Cephalosporin MIC creep among gonococci: Time for a pharmacodynamic rethink?

Stephanie Chisholm, Johan W. Mouton, David A. Lewis, Thomas Nichols, Catherine Ison, David Livermore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numberdkq289
Pages (from-to)2141-2148
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume65
Issue number10
DOIs
Publication statusPublished - 6 Aug 2010

Bibliographical note

Funding Information:
The Gonococcal Resistance to Antimicrobials Surveillance Programme was funded totally (2000–2004) and partially (2005 to date) by the Department of Health (London), and was partially funded by the Health Protection Agency (2005 to date).

Keywords

  • Cefixime
  • Ceftriaxone
  • Gonorrhoea
  • Neisseria gonorrhoeae

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