Publisher: Oxford University Press   (Total: 409 journals)

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Showing 1 - 200 of 409 Journals sorted alphabetically
ACS Symposium Series     Full-text available via subscription   (Followers: 3, SJR: 0.189, CiteScore: 0)
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.79, CiteScore: 2)
Adaptation     Hybrid Journal   (Followers: 9, SJR: 0.143, CiteScore: 0)
Advances in Nutrition     Hybrid Journal   (Followers: 57, SJR: 2.196, CiteScore: 5)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.434, CiteScore: 1)
Aesthetic Surgery J. Open Forum     Open Access  
African Affairs     Hybrid Journal   (Followers: 70, SJR: 1.869, CiteScore: 2)
Age and Ageing     Hybrid Journal   (Followers: 94, SJR: 1.989, CiteScore: 4)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 19, SJR: 1.376, CiteScore: 3)
American Entomologist     Hybrid Journal   (Followers: 8)
American Historical Review     Hybrid Journal   (Followers: 204, SJR: 0.467, CiteScore: 1)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 47, SJR: 2.113, CiteScore: 3)
American J. of Clinical Nutrition     Hybrid Journal   (Followers: 209, SJR: 3.438, CiteScore: 6)
American J. of Epidemiology     Hybrid Journal   (Followers: 212, SJR: 2.713, CiteScore: 3)
American J. of Health-System Pharmacy     Full-text available via subscription   (Followers: 60, SJR: 0.595, CiteScore: 1)
American J. of Hypertension     Hybrid Journal   (Followers: 28, SJR: 1.322, CiteScore: 3)
American J. of Jurisprudence     Hybrid Journal   (Followers: 19, SJR: 0.281, CiteScore: 1)
American J. of Legal History     Full-text available via subscription   (Followers: 10, SJR: 0.116, CiteScore: 0)
American Law and Economics Review     Hybrid Journal   (Followers: 29, SJR: 1.053, CiteScore: 1)
American Literary History     Hybrid Journal   (Followers: 18, SJR: 0.391, CiteScore: 0)
Analysis     Hybrid Journal   (Followers: 24, SJR: 1.038, CiteScore: 1)
Animal Frontiers     Hybrid Journal   (Followers: 2)
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 15, SJR: 1.423, CiteScore: 3)
Annals of Botany     Hybrid Journal   (Followers: 37, SJR: 1.721, CiteScore: 4)
Annals of Oncology     Hybrid Journal   (Followers: 57, SJR: 5.599, CiteScore: 9)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 11, SJR: 0.722, CiteScore: 1)
Annals of Work Exposures and Health     Hybrid Journal   (Followers: 36, SJR: 0.728, CiteScore: 2)
Antibody Therapeutics     Open Access  
AoB Plants     Open Access   (Followers: 4, SJR: 1.28, CiteScore: 3)
Applied Economic Perspectives and Policy     Hybrid Journal   (Followers: 16, SJR: 0.858, CiteScore: 2)
Applied Linguistics     Hybrid Journal   (Followers: 60, SJR: 2.987, CiteScore: 3)
Applied Mathematics Research eXpress     Hybrid Journal   (Followers: 1, SJR: 1.241, CiteScore: 1)
Arbitration Intl.     Full-text available via subscription   (Followers: 22)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 14)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 31, SJR: 0.731, CiteScore: 2)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 2)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 45, SJR: 0.146, CiteScore: 0)
Behavioral Ecology     Hybrid Journal   (Followers: 55, SJR: 1.871, CiteScore: 3)
Bioinformatics     Hybrid Journal   (Followers: 380, SJR: 6.14, CiteScore: 8)
Biology Methods and Protocols     Hybrid Journal   (Followers: 1)
Biology of Reproduction     Full-text available via subscription   (Followers: 11, SJR: 1.446, CiteScore: 3)
Biometrika     Hybrid Journal   (Followers: 20, SJR: 3.485, CiteScore: 2)
BioScience     Hybrid Journal   (Followers: 30, SJR: 2.754, CiteScore: 4)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 3, SJR: 0.146, CiteScore: 0)
Biostatistics     Hybrid Journal   (Followers: 17, SJR: 1.553, CiteScore: 2)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 207, SJR: 2.115, CiteScore: 3)
BJA Education     Hybrid Journal   (Followers: 67)
Brain     Hybrid Journal   (Followers: 74, SJR: 5.858, CiteScore: 7)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 52, SJR: 2.505, CiteScore: 5)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 3, SJR: 2.15, CiteScore: 3)
British J. for the Philosophy of Science     Hybrid Journal   (Followers: 40, SJR: 2.161, CiteScore: 2)
British J. of Aesthetics     Hybrid Journal   (Followers: 24, SJR: 0.508, CiteScore: 1)
British J. of Criminology     Hybrid Journal   (Followers: 621, SJR: 1.828, CiteScore: 3)
British J. of Social Work     Hybrid Journal   (Followers: 89, SJR: 1.019, CiteScore: 2)
British Medical Bulletin     Hybrid Journal   (Followers: 6, SJR: 1.355, CiteScore: 3)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 35)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 3, SJR: 1.376, CiteScore: 1)
Cambridge J. of Economics     Hybrid Journal   (Followers: 71, SJR: 0.764, CiteScore: 2)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 12, SJR: 2.438, CiteScore: 4)
Cambridge Quarterly     Hybrid Journal   (Followers: 10, SJR: 0.104, CiteScore: 0)
Capital Markets Law J.     Hybrid Journal   (Followers: 2, SJR: 0.222, CiteScore: 0)
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.135, CiteScore: 5)
Cardiovascular Research     Hybrid Journal   (Followers: 15, SJR: 3.002, CiteScore: 5)
Cerebral Cortex     Hybrid Journal   (Followers: 54, SJR: 3.892, CiteScore: 6)
CESifo Economic Studies     Hybrid Journal   (Followers: 24, SJR: 0.483, CiteScore: 1)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.42, CiteScore: 3)
Children and Schools     Hybrid Journal   (Followers: 8, SJR: 0.246, CiteScore: 0)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 5, SJR: 0.412, CiteScore: 0)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 24, SJR: 0.329, CiteScore: 0)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 11, SJR: 1.392, CiteScore: 2)
Christian Bioethics: Non-Ecumenical Studies in Medical Morality     Hybrid Journal   (Followers: 10, SJR: 0.183, CiteScore: 0)
Classical Receptions J.     Hybrid Journal   (Followers: 29, SJR: 0.123, CiteScore: 0)
Clean Energy     Open Access   (Followers: 1)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 77, SJR: 5.051, CiteScore: 5)
Communication Theory     Hybrid Journal   (Followers: 26, SJR: 2.424, CiteScore: 3)
Communication, Culture & Critique     Hybrid Journal   (Followers: 28, SJR: 0.222, CiteScore: 1)
Community Development J.     Hybrid Journal   (Followers: 27, SJR: 0.268, CiteScore: 1)
Computer J.     Hybrid Journal   (Followers: 9, SJR: 0.319, CiteScore: 1)
Conservation Physiology     Open Access   (Followers: 3, SJR: 1.818, CiteScore: 3)
Contemporary Women's Writing     Hybrid Journal   (Followers: 11, SJR: 0.121, CiteScore: 0)
Contributions to Political Economy     Hybrid Journal   (Followers: 6, SJR: 0.906, CiteScore: 1)
Critical Values     Full-text available via subscription  
Current Developments in Nutrition     Open Access   (Followers: 5)
Current Legal Problems     Hybrid Journal   (Followers: 29)
Current Zoology     Full-text available via subscription   (Followers: 4, SJR: 1.164, CiteScore: 2)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 9, SJR: 1.791, CiteScore: 3)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 14, SJR: 0.259, CiteScore: 1)
Diplomatic History     Hybrid Journal   (Followers: 24, SJR: 0.45, CiteScore: 1)
DNA Research     Open Access   (Followers: 5, SJR: 2.866, CiteScore: 6)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 4)
Early Music     Hybrid Journal   (Followers: 17, SJR: 0.139, CiteScore: 0)
Econometrics J.     Hybrid Journal   (Followers: 33, SJR: 2.926, CiteScore: 1)
Economic J.     Hybrid Journal   (Followers: 118, SJR: 5.161, CiteScore: 3)
Economic Policy     Hybrid Journal   (Followers: 48, SJR: 3.584, CiteScore: 3)
ELT J.     Hybrid Journal   (Followers: 25, SJR: 0.942, CiteScore: 1)
English Historical Review     Hybrid Journal   (Followers: 57, SJR: 0.612, CiteScore: 1)
English: J. of the English Association     Hybrid Journal   (Followers: 21, SJR: 0.1, CiteScore: 0)
Environmental Entomology     Full-text available via subscription   (Followers: 12, SJR: 0.818, CiteScore: 2)
Environmental Epigenetics     Open Access   (Followers: 2)
Environmental History     Hybrid Journal   (Followers: 26, SJR: 0.408, CiteScore: 1)
EP-Europace     Hybrid Journal   (Followers: 3, SJR: 2.748, CiteScore: 4)
Epidemiologic Reviews     Hybrid Journal   (Followers: 9, SJR: 4.505, CiteScore: 8)
ESHRE Monographs     Hybrid Journal  
Essays in Criticism     Hybrid Journal   (Followers: 22, SJR: 0.113, CiteScore: 0)
European Heart J.     Hybrid Journal   (Followers: 67, SJR: 9.315, CiteScore: 9)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 10, SJR: 3.625, CiteScore: 3)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 3)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. : Case Reports     Open Access   (Followers: 1)
European Heart J. Supplements     Hybrid Journal   (Followers: 8, SJR: 0.223, CiteScore: 0)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 9, SJR: 1.681, CiteScore: 2)
European J. of Intl. Law     Hybrid Journal   (Followers: 222, SJR: 0.694, CiteScore: 1)
European J. of Orthodontics     Hybrid Journal   (Followers: 5, SJR: 1.279, CiteScore: 2)
European J. of Public Health     Hybrid Journal   (Followers: 21, SJR: 1.36, CiteScore: 2)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 10, SJR: 1.172, CiteScore: 2)
European Review of Economic History     Hybrid Journal   (Followers: 30, SJR: 0.702, CiteScore: 1)
European Sociological Review     Hybrid Journal   (Followers: 44, SJR: 2.728, CiteScore: 3)
Evolution, Medicine, and Public Health     Open Access   (Followers: 12)
Family Practice     Hybrid Journal   (Followers: 15, SJR: 1.018, CiteScore: 2)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 19, SJR: 1.492, CiteScore: 4)
Fems Microbiology Letters     Hybrid Journal   (Followers: 29, SJR: 0.79, CiteScore: 2)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 38, SJR: 7.063, CiteScore: 13)
Fems Yeast Research     Hybrid Journal   (Followers: 14, SJR: 1.308, CiteScore: 3)
Food Quality and Safety     Open Access   (Followers: 1)
Foreign Policy Analysis     Hybrid Journal   (Followers: 25, SJR: 1.425, CiteScore: 1)
Forest Science     Hybrid Journal   (Followers: 8, SJR: 0.89, CiteScore: 2)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 16, SJR: 1.133, CiteScore: 3)
Forum for Modern Language Studies     Hybrid Journal   (Followers: 6, SJR: 0.104, CiteScore: 0)
French History     Hybrid Journal   (Followers: 35, SJR: 0.118, CiteScore: 0)
French Studies     Hybrid Journal   (Followers: 21, SJR: 0.148, CiteScore: 0)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.152, CiteScore: 0)
Gastroenterology Report     Open Access   (Followers: 3)
Genome Biology and Evolution     Open Access   (Followers: 17, SJR: 2.578, CiteScore: 4)
Geophysical J. Intl.     Hybrid Journal   (Followers: 38, SJR: 1.506, CiteScore: 3)
German History     Hybrid Journal   (Followers: 24, SJR: 0.161, CiteScore: 0)
GigaScience     Open Access   (Followers: 6, SJR: 5.022, CiteScore: 7)
Global Summitry     Hybrid Journal   (Followers: 1)
Glycobiology     Hybrid Journal   (Followers: 12, SJR: 1.493, CiteScore: 3)
Health and Social Work     Hybrid Journal   (Followers: 60, SJR: 0.388, CiteScore: 1)
Health Education Research     Hybrid Journal   (Followers: 15, SJR: 0.854, CiteScore: 2)
Health Policy and Planning     Hybrid Journal   (Followers: 25, SJR: 1.512, CiteScore: 2)
Health Promotion Intl.     Hybrid Journal   (Followers: 23, SJR: 0.812, CiteScore: 2)
History Workshop J.     Hybrid Journal   (Followers: 33, SJR: 1.278, CiteScore: 1)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 30, SJR: 0.105, CiteScore: 0)
Human Communication Research     Hybrid Journal   (Followers: 15, SJR: 2.146, CiteScore: 3)
Human Molecular Genetics     Hybrid Journal   (Followers: 11, SJR: 3.555, CiteScore: 5)
Human Reproduction     Hybrid Journal   (Followers: 74, SJR: 2.643, CiteScore: 5)
Human Reproduction Open     Open Access   (Followers: 1)
Human Reproduction Update     Hybrid Journal   (Followers: 19, SJR: 5.317, CiteScore: 10)
Human Rights Law Review     Hybrid Journal   (Followers: 65, SJR: 0.756, CiteScore: 1)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 59, SJR: 1.591, CiteScore: 3)
ICSID Review : Foreign Investment Law J.     Hybrid Journal   (Followers: 12)
ILAR J.     Hybrid Journal   (Followers: 3, SJR: 1.732, CiteScore: 4)
IMA J. of Applied Mathematics     Hybrid Journal   (SJR: 0.679, CiteScore: 1)
IMA J. of Management Mathematics     Hybrid Journal   (SJR: 0.538, CiteScore: 1)
IMA J. of Mathematical Control and Information     Hybrid Journal   (Followers: 2, SJR: 0.496, CiteScore: 1)
IMA J. of Numerical Analysis - advance access     Hybrid Journal   (SJR: 1.987, CiteScore: 2)
Industrial and Corporate Change     Hybrid Journal   (Followers: 10, SJR: 1.792, CiteScore: 2)
Industrial Law J.     Hybrid Journal   (Followers: 44, SJR: 0.249, CiteScore: 1)
Inflammatory Bowel Diseases     Hybrid Journal   (Followers: 45, SJR: 2.511, CiteScore: 4)
Information and Inference     Free  
Innovation in Aging     Open Access   (Followers: 1)
Insect Systematics and Diversity     Hybrid Journal  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 10, SJR: 1.319, CiteScore: 2)
Integrative Biology     Full-text available via subscription   (Followers: 5, SJR: 1.36, CiteScore: 3)
Integrative Organismal Biology     Open Access  
Interacting with Computers     Hybrid Journal   (Followers: 10, SJR: 0.292, CiteScore: 1)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 7, SJR: 0.762, CiteScore: 1)
Intl. Affairs     Hybrid Journal   (Followers: 69, SJR: 1.505, CiteScore: 3)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 26)
Intl. Health     Hybrid Journal   (Followers: 6, SJR: 0.851, CiteScore: 2)
Intl. Immunology     Hybrid Journal   (Followers: 3, SJR: 2.167, CiteScore: 4)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 37, SJR: 1.348, CiteScore: 2)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 62, SJR: 0.601, CiteScore: 1)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 278, SJR: 3.969, CiteScore: 5)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 5, SJR: 0.202, CiteScore: 1)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 25, SJR: 0.223, CiteScore: 1)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 9, SJR: 0.285, CiteScore: 1)
Intl. J. of Low-Carbon Technologies     Open Access   (Followers: 1, SJR: 0.403, CiteScore: 1)
Intl. J. of Neuropsychopharmacology     Open Access   (Followers: 3, SJR: 1.808, CiteScore: 4)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 11, SJR: 1.545, CiteScore: 1)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 39, SJR: 0.389, CiteScore: 1)
Intl. J. of Transitional Justice     Hybrid Journal   (Followers: 14, SJR: 0.724, CiteScore: 2)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.168, CiteScore: 1)
Intl. Political Sociology     Hybrid Journal   (Followers: 41, SJR: 1.465, CiteScore: 3)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 24, SJR: 0.401, CiteScore: 1)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 9, SJR: 0.983, CiteScore: 1)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 55, SJR: 2.581, CiteScore: 2)
Intl. Studies Review     Hybrid Journal   (Followers: 24, SJR: 1.201, CiteScore: 1)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 2, SJR: 0.15, CiteScore: 0)
ITNOW     Hybrid Journal   (Followers: 1, SJR: 0.103, CiteScore: 0)
J. of African Economies     Hybrid Journal   (Followers: 18, SJR: 0.533, CiteScore: 1)
J. of American History     Hybrid Journal   (Followers: 50, SJR: 0.297, CiteScore: 1)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 14, SJR: 1.065, CiteScore: 2)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 16, SJR: 2.419, CiteScore: 4)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 1)
J. of Applied Poultry Research     Hybrid Journal   (Followers: 5, SJR: 0.585, CiteScore: 1)
J. of Biochemistry     Hybrid Journal   (Followers: 43, SJR: 1.226, CiteScore: 2)
J. of Breast Imaging     Full-text available via subscription   (Followers: 2)

