Dataset Information

Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx.

ABSTRACT:

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.

SUBMITTER: Barbee LA

PROVIDER: S-EPMC7755014 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx.

Barbee Lindley A LA Soge Olusegun O OO Morgan Jennifer J Leclair Angela A Bass Tamara T Werth Brian J BJ Hughes James P JP Golden Matthew R MR

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20201101 8

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 31712813

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Project description:BackgroundA high level of resistance in Neisseria gonorrhoeae has developed against penicillins, sulphonamides, tetracyclines and quinolones, and recent surveillance data have shown a gradual reduction in sensitivity to current first-line agents with an upward drift in the minimum inhibitory concentration of ceftriaxone. Laboratory sensitivity testing suggests that gentamicin, an aminoglycoside, may be an effective treatment option for gonorrhoea infection when used as a single intramuscular dose.MethodsA search of electronic reference databases and grey literature was used to identify randomised trials and well-conducted prospective studies with concurrent controls evaluating single-dose gentamicin against placebo or a comparator regimen in the treatment of uncomplicated gonorrhoea infection in men and women aged 16 years and over. The primary outcome was microbiological cure of N. gonorrhoeae.ResultsEight hundred and thirty-nine studies were identified, of which five (1,063 total participants) were included. All five studies administered single-dose gentamicin via intramuscular injection to men with uncomplicated gonococcal urethritis. Three studies were randomised trials, one was quasi-randomised and one was non-randomised but included a comparator arm. Comparator antibiotics included an alternative aminoglycoside or antibiotic used in the syndromic management of male urethritis. Methodology was poorly described in all five included studies. The high risk of bias within studies and clinical heterogeneity between studies meant that it was inappropriate to pool data for meta-analysis. Cure rates of 62% to 98% were reported with gentamicin treatment. The relative risk of cure was comparable between gentamicin and comparator antibiotics.ConclusionsThe studies identified provide insufficient data to support or refute the efficacy and safety of single-dose intramuscular gentamicin in the treatment of uncomplicated gonorrhoea infection. Additional randomised trials to evaluate gentamicin for this indication are therefore required.Systematic review registrationPROSPERO CRD42012002490.

Project description:Many clinical isolates of the human pathogen Neisseria gonorrhoeae contain conjugative plasmids. The host range of these plasmids is limited to Neisseria species, but presence of a tetracycline (tetM) determinant inserted in several of these plasmids is an important cause of the rapid spread of tetracycline resistance. Previously plasmids with different backbones (Dutch and American type backbones) and with and without different tetM determinants (Dutch and American type tetM determinants) have been identified. Within the isolates tested, all plasmids with American or Dutch type tetM determinants contained a Dutch type plasmid backbone. This demonstrated that tetM determinants should not be used to differentiate between conjugal plasmid backbones. The nucleotide sequences of conjugative plasmids with Dutch type plasmid backbones either not containing the tetM determinant (pEP5233) or containing Dutch (pEP5289) or American (pEP5050) type tetM determinants were determined. Analysis of the backbone sequences showed that they belong to a novel IncP1 subfamily divergent from the IncP1alpha, beta, gamma, delta and epsilon subfamilies. The tetM determinants were inserted in a genetic load region found in all these plasmids. Insertion was accompanied by the insertion of a gene with an unknown function, and rearrangement of a toxin/antitoxin gene cluster. The genetic load region contains two toxin/antitoxins of the Zeta/Epsilon toxin/antitoxin family previously only found in Gram positive organisms and the virulence associated protein D of the VapD/VapX toxin/antitoxin family. Remarkably, presence of VapX of pJD1, a small cryptic neisserial plasmid, in the acceptor strain strongly increased the conjugation efficiency, suggesting that it functions as an antitoxin for the conjugative plasmid. The presence of the toxin and antitoxin on different plasmids might explain why the host range of this IncP1 plasmid is limited to Neisseria species. The isolated plasmids conjugated efficiently between N. gonorrhoeae strains, but did not enhance transfer of a genetic marker.

Dataset Information

Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx.

Background

Methods

Results

Conclusions

Clinical trials registration

Publications

Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx.

Similar Datasets

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