Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx.
Neisseria gonorrhoeae
clinical trial
gonorrhea
pharynx
sexually transmitted infections
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
05 11 2020
05 11 2020
Historique:
received:
14
08
2019
accepted:
08
11
2019
pubmed:
13
11
2019
medline:
28
4
2021
entrez:
13
11
2019
Statut:
ppublish
Résumé
Centers for Disease Control and Prevention (CDC) guidelines recommend 240 mg gentamicin plus 2 g azithromycin for the treatment of gonorrhea in cephalosporin-allergic patients. The efficacy of gentamicin alone in the treatment of pharyngeal gonorrhea is uncertain. Between September 2018 and March 2019, we enrolled men who have sex with men with nucleic acid amplification test-diagnosed pharyngeal gonorrhea in a single-arm, unblinded clinical trial. Men received a single 360-mg intramuscular dose of gentamicin and underwent test of cure by culture 4-7 days later. The study measured creatinine at enrollment and test of cure, serum gentamicin concentration postdose to establish peak concentration (Cmax), and standard antimicrobial minimum inhibitory concentrations (MICs) by agar dilution. The trial was designed to establish a point estimate for gentamicin's efficacy for pharyngeal gonorrhea. We planned to enroll 50 evaluable participants; assuming gentamicin was 80% efficacious, the trial would establish a 95% confidence interval (CI) of 66%-90%. We planned interim analyses at n = 10 and n = 25. The study was stopped early due to poor efficacy. Of 13 enrolled men, 10 were evaluable, and only 2 (20% [95% CI, 2.5%-55.6%]) were cured. Efficacy was not associated with gentamicin Cmax or MIC. No participants experienced renal insufficiency. The mean creatinine percentage change was +5.2% (range, -6.7% to 21.3%). Six (46%) participants experienced headache, all deemed unrelated to treatment. Gentamicin alone failed to eradicate Neisseria gonorrhoeae from the pharynx. Clinicians should use caution when treating gonorrhea with the CDC's current alternative regimen (gentamicin 240 mg plus azithromycin 2 g) given increases in azithromycin resistance and gentamicin's poor efficacy at the pharynx. NCT03632109.
Sections du résumé
BACKGROUND
Centers for Disease Control and Prevention (CDC) guidelines recommend 240 mg gentamicin plus 2 g azithromycin for the treatment of gonorrhea in cephalosporin-allergic patients. The efficacy of gentamicin alone in the treatment of pharyngeal gonorrhea is uncertain.
METHODS
Between September 2018 and March 2019, we enrolled men who have sex with men with nucleic acid amplification test-diagnosed pharyngeal gonorrhea in a single-arm, unblinded clinical trial. Men received a single 360-mg intramuscular dose of gentamicin and underwent test of cure by culture 4-7 days later. The study measured creatinine at enrollment and test of cure, serum gentamicin concentration postdose to establish peak concentration (Cmax), and standard antimicrobial minimum inhibitory concentrations (MICs) by agar dilution. The trial was designed to establish a point estimate for gentamicin's efficacy for pharyngeal gonorrhea. We planned to enroll 50 evaluable participants; assuming gentamicin was 80% efficacious, the trial would establish a 95% confidence interval (CI) of 66%-90%. We planned interim analyses at n = 10 and n = 25.
RESULTS
The study was stopped early due to poor efficacy. Of 13 enrolled men, 10 were evaluable, and only 2 (20% [95% CI, 2.5%-55.6%]) were cured. Efficacy was not associated with gentamicin Cmax or MIC. No participants experienced renal insufficiency. The mean creatinine percentage change was +5.2% (range, -6.7% to 21.3%). Six (46%) participants experienced headache, all deemed unrelated to treatment.
CONCLUSIONS
Gentamicin alone failed to eradicate Neisseria gonorrhoeae from the pharynx. Clinicians should use caution when treating gonorrhea with the CDC's current alternative regimen (gentamicin 240 mg plus azithromycin 2 g) given increases in azithromycin resistance and gentamicin's poor efficacy at the pharynx.
CLINICAL TRIALS REGISTRATION
NCT03632109.
Identifiants
pubmed: 31712813
pii: 5622607
doi: 10.1093/cid/ciz1109
pmc: PMC7755014
doi:
Substances chimiques
Anti-Bacterial Agents
0
Gentamicins
0
Azithromycin
83905-01-5
Banques de données
ClinicalTrials.gov
['NCT03632109']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1877-1882Subventions
Organisme : NIAID NIH HHS
ID : K23 AI113185
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI132994
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136979
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Références
Clin Pharm. 1984 Jul-Aug;3(4):411-6
pubmed: 6380903
Lancet. 2019 Jun 22;393(10190):2511-2520
pubmed: 31056291
Med Clin North Am. 1982 Jan;66(1):303-12
pubmed: 7038338
Clin Infect Dis. 2014 Oct 15;59(8):1083-91
pubmed: 25031289
Clin Infect Dis. 1998 Jul;27(1):23-7
pubmed: 9675444
Sex Transm Infect. 2012 Feb;88(1):6-8
pubmed: 22250178
Methods Mol Biol. 2019;1997:37-58
pubmed: 31119616
Sex Transm Dis. 2018 Oct;45(10):677-683
pubmed: 29624558
Sex Transm Dis. 2014 Mar;41(3):168-72
pubmed: 24521722
Sex Transm Dis. 2019 May;46(5):287-289
pubmed: 30870311
Sex Transm Dis. 1995 Jan-Feb;22(1):39-47
pubmed: 7709324
J Antimicrob Chemother. 2004 Aug;54(2):542-5
pubmed: 15215227
Euro Surveill. 2019 Mar;24(10):
pubmed: 30862336
Pharmacotherapy. 2007 Aug;27(8):1081-91
pubmed: 17655508
J Antimicrob Chemother. 2014 Jun;69(6):1572-8
pubmed: 24468865
Sex Transm Infect. 2012 Dec;88(8):589-94
pubmed: 22917693
Infect Dis Obstet Gynecol. 2016;2016:5758387
pubmed: 27366021
Sex Transm Dis. 2010 Mar;37(3):169-72
pubmed: 19901860
Pediatrics. 2005 Oct;116(4):927-32
pubmed: 16199703