Efficacy and Safety of Injectable and Oral Antibiotics in Treating Gonorrhea: A Systematic Review and Network Meta-Analysis

Abstract

Gonorrhea is the second most frequently reported sexually transmitted infectious disease of bacterial origin in the world. Current empiric therapies rely on broad-spectrum antibiotics. However, treatment options are becoming limited due to the rise of drug-resistant gonorrhea. To control the rise of drug-resistant gonorrhea and to identify alternative treatment options, clinicians will have to increasingly rely on experimental evidence for the treatment of gonorrhea patients. Thus, we performed a systematic review and network meta-analysis of all randomized clinical trials about the efficacy and safety of various antibiotic regimens in adults with gonorrhea. We searched all references in Embase and PubMed from the date of their inception to January 2019, and then an updated search was performed in March 2019. Of the 28,843 identified references, 44 fulfilled our selection criteria. We used a network meta-analysis based on a frequentist approach to evaluate the efficacy and safety of 12 injectable and 11 oral antibiotics. The efficacy of treatments was ranked by p score and inconsistency was assessed by a back-calculation method. Certainty of evidence was evaluated by the GRADE system. For injectable drugs, there was no difference in efficacy between a reference antibiotic and other drugs. However, ceftriaxone had significantly better efficacy than cefuroxime (OR, 12.03; 95% CI 3.73–38.79), cephaloridine (OR, 42.41; 95% CI 8.77–205.07), kanamycin (OR, 5.45; 95% CI 1.25–23.70), penicillin (OR, 13.11; 95% CI 4.48–38.37), and spectinomycin (OR, 4.70; 95% CI 1.62–13.62). Thus, ceftriaxone was the most effective injectable drug (p score of 0.924). As for oral drugs, azithromycin was the most effective compound (p score of 0.8633). There were no significant differences in safety between injectable and oral treatments. In our systematic review of randomized controlled trials, we found azithromycin and ceftriaxone to be the most effective antibiotics for the treatment of gonorrhea. This is in line with current guidelines which recommend a combination therapy of azithromycin and ceftriaxone for the treatment of gonorrhea due to increased antimicrobial resistance. Our analysis identified gentamicin and ofloxacin as alternative therapeutics to treat drug-resistant gonorrhea.