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Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea; the relationship between antibiotic minimum inhibitory concentration and clinical outcome

Cole, Michelle; Tan, Wei; Fifer, Helen; Brittain, Clare; Duley, Lelia; Hepburn, Trish; Lawrence, Tessa; Montgomery, Alan; SPRANGE, KIRSTY; Thandi, Sukhwinder; Churchward, Colin; Tripodo, Francesco; Woodford, Neil; Ross, Jonathan

Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea; the relationship between antibiotic minimum inhibitory concentration and clinical outcome Thumbnail


Authors

Michelle Cole

Wei Tan

Helen Fifer

Lelia Duley

TRISH HEPBURN Trish.Hepburn@nottingham.ac.uk
Senior Medical Statistician

Tessa Lawrence

ALAN MONTGOMERY ALAN.MONTGOMERY@NOTTINGHAM.AC.UK
Director Nottingham Clinical Trials Unit

Sukhwinder Thandi

Colin Churchward

Francesco Tripodo

Neil Woodford

Jonathan Ross



Contributors

Michelle Cole
Project Member

Wei Tan
Project Member

Helen Fifer
Project Member

Lelia Duley
Project Member

Tessa Lawrence
Project Member

Sukhwinder Thandi
Project Member

Colin Churchward
Project Member

Francesco Tripodo
Project Member

Neil Woodford
Project Member

Jonathan Ross
Project Leader

Abstract

© Crown copyright 2019. OBJECTIVES: To investigate the relationship between MIC and clinical outcome in a randomized controlled trial that compared gentamicin 240 mg plus azithromycin 1 g with ceftriaxone 500 mg plus azithromycin 1 g. MIC analysis was performed on Neisseria gonorrhoeae isolates from all participants who were culture positive before they received treatment. METHODS: Viable gonococcal cultures were available from 279 participants, of whom 145 received ceftriaxone/azithromycin and 134 received gentamicin/azithromycin. Four participants (6 isolates) and 14 participants (17 isolates) did not clear infection in the ceftriaxone/azithromycin and gentamicin/azithromycin arms, respectively. MICs were determined by Etest on GC agar base with 1% Vitox. The geometric mean MICs of azithromycin, ceftriaxone and gentamicin were compared using logistic and linear regression according to treatment received and N. gonorrhoeae clearance. RESULTS: As the azithromycin MIC increased, gentamicin/azithromycin treatment was less effective than ceftriaxone/azithromycin at clearing N. gonorrhoeae. There was a higher geometric mean MIC of azithromycin for isolates from participants who had received gentamicin/azithromycin and did not clear infection compared with those who did clear infection [ratio 1.95 (95% CI 1.28-2.97)], but the use of categorical MIC breakpoints did not accurately predict the treatment response. The geometric mean MIC of azithromycin was higher in isolates from the pharynx compared with genital isolates. CONCLUSIONS: We found that categorical resistance to azithromycin or ceftriaxone in vitro, and higher gentamicin MICs in the absence of breakpoints, were poorly predictive of treatment failure.

Citation

Cole, M., Tan, W., Fifer, H., Brittain, C., Duley, L., Hepburn, T., …Ross, J. (2020). Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea; the relationship between antibiotic minimum inhibitory concentration and clinical outcome. Journal of Antimicrobial Chemotherapy, 75(2), 449–457. https://doi.org/10.1093/jac/dkz436

Journal Article Type Article
Acceptance Date Sep 23, 2019
Online Publication Date Oct 31, 2019
Publication Date 2020-02
Deposit Date Sep 25, 2019
Publicly Available Date Mar 29, 2024
Journal Journal of Antimicrobial Chemotherapy
Print ISSN 0305-7453
Electronic ISSN 1460-2091
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 75
Issue 2
Pages 449–457
DOI https://doi.org/10.1093/jac/dkz436
Keywords Pharmacology (medical); Pharmacology; Infectious Diseases
Public URL https://nottingham-repository.worktribe.com/output/2657379
Publisher URL https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkz436/5610560

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