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Publisher: Oxford University Press   (Total: 406 journals)

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Showing 1 - 200 of 406 Journals sorted alphabetically
ACS Symposium Series     Full-text available via subscription   (Followers: 1, 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: 54, 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: 66, SJR: 1.869, CiteScore: 2)
Age and Ageing     Hybrid Journal   (Followers: 90, SJR: 1.989, CiteScore: 4)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 18, SJR: 1.376, CiteScore: 3)
American Entomologist     Full-text available via subscription   (Followers: 8)
American Historical Review     Hybrid Journal   (Followers: 180, SJR: 0.467, CiteScore: 1)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 2.113, CiteScore: 3)
American J. of Clinical Nutrition     Hybrid Journal   (Followers: 184, SJR: 3.438, CiteScore: 6)
American J. of Epidemiology     Hybrid Journal   (Followers: 196, SJR: 2.713, CiteScore: 3)
American J. of Health-System Pharmacy     Full-text available via subscription   (Followers: 54, SJR: 0.595, CiteScore: 1)
American J. of Hypertension     Hybrid Journal   (Followers: 26, 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: 9, SJR: 0.116, CiteScore: 0)
American Law and Economics Review     Hybrid Journal   (Followers: 28, SJR: 1.053, CiteScore: 1)
American Literary History     Hybrid Journal   (Followers: 17, SJR: 0.391, CiteScore: 0)
Analysis     Hybrid Journal   (Followers: 23, SJR: 1.038, CiteScore: 1)
Animal Frontiers     Hybrid Journal   (Followers: 1)
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 16, SJR: 1.423, CiteScore: 3)
Annals of Botany     Hybrid Journal   (Followers: 38, SJR: 1.721, CiteScore: 4)
Annals of Oncology     Hybrid Journal   (Followers: 55, 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: 34, 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: 17, 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: 21)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 14)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 30, SJR: 0.731, CiteScore: 2)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 3)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 44, SJR: 0.146, CiteScore: 0)
Behavioral Ecology     Hybrid Journal   (Followers: 53, SJR: 1.871, CiteScore: 3)
Bioinformatics     Hybrid Journal   (Followers: 347, SJR: 6.14, CiteScore: 8)
Biology Methods and Protocols     Hybrid Journal  
Biology of Reproduction     Full-text available via subscription   (Followers: 10, SJR: 1.446, CiteScore: 3)
Biometrika     Hybrid Journal   (Followers: 20, SJR: 3.485, CiteScore: 2)
BioScience     Hybrid Journal   (Followers: 29, SJR: 2.754, CiteScore: 4)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 2, SJR: 0.146, CiteScore: 0)
Biostatistics     Hybrid Journal   (Followers: 17, SJR: 1.553, CiteScore: 2)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 187, SJR: 2.115, CiteScore: 3)
BJA Education     Hybrid Journal   (Followers: 67)
Brain     Hybrid Journal   (Followers: 70, SJR: 5.858, CiteScore: 7)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 49, 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: 38, SJR: 2.161, CiteScore: 2)
British J. of Aesthetics     Hybrid Journal   (Followers: 25, SJR: 0.508, CiteScore: 1)
British J. of Criminology     Hybrid Journal   (Followers: 604, SJR: 1.828, CiteScore: 3)
British J. of Social Work     Hybrid Journal   (Followers: 87, 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: 4, 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: 14, SJR: 3.002, CiteScore: 5)
Cerebral Cortex     Hybrid Journal   (Followers: 52, SJR: 3.892, CiteScore: 6)
CESifo Economic Studies     Hybrid Journal   (Followers: 23, SJR: 0.483, CiteScore: 1)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.42, CiteScore: 3)
Children and Schools     Hybrid Journal   (Followers: 6, 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: 23, SJR: 0.329, CiteScore: 0)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 10, 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: 27, SJR: 0.123, CiteScore: 0)
Clean Energy     Open Access   (Followers: 1)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 69, SJR: 5.051, CiteScore: 5)
Communication Theory     Hybrid Journal   (Followers: 25, 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: 9, 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: 3)
Current Legal Problems     Hybrid Journal   (Followers: 29)
Current Zoology     Full-text available via subscription   (Followers: 3, 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: 21, 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: 32, SJR: 2.926, CiteScore: 1)
Economic J.     Hybrid Journal   (Followers: 116, SJR: 5.161, CiteScore: 3)
Economic Policy     Hybrid Journal   (Followers: 48, SJR: 3.584, CiteScore: 3)
ELT J.     Hybrid Journal   (Followers: 24, SJR: 0.942, CiteScore: 1)
English Historical Review     Hybrid Journal   (Followers: 56, SJR: 0.612, CiteScore: 1)
English: J. of the English Association     Hybrid Journal   (Followers: 17, SJR: 0.1, CiteScore: 0)
Environmental Entomology     Full-text available via subscription   (Followers: 11, 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: 19, SJR: 0.113, CiteScore: 0)
European Heart J.     Hybrid Journal   (Followers: 66, 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: 2)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. : Case Reports     Open Access  
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: 205, 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: 19, 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: 43, 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: 16, SJR: 1.492, CiteScore: 4)
Fems Microbiology Letters     Hybrid Journal   (Followers: 28, SJR: 0.79, CiteScore: 2)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 33, 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: 24, 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: 34, 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: 16, SJR: 2.578, CiteScore: 4)
Geophysical J. Intl.     Hybrid Journal   (Followers: 39, SJR: 1.506, CiteScore: 3)
German History     Hybrid Journal   (Followers: 23, 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: 13, SJR: 1.493, CiteScore: 3)
Health and Social Work     Hybrid Journal   (Followers: 57, SJR: 0.388, CiteScore: 1)
Health Education Research     Hybrid Journal   (Followers: 15, SJR: 0.854, CiteScore: 2)
Health Policy and Planning     Hybrid Journal   (Followers: 24, SJR: 1.512, CiteScore: 2)
Health Promotion Intl.     Hybrid Journal   (Followers: 22, SJR: 0.812, CiteScore: 2)
History Workshop J.     Hybrid Journal   (Followers: 33, SJR: 1.278, CiteScore: 1)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 28, SJR: 0.105, CiteScore: 0)
Human Communication Research     Hybrid Journal   (Followers: 15, SJR: 2.146, CiteScore: 3)
Human Molecular Genetics     Hybrid Journal   (Followers: 9, SJR: 3.555, CiteScore: 5)
Human Reproduction     Hybrid Journal   (Followers: 75, SJR: 2.643, CiteScore: 5)
Human Reproduction Open     Open Access   (Followers: 1)
Human Reproduction Update     Hybrid Journal   (Followers: 21, SJR: 5.317, CiteScore: 10)
Human Rights Law Review     Hybrid Journal   (Followers: 64, SJR: 0.756, CiteScore: 1)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 58, SJR: 1.591, CiteScore: 3)
ICSID Review : Foreign Investment Law J.     Hybrid Journal   (Followers: 11)
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: 41, SJR: 0.249, CiteScore: 1)
Inflammatory Bowel Diseases     Hybrid Journal   (Followers: 47, SJR: 2.511, CiteScore: 4)
Information and Inference     Free  
Innovation in Aging     Open Access  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 9, SJR: 1.319, CiteScore: 2)
Integrative Biology     Full-text available via subscription   (Followers: 6, SJR: 1.36, CiteScore: 3)
Integrative Organismal Biology     Open Access  
Interacting with Computers     Hybrid Journal   (Followers: 11, SJR: 0.292, CiteScore: 1)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 7, SJR: 0.762, CiteScore: 1)
Intl. Affairs     Hybrid Journal   (Followers: 68, 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: 36, SJR: 1.348, CiteScore: 2)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 65, SJR: 0.601, CiteScore: 1)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 259, 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: 28, SJR: 0.223, CiteScore: 1)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 10, 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: 11, SJR: 0.724, CiteScore: 2)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.168, CiteScore: 1)
Intl. Political Sociology     Hybrid Journal   (Followers: 40, 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: 50, SJR: 2.581, CiteScore: 2)
Intl. Studies Review     Hybrid Journal   (Followers: 25, 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: 17, SJR: 0.533, CiteScore: 1)
J. of American History     Hybrid Journal   (Followers: 46, 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: 15, 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: 41, SJR: 1.226, CiteScore: 2)
J. of Breast Imaging     Full-text available via subscription   (Followers: 1)
J. of Burn Care & Research     Hybrid Journal   (Followers: 11, SJR: 0.768, CiteScore: 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: 15  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0305-7453 - ISSN (Online) 1460-2091
Published by Oxford University Press Homepage  [406 journals]
  • Valaciclovir therapy for herpes encephalitis: caution advised
    • Authors: Bodilsen J; Nielsen H, Whitley R.
      Pages: 1467 - 1468
      Abstract: Recently some authors have suggested that oral valaciclovir 1 g q8h is a valid alternative to intravenous aciclovir for herpes encephalitis. We are concerned about numerous caveats that we think have not been sufficiently addressed to allow such use outside of a controlled research setting.
      PubDate: Fri, 18 Jan 2019 00:00:00 GMT
      DOI: 10.1093/jac/dky568
      Issue No: Vol. 74, No. 6 (2019)
  • Emergence of optrA-mediated linezolid resistance in enterococci from
           France, 2006–16
    • Authors: Sassi M; Guérin F, Zouari A, et al.
      Pages: 1469 - 1472
      Abstract: ObjectivesTo describe the epidemiological trend of linezolid-resistant enterococci (LRE) collected in France from 2006 to 2016 and to extensively characterize LRE isolates.MethodsThe National Reference Center for Enterococci (NRC-Enc) received enterococcal isolates suspected to be VRE and/or LRE from all French hospitals between 2006 and 2016. LRE isolates were phenotypically characterized and their genomes were entirely sequenced by Miseq (Illumina). Transfer of linezolid resistance was attempted by filter mating experiments.ResultsOut of 3974 clinical isolates of enterococci received at the NRC-Enc over the period, 9 (0.2%) were LRE (MICs 8 to >32 mg/L), including 6 Enterococcus faecium and 3 Enterococcus faecalis. This overall prevalence significantly increased over the study period, reaching 0.8% in 2016. The five LRE isolated before 2016 were vanA-positive E. faecium whereas strains isolated in 2016 (one E. faecium and three E. faecalis) were susceptible to vancomycin. None of these isolates was part of an outbreak, while E. faecium strains were assigned to four different STs [17 (1), 80 (3), 412 (1) and 650 (1)] and all three E. faecalis belonged to ST480. Except for the strain isolated in 2010, all LRE were positive for optrA, which was located on plasmids (5/8) or in the chromosome (3/8). Plasmid transfer of optrA was successful in three cases.ConclusionsThere has been a significant increase in the prevalence of LRE in France over time; this is due to the spread of optrA among E. faecium and E. faecalis human clinical isolates (VRE or not).
