Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.
Female
Humans
Male
Anti-Bacterial Agents
/ pharmacology
Azithromycin
/ pharmacology
Cefixime
/ therapeutic use
Ceftriaxone
/ pharmacology
Ciprofloxacin
/ pharmacology
Gentamicins
/ pharmacology
Gonorrhea
/ drug therapy
Malawi
/ epidemiology
Microbial Sensitivity Tests
Neisseria gonorrhoeae
Spectinomycin
/ pharmacology
Tetracycline
/ pharmacology
Treatment Outcome
Polymorphism, Single Nucleotide
Journal
Sexually transmitted diseases
ISSN: 1537-4521
Titre abrégé: Sex Transm Dis
Pays: United States
ID NLM: 7705941
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
pubmed:
14
11
2021
medline:
6
5
2022
entrez:
13
11
2021
Statut:
ppublish
Résumé
Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 μg/mL; 111 (78.7%), MIC = 4 μg/mL; and 28 (19.9%), MIC = 8 μg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 μg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.
Sections du résumé
BACKGROUND
Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically.
METHODS
Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure.
RESULTS
Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 μg/mL; 111 (78.7%), MIC = 4 μg/mL; and 28 (19.9%), MIC = 8 μg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 μg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism).
CONCLUSIONS
Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.
Identifiants
pubmed: 34772893
doi: 10.1097/OLQ.0000000000001580
pii: 00007435-202204000-00001
pmc: PMC8940620
mid: NIHMS1754284
doi:
Substances chimiques
Anti-Bacterial Agents
0
Azithromycin
83905-01-5
Cefixime
97I1C92E55
Ceftriaxone
75J73V1629
Ciprofloxacin
5E8K9I0O4U
Gentamicins
0
Spectinomycin
93AKI1U6QF
Tetracycline
F8VB5M810T
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
251-256Subventions
Organisme : NIAID NIH HHS
ID : R01 AI114320
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI083059
Pays : United States
Organisme : FIC NIH HHS
ID : D43 TW009340
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108424
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI070114
Pays : United States
Informations de copyright
Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of Interest and Sources of Funding: None declared.
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