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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Cephalosporin MIC creep among gonococci: Time for a pharmacodynamic rethink?
Journal of Antimicrobial Chemotherapy, Volume 65, No. 10, Article dkq289, Year 2010
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Description
Background: Gonorrhoea has been among the easiest infections to cure with antibiotics. Nevertheless, emerging resistance has driven repeated treatment shifts. Decreased cephalosporin susceptibility is now being reported. We examined cephalosporin MIC trends for Neisseria gonorrhoeae in the UK and undertook pharmacodynamic analyses to predict efficacy against strains with raised MICs. Methods: Neisseria gonorrhoeae isolates were collected annually in a structured surveillance from 26 genitourinary medicine clinics in England and Wales. MICs were determined by agar dilution and confirmed by Etests. Pharmacodynamic modelling was performed for cefixime and ceftriaxone with Monte Carlo simulations. Results: There was a progressive emergence of small numbers of gonococci with cephalosporin MICs of 0.125-0.25 mg/L; these were not seen before 2005 but, for ceftriaxone and cefixime, respectively, accounted for 0.4% (95% confidence interval 0.2%-1.1%) and 2.8% (1.6%-4.8%) of the 1253 isolates collected in 2008; such MICs are 16-64 times the modal values for the species. Pharmacodynamic analysis was complicated by evidence that cephalosporins need a longer period with the free drug level above MIC than the 7-10 h required for penicillin G; nevertheless, pharmacodynamic analyses predict that failures with the standard 400 mg cefixime po and 250 mg ceftriaxone im regimens become likely around the present MIC maxima. Conclusions: Gonococci with ceftriaxone and cefixime MICs of 0.125-0.25 mg/L are accumulating in the UK. These MICs lie on the edge of likely responsiveness to current regimens, which need review. Possible responses include: (i) higher cephalosporin doses; (ii) multidose cephalosporin regimens; (iii) multidrug regimens; (iv) microbiologically directed treatment; or, in the future, (v) drug cycling. The practicalities of these approaches are discussed. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Authors & Co-Authors
Chisholm, Stephanie A.
United Kingdom, London
Public Health England
Mouton, Johan Willem
Netherlands, Nijmegen
Radboud University Medical Center
LEWIS, D. A.
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Nichols, Tom
United Kingdom, London
Public Health England
Ison, Catherine A.
United Kingdom, London
Public Health England
Livermore, David M.
United Kingdom, London
Public Health England
Statistics
Citations: 166
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.1093/jac/dkq289
ISSN:
03057453
e-ISSN:
14602091
Research Areas
Cancer
Health System And Policy