      PubDate: Wed, 20 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz097
      Issue No: Vol. 74, No. 6 (2019)
  • LRE-Finder, a Web tool for detection of the 23S rRNA mutations and the
           optrA, cfr, cfr(B) and poxtA genes encoding linezolid resistance in
           enterococci from whole-genome sequences
    • Authors: Hasman H; Clausen P, Kaya H, et al.
      Pages: 1473 - 1476
      Abstract: ObjectivesIn enterococci, resistance to linezolid is often mediated by mutations in the V domain of the 23S rRNA gene (G2576T or G2505A). Furthermore, four genes [optrA, cfr, cfr(B) and poxtA] encode linezolid resistance in enterococci. We aimed to develop a Web tool for detection of the two mutations and the four genes encoding linezolid resistance in enterococci from whole-genome sequence data.MethodsLRE-Finder (where LRE stands for linezolid-resistant enterococci) detected the fraction of Ts in position 2576 and the fraction of As in position 2505 of the 23S rRNA and the cfr, cfr(B), optrA and poxtA genes by aligning raw sequencing reads (fastq format) with k-mer alignment. For evaluation, fastq files from 21 LRE isolates were submitted to LRE-Finder. As negative controls, fastq files from 1473 non-LRE isolates were submitted to LRE-Finder. The MICs of linezolid were determined for the 21 LRE isolates. As LRE-negative controls, 26 VRE isolates were additionally selected for linezolid MIC determination.ResultsLRE-Finder was validated and showed 100% concordance with phenotypic susceptibility testing. A cut-off of 10% mutations in position 2576 and/or position 2505 was set in LRE-Finder for predicting a linezolid resistance phenotype. This cut-off allows for detection of a single mutated 23S allele in both Enterococcus faecalis and Enterococcus faecium, while ignoring low-level sequencing noise.ConclusionsA Web tool for detection of the 23S rRNA mutations (G2576T and G2505A) and the optrA, cfr, cfr(B) and poxtA genes from whole-genome sequences from enterococci is now available online.
      PubDate: Tue, 12 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz092
      Issue No: Vol. 74, No. 6 (2019)
  • Rifampicin and rifabutin resistance in 1003 Mycobacterium tuberculosis
           clinical isolates
    • Authors: Farhat M; Sixsmith J, Calderon R, et al.
      Pages: 1477 - 1483
      Abstract: ObjectivesDrug-resistant TB remains a public health challenge. Rifamycins are among the most potent anti-TB drugs. They are known to target the RpoB subunit of RNA polymerase; however, our understanding of how rifamycin resistance is genetically encoded remains incomplete. Here we investigated rpoB genetic diversity and cross-resistance between the two rifamycin drugs rifampicin and rifabutin.MethodsWe performed WGS of 1003 Mycobacterium tuberculosis clinical isolates and determined MICs of both rifamycin agents on 7H10 agar using the indirect proportion method. We generated rpoB mutants in a laboratory strain and measured their antibiotic susceptibility using the alamarBlue reduction assay.ResultsOf the 1003 isolates, 766 were rifampicin resistant and 210 (27%) of these were rifabutin susceptible; 102/210 isolates had the rpoB mutation D435V (Escherichia coli D516V). Isolates with discordant resistance were 17.2 times more likely to harbour a D435V mutation than those resistant to both agents (OR 17.2, 95% CI 10.5–27.9, P value <10−40). Compared with WT, the D435V in vitro mutant had an increased IC50 of both rifamycins; however, in both cases to a lesser degree than the S450L (E. coli S531L) mutation.ConclusionsThe observation that the rpoB D435V mutation produces an increase in the IC50 of both drugs contrasts with findings from previous smaller studies that suggested that isolates with the D435V mutation remain rifabutin susceptible despite being rifampicin resistant. Our finding thus suggests that the recommended critical testing concentration for rifabutin should be revised.
      PubDate: Thu, 21 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz048
      Issue No: Vol. 74, No. 6 (2019)
  • Using WGS to identify antibiotic resistance genes and predict
           antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in
    • Authors: Kumburu H; Sonda T, van Zwetselaar M, et al.
      Pages: 1484 - 1493
      Abstract: BackgroundReliable phenotypic antimicrobial susceptibility testing can be a challenge in clinical settings in low- and middle-income countries. WGS is a promising approach to enhance current capabilities.AimTo study diversity and resistance determinants and to predict and compare resistance patterns from WGS data of Acinetobacter baumannii with phenotypic results from classical microbiological testing at a tertiary care hospital in Tanzania.Methods and resultsMLST using Pasteur/Oxford schemes yielded eight different STs from each scheme. Of the eight, two STs were identified to be global clones 1 (n = 4) and 2 (n = 1) as per the Pasteur scheme. Resistance testing using classical microbiology determined between 50% and 92.9% resistance across all drugs. Percentage agreement between phenotypic and genotypic prediction of resistance ranged between 57.1% and 100%, with coefficient of agreement (κ) between 0.05 and 1. Seven isolates harboured mutations at significant loci (S81L in gyrA and S84L in parC). A number of novel plasmids were detected, including pKCRI-309C-1 (219000 bp) carrying 10 resistance genes, pKCRI-43-1 (34935 bp) carrying two resistance genes and pKCRI-49-1 (11681 bp) and pKCRI-28-1 (29606 bp), each carrying three resistance genes. New ampC alleles detected included ampC-69, ampC-70 and ampC-71. Global clone 1 and 2 isolates were found to harbour ISAba1 directly upstream of the ampC gene. Finally, SNP-based phylogenetic analysis of the A. baumannii isolates revealed closely related isolates in three clusters.ConclusionsThe validity of the use of WGS in the prediction of phenotypic resistance can be appreciated, but at this stage is not sufficient for it to replace conventional antimicrobial susceptibility testing in our setting.
      PubDate: Wed, 06 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz055
      Issue No: Vol. 74, No. 6 (2019)
  • Identification of the novel class D β-lactamase OXA-679 involved in
           carbapenem resistance in Acinetobacter calcoaceticus
    • Authors: Tietgen M; Kramer J, Brunst S, et al.
      Pages: 1494 - 1502
      Abstract: ObjectivesThe aim of this study was to characterize the Acinetobacter calcoaceticus clinical isolate AC_2117 with the novel carbapenem-hydrolysing class D β-lactamase (CHDL) OXA-679.MethodsIdentification of the species and β-lactamases was verified by genome sequencing (PacBio) and phylogenetic analyses. Antibiotic susceptibility of AC_2117 and transformants harbouring cloned blaOXA-679 was evaluated using antibiotic gradient strips and microbroth dilution. OXA-679 was purified heterologously and kinetic parameters were determined using spectrometry or isothermal titration calorimetry. The impact of OXA-679 production during imipenem therapy was evaluated in the Galleria mellonella infection model.ResultsSequencing of the complete genome of the clinical A. calcoaceticus isolate AC_2117 identified a novel CHDL, termed OXA-679. This enzyme shared sequence similarity of 71% to each of the families OXA-143 and OXA-24/40. Phylogenetic analyses revealed that OXA-679 represents a member of a new OXA family. Cloning and expression of blaOXA-679 as well as measurement of kinetic parameters revealed the effective hydrolysis of carbapenems which resulted in reduced susceptibility to carbapenems in Escherichia coli and A. calcoaceticus, and high-level carbapenem resistance in Acinetobacter baumannii. Infection of larvae of G. mellonella with a sublethal dose of blaOXA-679-expressing A. baumannii could not be cured by high-dose imipenem therapy, indicating carbapenem resistance in vivo.ConclusionsWe identified blaOXA-679 in a clinical A. calcoaceticus isolate that represents a member of the new OXA-679 family and that conferred high-level carbapenem resistance in vitro and in vivo.
      PubDate: Thu, 07 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz080
      Issue No: Vol. 74, No. 6 (2019)
  • Fluoroquinolone resistance in carbapenem-resistant Elizabethkingia
           anophelis: phenotypic and genotypic characteristics of clinical isolates
           with topoisomerase mutations and comparative genomic analysis
    • Authors: Jian M; Cheng Y, Chung H, et al.
      Pages: 1503 - 1510
      Abstract: BackgroundMDR Elizabethkingia anophelis strains are implicated in an increasing number of healthcare-associated infections worldwide, including a recent cluster of E. anophelis infections in the Midwestern USA associated with significant morbidity and mortality. However, there is minimal information on the antimicrobial susceptibilities of E. anophelis strains or their antimicrobial resistance to carbapenems and fluoroquinolones.ObjectivesOur aim was to examine the susceptibilities and genetic profiles of clinical isolates of E. anophelis from our hospital, characterize their carbapenemase genes and production of MBLs, and determine the mechanism of fluoroquinolone resistance.MethodsA total of 115 non-duplicated isolates of E. anophelis were examined. MICs of antimicrobial agents were determined using the Sensititre 96-well broth microdilution panel method. QRDR mutations and MBL genes were identified using PCR. MBL production was screened for using a combined disc test.ResultsAll E. anophelis isolates harboured the blaGOB and blaB genes with resistance to carbapenems. Antibiotic susceptibility testing indicated different resistance patterns to ciprofloxacin and levofloxacin in most isolates. Sequencing analysis confirmed that a concurrent GyrA amino acid substitution (Ser83Ile or Ser83Arg) in the hotspots of respective QRDRs was primarily responsible for high-level ciprofloxacin/levofloxacin resistance. Only one isolate had no mutation but a high fluoroquinolone MIC.ConclusionsOur study identified a strong correlation between antibiotic susceptibility profiles and mechanisms of fluoroquinolone resistance among carbapenem-resistant E. anophelis isolates, providing an important foundation for continued surveillance and epidemiological analyses of emerging E. anophelis opportunistic infections. Minocycline or ciprofloxacin has the potential for treatment of severe E. anophelis infections.
      PubDate: Mon, 04 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz045
      Issue No: Vol. 74, No. 6 (2019)
  • Antimicrobial resistance-encoding plasmid clusters with heterogeneous MDR
           regions driven by IS26 in a single Escherichia coli isolate
    • Authors: He D; Zhao S, Wu H, et al.