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Similar Journals
Journal Cover
Journal of Antimicrobial Chemotherapy
Journal Prestige (SJR): 2.419
Citation Impact (citeScore): 4
Number of Followers: 16  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0305-7453 - ISSN (Online) 1460-2091
Published by Oxford University Press Homepage  [409 journals]
  • Molecular and genetic basis of azole antifungal resistance in the
           opportunistic pathogenic fungus Candida albicans
    • Authors: Nishimoto A; Sharma C, Rogers P.
      Pages: 257 - 270
      Abstract: AbstractCandida albicans is an opportunistic yeast and the major human fungal pathogen in the USA, as well as in many other regions of the world. Infections with C. albicans can range from superficial mucosal and dermatological infections to life-threatening infections of the bloodstream and vital organs. The azole antifungals remain an important mainstay treatment of candidiasis and therefore the investigation and understanding of the evolution, frequency and mechanisms of azole resistance are vital to improving treatment strategies against this organism. Here the organism C. albicans and the genetic changes and molecular bases underlying the currently known resistance mechanisms to the azole antifungal class are reviewed, including up-regulated expression of efflux pumps, changes in the expression and amino acid composition of the azole target Erg11 and alterations to the organism’s typical sterol biosynthesis pathways. Additionally, we update what is known about activating mutations in the zinc cluster transcription factor (ZCF) genes regulating many of these resistance mechanisms and review azole import as a potential contributor to azole resistance. Lastly, investigations of azole tolerance in C. albicans and its implicated clinical significance are reviewed.
      PubDate: Fri, 11 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz400
      Issue No: Vol. 75, No. 2 (2019)
       
