points (reinfection-free ΔCRP of −11 mg/L and ΔWBC count of −1000/µL vs. reinfection ΔCRP of −5 mg/L (p = 0.131) and ΔWBC count of −1100/µL) (p = 0.424). The diagnostic value was poor for the calculated parameters (area under the curve (AUC) 0.5–0.6). The courses of the mean CRP values of both groups were similar. We conclude that the CRP and WBC count are not helpful to guide the decision making in individual cases.
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081098
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1099: Antibacterial, Antibiofilm, and
           Antioxidant Activity of 15 Different Plant-Based Natural Compounds in
           Comparison with Ciprofloxacin and Gentamicin

    • Authors: Ali Pormohammad, Dave Hansen, Raymond J. Turner
      First page: 1099
      Abstract: Plant-based natural compounds (PBCs) are comparatively explored in this study to identify the most effective and safe antibacterial agent/s against six World Health Organization concern pathogens. Based on a contained systematic review, 11 of the most potent PBCs as antibacterial agents are included in this study. The antibacterial and antibiofilm efficacy of the included PBCs are compared with each other as well as common antibiotics (ciprofloxacin and gentamicin). The whole plants of two different strains of Cannabis sativa are extracted to compare the results with sourced ultrapure components. Out of 15 PBCs, tetrahydrocannabinol, cannabidiol, cinnamaldehyde, and carvacrol show promising antibacterial and antibiofilm efficacy. The most common antibacterial mechanisms are explored, and all of our selected PBCs utilize the same pathway for their antibacterial effects. They mostly target the bacterial cell membrane in the initial step rather than the other mechanisms. Reactive oxygen species production and targeting [Fe-S] centres in the respiratory enzymes are not found to be significant, which could be part of the explanation as to why they are not toxic to eukaryotic cells. Toxicity and antioxidant tests show that they are not only nontoxic but also have antioxidant properties in Caenorhabditis elegans as an animal model.
      Citation: Antibiotics
      PubDate: 2022-08-12
      DOI: 10.3390/antibiotics11081099
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1100: Molecular Epidemiology of Antimicrobial
           Resistance, Virulence and Capsular Serotypes of Carbapenemase-Carrying
           Klebsiella pneumoniae in China

    • Authors: Lina Zhao, Xinxin Xia, Ting Yuan, Junying Zhu, Zhen Shen, Min Li
      First page: 1100
      Abstract: This study analyzed genomic data of 4643 strains of carbapenemase-carrying Klebsiella pneumoniae (KPN) in China by using the Kleborate software package. The data showed rich diversity in carbapenemase-carrying KPN genomes, which contain not only 152 sequence types but also 90 capsular serotypes. In 2013, the transfer of carbapenemase to hypervirulent Klebsiella pneumoniae (HvKP) of KL1 and KL2 occurred, and since 2014, the propagation of carbapenemase into mammals, poultry, and insects has been detected. The ST11 capsular serotype had a reversal of the prevalence of KL47 and KL64 in 2016, with KL64 replacing KL47 as the dominant serotype. Colibactin is a very suitable indicator to differentiate KL1-type HvKP and classic Klebsiella pneumoniae. The most prevalent yersiniabactin of KL1 is ybt1 ICEKp10, and that of ST11 carbapenem-resistant KPN(ST11-CRKP) is ybt9 ICEKp3. The virulence genes of KL1 carbapenem-resistant hypervirulent KPN (KL1-CRHvKP), as well as ST65- and ST86-type KL2-CRHvKP, were not lost after carbapenemase was obtained.
      Citation: Antibiotics
      PubDate: 2022-08-13
      DOI: 10.3390/antibiotics11081100
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1101: Comparative In Vitro Activity of
           Ceftolozane/Tazobactam against Clinical Isolates of Pseudomonas aeruginosa
           and Enterobacterales from Five Latin American Countries