      Pages: 1511 - 1516
      Abstract: BackgroundIS26-flanked transposons played an increasingly important part in the mobilization and development of resistance determinants. Heterogeneous resistance-encoding plasmid clusters with polymorphic MDR regions (MRRs) conferred by IS26 in an individual Escherichia coli isolate have not yet been detected.ObjectivesTo characterize the complete sequence of a novel blaCTX-M-65- and fosA3-carrying IncZ-7 plasmid with dynamic MRRs from an E. coli isolate, and to depict the mechanism underlying the spread of resistance determinants and genetic polymorphisms.MethodsThe molecular characterization of a strain carrying blaCTX-M-65 and fosA3 was analysed by antimicrobial susceptibility testing and MLST. The transferability of a plasmid bearing blaCTX-M-65 and fosA3 was determined by conjugation assays, and the complete structure of the plasmid was obtained by Illumina, PacBio and conventional PCR mapping, respectively. The circular forms derived from IS26-flanked transposons were detected by reverse PCR and sequencing.ResultsA novel IncZ-7 plasmid pEC013 (∼118kb) harbouring the blaCTX-M-65 and fosA3 genes was recovered from E. coli isolate EC013 belonging to D-ST117. The plasmid was found to have heterogeneous and dynamic MRRs in an individual strain and the IS26-flanked composite transposon-derived circular intermediates were identified and characterized in pEC013.ConclusionsThe heterogeneous MRRs suggested that a single plasmid may actually be a cluster of plasmids with the same backbone but varied MRRs, reflecting the plasmid’s heterogeneity and the survival benefits of having a response to antimicrobial-related threatening conditions in an individual strain.
      PubDate: Thu, 28 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz044
      Issue No: Vol. 74, No. 6 (2019)
  • Identification of a novel hybrid plasmid coproducing MCR-1 and MCR-3
           variant from an Escherichia coli strain
    • Authors: Li R; Zhang P, Yang X, et al.
      Pages: 1517 - 1520
      Abstract: ObjectivesTo characterize the genome of an Escherichia coli harbouring both mcr-1 and mcr-3.19 on a hybrid plasmid and the underlying transmission mechanisms.MethodsBroth microdilution was used to perform antimicrobial susceptibility testing. Conjugation assays and S1-PFGE were used to assess the transferability of mcr genes. Resistance genotypes and genetic contexts were investigated, based on WGS data from the Illumina and MinION platforms. Inverse PCR was performed to test the mcr-3.19-bearing circular intermediate. Bioinformatic tools were used to further characterize the hybrid plasmid.ResultsE. coli CP53 was identified as harbouring both mcr-1 and mcr-3.19 on a 231 859 bp hybrid plasmid pCP53-mcr1_3 containing IncFIA, IncHI1A, IncHI1B and IncN replicons. The genetic structures of mcr-1 and mcr-3.19 were similar to those reported in other mcr-1 and mcr-3.19-bearing plasmids, which suggested that recombination between mcr-bearing plasmids had been mediated by ISs. However, the MDR plasmid pCP53-mcr1_3 cannot transfer via conjugation. Furthermore, another three plasmids were identified in the isolate, two of which encoded resistance genes. In640 duplication between two MDR plasmids was observed. An MDR-region recombination existed in E. coli CP53. A core structure consisting of mcr-3-dgkA existed in mcr-3-bearing plasmids reported, to date. Circular intermediates were observed for mcr-1 and mcr-3.19 regions.ConclusionsA novel mcr-3.19 was identified along with mcr-1 contained in a hybrid plasmid. This finding suggested that evolution of mcr genes among various plasmids was being driven by mobile elements. Molecular surveillance of mcr gene co-occurrence warrants further investigation to evaluate the public health risk.
      PubDate: Thu, 21 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz058
      Issue No: Vol. 74, No. 6 (2019)
  • Colistin resistance in Parisian inpatient faecal Escherichia coli as the
           result of two distinct evolutionary pathways
    • Authors: Bourrel A; Poirel L, Royer G, et al.
      Pages: 1521 - 1530
      Abstract: BackgroundBeyond plasmid-encoded resistance (mcr genes) prevalence in strain collections, large epidemiological studies to estimate the human burden of colistin-resistant Escherichia coli gut carriage are lacking.ObjectivesTo evaluate the prevalence of colistin-resistant E. coli carriage in inpatients and decipher the molecular support of resistance and the genetic background of the strains.MethodsDuring a 3 month period in 2017, we prospectively screened patients in six Parisian hospitals for rectal carriage of colistin-resistant E. coli using a selective medium, a biochemical confirmatory test and MIC determination. WGS of the resistant strains and their corresponding plasmids was performed.ResultsAmong the 1217 screened patients, 153 colistin-resistant E. coli strains were isolated from 152 patients (12.5%). The mcr-1 gene was identified in only seven isolates (4.6%) on different plasmid scaffolds. The genetic background of these MCR-1 producers argued for an animal origin. Conversely, the remaining 146 colistin-resistant E. coli exhibited a phylogenetic distribution corresponding to human gut commensal/clinical population structure (B2 and D phylogroup predominance); 72.6% of those isolates harboured convergent mutations in the PmrA and PmrB proteins, constituting a two-component system shown to be associated with colistin resistance.ConclusionsWe showed that the occurrence at a high rate of colistin resistance in human faecal E. coli is the result of two distinct evolutionary pathways, i.e. the occurrence of chromosomal mutations in an endogenous E. coli population and the rare acquisition of exogenous mcr-1-bearing strains probably of animal origin. The involved selective pressures need to be identified in order to develop preventative strategies.
      PubDate: Tue, 12 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz090
      Issue No: Vol. 74, No. 6 (2019)
  • Dynamics of faecal shedding of ESBL- or AmpC-producing Escherichia coli on
           dairy farms
    • Authors: Hordijk J; Fischer E, van Werven T, et al.
      Pages: 1531 - 1538
      Abstract: ObjectivesTo explore the dynamics of faecal ESBL/AmpC shedding in dairy cattle and farmers, a study was conducted to examine changes in shedding by individual animals, as well as environmental exposure, and to study the association between antimicrobial use (AMU) and ESBL/AmpC shedding.MethodsThe study comprised a cross-sectional survey of 20 farms and a 1 year follow-up of 10 farms. Faecal samples were cultured by both direct inoculation on MacConkey agar + 1 mg/L cefotaxime (MC+) and enrichment in LB-broth + 1 mg/L cefotaxime with subsequent inoculation on MC+. Dust samples were collected using electrostatic dustfall collectors (EDCs). Human faecal samples were collected by the farmers. Presence of ESBL/AmpC genes was screened for by PCR and sequencing. Using mixed effects logistic regression, ORs were determined and population-attributable fractions (PAFs) calculated subsequently.ResultsIn Phase 1, 8/20 farms were positive for ESBL/AmpC and, with 2 negative farms, were selected for Phase 2. Transient shedding of dominant allele variants was observed in the animals. EDCs and human faecal samples did not reflect what was observed in the animals. AMU was related to shedding of ESBLs in the next sampling moment [OR 14.6 (95% CI 3.0–80.0)] and the PAF of AMU was 0.36 (95% CI 0.08–0.77). Calves fed with colostrum from cows on dry-off therapy was not a risk factor [OR 1.7 (95% CI 0.7–4.9, P = 0.28)].ConclusionsThe presence of ESBL/AmpC could only be partly explained by AMU. No link was shown between shedding in cattle and humans or the environment. Interventions should focus on prevention of introduction.
      PubDate: Fri, 08 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz035
      Issue No: Vol. 74, No. 6 (2019)
  • Genetic characterization of an MDR/virulence genomic element carrying two
           T6SS gene clusters in a clinical Klebsiella pneumoniae isolate of swine
    • Authors: Chen F; Zhang W, Schwarz S, et al.
      Pages: 1539 - 1544
      Abstract: ObjectivesMultiresistant Klebsiella pneumoniae isolates rarely cause infections in pigs. The aim of this study was to investigate a multiresistant porcine K. pneumoniae isolate for plasmidic and chromosomal antimicrobial resistance and virulence genes and their genetic environment.MethodsK. pneumoniae strain ZYST1 originated from a pig with pneumonia. Antimicrobial susceptibility testing was performed using broth microdilution. Conjugation experiments were conducted using Escherichia coli J53 as the recipient. The complete sequences of the chromosomal DNA and the plasmids were generated by WGS and analysed for the presence of resistance and virulence genes.ResultsThe MDR K. pneumoniae ST1 strain ZYST1 contained three plasmids belonging to incompatibility groups IncFIIk5-FIB, IncI1 and IncX4, respectively. The IncFIIk5-FIB plasmid carried the resistance genes aadA2, mph(A), sul1 and aph(3′)-Ia, and the IncI1 plasmid carried aadA22 and erm(B). No resistance genes were present on the IncX4 plasmid. Plasmids related to the aforementioned three plasmids were also present in other Enterobacteriaceae species from humans, animals and the environment. Bioinformatic analyses identified a chromosomal 904 kb MDR element flanked by two copies of ISKpn26. This element included virulence factors, such as a type VI secretion system (T6SS) and genes for type 1 fimbriae, the toxin–antitoxin system HipA/HipB, antimicrobial resistance genes, such as blaSHV-187, mdtk, catA and the multiple antibiotic resistance operon marRABC, and heavy metal resistance determinants, such as chrB/chrA and tehA/tehB.ConclusionsThis study reports a novel 904 kb MDR/virulence genomic element and three important plasmids coexisting in a clinical K. pneumoniae isolate of animal origin.
      PubDate: Thu, 21 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz093
      Issue No: Vol. 74, No. 6 (2019)
  • Susceptibility of Legionella pneumophila to antimicrobial agents and the
           presence of the efflux pump LpeAB
    • Authors: Natås O; Brekken A, Bernhoff E, et al.
      Pages: 1545 - 1550
      Abstract: ObjectivesLegionella pneumophila strains resistant to antimicrobial agents are rare. We tested 10 antimicrobial agents against clinical and environmental strains and performed WGS to screen for the presence of resistance mechanisms.MethodsA total of 122 clinical and environmental strains of L. pneumophila collected between 2000 and 2017 and characterized by serogroup and ST were included. Antimicrobial susceptibility was tested by gradient diffusion tests on buffered charcoal yeast extract agar medium supplemented with α-ketoglutarate (BCYE-α) and a subgroup of strains were whole-genome sequenced using Illumina technology and analysed.ResultsAll strains showed a WT MIC distribution for ciprofloxacin, levofloxacin, moxifloxacin, rifampicin, cefotaxime, tetracycline and trimethoprim/sulfamethoxazole. All strains of L. pneumophila serogroup 1, ST1 (18/122; 14.7%) showed reduced susceptibility to azithromycin (MIC 0.5–1 mg/L) and harboured the efflux pump component lpeAB. Two strains of L. pneumophila serogroup 5 (ST1328) and one strain of serogroup 4 (ST1973) also showed reduced susceptibility to azithromycin (MIC 0.5 mg/L). They harboured lpeAB gene variants with 91.37% and 92.52% nucleotide identity, respectively, compared with the lpeAB genes of serogroup 1, ST1 strains.ConclusionsOur collection of L. pneumophila strains was susceptible to most antimicrobial agents except azithromycin. Gradient diffusion tests on BCYE-α test medium detected strains with reduced susceptibility to azithromycin. All L. pneumophila serogroup 1, ST1 strains showed reduced susceptibility to macrolides and contained the efflux pump component lpeAB. Reduced susceptibility to azithromycin in non-serogroup 1 strains may be due to the presence of an lpeAB efflux pump variant.
