Single-Arm Open-Label Clinical Trial of Two Grams of Aztreonam for the Treatment of Neisseria gonorrhoeae

Abstract

The threat of ceftriaxone-resistant Neisseria gonorrhoeae necessitates new gonorrhea treatment regimens. Repurposing older antibiotics not routinely used for N. gonorrhoeae may expeditiously identify new therapies. Ideally, all recommended therapies should eradicate gonorrhea at the pharynx. Between April and September 2019, we enrolled men in an open-label, one-arm clinical trial of single-dose intramuscular aztreonam (2 g). Enrollment criterion included (i) nucleic acid amplification test (NAAT)-positive pharyngeal gonorrhea for ≤14 days or (ii) Gram stain-positive gonococcal urethritis plus report of performing oral sex in ≤2 months. At enrollment, we collected cultures from NAAT-positive or screening sites, and men returned 3 to 8 days following treatment for a test of cure (TOC) by culture. The per-protocol analysis required men to be culture positive at enrollment and to return for TOC. We calculated efficacy as the number of subjects with negative culture at TOC divided by the number culture positive at enrollment by anatomic site. Thirty-two men enrolled in the study; 21 were pharyngeal NAAT positive, and 11 had gonococcal urethritis. The per-protocol analysis included 17 men, 6 with pharyngeal, 9 with urethral, and 4 with rectal gonococcal infections. Aztreonam cured 2 of 6 pharyngeal infections (33%; 95% confidence interval [CI], 4.3% to 78%) and 3 of 4 rectal infections (75%; 95% CI, 19% to 99%). All 11 men with urethritis were cured (100%; 95% CI, 66% to 100%). The aztreonam MIC90 was 0.5 μg/ml (range, 0.06 to 2.0 μg/ml). All treatment failures occurred at a MIC of ≥0.25 μg/ml. Single-dose aztreonam is not a reliable treatment for gonorrhea at the pharynx but may be useful for men with gonococcal urethritis and beta-lactam allergy. (This study has been registered at ClinicalTrials.gov under identifier NCT03867734.).

Keywords: N. gonorrhoeae; aztreonam; treatment.

Copyright © 2020 American Society for Microbiology.

Figures

FIG 1

Study flow diagram. LTFU, lost to follow-up.

FIG 2

N. gonorrhoeae infection outcomes by aztreonam MIC and anatomic site. *, N = 18; one isolate was nonviable for antimicrobial susceptibility testing.