The Use of Gentamicin for Treatment of Urogenital and Extragenital Gonorrhea: A Systematic Review of Efficacy Data

Abstract

Objective: To evaluate clinical efficacy data for gentamicin in the treatment of gonorrhea. Data Sources: A keyword search of PubMed (1966 to April 2020), EMBASE (1947 to April 2020), and International Pharmaceutical Abstracts (1970 to April 2020) was conducted. The electronic search was supplemented with manual screening of references from identified articles and a search of ClinicalTrials.gov to identify ongoing trials. Study Selection and Data Extraction: Comparator and noncomparator studies reporting microbiological outcomes of treatment with gentamicin for gonorrhea in humans were included. Data extracted included study year, authors, aim, setting, population, dosing protocols, and outcome results. Risk of bias was assessed according to the Cochrane Risk of Bias Assessment Tool. Data Synthesis: A total of 407 articles were identified, of which 11 met inclusion criteria. Two studies were randomized controlled trials, and 1 additional randomized noncomparator study was identified. All other studies were nonrandomized and noncomparator in nature. The highest quality evidence suggests that gentamicin is not noninferior to ceftriaxone (both in addition to azithromycin) for treatment of gonorrhea but may achieve cure rates >90%. Conflicting evidence exists regarding the efficacy of gentamicin-based regimens for the specific treatment of extragenital gonorrhea. Relevance to Patient Care and Clinical Practice: Results of this review could affect patient care and clinical practice because they clearly demonstrate the role of gentamicin for the treatment of gonorrhea as a second-line agent. Future research should confirm findings, especially for the role of gentamicin in extragenital infections. Conclusions: Gentamicin-based regimens should be reserved for second-line treatment of urogenital and extragenital gonorrhea infections.

Thiostrepton, a resurging drug inhibiting the stringent response to counteract antibiotic-resistance and expression of virulence determinants in Neisseria gonorrhoeae

“…After this time, the decline in the number of CFU was more pronounced. This result, which was indicative of tolerance of strain T9 against gentamicin, was rather surprising because gentamicin is considered bactericidal and usually yields substantial and rapid killing against aerobic bacteria (Young and Hewitt, 1973), and is recommended for the treatment of gonorrhea as a second-line agent (Burmeister et al, 2020). With rifampicin the killing started after 1 h, and the killing rate was steady and moderate up to 6 h. No further reduction was observed from 6 h to 24 h of incubation.…”

In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides

“…The Centers for Disease Control and Prevention (CDC) recommend a single dose of gentamicin as a cephalosporin-sparing alternative for the treatment of urogenital gonorrhea [ 1 ]. A number of clinical studies have consistently suggested safety and clinical efficacy of 240 to 400 mg of gentamicin intramuscular injection with cure rates ranging from 84 to 100% for urogenital gonorrhea depending on study design [ 2 – 5 ], whereas conflicting evidence suggested cure rates of 20 to 100% for extragenital, i.e., oropharyngeal and anorectal, gonorrhea treated with 240 to 360 mg of gentamicin alone, i.e., not in combination with azithromycin [ 3 ]. It is conceivable that higher doses and thus higher exposures of gentamicin at the relevant sites of infection may hold potential to more reliably enhance the efficacy of gentamicin including extragenital gonorrhea.…”

Safety of Single-Dose Oral Cefixime, Intramuscular Ceftriaxone, or Intramuscular Gentamicin for the Treatment of Gonorrhea: A Systematic Review and Meta-analysis

“…We previously published a systematic review on the efficacy of this combination, but comparative safety to cephalosporinbased regimens is largely unknown. 7 Gonorrhea differs from other infections because patients may appear to be asymptomatic, and depending on local guidelines, treatment may extend to an infected person's sexual partners to prevent undetected transmission. 8 This strategy has been shown to reduce reinfection, especially for patients unlikely to otherwise seek care.…”

“…We previously published a systematic review on the efficacy of this combination, but comparative safety to cephalosporin-based regimens is largely unknown. 7…”