Lindley A Barbee1,2, Olusegun O Soge3, Jennifer Morgan2, Angela Leclair1, Tamara Bass2, Brian J Werth4, James P Hughes5, Matthew R Golden1,2,6. 1. Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA. 2. Human Immunodeficiency Virus/Sexually Transmitted Disease Program, Public Health-Seattle & King County, Seattle, Washington, USA. 3. Department of Global Health, University of Washington, Seattle, Washington, USA. 4. Department of Pharmacy, University of Washington, Seattle, Washington, USA. 5. Department of Biostatistics, University of Washington, Seattle, Washington, USA. 6. Department of Epidemiology, University of Washington, Seattle, Washington, USA.
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.
BACKGROUND: Centers for Disease Control and Prevention (CDC) guidelines recommend 240 mg gentamicin plus 2 g azithromycin for the treatment of gonorrhea in cephalosporin-allergicpatients. 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.
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