    • Authors: Juan Carlos García-Betancur, Elsa De La Cadena, María F. Mojica, Cristhian Hernández-Gómez, Adriana Correa, Marcela A. Radice, Paulo Castañeda-Méndez, Diego A. Jaime-Villalon, Ana C. Gales, José M. Munita, María Virginia Villegas
      First page: 1101
      Abstract: Background: Ceftolozane/tazobactam (C/T) is a combination of an antipseudomonal oxyiminoaminothiazolyl cephalosporin with potent in vitro activity against Pseudomonas aeruginosa and tazobactam, a known β-lactamase inhibitor. The aim of this study was to evaluate the activity of C/T against clinical isolates of P. aeruginosa and Enterobacterales collected from five Latin American countries between 2016 and 2017, before its clinical use in Latin America, and to compare it with the activity of other available broad-spectrum antimicrobial agents. Methods: a total of 2760 clinical isolates (508 P. aeruginosa and 2252 Enterobacterales) were consecutively collected from 20 hospitals and susceptibility to C/T and comparator agents was tested and interpreted following the current guidelines. Results: according to the CLSI breakpoints, 68.1% (346/508) of P. aeruginosa and 83.9% (1889/2252) of Enterobacterales isolates were susceptible to C/T. Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins, piperacillin/tazobactam and carbapenems when tested against P. aeruginosa, and its performance in vitro was comparable to fosfomycin. When tested against Enterobacterales, it showed higher activity than cephalosporins and piperacillin/tazobactam, and similar activity to ertapenem. Conclusions: these results show that C/T is an active β-lactam agent against clinical isolates of P. aeruginosa and Enterobacterales.
      Citation: Antibiotics
      PubDate: 2022-08-13
      DOI: 10.3390/antibiotics11081101
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1102: Antifouling Performance of Carbon-Based
           Coatings for Marine Applications: A Systematic Review

    • Authors: Francisca Sousa-Cardoso, Rita Teixeira-Santos, Filipe J. M. Mergulhão
      First page: 1102
      Abstract: Although carbon materials are widely used in surface engineering, particularly graphene (GP) and carbon nanotubes (CNTs), the application of these nanocomposites for the development of antibiofilm marine surfaces is still poorly documented. The aim of this study was, thus, to gather and discuss the relevant literature concerning the antifouling performance of carbon-based coatings against marine micro- and macrofoulers. For this purpose, a PRISMA-oriented systematic review was conducted based on predefined criteria, which resulted in the selection of thirty studies for a qualitative synthesis. In addition, the retrieved publications were subjected to a quality assessment process based on an adapted Methodological Index for Non-Randomized Studies (MINORS) scale. In general, this review demonstrated the promising antifouling performance of these carbon nanomaterials in marine environments. Further, results from the revised studies suggested that functionalized GP- and CNTs-based marine coatings exhibited improved antifouling performance compared to these materials in pristine forms. Thanks to their high self-cleaning and enhanced antimicrobial properties, as well as durability, these functionalized composites showed outstanding results in protecting submerged surfaces from the settlement of fouling organisms in marine settings. Overall, these findings can pave the way for the development of new carbon-engineered surfaces capable of preventing marine biofouling.
      Citation: Antibiotics
      PubDate: 2022-08-14
      DOI: 10.3390/antibiotics11081102
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1103: Microbial Resistance to Carbapenems in
           Effluents from Gynaecological, Paediatric and Surgical Hospital Units