      PubDate: Wed, 27 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz081
      Issue No: Vol. 74, No. 6 (2019)
  • Genome-based epidemiology and antimicrobial resistance determinants of
           Neisseria gonorrhoeae isolates with decreased susceptibility and
           resistance to extended-spectrum cephalosporins in Argentina in 2011–16
    • Authors: Gianecini R; Golparian D, Zittermann S, et al.
      Pages: 1551 - 1559
      Abstract: ObjectivesOur aim was to describe the molecular epidemiology and antimicrobial resistance determinants of isolates of Neisseria gonorrhoeae with decreased susceptibility and resistance to extended-spectrum cephalosporins (ESCs) in Argentina in 2011–16.MethodsGonococcal isolates (n=158) with decreased susceptibility and resistance to ESCs collected in 2011–16 across Argentina were subjected to WGS and antimicrobial susceptibility testing for six antimicrobials.ResultsIn total, 50% of the isolates were resistant to cefixime, 1.9% were resistant to ceftriaxone, 37.3% were resistant to azithromycin and 63.9% of the isolates showed an MDR phenotype. Resistance and decreased susceptibility to ESCs was mainly associated with isolates possessing the mosaic penA-34.001, in combination with an mtrR promoter A deletion, and PorB1b amino acid substitutions G120K/A121N. Phylogenetic analysis revealed two main clades of circulating strains, which were associated with the N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 and closely related STs, and characterized by a high prevalence rate, wide geographical distribution and temporal persistence.ConclusionsN. gonorrhoeae isolates with decreased susceptibility and resistance to ESCs in Argentina have emerged and rapidly spread mainly due to two clonal expansions after importation of one or two strains, which are associated with the international MDR NG-MAST ST1407 clone. The identification of the geographical dissemination and characteristics of these predominant clones may help to focus action plans and public health policies to control the spread of ESC resistance in Argentina. Dual antimicrobial therapy (ceftriaxone plus azithromycin) for gonorrhoea needs to be considered in Argentina.
      PubDate: Thu, 28 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz054
      Issue No: Vol. 74, No. 6 (2019)
  • Proteae: a reservoir of class 2 integrons'
    • Authors: Mendes Moreira A; Couvé-Deacon E, Bousquet P, et al.
      Pages: 1560 - 1562
      Abstract: ObjectivesOur aim was to confirm with a large panel of clinical isolates that class 2 integrons are highly prevalent in Proteae and to analyse their genetic characteristics.MethodsProteae (Proteus spp., Morganella spp. and Providencia spp.) isolates were collected from clinical samples during 2013 at Limoges University Hospital, France. The presence of class 1, 2 and 3 integrons was investigated by quantitative PCR. The presence of a stop codon in the intI2 gene was determined by Sanger sequencing. The gene cassette arrays of class 2 integrons were determined by PCR-RFLP and Sanger sequencing or next-generation sequencing when needed.ResultsOf the 327 Proteae collected, 103 (31.5%) harboured a class 2 integron and 45 (13.8%) a class 1 integron. No class 3 integrons were detected. One functional IntI2 integrase was detected in a Morganella morganii isolate. Six different gene cassette arrays were detected. Four had already been described in the literature: dfrA1–sat2–aadA1 (72 isolates), dfrA1–catB2–sat2–aadA1 (17), sat2–aadA1 (6) and lnu(F), dfrA1, aadA1 (1). We identified two new gene cassette arrays: (i) a new variant of the dfrA1 gene cassette (one isolate; the one with the functional IntI2); and (ii) the array dfrA1–gcu115–sat2 harbouring the new gcu115 gene cassette with two ORFs encoding proteins of unknown functions (five isolates).ConclusionsWe showed a high frequency of class 2 integrons, as well as a diversity of gene cassette arrays, among Proteae. This work highlights that the Proteae tribe plays an important role as a reservoir of class 2 integrons.
      PubDate: Mon, 25 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz079
      Issue No: Vol. 74, No. 6 (2019)
  • Identification of a novel metallo-β-lactamase, CAM-1, in clinical
           Pseudomonas aeruginosa isolates from Canada
    • Authors: Boyd D; Lisboa L, Rennie R, et al.
      Pages: 1563 - 1567
      Abstract: ObjectivesTo identify the β-lactamase responsible for the positive detection of carbapenemase production in four clinical isolates of Pseudomonas aeruginosa that were negative by PCR for KPC, OXA-48, NDM, VIM, IMP, GES and NMC/IMI carbapenemase genes.MethodsWGS using short-read and long-read methods was used to characterize the isolates. Bioinformatic analysis was used to identify the potential gene encoding a carbapenemase. Cloning, antimicrobial susceptibility testing and biochemical and phenotypic characterization were used to determine metallo-enzyme activity. Single-nucleotide variant (SNV) typing was used to determine strain relatedness. Conjugation experiments were used to determine transmissibility of the novel carbapenemase-encoding gene.ResultsWGS analysis revealed a novel class B β-lactamase gene, blaCAM-1 (Central Alberta Metallo-β-lactamase), located in a 73 kb integrative element, named IMEPaCAM-1, in the chromosome of four clinical isolates of P. aeruginosa. The cloned blaCAM-1 gene conferred carbapenem resistance to Escherichia coli TOP10. The four isolates, which were all closely related, were from three patients, all of whom spent time in the same hospital in 2008 and/or 2009. IMEPaCAM-1 could not be transferred by conjugation.ConclusionsA novel metallo-enzyme, CAM-1, is encoded on an integrative element, IMEPaCAM-1, located in the chromosome of clinical isolates of P. aeruginosa. No additional isolates harbouring CAM-1 have been identified in Alberta since 2007.
      PubDate: Wed, 20 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz066
      Issue No: Vol. 74, No. 6 (2019)
  • ZHO-1, an intrinsic MBL from the environmental Gram-negative species
           Zhongshania aliphaticivorans
    • Authors: Kieffer N; Guzmán-Puche J, Poirel L, et al.
      Pages: 1568 - 1571
      Abstract: ObjectivesOur aim was to characterize the putative MBL of the environmental strain Zhongshania aliphaticivorans isolated from a marine environment.MethodsThe putative MBL was identified in silico using the NCBI database. The β-lactamase gene was cloned into different Escherichia coli backgrounds. Kinetic parameters were determined using the purified enzyme.ResultsThe enzyme named ZHO-1 shared 51% amino acid identity with the acquired class B carbapenemases IMP-1, KHM-1 and DIM-1. Expression of the blaZHO-1 gene in a susceptible E. coli resulted in a carbapenemase phenotype. Kinetic parameters determined from purified ZHO-1 enzyme showed that it had significant hydrolytic activity against most β-lactams including penicillins, cephalosporins and carbapenems, with the exception of aztreonam and cefepime.ConclusionsThis study adds to the knowledge regarding environmental species as a reservoir of possible clinically relevant MBLs.
      PubDate: Mon, 18 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz057
      Issue No: Vol. 74, No. 6 (2019)
  • Enhanced emergence of antibiotic-resistant pathogenic bacteria after in
           vitro induction with cancer chemotherapy drugs
    • Authors: Meunier A; Nerich V, Fagnoni-Legat C, et al.
      Pages: 1572 - 1577
      Abstract: BackgroundInfections with antibiotic-resistant pathogens in cancer patients are a leading cause of mortality. Cancer patients are treated with compounds that can damage bacterial DNA, potentially triggering the SOS response, which in turn enhances the bacterial mutation rate. Antibiotic resistance readily occurs after mutation of bacterial core genes. Thus, we tested whether cancer chemotherapy drugs enhance the emergence of resistant mutants in commensal bacteria.MethodsInduction of the SOS response was tested after the incubation of Escherichia coli biosensors with 39 chemotherapeutic drugs at therapeutic concentrations. The mutation frequency was assessed after induction with the SOS-inducing chemotherapeutic drugs. We then tested the ability of the three most highly inducing drugs to drive the emergence of resistant mutants of major bacterial pathogens to first-line antibiotics.ResultsTen chemotherapeutic drugs activated the SOS response. Among them, eight accelerated the evolution of the major commensal E. coli, mostly through activation of the SOS response, with dacarbazine, azacitidine and streptozotocin enhancing the mutation rate 21.3-fold (P < 0.001), 101.7-fold (P = 0.01) and 1158.7-fold (P = 0.02), respectively. These three compounds also spurred the emergence of imipenem-resistant Pseudomonas aeruginosa (up to 6.21-fold; P = 0.05), ciprofloxacin-resistant Staphylococcus aureus (up to 57.72-fold; P = 0.016) and cefotaxime-resistant Enterobacteria cloacae (up to 4.57-fold; P = 0.018).ConclusionsOur results suggest that chemotherapy could accelerate evolution of the microbiota and drive the emergence of antibiotic-resistant mutants from bacterial commensals in patients. This reveals an additional level of complexity of the interactions between cancer, chemotherapy and the gut microbiota.
      PubDate: Wed, 20 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz070
      Issue No: Vol. 74, No. 6 (2019)
  • Silver nanoparticles present high intracellular and extracellular killing
           against Staphylococcus aureus
    • Authors: Kang J; Dietz M, Hughes K, et al.
      Pages: 1578 - 1585
      Abstract: ObjectivesBone and joint infections caused by Staphylococcus aureus are becoming increasingly difficult to treat due to rising antibiotic resistance, resilient biofilms and intracellular survival of S. aureus. It has been challenging to identify and develop antimicrobial agents that can be used to kill extracellular and intracellular bacteria while having limited toxicity towards host cells. In addressing this challenge, this study investigates the antimicrobial efficacy and toxicity of silver nanoparticles (AgNPs).MethodsIntracellular bacteria were generated using a co-culture model of human osteoblast cells and S. aureus. Extracellular and intracellular S. aureus were treated with AgNPs, antibiotics and their combinations, and numbers of colonies were quantified. Toxicity of AgNPs against human osteoblast cells was determined by quantifying the number of viable cells after treatment.ResultsAgNPs demonstrated excellent antimicrobial activity against extracellular S. aureus with a 100% killing efficacy at concentrations as low as 56 μM, along with a high intracellular killing efficacy of 76% at 371 μM. AgNPs were non-toxic or slightly toxic towards human osteoblasts at the concentrations studied (up to 927 μM). Moreover, smaller-sized (40 nm) AgNPs were more efficacious in killing bacteria compared with their larger-sized (100 nm) counterparts and synergistic antimicrobial effects against extracellular bacteria were observed when AgNPs were combined with gentamicin.ConclusionsAgNPs and their combination with antibiotics have demonstrated high extracellular and intracellular bacterial killing and presented unique aspects for potential clinical applications, especially for chronic and recurrent infections where intracellular bacteria may be the cause.
