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 aztreonam 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
aztreonam appears to be >98.6% efficacious for anogenital NG, its efficacy at the pharynx may
be less. Only 8 cases of pharyngeal gonorrhea have been documented to be treated with
aztreonam, but of those, only 5 (62.5%) were cured. The dose used in those studies was 1g of
aztreonam. Most antibiotics have a lower efficacy at the pharynx than anogenital sites, which
is likely due to drug pharmacokinetics, i.e. difficulty in penetrating pharyngeal tissue.
Thus, in the proposed study, we plan to treat 50 subjects with untreated pharyngeal gonorrhea
with 2g IM Aztreonam.
Objectives:
The proposed study aims to evaluate the efficacy of a single 2g intramuscular (IM) dose of
aztreonam in the treatment of pharyngeal gonorrhea. Secondary objectives include documenting
the efficacy stratified by minimal inhibitory concentration (MIC) compared with the
previously document area under the curve (AUC) in order to estimate a pharmacodynamic
criterion. We will also attempt to determine whether aztreonam monotherapy induces
antimicrobial resistance among treatment failures. Lastly, we will evaluate the tolerability
of 2g of IM aztreonam. The specific aims are:
1. Determine the proportion of persons whose pharyngeal gonococcal infections are cured
with a single dose of 2g aztreonam intramuscularly.
2. Determine the proportion of persons with urethral and/or rectal gonorrhea whose
infections are cured with a single dose of 2g aztreonam IM.
3. Evaluate the tolerability of 2g IM of aztreonam .
4. Estimate the best pharmacodynamics criterion (i.e. AUC/MIC ratio) for pharyngeal
gonorrhea treated with aztreonam using previously published AUC for 2g aztreonam and NG
isolate MIC.
5. Among treatment failures, conduct exploratory analyses comparing pre- and post-treatment
MIC for evidence of induced resistance.
Study Design: Prospective cohort
Study Population & Inclusion Criteria:
Persons diagnosed with pharyngeal gonorrhea or gonococcal urethritis who are undergoing
pharyngeal gonorrhea testing, who are not yet treated.
Intervention: 2g IM aztreonam x 1
Primary Outcome: Negative gonorrhea culture 4-7 days (+/- 1 day) after treatment
Sample Size: 50 persons