    • Authors: El hassan Loumame, Abdessamad Tounsi, Soumia Amir, Nabila Soraa, Naaila Ouazzani
      First page: 1103
      Abstract: The aim of this work is to identify and count antimicrobial resistance (AMR) in hospital effluents (HEs) of 2 units of the University Hospital Mohamed VI the Mother and Child Hospital (MCH) and the Ar-razi Surgical Hospital (ArzH), and to compare the two hospital units in terms of ARMs and seasonal variation. Each HE was sampled during 2016 and 2017. After identification of the pathogenic strains and determination of AMR, the results were reported for 24 ABs, including 3 carbapenems (CBP), and their consumption rates. The Predicted environmental concentration (PEC) rate of carbapenems in the HE of the study sites is calculated. A comparative analysis of the AMR of the isolated bacterial species was performed and related to the evolution of PEC in HEs. In the ArzH effluents:15 strains isolated, 7 are carbanepenem-resistant Enterobacteria (CRE) and are resistant to at least one of the 3 carbapenems tested. ArzH and MCH effluents respectively show some similarities: 26.87% and 28.57% of isolated bacteria are resistant to ertapenem while 43.48% and 57.14% are resistant to meropenem. However, for imipenem, the MCH effluent has a higher percentage of bacterial antibiotic resistance than ArzH. In addition, the percentage of resistance in each hospital unit effluent is mainly in relation with the increasing antibiotic consumption and predicted environmental values PEC for very antibiotic in each unit in the same period.
      Citation: Antibiotics
      PubDate: 2022-08-15
      DOI: 10.3390/antibiotics11081103
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1104: Comparing the Outcomes of Ceftaroline
           plus Vancomycin or Daptomycin Combination Therapy versus Vancomycin or
           Daptomycin Monotherapy in Adults with Methicillin-Resistant Staphylococcus
           aureus Bacteremia—A Meta-Analysis

    • Authors: Chienhsiu Huang, Ihung Chen, Lichen Lin
      First page: 1104
      Abstract: Introduction: Combination therapy with daptomycin plus ceftaroline to treat methicillin-resistant Staphylococcus aureus bacteremia has been reported to reduce methicillin-resistant Staphylococcus aureus bacteremia-related mortality. The purpose of the current meta-analysis was to compare the clinical outcome of methicillin-resistant Staphylococcus aureus bacteremia in patients treated with daptomycin or vancomycin plus ceftaroline combination therapy versus daptomycin or vancomycin monotherapy. Methods: Studies were included if they directly compared the efficacy of daptomycin or vancomycin plus ceftaroline combination therapy with that of daptomycin or vancomycin monotherapy in the treatment of methicillin-resistant Staphylococcus aureus bacteremia in adult patients. Results: One randomized controlled trial and five retrospective studies were included in the meta-analysis. The combination therapy group had an in-hospital mortality, duration of bacteremia, and adverse event rate similar to those patients who had monotherapy. There was less bacteremia recurrence in the combination group. Initial combination therapy with ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia showed a trend of reducing the risk of in-hospital mortality in the current meta-analysis. Conclusions: Randomized controlled trials are needed to further study the role of initial combination therapy with daptomycin or vancomycin plus ceftaroline in the treatment of methicillin-resistant Staphylococcus aureus bacteremia.
      Citation: Antibiotics
      PubDate: 2022-08-15
      DOI: 10.3390/antibiotics11081104
      Issue No: Vol. 11, No. 8 (2022)
  • Antibiotics, Vol. 11, Pages 1105: Chelation in Antibacterial Drugs: From
           Nitroxoline to Cefiderocol and Beyond

    • Authors: Davorka Repac Antić, Marijo Parčina, Ivana Gobin, Mirna Petković Didović
      First page: 1105
      Abstract: In the era of escalating antimicrobial resistance, the need for antibacterial drugs with novel or improved modes of action (MOAs) is a health concern of utmost importance. Adding or improving the chelating abilities of existing drugs or finding new, nature-inspired chelating agents seems to be one of the major ways to ensure progress. This review article provides insight into the modes of action of antibacterial agents, class by class, through the perspective of chelation. We covered a wide scope of antibacterials, from a century-old quintessential chelating agent nitroxoline, currently unearthed due to its newly discovered anticancer and antibiofilm activities, over the commonly used antibacterial classes, to new cephalosporin cefiderocol and a potential future class of tetramates. We show the impressive spectrum of roles that chelation plays in antibacterial MOAs. This, by itself, demonstrates the importance of understanding the fundamental chemistry behind such complex processes.
      Citation: Antibiotics
      PubDate: 2022-08-15
      DOI: 10.3390/antibiotics11081105
      Issue No: Vol. 11, No. 8 (2022)
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