      PubDate: Mon, 18 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz053
      Issue No: Vol. 74, No. 6 (2019)
  • In vitro activity of olorofim (F901318) against clinical isolates of
           cryptic species of Aspergillus by EUCAST and CLSI methodologies
    • Authors: Rivero-Menendez O; Cuenca-Estrella M, Alastruey-Izquierdo A.
      Pages: 1586 - 1590
      Abstract: ObjectivesTo investigate the in vitro activity of olorofim (F901318), a novel broad-spectrum antifungal agent, against 150 strains belonging to 16 different cryptic species of Aspergillus by EUCAST and CLSI methodologies.MethodsOlorofim, amphotericin B, micafungin, posaconazole and voriconazole were tested against cryptic species belonging to Aspergillus fumigatus complex (n = 57), Aspergillus ustus complex (n = 25), Aspergillus niger complex (n = 20), Aspergillus flavus complex (n = 20), Aspergillus circumdati complex (n = 15) and Aspergillus terreus complex (n = 13) using EUCAST and CLSI methodologies for broth microdilution susceptibility testing of antifungal agents.ResultsOlorofim was the only drug with activity against all cryptic species of Aspergillus tested, including the multiresistant species Aspergillus lentulus, Aspergillus fumigatiaffinis and Aspergillus calidoustus. Geometric means of MICs for olorofim were lower (0.017, 0.015 and 0.098 mg/L, respectively, for EUCAST; and 0.015, 0.015 and 0.048 mg/L, respectively, for CLSI) than for amphotericin B (4.438, 12.699 and 0.554 mg/L, respectively, for EUCAST; and 0.758, 1.320 and 0.447 mg/L, respectively, for CLSI), voriconazole (2.549, 2.297 and 5.856 mg/L, respectively, for EUCAST; and 2.071, 1.741 and 5.657 mg/L, respectively, for CLSI) and posaconazole (0.307, 0.308 and 12.996 mg/L, respectively, for EUCAST; and 0.391, 0.215 and 9.514 mg/L, respectively, for CLSI).ConclusionsOlorofim shows encouraging in vitro activity against cryptic species of Aspergillus that can be hard to treat with current antifungal therapies. Further studies are warranted in order to assess its efficacy.
      PubDate: Tue, 19 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz078
      Issue No: Vol. 74, No. 6 (2019)
  • In vitro activity of the novel oral antimicrobial SMT-571, with a new
           mechanism of action, against MDR and XDR Neisseria gonorrhoeae: future
           treatment option for gonorrhoea'
    • Authors: Jacobsson S; Mason C, Khan N, et al.
      Pages: 1591 - 1594
      Abstract: BackgroundLack of effective treatment of gonorrhoea due to increasing antimicrobial resistance in Neisseria gonorrhoeae is a serious threat to the management and control of the infection. Novel antimicrobials are required to prevent the infection becoming untreatable.ObjectivesHerein, we investigated the in vitro activity of a novel small-molecule antimicrobial with a new mechanism of action, SMT-571, against a large collection of clinical N. gonorrhoeae isolates (n = 228) and international gonococcal reference strains (n = 34), including numerous MDR and XDR gonococcal isolates.MethodsMICs of SMT-571 were determined by agar dilution and MICs of ceftriaxone, cefixime, azithromycin, ciprofloxacin, ampicillin, spectinomycin and tetracycline were determined by Etest.ResultsSMT-571 showed potent in vitro activity against all the tested N. gonorrhoeae isolates (n = 262). The MICs ranged from 0.064 to 0.125 mg/L and the MIC50, MIC90 and modal MIC were all 0.125 mg/L. No cross-resistance or correlation between the MICs of SMT-571 and comparator agents was seen.ConclusionsSMT-571 demonstrated potent in vitro activity against all tested gonococcal isolates and no cross-resistance to previously and currently used antimicrobials was seen. With its promising supplementary in vitro and in vivo preclinical data, including high levels of oral bioavailability, SMT-571 could be an effective option for the oral treatment of gonorrhoea. Randomized controlled clinical trials for gonorrhoea that examine the treatment efficacy, pharmacokinetics/pharmacodynamics, toxicity and safety of SMT-571, and include urogenital and extragenital (rectal and pharyngeal) samples, are crucial.
      PubDate: Mon, 18 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz060
      Issue No: Vol. 74, No. 6 (2019)
  • Geographical and temporal variation in the frequency and antimicrobial
           susceptibility of bacteria isolated from patients hospitalized with
           bacterial pneumonia: results from 20 years of the SENTRY Antimicrobial
           Surveillance Program (1997–2016)
    • Authors: Sader H; Castanheira M, Arends S, et al.
      Pages: 1595 - 1606
      Abstract: BackgroundThe SENTRY Antimicrobial Surveillance Program monitors the frequency of occurrence and antimicrobial susceptibility of organisms from various infection types worldwide.MethodsA total of 102 995 bacterial isolates were consecutively collected (one per patient) in 1997–2016 from 258 medical centres in North America (n = 44 999; 113 centres), Europe (n = 30 988; 61 centres from 22 nations), the Asia-Pacific region (APAC; n = 16 503; 67 centres from 12 nations) and Latin America (n = 10 505; 17 centres from 7 nations). Organisms were isolated from respiratory tract specimens and tested for susceptibility by broth microdilution methods in a central laboratory.ResultsStaphylococcus aureus (n = 24 351) and Pseudomonas aeruginosa (n = 22 279) were the most common organisms overall. Klebsiella spp. (n = 10 565) ranked third in North America, Europe and APAC. The proportion of Gram-negatives increased from 70.0%–74.7% to 80.9%–82.6% in Europe, APAC and Latin America, and remained stable (65.5%–66.1%) in North America. Methicillin resistance rates decreased substantially in all four regions from 2005–06 to 2015–16 among S. aureus isolates. P. aeruginosa susceptibility to meropenem decreased overall in the initial years, but increased in the last years of the investigation. Among Klebsiella spp. isolates, susceptibility to ceftriaxone/meropenem decreased from 85.9%/99.3% to 58.6%/85.8% in Europe and from 91.8%/99.5% to 81.6%/93.9% in APAC during the study period.ConclusionsRank order and susceptibility rates varied widely by geographical region and over time. The occurrence of some resistance phenotypes increased, though others decreased over the 20 years of the SENTRY Antimicrobial Surveillance Program.
      PubDate: Wed, 06 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz074
      Issue No: Vol. 74, No. 6 (2019)
  • Once-a-week tigecycline for the treatment of drug-resistant TB
    • Authors: Deshpande D; Magombedze G, Srivastava S, et al.
      Pages: 1607 - 1617
      Abstract: BackgroundMDR-TB and XDR-TB have poor outcomes.ObjectivesTo examine the efficacy of tigecycline monotherapy in the hollow fibre system model of TB.MethodsWe performed pharmacokinetic/pharmacodynamic studies using tigecycline human-like concentration–time profiles in the hollow fibre system model of TB in five separate experiments using Mycobacterium tuberculosis in log-phase growth or as semi-dormant or intracellular bacilli, as monotherapy. We also compared efficacy with the isoniazid/rifampicin/pyrazinamide combination (standard therapy). We then applied extinction mathematics, morphisms and Latin hypercube sampling to identify duration of therapy with tigecycline monotherapy.ResultsThe median tigecycline MIC for 30 M. tuberculosis clinical and laboratory isolates (67% MDR/XDR) was 2 mg/L. Tigecycline monotherapy was highly effective in killing M. tuberculosis in log-phase-growth and semi-dormant and intracellular M. tuberculosis. Once-a-week dosing had the same efficacy as daily therapy for the same cumulative dose; thus, tigecycline efficacy was linked to the AUC0–24/MIC ratio. Tigecycline replacement by daily minocycline after 4 weeks of therapy was effective in sterilizing bacilli. The AUC0–24/MIC ratio associated with optimal kill was 42.3. Tigecycline monotherapy had a maximum sterilizing effect (day 0 minus day 28) of 3.06 ± 0.20 log10 cfu/mL (r2 = 0.92) compared with 3.92 ± 0.45 log10 cfu/mL (r2 = 0.80) with optimized standard therapy. In our modelling, at a tigecycline monotherapy duration of 12 months, the proportion of patients with XDR-TB who reached bacterial population extinction was 64.51%.ConclusionsTigecycline could cure patients with XDR-TB or MDR-TB who have failed recommended therapy. Once-a-week tigecycline could also replace second-line injectables in MDR-TB regimens.
      PubDate: Thu, 28 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz061
      Issue No: Vol. 74, No. 6 (2019)
  • A polymer-based anti-quorum catheter coating to challenge MDR
           Staphylococcus aureus: in vivo and in vitro approaches
    • Authors: Vasudevan S; Durai R, Chellappan D, et al.
      Pages: 1618 - 1626
      Abstract: BackgroundMDR Staphylococcus aureus is a major aetiological agent of catheter-associated infections. A quorum sensing targeted drug development approach proves to be an effective alternative strategy to combat such infections.MethodsIntravenous catheters were coated with polymethacrylate copolymers loaded with the antivirulent compound 2-[(methylamino)methyl]phenol (2MAMP). The in vitro drug release profile and kinetics were established. The anti-biofilm effect of the coated catheters was tested against clinical isolates of MDR S. aureus. The in vivo studies were carried out using adult male Wistar rats by implanting coated catheters in subcutaneous pockets. Histopathological analysis was done to understand the immunological reactions induced by 2MAMP.ResultsA uniform catheter coating of thickness 0.1 mm was achieved with linear sustained release of 2MAMP for 6 h. The coating formulation was cytocompatible. The in vitro and in vivo anti-adherence studies showed reduced bacterial accumulation in coated catheters after 48 h. The histopathological results confirmed that the coated catheter did not bring about any adverse inflammatory response.ConclusionsThe developed anti-quorum-coated catheter that is non-toxic and biocompatible has the potential to be used in other medical devices, thereby preventing catheter-associated infections.
      PubDate: Tue, 12 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz094
      Issue No: Vol. 74, No. 6 (2019)
  • Bedaquiline kills persistent Mycobacterium tuberculosis with no disease
           relapse: an in vivo model of a potential cure
    • Authors: Hu Y; Pertinez H, Liu Y, et al.
