Pharyngeal Gonococcal Infection Clinical Trial
Official title:
Gentamicin for Pharyngeal Gonorrhea - A Demonstration Study
The Centers for Disease Control and Prevention has identified antimicrobial-resistant (AMR)
Neisseria gonorrhoeae (NG) as one of the nation's top three urgent AMR threats. Since the
advent of antibiotics in the 1930s, NG has developed resistance to every first-line
antibiotic. Parenteral third-generation cephalosporins are now the only class of drug with
consistent efficacy against NG. New therapies are urgently needed. Although some novel
antimicrobials are under development, reevaluating older drugs is another option for quickly
identifying additional treatments for gonorrhea. We propose a demonstration study to test a
single dose of gentamicin for the treatment of pharyngeal gonorrhea. We chose to focus on
pharyngeal gonorrhea because these infections are common, play an important role in fostering
gonococcal resistance, and are harder to eradicate than genital infections. Although
gentamicin is 91% efficacious for genital NG, its efficacy at the pharynx may be less since
streptomycin, another aminoglycoside previously used to treat gonorrhea, was not effective
for pharyngeal NG. It is unknown if streptomycin's poor efficacy is indicative of limitations
of aminoglycosides as a class. We plan to enroll 60 men who have sex with men in a
demonstration study to be conducted at the Seattle & King County STD Clinic to test the
efficacy of 360 mg of gentamicin given intramuscularly for pharyngeal gonorrhea. Secondary
objectives include determining the ideal pharmacodynamic criterion (comparing in vitro
minimal inhibitory concentrations (MIC) of NG to peak gentamicin serum levels), estimating
resistance induction among treatment failures, and assessing the tolerability of 360 mg of IM
gentamicin.
Objectives
The proposed study aims to evaluate the efficacy of a single intramuscular (IM) dose of
gentamicin in the treatment of pharyngeal gonorrhea. Secondary objectives include documenting
the efficacy stratified by minimal inhibitory concentration (MIC) compared with the
gentamicin peak level in order to estimate a pharmacodynamic criterion. We will also attempt
to determine whether gentamicin monotherapy induces antimicrobial resistance among treatment
failures. Lastly, we will evaluate the tolerability of 360 mg of IM gentamicin, stratified by
subject weight (i.e. weight based dosing). The specific aims are:
1. Determine the proportion of persons whose pharyngeal gonococcal infections are cured
with a single dose of 360mg gentamicin intramuscularly alone.
2. Evaluate the renal safety and tolerability of 360mg IM of gentamicin.
3. Document mean peak gentamicin levels following 360mg IM of gentamicin stratified by
weight.
4. Estimate the best pharmacodynamics criterion (i.e. peak/MIC ratio) for pharyngeal
gonorrhea treated with gentamicin using individual and mean peak gentamicin levels and
NG isolate MIC.
5. Among treatment failures, conduct exploratory analyses comparing pre- and post-treatment
MIC for evidence of induced resistance.
n/a