  • Pandrug-resistant Gram-negative bacteria: a systematic review of current
           epidemiology, prognosis and treatment options
    • Authors: Karakonstantis S; Kritsotakis E, Gikas A.
      Pages: 271 - 282
      Abstract: AbstractBackgroundThe literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial.ObjectivesTo consolidate the relevant literature and identify treatment options for PDR GNB infections.MethodsA systematic search in MEDLINE, Scopus and clinical trial registries was conducted. Studies reporting PDR clinical isolates were eligible for review if susceptibility testing for all major antimicrobials had been performed. Characteristics and findings of retrieved studies were qualitatively synthesized.ResultsOf 81 studies reviewed, 47 (58%) were published in the last 5 years. The reports reflected a worldwide dissemination of PDR GNB in 25 countries in 5 continents. Of 526 PDR isolates reported, Pseudomonas aeruginosa (n=175), Acinetobacter baumannii (n=172) and Klebsiella pneumoniae (n=125) were most common. PDR GNB were typically isolated in ICUs, but several studies demonstrated wider outbreak potential, including dissemination to long-term care facilities and international spread. All-cause mortality was high (range 20%–71%), but appeared to be substantially reduced in studies reporting treatment regimens active in vitro. No controlled trial has been performed to date, but several case reports and series noted successful use of various regimens, predominantly synergistic combinations, and in selected patients increased exposure regimens and newer antibiotics.ConclusionsPDR GNB are increasingly being reported worldwide and are associated with high mortality. Several treatment regimens have been successfully used, of which synergistic combinations appear to be most promising and often the only available option. More pharmacokinetic/pharmacodynamic and outcome studies are needed to guide the use of synergistic combinations.
      PubDate: Sat, 05 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz401
      Issue No: Vol. 75, No. 2 (2019)
       
  • Tandem amplification of the vanM gene cluster drives vancomycin resistance
           in vancomycin-variable enterococci
    • Authors: Sun L; Chen Y, Hua X, et al.
      Pages: 283 - 291
      Abstract: AbstractBackgroundVancomycin-variable enterococci (VVE) are a potential risk factor for vancomycin resistance gene dissemination and clinical treatment failure. vanM has emerged as a new prevalent resistance determinant among clinical enterococci in China. A total of 54 vancomycin-susceptible enterococci (VSE) isolates carrying incomplete vanM gene clusters were isolated in our previous study.ObjectivesTo determine the potential of vanM-carrying VSE to develop vancomycin resistance and investigate the mechanism of alteration of the resistance phenotype.MethodsFifty-four vanM-positive VSE strains were induced in vitro by culturing in increasing concentrations of vancomycin. Genetic changes between three parent VVE strains and their resistant variants were analysed using Illumina and long-read sequencing technologies, quantitative PCR and Southern blot hybridization. Changes in expression level were determined by quantitative RT–PCR.ResultsTwenty-five of the 54 VSE strains carrying vanM became resistant upon vancomycin exposure. A significant increase in vanM copy number was observed ranging from 5.28 to 127.64 copies per cell in induced resistant VVE strains. The vanM transposon was identified as tandem repeats with IS1216E between them, and occurred in either the plasmid or the chromosome of resistant VVE cells. In addition, an increase in vanM expression was observed after resistance conversion in VVE.ConclusionsThis study identified tandem amplification of the vanM gene cluster as a new mechanism for vancomycin resistance in VVE strains, offering a competitive advantage for VVE under antibiotic pressure.
      PubDate: Tue, 19 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz461
      Issue No: Vol. 75, No. 2 (2019)
       
  • Identification of a mecA/mecC-positive MRSA ST1-t127 isolate from a
           racehorse in Japan
    • Authors: Sekizuka T; Niwa H, Kinoshita Y, et al.
      Pages: 292 - 295
      Abstract: AbstractObjectivesMRSA is a known pathogen that affects horses. We investigated an equine MRSA isolate for potential antimicrobial resistance genes, classified the staphylococcal cassette chromosome mec (SCCmec) and identified the strain-specific dissemination in the horse community based on WGS.MethodsWGS, using short-read sequencing, and subsequent long-read sequencing by hybrid assembly, was conducted to obtain a complete genome sequence. Pairwise sequence alignment of relative SCCmec sequences and core-genome phylogenetic analysis were performed to highlight transmission routes of the SCCmec and MRSA strain-specific lineages.ResultsIn 2018, we isolated the MRSA JRA307 strain from the pus of a wound on a racehorse and the complete genome sequence suggests that it is a clinically relevant pvl-negative ST1-t127 MRSA that harbours both mecA and mecC on SCCmec-307. SCCmec-307 exhibited marked sequence identity to the previously reported SCCmec–mecC in the Staphylococcus sciuri GVGS2 strain isolated from cattle. The JRA307 mecC gene was classified as a mecC allotype of S. sciuri rather than that of Staphylococcus aureus.ConclusionsWe demonstrated the complete genome sequence of equine isolate JRA307, which is a clinically relevant MRSA harbouring mecA and mecC on SCCmec-307. The finding of mecC MRSA suggests a possible SCCmec transmission between distinct staphylococcal species. To the best of our knowledge, this is the first report of mecC detection in Japan.
      PubDate: Wed, 06 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz459
      Issue No: Vol. 75, No. 2 (2019)
       
  • Heterogeneity of penicillin-non-susceptible group B streptococci isolated
           from a single patient in Germany
    • Authors: van der Linden M; Mamede R, Levina N, et al.
      Pages: 296 - 299
      Abstract: AbstractObjectivesStreptococcus agalactiae [group B streptococci (GBS)] have been considered uniformly susceptible to penicillin. However, increasing reports from Asia and North America are documenting penicillin-non-susceptible GBS (PRGBS) with mutations in pbp genes. Here we report, to the best of our knowledge, the first two PRGBS isolates recovered in Europe (AC-13238-1 and AC-13238-2), isolated from the same patient. MethodsTwo different colony morphologies of GBS were noted from a surgical abscess drainage sample. Both were serotyped and antimicrobial susceptibility testing was performed by different methodologies. High-throughput sequencing was done to compare the isolates at the genomic level, to identify their capsular type and ST, to evaluate mutations in the pbp genes and to compare the isolates with the genomes of other PRGBS isolates sharing the same serotype and ST.ResultsIsolates AC-13238-1 and AC-13238-2 presented MICs above the EUCAST and CLSI breakpoints for penicillin susceptibility. Both shared the capsular type Ia operon and ST23. Genomic analysis uncovered differences between the two isolates in seven genes, including altered pbp genes. Deduced amino acid sequences revealed critical substitutions in PBP2X in both isolates. Comparison with serotype Ia clonal complex 23 PRGBS from the USA reinforced the similarity between AC-13238-1 and AC-13238-2, and their divergence from the US strains.ConclusionsOur results support the in-host evolution of β-lactam-resistant GBS, with two PRGBS variants being isolated from one patient.
      PubDate: Mon, 18 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz465
      Issue No: Vol. 75, No. 2 (2019)
       