      Pages: 1627 - 1633
      Abstract: ObjectivesNon-replicating persistent Mycobacterium tuberculosis is difficult to kill since the organisms become undetectable using our conventional diagnostic methods and tolerant to anti-TB drugs. Resuscitation-promoting factors (RPFs) have been used to ‘wake up’ non-replicating persisters, making them easy to detect. Bedaquiline is a novel bactericidal and sterilizing anti-TB drug with the potential to eradicate RPF-dependent persistent M. tuberculosis. We present the first head-to-head comparison between the standard anti-TB regimen and a bedaquiline-modified regimen in eradicating RPF-dependent persistent M. tuberculosis, using the well-defined Cornell Model. MethodsM. tuberculosis-infected mice were treated for 14 weeks with either the standard regimen (rifampicin, isoniazid, pyrazinamide and ethambutol) or the same regimen where ethambutol was replaced by bedaquiline. The efficacy of both drug regimens was measured by cfu count elimination and eradication of persistent bacteria, which was evaluated using culture filtrate (CF) containing RPFs. At the end of treatment, the remaining cfu count-negative mice were administered hydrocortisone for 8 weeks. The induced disease relapse rates were determined by the percentage of mice that became positive for M. tuberculosis in the lung, spleen or both.ResultsThe bedaquiline-containing regimen achieved total organ cfu count clearance at 8 weeks after treatment initiation, faster than the standard regimen (14 weeks). Importantly, the bedaquiline-containing regimen removed CF-dependent persistent bacilli at 8 weeks, leading to no disease relapse.ConclusionsA bedaquiline regimen eradicated persistent TB infections and completely prevented disease relapse in mice. These findings offer the potential for a faster cure for TB, with reduced relapse rate.
      PubDate: Wed, 20 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz052
      Issue No: Vol. 74, No. 6 (2019)
  • Anti-leishmanial activity of a topical miltefosine gel in experimental
           models of New World cutaneous leishmaniasis
    • Authors: Neira L; Mantilla J, Escobar P.
      Pages: 1634 - 1641
      Abstract: ObjectivesTopical treatment for cutaneous leishmaniasis (CL) would be useful for treatment of some forms of the disease. The aim of this study was to develop and then evaluate a topical miltefosine gel for anti-leishmanial activity and toxicity in BALB/c mice infected with New World (NW)-CL species. MethodsA Carbopol-based gel of 0.5% miltefosine was prepared and physicochemical (colour, pH, consistency and antioxidant activity) and stability properties were determined using standard methodologies. Anti-leishmanial activities for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis were determined both in cultured parasites and in infected BALB/c mice after topical miltefosine gel treatment administered for 20 days. The gel was evaluated for its capacity to inhibit parasites at a 50% level after 3 days of treatment in vitro, and its capacity to reduce lesion size (mm2) and parasitic load after 20 days of treatment. Dermal irritation, contact hypersensitivity (CHS), clinical biochemical profile and the weight of the animals were determined after treatment.ResultsThe 0.5% miltefosine gel was transparent, homogeneous, colourless, of neutral pH, spreadable and stable at 4°C for at least 3 months. It was active against parasites in vitro and in vivo, reducing CL lesion size by 84%–100% with no detected parasites. No signs of irritation, CHS or changes in weight, food intake, urea or transaminase serum levels were observed after treatment. ConclusionsThe topical 0.5% miltefosine gel formulation was efficacious and non-toxic when administered topically in NW-CL murine models. This miltefosine formulation could be an appropriate candidate for further development.
      PubDate: Wed, 27 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz049
      Issue No: Vol. 74, No. 6 (2019)
  • Pharmacokinetics of ascending doses of ivermectin in Trichuris
           trichiura-infected children aged 2–12 years
    • Authors: Schulz J; Coulibaly J, Schindler C, et al.
      Pages: 1642 - 1647
      Abstract: BackgroundYearly, millions of children are treated globally with ivermectin mainly for neglected tropical diseases. Anatomical, physiological and biochemical differences between children and adults may result in changes in pharmacokinetics. However, paediatric pharmacokinetic data of ivermectin are lacking.MethodsIn the framework of a randomized controlled dose-finding trial in rural Côte d’Ivoire, Trichuris trichiura-infected pre-school-aged children (PSAC, 2–5 years) and school-aged children (SAC, 6–12 years) were assigned to 100 or 200 μg/kg and 200, 400 or 600 μg/kg ivermectin, respectively (ISRCTN registry no. ISRCTN15871729). Capillary blood was collected on dried blood spot cards until 72 h post-treatment. Ivermectin was quantified by LC-MS/MS, and pharmacokinetic parameters were evaluated by non-compartmental analysis.ResultsCmax and AUC increased in PSAC and SAC with ascending doses and were similar in both age groups when the current standard dose (200 μg/kg) was administered (∼23 ng/mL and ∼350 ng×h/mL, respectively). PSAC with lower BMI were associated with significantly higher AUCs. AUC and Cmax were ∼2-fold lower in children compared with parameters previously studied in adults, whereas body weight-adjusted CL/F (∼0.35 L/h/kg) was significantly higher in children. Tmax (∼6 h), t1/2 (∼18 h), mean residence time (MRTINF) (∼28 h) and V/F (∼8 L/kg) were similar in all paediatric treatment arms. ConclusionsA positive association of AUC or Cmax with dose was observed in both age groups. Undernutrition might influence the AUC of ivermectin in PSAC. Ivermectin shows a lower exposure profile in children compared with adults, highlighting the need to establish dosing recommendations for different age groups.
      PubDate: Mon, 11 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz083
      Issue No: Vol. 74, No. 6 (2019)
  • Population pharmacokinetics of continuous-infusion ceftazidime in febrile
           neutropenic children undergoing HSCT: implications for target attainment
           for empirical treatment against Pseudomonas aeruginosa
    • Authors: Cojutti P; Maximova N, Schillani G, et al.
      Pages: 1648 - 1655
      Abstract: ObjectivesTo conduct a population pharmacokinetic analysis of continuous-infusion ceftazidime in a retrospective cohort of paediatric HSCT patients who were empirically treated for febrile neutropenia (FN) and who underwent therapeutic drug monitoring of ceftazidime steady-state plasma concentrations (Css) for optimization of drug exposure.MethodsA non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations were performed to calculate the PTA of the pharmacodynamic determinant of efficacy (Css/MIC ≥4) against Pseudomonas aeruginosa with continuous-infusion ceftazidime dosages of 1–6 g daily. The Css safety threshold was arbitrarily placed at 100 mg/L and advisable dosages were used.ResultsA total of 46 patients with 70 ceftazidime Css values were included. Estimated glomerular filtration rate (eGFR) and body surface area were the covariates associated with drug clearance. At the EUCAST clinical breakpoint of 8 mg/L, simulations showed that continuous-infusion ceftazidime dosages of 4–6 g daily attained optimal PTAs (>90%) across most of 16 different clinical scenarios based on four classes of eGFR (50–145, 145.1–200, 200.1–286 and 286.1–422 mL/min/1.73 m2) and body surface area (0.30–0.64, 0.65–0.88, 0.89–1.34 and 1.35–1.84 m2). In patients with body surface area 0.30–0.64 m2 and eGFR ≤200 mL/min/1.73 m2 the advisable dose of 3 g daily allowed only suboptimal PTAs (<75%). The cumulative fraction of response against MIC distribution of P. aeruginosa was >87%.ConclusionsContinuous-infusion ceftazidime dosages ranging from 3 to 6 g daily according to different classes of eGFR and body surface area may allow optimized empirical treatment of P. aeruginosa infections in paediatric HSCT patients with FN.
      PubDate: Tue, 05 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz065
      Issue No: Vol. 74, No. 6 (2019)
  • The pharmacokinetics of nitrofurantoin in healthy female volunteers: a
           randomized crossover study
    • Authors: Huttner A; Wijma R, Stewardson A, et al.
      Pages: 1656 - 1661
      Abstract: BackgroundUse of nitrofurantoin has increased significantly since its recent repositioning as a first-line agent for uncomplicated cystitis by multiple guidelines. However, current dosing regimens were developed in an era before robust pharmacokinetic testing and may not be optimal. Furthermore, formulations have been modified over the years.ObjectivesTo reassess the plasma and urinary pharmacokinetic profile of macrocrystalline nitrofurantoin in two commonly used dosing regimens.MethodsIn this open-label, randomized crossover pharmacokinetic trial, 12 healthy adult female volunteers were randomized to receive oral nitrofurantoin 100 mg q8h on days 1 and 2 and, after a washout period, 50 mg q6h on days 30 and 31, or the same dosing schemes in reversed order. Urine and blood were collected at steady state and analysed by UPLC. Pharmacokinetic analysis was performed by WinNonlin.ResultsPlasma peak concentrations were low (mean 0.33 mg/L, SD 0.08, and 0.69 mg/L, SD 0.35, after 50 and 100 mg, respectively) and dose dependent. The AUC0–24 was higher (6.49 versus 4.43 mg·h/L, P = 0.021) for the 100 mg q8h dosing regimen, but the dose-normalized AUC was similar for the two regimens. In contrast, urinary concentrations were dose independent: increasing the nitrofurantoin dose delayed the time to peak urinary concentration, while steady-state AUC0–24 values remained unchanged (943.49 and 855.95 mg·h/L at 50 mg q6h and 100 mg q8h, respectively).ConclusionsPlasma concentrations were relatively low and dose dependent. The dose-independent urinary concentrations suggest that excretion of nitrofurantoin into the urine is saturable. Pharmacodynamic studies are urgently required to determine the impact of these findings.
      PubDate: Mon, 11 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz095
      Issue No: Vol. 74, No. 6 (2019)
  • Defining optimal dosing of ciprofloxacin in patients with septic shock
    • Authors: Roberts J; Alobaid A, Wallis S, et al.
      Pages: 1662 - 1669
      Abstract: BackgroundPatients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics.ObjectivesTo describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients.MethodsAdult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio >125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa.ResultsWe included 48 patients with median Simplified Acute Physiology Score (SAPS) II of 49 and 90 day mortality of 33%. Ciprofloxacin pharmacokinetics was best described by a two-compartment linear model including CLCR and body weight as covariates on CL and central volume respectively. With a dose of 400 mg q8h and CLCR of 80 mL/min, >95% PTA was achieved for bacteria with MICs ≤0.25 mg/L. For empirical treatment of P. aeruginosa, 600 mg q8h only reached a maximum of 68% FTA. For directed therapy against P. aeruginosa, a dose of 600 mg q8h was needed to achieve sufficient AUC/MIC ratios.ConclusionsIn patients with septic shock, standard ciprofloxacin dosing achieved concentrations to successfully treat bacteria with MICs ≤0.25 mg/L and then only in patients with normal or reduced CLCR. To cover pathogens with higher MICs or in patients with augmented renal CL, doses may have to be increased.
