To Örebro University

Background: Dual therapy including ceftriaxone plus azithromycin is currently the recommended first-line gonorrhea treatment internationally. However, for gonorrhea cases where ceftriaxone or other extended-spectrum cephalosporin can not be administered (e.g., cephalosporin resistance, allergy, or unavailability), the therapeutic options are very limited. In a previous randomized controlled clinical trial (RCT) by Kirk-caldy et al. (Clin Infect Dis. 2014), gentamicin 240 mg plus azithromycin 2 g showed 100% microbiological cure for uncomplicated gonorrhoea. However, only 10 pharyngeal infections and one rectal infection were examined. We further evaluated the efficacy and tolerability of gentamicin+azithroomycin for treatment of uncomplicated rectal and pharyngeal gonorrhea.

Methods: A non-inferiority, open-label, single center RCT was conducted in Prague, Czech Republic. Patients, 18–75 years of age, diagnosed with uncomplicated rectal or pharyngeal gonorrhea by nucleic acid amplification test (NAAT) (GeneProof®) were randomized to treatment with gentamicin 240 mg intramuscularly plus azithromycin 2 g orally or ceftriaxone 500 g intramuscularly plus azithromycin 2 g orally. The primary out-come was negative culture and negative NAAT, i.e., one week and three weeks, respectively, after treatment.

Results: Both clinical and microbiological cure was achieved by 100% of patients in the gentamicin+azithromycin arm (n=68; 40 rectal, 14 pharyngeal, and 14 infections in both localizations) and ceftriaxone+azithromycin arm (n=66; 36 rectal, 14 pharyngeal, and 16 infections in both localizations). Administration of gentamicin was significantly less painful than ceftriaxone according to the visual analog score (p<0.001). Gastrointestinal adverse events were slightly more common in ceftriaxone arm (50.0%) than in gentamicin arm (41.2%), but in most (64%) cases they were mild.

Conclusion: Both gentamicin+azithromycin and ceftriaxone+azithromycin were 100% effective for treatment of rectal and pharyngeal gonorrhea. Gentamicin 240 mg plus azithromycin 2 g appears to be an effective alternative for treatment of both urogenital and extragenital gonorrhea in case of ceftriaxone resistance, allergy, or unavailability.