  • Mutations that increase expression of the EmrAB-TolC efflux pump confer
           increased resistance to nitroxoline in Escherichia coli
    • Authors: Puértolas-Balint F; Warsi O, Linkevicius M, et al.
      Pages: 300 - 308
      Abstract: AbstractObjectivesTo determine the mechanism of resistance to the antibiotic nitroxoline in Escherichia coli.MethodsSpontaneous nitroxoline-resistant mutants were selected at different concentrations of nitroxoline. WGS and strain reconstruction were used to define the genetic basis for the resistance. The mechanistic basis of resistance was determined by quantitative PCR (qPCR) and by overexpression of target genes. Fitness costs of the resistance mutations and cross-resistance to other antibiotics were also determined.ResultsMutations in the transcriptional repressor emrR conferred low-level resistance to nitroxoline [nitroxoline MIC (MICNOX)=16 mg/L] by increasing the expression of the emrA and emrB genes of the EmrAB-TolC efflux pump. These resistant mutants showed no fitness reduction and displayed cross-resistance to nalidixic acid. Second-step mutants with higher-level resistance (MICNOX=32–64 mg/L) had mutations in the emrR gene, together with either a 50 kb amplification, a mutation in the gene marA, or an IS upstream of the lon gene. The latter mutations resulted in higher-level nitroxoline resistance due to increased expression of the tolC gene, which was confirmed by overexpressing tolC from an inducible plasmid in a low-level resistance mutant. Furthermore, the emrR mutations conferred a small increase in resistance to nitrofurantoin only when combined with an nfsAB double-knockout mutation. However, nitrofurantoin-resistant nfsAB mutants showed no cross-resistance to nitroxoline.ConclusionsMutations in different genes causing increased expression of the EmrAB-TolC pump lead to an increased resistance to nitroxoline. The structurally similar antibiotics nitroxoline and nitrofurantoin appear to have different modes of action and resistance mechanisms.
      PubDate: Mon, 21 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz434
      Issue No: Vol. 75, No. 2 (2019)
       
  • Tigecycline-non-susceptible hypervirulent Klebsiella pneumoniae strains in
           Taiwan
    • Authors: Cheng Y; Huang T, Juan C, et al.
      Pages: 309 - 317
      Abstract: AbstractObjectivesEmergent antimicrobial-resistant hypervirulent Klebsiella pneumoniae (hvKp) is an important public health issue. We aimed to investigate resistance mechanisms and hypervirulent traits among tigecycline-non-susceptible (TNS) K. pneumoniae clinical strains, focusing on one hvKp strain with in vivo evolution of tigecycline resistance.MethodsTNS K. pneumoniae strains causing invasive diseases in a medical centre in Taiwan between July 2015 and April 2018 were collected. Resistance mechanisms were determined and hvKp strains were defined as rmpA/rmpA2-carrying strains. Isogenic strains with and without tigecycline resistance were subjected to WGS and in vivo virulence testing. Further, site-directed mutagenesis was used to confirm the resistance mechanism.ResultsIn total, 31 TNS K. pneumoniae strains were isolated, including six hypervirulent strains. Tigecycline resistance mechanisms were mostly caused by overexpression of AcrAB and OqxAB together with up-regulation of RamA or RarA, respectively. One TNS hypervirulent strain (KP1692; MIC=6 mg/L) derived from its tigecycline-susceptible counterpart (KP1677; MIC=0.75 mg/L) showed acrAB overexpression. WGS revealed four genetic variations between KP1677 and KP1692. In addition, using site-directed mutagenesis, we confirmed that a 1 bp insertion in the ramA upstream region (RamR-binding site), leading to ramA and acrAB overexpression in KP1692, was responsible for tigecycline resistance. The in vivo virulence experiment showed that the TNS hvKp strain KP1692 still retained its high virulence compared with KP1677.ConclusionshvKp strains accounted for 19.4% among TNS strains. We identified alterations in the ramA upstream region as a mechanism of in vivo tigecycline resistance development in an hvKp strain.
      PubDate: Fri, 08 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz450
      Issue No: Vol. 75, No. 2 (2019)
       
  • Transmission and evolution of OXA-48-producing Klebsiella pneumoniae ST11
           in a single hospital in Taiwan
    • Authors: Lu M; Chen Y, Tang H, et al.
      Pages: 318 - 326
      Abstract: AbstractObjectivesEpidemic spread of OXA-48-producing Klebsiella pneumoniae, mainly mediated by the transmission of a blaOXA-48-carrying plasmid, has threatened global health during the last decade. Since its introduction to Taiwan in 2013, OXA-48 has become the second most common carbapenemase. We described the transmission and evolution of an OXA-producing K. pneumoniae clone in a single hospital.MethodsTwenty-two OXA-48 K. pneumoniae were isolated between October 2013 and December 2015. Comparative genomic analysis was performed based on the WGS data generated with Illumina and MinION techniques.ResultsSeventeen of the 22 OXA-48 K. pneumoniae that belonged to ST11, with the same capsular genotype, KL64, and differed from each other by seven or fewer SNPs, were considered outbreak strains. Eight of the 17 outbreak strains harboured a 65499 bp blaOXA-48-carrying IncL plasmid (called pOXA48). pOXA48 was absent from the remaining nine strains. Instead, a 24.9 kb blaOXA-48-carrying plasmid fragment was integrated into a prophage region of their chromosomes. Transmission routes of the ST11_KL64 K. pneumoniae sublineages, which carried either pOXA48 or chromosomally integrated blaOXA-48, were reconstructed.ConclusionsClonal expansion of ST11_KL64 sublineages contributed to the nosocomial outbreak of OXA-48 K. pneumoniae. The chromosome-borne blaOXA-48 lineage emerged during a 2 year period in a single hospital. Dissemination of OXA-48, which is vertically transmitted in K. pneumoniae even in the absence of selective pressure from antimicrobials, deserves public health attention.
      PubDate: Wed, 30 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz431
      Issue No: Vol. 75, No. 2 (2019)
       
  • Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae
           in China: a multicentre, molecular epidemiological analysis
    • Authors: Zhang Y; Jin L, Ouyang P, et al.
      Pages: 327 - 336
      Abstract: AbstractObjectivesCarbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been increasingly reported in China. Here, a multicentre, longitudinal surveillance study on CR-hvKP is described.MethodsWe retrospectively investigated carbapenem-resistant K. pneumoniae (CRKP) in 56 centres across China during 2015–17 and screened the virulence genes (iucA, iroN, rmpA and rmpA2) for the presence of virulence plasmids. Hypermucoviscosity, serum killing and Galleria mellonella lethality experiments were conducted to identify CR-hvKP among strains with all four virulence genes. Capsule typing, fitness and plasmid features of CR-hvKP were also investigated.ResultsA total of 1052 CRKP were collected. Among these, 34.2% (360/1052) carried virulence genes and 72 of them had all four of the virulence genes tested. Fifty-five (76.4%) were considered to be CR-hvKP using the G. mellonella infection model, with KPC-2-producing K64-ST11 being the most common type (80%, 44/55). Prevalence of CR-hvKP differed greatly between regions, with the highest in Henan (25.4%, 17/67) and Shandong (25.8%, 25/97). A significant increase in CR-hvKP among KPC-2-producing ST11 strains was observed, from 2.1% (3/141) in 2015 to 7.0% (23/329) in 2017 (P=0.045). Alarmingly, compared with classic CRKP, no difference in growth was found among CR-hvKP (P=0.7028), suggesting a potential risk for dissemination. The hybrid virulence and resistance-encoding plasmid evolved from pLVPK and the resistance plasmid harbouring blaKPC-2, indicating evolution existed between the hypervirulence and hyper-resistance plasmid.ConclusionsCR-hvKP were more frequently detected than previously assumed, especially among KPC-2-producing ST11. Dissemination of hypervirulence could be extremely rapid due to limited fitness cost. Also, the evolution of resistance genes into hypervirulence plasmids was identified, presenting significant challenges for public health and infection control.
      PubDate: Tue, 12 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz446
      Issue No: Vol. 75, No. 2 (2019)
       
  • Persistent circulation of a fluoroquinolone-resistant Salmonella enterica
           Typhi clone in the Indian subcontinent
    • Authors: Britto C; Dyson Z, Mathias S, et al.
      Pages: 337 - 341
      Abstract: AbstractBackgroundThe molecular structure of circulating enteric fever pathogens was studied using hospital-based genomic surveillance in a tertiary care referral centre in South India as a first genomic surveillance study, to our knowledge, of blood culture-confirmed enteric fever in the region.MethodsBlood culture surveillance was conducted at St John’s Medical College Hospital, Bengaluru, between July 2016 and June 2017. The bacterial isolates collected were linked to demographic variables of patients and subjected to WGS. The resulting pathogen genomic data were also globally contextualized to gauge possible phylogeographical patterns.ResultsHospital-based genomic surveillance for enteric fever in Bengaluru, India, identified 101 Salmonella enterica Typhi and 14 S. Paratyphi A in a 1 year period. Ninety-six percent of isolates displayed non-susceptibility to fluoroquinolones. WGS showed the dominant pathogen was S. Typhi genotype 4.3.1.2 (H58 lineage II). A fluoroquinolone-resistant triple-mutant clone of S. Typhi 4.3.1.2 previously associated with gatifloxacin treatment failure in Nepal was implicated in 18% of enteric fever cases, indicating ongoing inter-regional circulation.ConclusionsEnteric fever in South India continues to be a major public health issue and is strongly associated with antimicrobial resistance. Robust microbiological surveillance is necessary to direct appropriate treatment and preventive strategies. Of particular concern is the emergence and expansion of the highly fluoroquinolone-resistant triple-mutant S. Typhi clone and its ongoing inter- and intra-country transmission in South Asia, which highlights the need for regional coordination of intervention strategies, including vaccination and longer-term strategies such as improvements to support hygiene and sanitation.
      PubDate: Sat, 26 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz435
      Issue No: Vol. 75, No. 2 (2019)
       