      PubDate: Tue, 26 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz069
      Issue No: Vol. 74, No. 6 (2019)
  • Rifampicin effect on intracellular and plasma pharmacokinetics of
           tenofovir alafenamide
    • Authors: Cerrone M; Alfarisi O, Neary M, et al.
      Pages: 1670 - 1678
      Abstract: ObjectivesTenofovir alafenamide produces lower plasma tenofovir and higher intracellular tenofovir diphosphate (DP) concentrations than tenofovir disoproxil fumarate but it is likely a victim of interactions with rifampicin. We aimed to investigate the pharmacokinetics of tenofovir alafenamide/emtricitabine with rifampicin.Patients and methodsHealthy volunteers received tenofovir alafenamide/emtricitabine at 25/200 mg once daily, followed by tenofovir alafenamide/emtricitabine + rifampicin daily followed by tenofovir disoproxil fumarate. Plasma tenofovir alafenamide, tenofovir, emtricitabine and intracellular tenofovir-DP and emtricitabine triphosphate pharmacokinetics and genetic polymorphisms were assessed.ResultsTenofovir alafenamide exposure decreased when tenofovir alafenamide/emtricitabine + rifampicin was used compared with tenofovir alafenamide/emtricitabine [geometric mean ratio (GMR) (90% CI): 0.45 (0.33–0.60)]. Plasma tenofovir and intracellular tenofovir-DP concentrations decreased with rifampicin [GMR (90% CI): 0.46 (0.40–0.52) and 0.64 (0.54–0.75), respectively]. GMR (90% CI) of intracellular tenofovir-DP AUC0–24 for tenofovir alafenamide/emtricitabine + rifampicin versus tenofovir disoproxil fumarate was 4.21 (2.98–5.95). Rifampicin did not affect emtricitabine pharmacokinetics. CYP3A4*22 rs35599367 was associated with higher plasma tenofovir alafenamide AUC0–24 at day 56.ConclusionsFollowing tenofovir alafenamide/emtricitabine administration with rifampicin, intracellular tenofovir-DP concentrations were still 4.21-fold higher than those achieved by tenofovir disoproxil fumarate, supporting further study during HIV/TB co-infection.
      PubDate: Wed, 27 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz068
      Issue No: Vol. 74, No. 6 (2019)
  • HIV-1 protease, Gag and gp41 baseline substitutions associated with
           virological response to a PI-based regimen
    • Authors: Perrier M; Castain L, Regad L, et al.
      Pages: 1679 - 1692
      Abstract: ObjectivesTo assess, at ART initiation, the impact of baseline substitutions in protease, Gag and gp41 regions on the virological response to a first-line PI-based regimen.Patients and methodsOne hundred and fifty-four HIV-infected ART-naive patients initiating a PI-based regimen including darunavir (n = 129) or atazanavir (n = 25) were assessed, including 36 experiencing virological failure (VF). Whole pol, gag and gp41 genes were sequenced at ART baseline by ultra-deep sequencing (UDS) using Illumina® technology. Supervised data-mining analyses were performed to identify mutations associated with virological response. Structural analyses were performed to assess the impact of mutations on protease conformation.ResultsUDS was successful in 127, 138 and 134 samples for protease, Gag and gp41, respectively (31% subtype B and 38% CRF02_AG). Overall, T4A and S37T mutations in protease were identified as being associated with VF (P = 0.02 and P = 0.005, respectively). Among CRF02_AG sequences, I72M and E21D mutations were associated with VF (P = 0.03 for both). They all induced some conformational changes of some protease side-chain residues located near mutated residues. In Gag, mutations associated with VF were G62D, N315H and Y441S (P = 0.005, P = 0.007 and P = 0.0003, respectively). All were localized outside Gag cleavage sites (G62D, matrix; N315H, capsid; and Y441S, p1). In gp41, the I270T mutation, localized in the cytoplasmic tail, was associated with VF (P = 0.003), and the I4L mutation, in the fusion peptide, was associated with virological success (P = 0.004).ConclusionsIn this study, new baseline substitutions in Gag, protease and g41, potentially impacting PI-based regimen outcome, were evidenced. Phenotypic analyses are required to confirm their role in the PI-resistance mechanism.
      PubDate: Thu, 14 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz043
      Issue No: Vol. 74, No. 6 (2019)
  • Surveillance of transmitted drug resistance to integrase inhibitors in
           Spain: implications for clinical practice
    • Authors: Alvarez M; Casas P, de Salazar A, et al.
      Pages: 1693 - 1700
      Abstract: BackgroundIntegrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART.ObjectivesTo study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain.MethodsDuring the period 2012–17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used.ResultsClinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/lamivudine was 1.7%, 1.9% and 0.7%, respectively.ConclusionsGiven the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.
      PubDate: Tue, 05 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz067
      Issue No: Vol. 74, No. 6 (2019)
  • Posaconazole for the treatment of allergic bronchopulmonary aspergillosis
           in patients with cystic fibrosis
    • Authors: Periselneris J; Nwankwo L, Schelenz S, et al.
      Pages: 1701 - 1703
      Abstract: ObjectivesAllergic bronchopulmonary aspergillosis (ABPA) can accelerate lung function decline in patients with cystic fibrosis (CF). Antifungal medication can be used in addition to systemic corticosteroid treatment.Patients and methodsWe evaluated Aspergillus-specific IgE and the use of therapeutic drug monitoring of triazoles in a retrospective analysis of 32 patients.ResultsThere was a significant reduction in Aspergillus IgE with posaconazole but not with other triazoles (P = 0.026). Aspergillus IgE levels were inversely correlated with the therapeutic drug level of posaconazole.ConclusionsThese data suggest that posaconazole is better than comparator azoles at decreasing serological response to Aspergillus and that this response was better with therapeutic levels of posaconazole.
      PubDate: Mon, 25 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz075
      Issue No: Vol. 74, No. 6 (2019)
  • Development and validation of the European QUALity (EQUAL) score for
           mucormycosis management in haematology
    • Authors: Koehler P; Mellinghoff S, Lagrou K, et al.
      Pages: 1704 - 1712
      Abstract: BackgroundMucormycosis is a life-threatening infection in immunocompromised patients and in haematological malignancy patients in particular.ObjectivesOur aim was to develop and evaluate a scoring tool to measure adherence to current guidelines for mucormycosis.MethodsCurrent guidelines of scientific societies on mucormycosis management were reviewed. We assembled diagnostic, treatment and follow-up milestones and designed the EQUAL Mucormycosis Score. The EQUAL Mucormycosis Score was evaluated in the ECMM Excellence Centres.ResultsAn 18-item tool with one to three points per item resulted in a maximum achievable score depending on disease complexity and ranging from 25 to 32 points. Given variable patient disease course, the diagnostic score is higher in patients with positive fungal culture and biopsy, thus reflecting more decision points and higher management complexity. Eleven patients from two centres were included during the study period. A total of 200 EQUAL Mucormycosis Score points were achieved, which is 62.7% of the maximum EQUAL Mucormycosis Score of 319 points achievable in that cohort (median 18 points, range 7–27). The total score accomplished for diagnostic procedures was 112 of 165 points (67.9%), for first-line treatment 54 of 88 (61.4%) and for follow-up management 34 of 66 points (51.5%).ConclusionsThe EQUAL Mucormycosis Score quantitates adherence to current guideline recommendations for mucormycosis management. With 62.7% of maximum achievable score points, a first result is obtained that may serve as a reference for future evaluations. It remains to be shown whether guideline adherence and mortality rates correlate.
      PubDate: Fri, 15 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz051
      Issue No: Vol. 74, No. 6 (2019)
  • Antimicrobial management of Tropheryma whipplei endocarditis: the Spanish
           Collaboration on Endocarditis (GAMES) experience
    • Authors: García-Álvarez L; Sanz M, Marín M, et al.
      Pages: 1713 - 1717
      Abstract: ObjectivesTropheryma whipplei has been detected in 3.5% of the blood culture-negative cases of endocarditis in Spain. Experience in the management of T. whipplei endocarditis is limited. Here we report the long-term outcome of the treatment of previously reported patients who were diagnosed with infective endocarditis (IE) caused by T. whipplei from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) and discuss potential options for antimicrobial therapy for IE caused by T. whipplei.Patients and methodsSeventeen patients with T. whipplei endocarditis were recruited between 2008 and 2014 in 25 Spanish hospitals. Patients were classified according to the therapeutic regimen: ceftriaxone and trimethoprim/sulfamethoxazole, doxycycline + hydroxychloroquine and other treatment options.ResultsFollow-up data were obtained from 14 patients. The median follow-up was 46.5 months. All patients completed the antibiotic treatment prescribed, with a median duration of 13 months. Six patients were treated with ceftriaxone and trimethoprim/sulfamethoxazole (median duration 13 months), four with doxycycline + hydroxychloroquine (median duration 13.8 months) and four with other treatment options (median duration 22.3 months). The follow-up after the end of the treatments was between 5 and 84 months (median 24 months).ConclusionsAll treatment lines were effective and well tolerated. Therapeutic failures were not detected during the treatment. None of the patients died or experienced a relapse during the follow-up. Only six patients received antibiotic treatment in accordance with guidelines. These data suggest that shorter antimicrobial treatments could be effective.
      PubDate: Wed, 20 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz059
      Issue No: Vol. 74, No. 6 (2019)
  • A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy
           regimen achieves a high eradication rate as first-line anti-Helicobacter
           pylori treatment in Taiwan: a prospective randomized trial
    • Authors: Tai W; Liang C, Kuo C, et al.
      Pages: 1718 - 1724
      Abstract: BackgroundThe first-line eradication rate of standard triple therapy for Helicobacter pylori infection has declined to <80%, and alternative therapies with >90% success rates are needed. Inconsistent eradication rates were reported for proton pump inhibitor- and amoxicillin-containing high-dose dual therapy.ObjectivesWe performed a prospective, randomized controlled study to assess the efficacy of esomeprazole- and amoxicillin-containing high-dose dual therapy and investigated the influencing clinical factors.Patients and methodsWe recruited 240/278 eligible H. pylori-infected patients after exclusion. They were randomly assigned to 14 day high-dose dual therapy (esomeprazole 40 mg three times daily and amoxicillin 750 mg four times daily for 14 days; EA group) or 7 day non-bismuth quadruple therapy (esomeprazole 40 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily for 7 days; EACM group). Urea breath tests were followed up 8 weeks later.ResultsThe eradication rates for the EA and EACM groups were 91.7% (95% CI = 85.3%–96.0%) and 86.7% (95% CI = 79.3%–92.2%) (P = 0.21) in ITT analysis; and 95.7% (95% CI = 90.2%–98.6%) and 92.0% (95% CI = 85.4%–96.3%) (P = 0.26) in PP analysis. The adverse event rates were 9.6% versus 23.0% in the two groups (P = 0.01). The H. pylori culture positivity rate was 91.8%. The antibiotic resistance rates were amoxicillin, 0%; clarithromycin, 14.6%; and metronidazole, 33.7%.ConclusionsA 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy achieves a high eradication rate as first-line anti-H. pylori therapy, comparable to that with 7 day non-bismuth quadruple therapy but with fewer adverse events.
      PubDate: Thu, 14 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz046
      Issue No: Vol. 74, No. 6 (2019)
  • Evaluation of a pharmacist-led penicillin allergy de-labelling ward round:
           a novel antimicrobial stewardship intervention
    • Authors: Devchand M; Kirkpatrick C, Stevenson W, et al.
      Pages: 1725 - 1730
      Abstract: BackgroundAntibiotic allergy labels (AALs), reported by up to 25% of hospitalized patients, are a significant barrier to appropriate prescribing and a focus of antimicrobial stewardship (AMS) programmes.MethodsA prospective audit of a pharmacist-led AMS penicillin allergy de-labelling ward round at Austin Health (Melbourne, Australia) was evaluated. Eligible inpatients with a documented penicillin allergy receiving an antibiotic were identified via an electronic medical report and then reviewed by a pharmacist-led AMS team. The audit outcomes evaluated were: (i) AMS post-prescription review recommendations; (ii) direct de-labelling; (iii) inpatient oral rechallenge referral; (iv) skin prick testing/intradermal testing referral; and (v) outpatient antibiotic allergy clinic assessment.ResultsAcross a 5 month period, 106 patients were identified from a real-time electronic prescribing antibiotic allergy report. The highest rate of penicillin allergy de-labelling was demonstrated in patients who were referred for an inpatient oral rechallenge with 95.2% (n = 21) successfully having their penicillin AAL removed. From the 22 patients with Type A reactions, 63.6% had their penicillin AAL removed. We demonstrated a significant decrease in the prescribing of restricted antibiotics (defined as third- or fourth-generation cephalosporins, fluoroquinolones, glycopeptides, carbapenems, piperacillin/tazobactam, lincosamides, linezolid or daptomycin) in patients reviewed (pre 42.5% versus post 17.9%, P = 0.0002).ConclusionsA pharmacist-led AMS penicillin allergy de-labelling ward round reduced penicillin AALs and the prescribing of restricted antibiotics. This model could be implemented at other hospitals with existing AMS programmes.
      PubDate: Thu, 14 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz082
      Issue No: Vol. 74, No. 6 (2019)
  • Trends and patterns of outpatient and inpatient antibiotic use in
           China’s hospitals: data from the Center for Antibacterial Surveillance,
    • Authors: Li H; Yan S, Li D, et al.
      Pages: 1731 - 1740
      Abstract: BackgroundData surveillance and policy interventions can optimize antibiotic use, but few studies have focused on the changes in antibiotic use after a strict antibiotic stewardship policy was implemented in China in 2012.MethodsBased on the Center for Antibacterial Surveillance, data were collected from general hospitals in two provinces of China. Using indicators (e.g. percentage of antibiotic use and proportion of antibiotic costs) recommended by the WHO, this study aimed to identify trends and patterns of systemic antibiotic (Anatomical Therapeutic Chemical code J01) use in hospitals in 2012–16 and to explore inappropriate antibiotic use.ResultsThis study obtained 282479 outpatient prescriptions and 86070 inpatient records from 52 hospitals. The percentage of antibiotic use in outpatients and non-surgical and surgical inpatients significantly declined from 20.17%, 41.92% and 74.15% in 2012 to 12.94%, 33.88% and 69.03% in 2016, respectively. Among antibiotic prescriptions and records, the percentage of antibiotic combination therapy, the percentage of antibiotic use for prophylaxis and the proportion of antibiotic costs showed a decreasing trend over time. However, in 2016, the percentage of antibiotic use for surgical prophylaxis was still >80%, with more than one-third involving inappropriate timing of antibiotic usage according to the predefined criteria. In non-surgical inpatients, the usage rates in acute upper respiratory infections, diarrhoea in children <5 years and fever or cough symptoms all exceeded 55%.ConclusionsA significant downward trend in antibiotic use was identified in China’s hospitals, which indicates that policy intervention might reduce the overuse of antibiotics. Furthermore, strengthening appropriate antibiotic use should be the focus of antibiotic stewardship.
      PubDate: Thu, 28 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz062
      Issue No: Vol. 74, No. 6 (2019)
  • Parents’ perceptions of antibiotic use and antibiotic resistance
           (PAUSE): a qualitative interview study
    • Authors: Van Hecke O; Butler C, Wang K, et al.
      Pages: 1741 - 1747
      Abstract: BackgroundThere remains public misconception about antibiotic use and resistance. Preschool children are at particular risk of receiving unnecessary antibiotics because they commonly present in primary care and many childhood infections are self-limiting.ObjectivesThe aim of our study was to explore parents’ perceptions and understanding of antibiotic use and resistance in the context of their young child with an acute respiratory tract infection (RTI) and to explore strategies parents would find acceptable to minimize antibiotic resistance for their families.MethodsSemi-structured interviews were conducted with 23 parents of preschool children who recently had an acute RTI across greater Oxfordshire, UK (2016–17 winter). We explored their beliefs about antibiotics, understanding of antibiotic resistance and views on current public antibiotic awareness campaigns at the time. Thematic analysis was used to analyse the data.ResultsParents had a sense of optimism and considered their families to be at low risk of antibiotic resistance because their families were ‘low users’ of antibiotics. Very few parents considered antibiotic resistance as a possible harm of antibiotics. Parents thought they were acting morally responsibly by following campaign messages. They wanted future campaigns to have a relevant, accessible message for families about the impact of antibiotic resistance.ConclusionsFuture communication about the potential impact of unnecessary antibiotic use and antibiotic resistance needs to focus on outcomes that parents of young children can relate to (e.g. infection recurrence) and in a format that parents will engage with (e.g. face-to-face dissemination at playgroups and parent/child community events) to make a more informed decision about the risks and benefits of antibiotics for their child.
      PubDate: Sat, 16 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz091
      Issue No: Vol. 74, No. 6 (2019)
  • Report of a KPC-producing Pseudomonas aeruginosa isolate in Canada
    • Authors: Walkty A; Alexander D, Karlowsky J, et al.
      Pages: 1748 - 1749
      Abstract: Sir,
      PubDate: Tue, 19 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz064
      Issue No: Vol. 74, No. 6 (2019)
  • Rapid identification of NDM-, KPC-, IMP-, VIM- and OXA-48-like
           carbapenemase-producing Enterobacteriales from blood cultures by a
           multiplex lateral flow immunoassay
    • Authors: Bodendoerfer E; Keller P, Mancini S.
      Pages: 1749 - 1751
      Abstract: Sir,
      PubDate: Wed, 20 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz056
      Issue No: Vol. 74, No. 6 (2019)
  • Isavuconazole brain penetration in cerebral aspergillosis
    • Authors: Lamoth F; Mercier T, André P, et al.
      Pages: 1751 - 1753
      Abstract: Sir,
      PubDate: Mon, 11 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz050
      Issue No: Vol. 74, No. 6 (2019)
  • CSF concentration of ceftriaxone following high-dose administration:
           pharmacological data from two French cohorts
    • Authors: Le Turnier P; Grégoire M, Garot D, et al.
      Pages: 1753 - 1755
      Abstract: Sir,
      PubDate: Thu, 21 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz047
      Issue No: Vol. 74, No. 6 (2019)
  • High-dose oral linezolid achieved rapid clinical and microbiological
    • Authors: Selvaskandan H; Modha D, Denton-Beaumont R, et al.
      Pages: 1755 - 1757
      PubDate: Tue, 19 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz071
      Issue No: Vol. 74, No. 6 (2019)
  • Successful treatment of Pseudomonas aeruginosa infective endocarditis via
           haemodialysis outpatient parenteral antimicrobial therapy: case report
    • Authors: Maxwell-Scott H; Thangarajah R, Arnold A, et al.
      Pages: 1757 - 1759
      Abstract: Sir,
      PubDate: Mon, 04 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz096
      Issue No: Vol. 74, No. 6 (2019)
  • Comment on: Variation of MIC measurements: the contribution of strain and
           laboratory variability to measurement precision
    • Authors: Molitor E.
      Pages: 1760 - 1761
      Abstract: Sir,
      PubDate: Thu, 21 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz073
      Issue No: Vol. 74, No. 6 (2019)
  • Variation of MIC measurements: the contribution of strain and laboratory
           variability to measurement precision—authors’ response
    • Authors: Mouton J; Meletiadis J, Voss A, et al.
      Pages: 1761 - 1762
      Abstract: Sir,
      PubDate: Mon, 15 Apr 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz142
      Issue No: Vol. 74, No. 6 (2019)
  • Comment on: Risk of neuropsychiatric adverse events associated with the
           use of oseltamivir: a nationwide population-based case-crossover study
    • Authors: Ohkusa Y; Sugawara T, Taniguchi K, et al.
      Pages: 1762 - 1764
      Abstract: Sir,
      PubDate: Mon, 08 Apr 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz063
      Issue No: Vol. 74, No. 6 (2019)
  • Risk of neuropsychiatric adverse events associated with the use of
           oseltamivir: a nationwide population-based case-crossover
           study—authors’ response
    • Authors: Kang H; Kim J, Lee E, et al.
      Pages: 1764 - 1765
      Abstract: Sir,
      PubDate: Mon, 15 Apr 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz131
      Issue No: Vol. 74, No. 6 (2019)
  • Comment on: Doxycycline in UK guidelines for hospital-acquired pneumonia:
           where is the evidence base'
    • Authors: Cevik M; Russell C, Evans M.
      Pages: 1765 - 1766
      PubDate: Thu, 21 Feb 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz072
      Issue No: Vol. 74, No. 6 (2019)
  • Doxycycline in UK guidelines for hospital-acquired pneumonia: where is the
           evidence base'—authors’ response
    • Authors: Russell A; , Horner C, et al.
      Pages: 1767 - 1767
      Abstract: Sir,
      PubDate: Tue, 26 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz105
      Issue No: Vol. 74, No. 6 (2019)
  • Antimicrobial management of Tropheryma whipplei endocarditis: the Spanish
           Collaboration on Endocarditis (GAMES) experience
    • Authors: García-Álvarez L; , Sanz M, et al.
      Pages: 1768 - 1768
      Abstract: J Antimicrob Chemother 2019; 74: 1713–17
      PubDate: Thu, 14 Mar 2019 00:00:00 GMT
      DOI: 10.1093/jac/dkz111
      Issue No: Vol. 74, No. 6 (2019)
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