  • Faecal carriage, risk factors, acquisition and persistence of
           ESBL-producing Enterobacteriaceae in dogs and cats and co-carriage with
           humans belonging to the same household
    • Authors: van den Bunt G; Fluit A, Spaninks M, et al.
      Pages: 342 - 350
      Abstract: AbstractBackgroundESBL-producing Enterobacteriaceae (ESBL-E) are observed in many reservoirs. Pets might play an important role in the dissemination of ESBL-E to humans since they live closely together.ObjectivesTo identify prevalence, risk factors, molecular characteristics, persistence and acquisition of ESBL-E in dogs and cats, and co-carriage in human–pet pairs belonging to the same household.MethodsIn a nationwide study, one person per household was randomly invited to complete a questionnaire and to submit a faecal sample. Dog and cat owners were invited to also submit a faecal sample from their pet. Repeated sampling after 1 and 6 months was performed in a subset. ESBL-E were obtained through selective culture and characterized by WGS. Logistic regression analyses and random forest models were performed to identify risk factors.ResultsThe prevalence of ESBL-E carriage in these cohorts was 3.8% (95% CI: 2.7%–5.4%) for human participants (n=550), 10.7% (95% CI: 8.3%–13.7%) for dogs (n=555) and 1.4% (95% CI: 0.5%–3.8%) for cats (n=285). Among animals, blaCTX-M-1 was most abundant, followed by blaCTX-M-15. In dogs, persistence of carriage was 57.1% at 1 month and 42.9% at 6 months. Eating raw meat [OR: 8.8, 95% CI: 4.7–16.4; population attributable risk (PAR): 46.5%, 95% CI: 41.3%–49.3%] and dry food (OR: 0.2, 95% CI: 0.1–0.5; PAR: 56.5%, 95% CI: 33.2%–66.6%) were predictors for ESBL-E carriage in dogs. Human–dog co-carriage was demonstrated in five households. Human–cat co-carriage was not observed.ConclusionsESBL-E prevalence was higher in dogs than in humans and lowest in cats. The main risk factor for ESBL-E carriage was eating raw meat. Co-carriage in dogs and household members was uncommon.
      PubDate: Mon, 11 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz462
      Issue No: Vol. 75, No. 2 (2019)
       
  • Impact of oral amoxicillin and amoxicillin/clavulanic acid treatment on
           bacterial diversity and β-lactam resistance in the canine faecal
           microbiota
    • Authors: Espinosa-Gongora C; Jessen L, Kieler I, et al.
      Pages: 351 - 361
      Abstract: AbstractBackgroundAminopenicillins with or without a β-lactamase inhibitor are widely used in both human and veterinary medicine. However, little is known about their differential impact on the gut microbiota and development of antimicrobial resistance.ObjectivesTo investigate changes in the faecal microbiota of dogs treated with amoxicillin or amoxicillin/clavulanic acid.MethodsFaeces collected from 42 dogs (21 per treatment group) immediately before, during and 1 week after termination of oral treatment with amoxicillin or amoxicillin/clavulanic acid were analysed by culture and 16S rRNA gene sequence analysis.ResultsIn both groups, bacterial counts on ampicillin selective agar revealed an increase in the proportion of ampicillin-resistant Escherichia coli during treatment, and an increased occurrence and proportion of ampicillin-resistant enterococci during and after treatment. 16S rRNA gene analysis showed reductions in microbial richness and diversity during treatment followed by a return to pre-treatment conditions approximately 1 week after cessation of amoxicillin or amoxicillin/clavulanic acid treatment. While no significant differences were observed between the effects of amoxicillin and amoxicillin/clavulanic acid on microbial richness and diversity, treatment with amoxicillin/clavulanic acid reduced the abundance of taxa that are considered part of the beneficial microbiota (such as Roseburia, Dialister and Lachnospiraceae) and enriched Escherichia, although the latter result was not corroborated by phenotypic counts.ConclusionsOur results suggest a limited effect of clavulanic acid on selection of antimicrobial resistance and microbial richness when administered orally in combination with amoxicillin. However, combination with this β-lactamase inhibitor appears to broaden the spectrum of amoxicillin, with potential negative consequences on gut health.
      PubDate: Thu, 28 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz458
      Issue No: Vol. 75, No. 2 (2019)
       
  • The relative rate of kill of the MMV Malaria Box compounds provides links
           to the mode of antimalarial action and highlights scaffolds of medicinal
           chemistry interest
    • Authors: Ullah I; Sharma R, Mete A, et al.
      Pages: 362 - 370
      Abstract: AbstractObjectivesRapid rate-of-kill (RoK) is a key parameter in the target candidate profile 1 (TCP1) for the next-generation antimalarial drugs for uncomplicated malaria, termed Single Encounter Radical Cure and Prophylaxis (SERCaP). TCP1 aims to rapidly eliminate the initial parasite burden, ideally as fast as artesunate, but minimally as fast as chloroquine. Here we explore whether the relative RoK of the Medicine for Malaria Venture (MMV) Malaria Box compounds is linked to their mode of action (MoA) and identify scaffolds of medicinal chemistry interest.MethodsWe used a bioluminescence relative RoK (BRRoK) assay over 6 and 48 h, with exposure to equipotent IC50 concentrations, to compare the cytocidal effects of Malaria Box compounds with those of benchmark antimalarials.ResultsBRRoK assay data demonstrate the following relative RoKs, from fast to slow: inhibitors of PfATP4>parasite haemoglobin catabolism>dihydrofolate reductase-thymidylate synthase (DHFR-TS)>dihydroorotate dehydrogenase (DHODH)>bc1 complex. Core-scaffold clustering analyses revealed intrinsic rapid cytocidal action for diamino-glycerols and 2-(aminomethyl)phenol, but slow action for 2-phenylbenz-imidazoles, 8-hydroxyquinolines and triazolopyrimidines.ConclusionsThis study provides proof of principle that a compound’s RoK is related to its MoA and that the target’s intrinsic RoK is also modified by factors affecting a drug’s access to it. Our findings highlight that as we use medicinal chemistry to improve potency, we can also improve the RoK for some scaffolds. Our BRRoK assay provides the necessary throughput for drug discovery and a critical decision-making tool to support development campaigns. Finally, two scaffolds, diamino-glycerols and 2-phenylbenzimidazoles, exhibit fast cytocidal action, inviting medicinal chemistry improvements towards TCP1 candidates.
      PubDate: Tue, 29 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz443
      Issue No: Vol. 75, No. 2 (2019)
       
  • Helcococcus kunzii methyltransferase Erm(47) responsible for MLSB
           resistance is induced by diverse ribosome-targeting antibiotics
    • Authors: Guerin F; Rose S, Cattoir V, et al.
      Pages: 371 - 378
      Abstract: AbstractObjectivesTo determine the mechanism of induction of erm(47) and its atypical expression in the Gram-positive opportunistic pathogen Helcococcus kunzii, where it confers resistance to a subset of clinically important macrolide, lincosamide and streptogramin B (MLSB) antibiotics.MethodsThe resistant H. kunzii clinical isolate UCN99 was challenged with subinhibitory concentrations of a wide range of ribosome-targeting drugs. The methylation status of the H. kunzii ribosomal RNA at the MLSB binding site was then determined using an MS approach and was correlated with any increase in resistance to the drugs. ResultsThe H. kunzii erm(47) gene encodes a monomethyltransferase. Expression is induced by subinhibitory concentrations of the macrolide erythromycin, as is common for many erm genes, and surprisingly also by 16-membered macrolide, lincosamide, streptogramin, ketolide, chloramphenicol and linezolid antibiotics, all of which target the 50S ribosomal subunit. No induction was detected with spectinomycin, which targets the 30S subunit.ConclusionsThe structure of the erm(47) leader sequence functions as a hair trigger for the induction mechanism that expresses resistance. Consequently, translation of the erm(47) mRNA is tripped by MLSB compounds and also by drugs that target the 50S ribosomal subunit outside the MLSB site. Expression of erm(47) thus extends previous assumptions about how erm genes can be induced.
      PubDate: Thu, 31 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz441
      Issue No: Vol. 75, No. 2 (2019)
       
  • Impact of relebactam-mediated inhibition of Mycobacterium abscessus BlaMab
           β-lactamase on the in vitro and intracellular efficacy of imipenem
    • Authors: Le Run E; Atze H, Arthur M, et al.
      Pages: 379 - 383
      Abstract: AbstractObjectivesImipenem is one of the recommended β-lactams for the treatment of Mycobacterium abscessus pulmonary infections in spite of the production of BlaMab β-lactamase. Avibactam, a second-generation β-lactamase inhibitor, was previously shown to inactivate BlaMab, but its partner drug, ceftazidime, is devoid of any antibacterial activity against M. abscessus. Here, we investigate whether relebactam, a novel second-generation inhibitor developed in combination with imipenem, improves the activity of this carbapenem against M. abscessus.MethodsThe impact of BlaMab inhibition by relebactam was evaluated by determining MICs, time–kill curves and M. abscessus intracellular proliferation in human macrophages. Kinetic parameters for the inhibition of BlaMab by relebactam were determined by spectrophotometry using nitrocefin as the substrate. The data were compared with those obtained with avibactam.ResultsCombination of relebactam (4 mg/L) with β-lactams led to >128- and 2-fold decreases in the MICs of amoxicillin (from >4096 to 32 mg/L) and imipenem (from 8 to 4 mg/L). In vitro, M. abscessus was not killed by the imipenem/relebactam combination. In contrast, relebactam increased the intracellular activity of imipenem, leading to 88% killing. Relebactam and avibactam similarly potentiated the antibacterial activities of β-lactams although BlaMab was inactivated 150-fold less effectively by relebactam than by avibactam.ConclusionsInhibition of BlaMab by relebactam improves the efficacy of imipenem against M. abscessus in macrophages, indicating that the imipenem/relebactam combination should be clinically considered for the treatment of infections due to M. abscessus.
      PubDate: Mon, 21 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz433
      Issue No: Vol. 75, No. 2 (2019)
       
  • In vitro activity of ceftazidime/avibactam against isolates of
           carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM
           global surveillance programme (2015–17)
    • Authors: Spiliopoulou I; Kazmierczak K, Stone G.
      Pages: 384 - 391
      Abstract: AbstractObjectivesTo report data for ceftazidime/avibactam and comparators against meropenem-non-susceptible Enterobacteriaceae collected globally (excluding centres in the USA) from 2015 to 2017 as part of the International Network For Optimal Resistance Monitoring (INFORM) surveillance programme.MethodsMICs and susceptibility were determined using EUCAST broth microdilution methodology and EUCAST breakpoints. Isolates were screened to detect genes encoding β-lactamases using multiplex PCR assays. MBL-positive isolates were those in which one or more of the IMP, VIM and/or NDM genes were detected.ResultsA total of 1460 meropenem-non-susceptible isolates were collected and, of the agents on the panel, susceptibility was highest to ceftazidime/avibactam, colistin and tigecycline [73.0%, 77.0% (1081/1403) and 78.1%, respectively]. Ceftazidime/avibactam was not active against MBL-positive isolates (n=367); these isolates showed the highest rates of susceptibility to colistin (92.1%, 303/329), tigecycline (71.9%) and amikacin (46.6%). A total of 394 isolates were resistant to ceftazidime/avibactam and, of the 369 isolates that were screened, 98.4% were found to carry a gene encoding an MBL enzyme. Among isolates that were identified as carbapenemase positive and MBL negative (n=910), susceptibility was highest to ceftazidime/avibactam (99.8%). Susceptibility was also highest to ceftazidime/avibactam among isolates that were carbapenemase negative and MBL negative (94/98, 95.9%).ConclusionsThese data highlight the need for continued surveillance of antimicrobial activity as well as the need for new antimicrobials to treat infections caused by meropenem-non-susceptible Enterobacteriaceae, for which the options are extremely limited.
      PubDate: Tue, 19 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz456
      Issue No: Vol. 75, No. 2 (2019)
       
  • Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with
           standard therapy based on time-to-extinction mathematics
    • Authors: Srivastava S; Deshpande D, Magombedze G, et al.
      Pages: 392 - 399
      Abstract: AbstractObjectivesAnimal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3–4 months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB).MethodsA series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28 days, intracellular bacilli treated daily for 28 days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56 days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6 months with each regimen.ResultsUsing linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56 days were 0.18 (95% credible interval=0.13–0.23) versus 0.15 (95% credible interval=0.08–0.21) log10 cfu/mL/day, compared with 0.16 (95% credible interval=0.13–0.18) versus 0.11 (95% credible interval=0.09–0.13) log10 cfu/mL/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1–41.34) and 72.30% (95% credible interval=71.41–73.17) at 3 and 4 months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18–94.13) at 6 months for standard therapy. ConclusionsThe kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6 months in most patients.
      PubDate: Tue, 12 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz460
      Issue No: Vol. 75, No. 2 (2019)
       
  • A novel mechanism-based pharmacokinetic–pharmacodynamic (PKPD) model
           describing ceftazidime/avibactam efficacy against β-lactamase-producing
           Gram-negative bacteria
    • Authors: Kristoffersson A; Bissantz C, Okujava R, et al.
      Pages: 400 - 408
      Abstract: AbstractBackgroundDiazabicyclooctanes (DBOs) are an increasingly important group of non β-lactam β-lactamase inhibitors, employed clinically in combinations such as ceftazidime/avibactam. The dose finding of such combinations is complicated using the traditional pharmacokinetic/pharmacodynamic (PK/PD) index approach, especially if the β-lactamase inhibitor has an antibiotic effect of its own.ObjectivesTo develop a novel mechanism-based pharmacokinetic–pharmacodynamic (PKPD) model for ceftazidime/avibactam against Gram-negative pathogens, with the potential for combination dosage simulation.MethodsFour β-lactamase-producing Enterobacteriaceae, covering Ambler classes A, B and D, were exposed to ceftazidime and avibactam, alone and in combination, in static time–kill experiments. A PKPD model was developed and evaluated using internal and external evaluation, and combined with a population PK model and applied in dosage simulations.ResultsThe developed PKPD model included the effects of ceftazidime alone, avibactam alone and an ‘enhancer’ effect of avibactam on ceftazidime in addition to the β-lactamase inhibitory effect of avibactam. The model could describe an extensive external Pseudomonas aeruginosa data set with minor modifications to the enhancer effect, and the utility of the model for clinical dosage simulation was demonstrated by investigating the influence of the addition of avibactam.ConclusionsA novel mechanism-based PKPD model for the DBO/β-lactam combination ceftazidime/avibactam was developed that enables future comparison of the effect of avibactam with other DBO/β-lactam inhibitors in simulations, and may be an aid in translating PKPD results from in vitro to animals and humans.
      PubDate: Thu, 31 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz440
      Issue No: Vol. 75, No. 2 (2019)
       
  • Repurposing auranofin as a Clostridioides difficile therapeutic
    • Authors: Hutton M; Pehlivanoglu H, Vidor C, et al.
      Pages: 409 - 417
      Abstract: AbstractBackgroundClostridioides difficile (previously Clostridium difficile) is the leading cause of nosocomial, antibiotic-associated diarrhoea worldwide. Currently, the gold standard of treatment for C. difficile infection (CDI) is vancomycin or metronidazole, although these antibiotics also perturb the protective resident microbiota, often resulting in disease relapse. Thus, an urgent need remains for the development of new treatment strategies. Auranofin is an FDA-approved oral antirheumatic drug that was previously shown to inhibit C. difficile vegetative cell growth, toxin production and spore production in vitro.ObjectivesTo determine the efficacy of auranofin as a CDI therapeutic by examining the effect of treatment on toxin and spore production in vitro and in vivo, and on disease outcomes in mice.MethodsC. difficile cultures were treated with auranofin and examined for effects on sporulation and toxin production by sporulation assay and ELISA, respectively. Mice were pretreated with auranofin prior to infection with C. difficile and monitored for physiological conditions, survival and gut damage compared with control animals. Faeces from mice were analysed to determine whether auranofin reduces sporulation and toxin production in vivo.ResultsAuranofin significantly reduces sporulation and toxin production under in vitro conditions and in infected mice in vivo. Mice treated with auranofin lost less weight, displayed a significant increase in survival rates and had significantly less toxin-mediated damage in their colon and caecum compared with control mice.ConclusionsAuranofin shows promise as a prospective therapeutic option for C. difficile infections.
      PubDate: Wed, 23 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz430
      Issue No: Vol. 75, No. 2 (2019)
       
  • Antibacterial properties and in vivo efficacy of a novel nitrofuran,
           IITR06144, against MDR pathogens
    • Authors: Bhando T; Bhattacharyya T, Gaurav A, et al.
      Pages: 418 - 428
      Abstract: AbstractObjectivesThe emergence of MDR Gram-negative pathogens and increasing prevalence of chronic infections presents an unmet need for the discovery of novel antibacterial agents. The aim of this study was to evaluate the biological properties of a small molecule, IITR06144, identified in a phenotypic screen against the Gram-negative model organism Escherichia coli.MethodsA small-molecule library of 10956 compounds was screened for growth inhibition against E. coli ATCC 25922 at concentration 50 μM. MICs of lead compounds were determined by the broth microdilution method. Time–kill kinetics, anti-persister activity, spontaneous frequency of resistance, biofilm inhibition and disruption were assessed by standard protocols. Resistant mutants were generated by serial passaging followed by WGS. In vitro toxicity studies were carried out via the MTT assay. In vivo toxicity and efficacy in a mouse model were also evaluated.ResultsIITR06144 was identified as the most promising candidate amongst 29 other potential antibacterial leads, exhibiting the lowest MIC, 0.5 mg/L. IITR06144 belongs to the nitrofuran class and exhibited broad-spectrum bactericidal activity against most MDR bacteria, including the ‘priority pathogen’, carbapenem-resistant Acinetobacter baumannii. IITR06144 retained its potency against nitrofurantoin-resistant clinical isolates. It displayed anti-persister, anti-biofilm activity and lack of spontaneous resistance development. IITR06144 demonstrated a large therapeutic index with no associated in vitro and in vivo toxicity.ConclusionsIn the light of excellent in vitro properties displayed by IITR06144 coupled with its considerable in vivo efficacy, further evaluation of IITR06144 as a therapeutic lead against antibiotic-resistant infections is warranted.
      PubDate: Sat, 26 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz428
      Issue No: Vol. 75, No. 2 (2019)
       
  • β-Lactam pharmacodynamics in Gram-negative bloodstream infections in
           the critically ill
    • Authors: Wong G; Taccone F, Villois P, et al.
      Pages: 429 - 433
      Abstract: AbstractObjectivesTo determine the β-lactam exposure associated with positive clinical outcomes for Gram-negative blood stream infection (BSI) in critically ill patients.Patients and methodsPooled data of critically ill patients with mono-microbial Gram-negative BSI treated with β-lactams were collected from two databases. Free minimum concentrations (fCmin) of aztreonam, cefepime, ceftazidime, ceftriaxone, piperacillin (co-administered with tazobactam) and meropenem were interpreted in relation to the measured MIC for targeted bacteria (fCmin/MIC). A positive clinical outcome was defined as completion of the treatment course or de-escalation, without other change of antibiotic therapy, and with no additional antibiotics commenced within 48 h of cessation. Drug exposure breakpoints associated with positive clinical outcome were determined by classification and regression tree (CART) analysis.ResultsData from 98 patients were included. Meropenem (46.9%) and piperacillin/tazobactam (36.7%) were the most commonly prescribed antibiotics. The most common pathogens were Escherichia coli (28.6%), Pseudomonas aeruginosa (19.4%) and Klebsiella pneumoniae (13.3%). In all patients, 87.8% and 71.4% achieved fCmin/MIC ≥1 and fCmin/MIC >5, respectively. Seventy-eight patients (79.6%) achieved positive clinical outcome. Two drug exposure breakpoints were identified: fCmin/MIC >1.3 for all β-lactams (predicted difference in positive outcome 84.5% versus 15.5%, P < 0.05) and fCmin/MIC >4.95 for meropenem, aztreonam or ceftriaxone (predicted difference in positive outcome 97.7% versus 2.3%, P < 0.05).ConclusionsA β-lactam fCmin/MIC >1.3 was a significant predictor of a positive clinical outcome in critically ill patients with Gram-negative BSI and could be considered an antibiotic dosing target.
      PubDate: Sat, 26 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz437
      Issue No: Vol. 75, No. 2 (2019)
       
  • Bayesian clinical decision support-guided versus clinician-guided
           vancomycin dosing in attainment of targeted pharmacokinetic parameters in
           a paediatric population
    • Authors: Hughes D; Goswami S, Keizer R, et al.
      Pages: 434 - 437
      Abstract: AbstractObjectivesTo compare a Bayesian clinical decision support (CDS) dose-optimizing software program with clinician judgement in individualizing vancomycin dosing regimens to achieve vancomycin pharmacokinetic (PK)/pharmacodynamic (PD) targets in a paediatric population.MethodsA retrospective review combined with a model-based simulation of vancomycin dosing was performed on children aged 1 year to 18 years at the University of California, San Francisco Benioff Children’s Hospital Mission Bay. Dosing regimens recommended by the clinical pharmacists, ‘clinician-guided’, were compared with alternative ‘CDS-guided’ dosing regimens. The primary outcome was the percentage of occasions predicted to achieve steady-state trough levels within the target range of 10–15 mg/L, with a secondary outcome of predicted attainment of AUC24 ≥400 mg·h/L. Statistical comparison between approaches was performed using a standard t-test.ResultsA total of n=144 patient occasions were included. CDS-guided regimens were predicted to achieve vancomycin steady-state troughs in the target range on 70.8% (102/144) of occasions, as compared with 37.5% (54/144) in the clinician-guided arm (P<0.0001). An AUC24 of ≥400 mg·h/L was achieved on 93% (112/121) of occasions in the CDS-guided arm versus 72% (87/121) of occasions in the clinician-guided arm (P<0.0001).ConclusionsIn a simulated analysis, the use of a Bayesian CDS tool was better than clinician judgement in recommending vancomycin dosing regimens in which PK/PD targets would be attained in children.
      PubDate: Thu, 31 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz444
      Issue No: Vol. 75, No. 2 (2019)
       
  • The effect of food on the pharmacokinetics of oral ivermectin
    • Authors: Duthaler U; Leisegang R, Karlsson M, et al.
      Pages: 438 - 440
      Abstract: AbstractBackgroundIvermectin is an older anthelminthic agent that is being studied more intensely given its potential for mass drug administration against scabies, malaria and other neglected tropical diseases. Its pharmacokinetics (PK) remain poorly characterized. Furthermore, the majority of PK trials are performed under fasted-state dosing conditions, and the effect of food is therefore not well known. To better plan and design field trials with ivermectin, a model that can account for both conditions would be valuable.ObjectivesTo develop a PK model and characterize the food effect with single oral doses of ivermectin.Patients and methodsWe performed a population-based PK analysis of data pooled from two previous trials of a single dose of 12 mg ivermectin, one with dosing after a high-fat breakfast (n=12) and one with fasted-state dosing (n=3).ResultsThe final model described concentration–time profiles after fed and fasted dosing accurately, and estimated the food effect associated with relative bioavailability to 1.18 (95% CI 1.10–1.67).ConclusionsIn this analysis, the effect of a high-fat breakfast compared with a fasted-state administration of a single oral dose of 12 mg ivermectin was minimal.
      PubDate: Wed, 06 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz466
      Issue No: Vol. 75, No. 2 (2019)
       
  • Continuous versus intermittent infusion of cefotaxime in critically ill
           patients: a randomized controlled trial comparing plasma concentrations
    • Authors: Aardema H; Bult W, van Hateren K, et al.
      Pages: 441 - 448
      Abstract: AbstractBackgroundIn critical care patients, reaching optimal β-lactam concentrations poses challenges, as infections are caused more often by microorganisms associated with higher MICs, and critically ill patients typically have an unpredictable pharmacokinetic/pharmacodynamic profile. Conventional intermittent dosing frequently yields inadequate drug concentrations, while continuous dosing might result in better target attainment. Few studies address cefotaxime concentrations in this population.ObjectivesTo assess total and unbound serum levels of cefotaxime and an active metabolite, desacetylcefotaxime, in critically ill patients treated with either continuously or intermittently dosed cefotaxime.MethodsAdult critical care patients with indication for treatment with cefotaxime were randomized to treatment with either intermittent dosing (1 g every 6 h) or continuous dosing (4 g/24 h, after a loading dose of 1 g). We defined a preset target of reaching and maintaining a total cefotaxime concentration of 4 mg/L from 1 h after start of treatment. CCMO trial registration number NL50809.042.14, Clinicaltrials.gov NCT02560207.ResultsTwenty-nine and 30 patients, respectively, were included in the continuous dosing group and the intermittent dosing group. A total of 642 samples were available for analysis. In the continuous dosing arm, 89.3% met our preset target, compared with 50% in the intermittent dosing arm. Patients not reaching this target had a significantly higher creatinine clearance on the day of admission.ConclusionsThese results support the application of a continuous dosing strategy of β-lactams in critical care patients and the practice of therapeutic drug monitoring in a subset of patients with higher renal clearance and need for prolonged treatment for further optimization, where using total cefotaxime concentrations should suffice.
      PubDate: Thu, 07 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz463
      Issue No: Vol. 75, No. 2 (2019)
       
  • Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea:
           the relationship between antibiotic MIC and clinical outcome
    • Authors: Cole M; Tan W, Fifer H, et al.
      Pages: 449 - 457
      Abstract: AbstractObjectivesTo investigate the relationship between MIC and clinical outcome in a randomized controlled trial that compared gentamicin 240 mg plus azithromycin 1 g with ceftriaxone 500 mg plus azithromycin 1 g. MIC analysis was performed on Neisseria gonorrhoeae isolates from all participants who were culture positive before they received treatment.MethodsViable gonococcal cultures were available from 279 participants, of whom 145 received ceftriaxone/azithromycin and 134 received gentamicin/azithromycin. Four participants (6 isolates) and 14 participants (17 isolates) did not clear infection in the ceftriaxone/azithromycin and gentamicin/azithromycin arms, respectively. MICs were determined by Etest on GC agar base with 1% Vitox. The geometric mean MICs of azithromycin, ceftriaxone and gentamicin were compared using logistic and linear regression according to treatment received and N. gonorrhoeae clearance.ResultsAs the azithromycin MIC increased, gentamicin/azithromycin treatment was less effective than ceftriaxone/azithromycin at clearing N. gonorrhoeae. There was a higher geometric mean MIC of azithromycin for isolates from participants who had received gentamicin/azithromycin and did not clear infection compared with those who did clear infection [ratio 1.95 (95% CI 1.28–2.97)], but the use of categorical MIC breakpoints did not accurately predict the treatment response. The geometric mean MIC of azithromycin was higher in isolates from the pharynx compared with genital isolates.ConclusionsWe found that categorical resistance to azithromycin or ceftriaxone in vitro, and higher gentamicin MICs in the absence of breakpoints, were poorly predictive of treatment failure.
      PubDate: Thu, 31 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz436
      Issue No: Vol. 75, No. 2 (2019)
       
  • Aminoglycoside versus carbapenem or piperacillin/tazobactam treatment for
           bloodstream infections of urinary source caused by Gram-negative
           ESBL-producing Enterobacteriaceae
    • Authors: Zohar I; Schwartz O, Yossepowitch O, et al.
      Pages: 458 - 465
      Abstract: AbstractObjectivesWe studied the performance of aminoglycosides in treating bloodstream infections (BSIs) of urinary source caused by ESBL-producing Enterobacteriaceae (ESBL-EB). MethodsIn a retrospective study of 193 patients with a clinical diagnosis of urinary tract infection, pyelonephritis or urosepsis and blood and urine cultures positive for ESBL-EB, patients were grouped according to whether they were treated with an aminoglycoside, a carbapenem or piperacillin/tazobactam. Multivariate analysis was used to define risk factors for mortality with inverse probability of treatment weighting used to minimize confounding. The primary efficacy outcome was 30 day mortality. The primary safety outcome was acute kidney injury (AKI) at 14 days. ResultsMean age was 79.3 years. Dementia, chronic kidney disease and the presence of a urinary catheter were common. Thirty-two (16.6%) patients died and risk factors for mortality included age, high Charlson score, presentation with severe sepsis/septic shock and infection with bacteria other than Escherichia coli. Aminoglycosides were non-inferior compared with other antibiotics regarding 30 day mortality [13.0% versus 21.2%, respectively; adjusted risk difference=10.29% (−0.82% to 21.41%)], but did not reach non-inferiority for bacteriuria recurrence [48.9% versus 44.7%, respectively; adjusted risk difference=−8.72% (−30.87% to 13.43%)]. AKI developed at a similar rate in both treatment groups: 12.0% versus 10.6%, respectively [OR=1.14 (0.46–2.81)]. Aminoglycosides were more efficacious in E. coli infections compared with other ESBL-EB.ConclusionsWe demonstrated the efficacy and safety of aminoglycosides in treating BSI of urinary source caused by ESBL-EB. This carbapenem-sparing approach can assist in avoiding excessive carbapenem use without compromising outcomes.
      PubDate: Wed, 06 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz457
      Issue No: Vol. 75, No. 2 (2019)
       
  • Physicians’ opinions on generic antiretroviral drugs and single-tablet
           regimen de-simplification for the treatment of HIV infection: a
           multicentre survey in Spain
    • Authors: Suárez-García I; Ruiz-Algueró M, García Yubero C, et al.
      Pages: 466 - 472
      Abstract: AbstractObjectivesTo assess the attitudes and opinions about generic antiretroviral drugs (ARVs) and single-tablet regimen (STR) de-simplification among physicians prescribing HIV treatment in the cohort of the Spanish HIV/AIDS Research Network (CoRIS).MethodsAn online questionnaire with 27 structured questions was sent to all physicians (n=199) who prescribed ARVs among the 45 centres participating in the cohort.ResultsA total of 169 (84.9%) physicians answered the questionnaire. Only 4.1% of the physicians would never prescribe generic ARVs, but 53.3% would not prescribe them if the number of pills per day increased and 89.3% would not prescribe them if the number of doses per day increased. However, 84.0% of the physicians agreed to prescribe generic ARVs if doing so would decrease costs for the public healthcare system. The percentages of physicians stating that generic ARVs (compared with branded ones) would be associated with worse adherence, more adverse effects or more probability of virological failure, provided that the number of pills and doses per day would not change, were low: 0.6%, 7.7% and 3.6%, respectively. However, these percentages were much higher if the generic ARV entailed breaking an STR: 63.9%, 18.9% and 42.0%, respectively. Most physicians stated that they needed more information about the effectiveness and safety of generic ARVs and the price difference compared with their branded equivalents.ConclusionsAlthough most physicians were confident about prescribing generic ARVs, the majority had strong concerns about de-simplifying STR, and they also needed more information about generic drugs.
      PubDate: Tue, 29 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz439
      Issue No: Vol. 75, No. 2 (2019)
       
  • Antibiotic use in pregnancy: knowledge, attitudes and practices among
           pregnant women in Cape Town, South Africa
    • Authors: Bulabula A; Dramowski A, Mehtar S.
      Pages: 473 - 481
      Abstract: AbstractObjectivesTo establish the knowledge, attitudes and practices (KAP) regarding antibiotic use and self-medication among pregnant women.MethodsWe conducted a KAP survey of 301 pregnant women hospitalized at a tertiary hospital obstetric service in Cape Town, South Africa in November and December 2017, using an interviewer-administered 12 item questionnaire. We stratified analysis of attitudes and practices by participants’ mean knowledge score (K-score) group (<6 versus ≥6 out of 7 questions). Multivariate models were built to identify independent predictors of antibiotic self-medication and K-score.ResultsThe mean age of pregnant women was 29 (SD 6.1) years, 44/247 (17.8%) were nulliparous, 69/247 (27.9%) were HIV-infected, 228/247 (92.3%) had completed secondary school and 78/247 (31.6%) reported a monthly household income in the lowest category of ≤50–100 US dollars (USD). The mean K-score was 6.1 (SD 1.02) out of 7 questions. Sixteen percent of the cohort reported antibiotic self-medication, with higher rates among pregnant women with K-score <6 [18/48 (37.5%) versus 32/253 (12.6%); P<0.001]. The monthly household income category of >500 USD (the highest category) was the only predictor of antibiotic self-medication behaviour [adjusted OR=6.4 (95% CI 1.2–35.2), P=0.03].ConclusionsHigher antibiotic knowledge scores are associated with lower rates of antibiotic self-medication, whereas higher household income is correlated with increasing self-medication behaviours. Education of pregnant women regarding the potential dangers of antibiotic self-medication and stricter enforcement of existing South African antibiotic prescribing and dispensing regulations are needed.
      PubDate: Mon, 21 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz427
      Issue No: Vol. 75, No. 2 (2019)
       
  • Identification of a poxtA- and cfr-carrying multiresistant Enterococcus
           hirae strain
    • Authors: Li D; Cheng Y, Schwarz S, et al.
      Pages: 482 - 484
      Abstract: Sir,
      PubDate: Wed, 06 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz449
      Issue No: Vol. 75, No. 2 (2019)
       
  • A novel SCCmec type V variant in porcine MRSA ST398 from China
    • Authors: Ji X; Krüger H, Feßler A, et al.
      Pages: 484 - 486
      Abstract: Sir,
      PubDate: Thu, 31 Oct 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz445
      Issue No: Vol. 75, No. 2 (2019)
       
  • Enterobacter sp. N18-03635 harbouring blaFRI-6 class A carbapenemase,
           Canada
    • Authors: Boyd D; Lefebvre B, Mataseje L, et al.
      Pages: 486 - 488
      Abstract: Sir,
      PubDate: Thu, 14 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz438
      Issue No: Vol. 75, No. 2 (2019)
       
  • Treatment failure of daptomycin for Streptococcus parasanguinis meningitis
    • Authors: Valanejad S; Hill B.
      Pages: 488 - 490
      Abstract: Sir,
      PubDate: Thu, 07 Nov 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz467
      Issue No: Vol. 75, No. 2 (2019)
       
 
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