Prior Exposure to Azithromycin and Azithromycin Resistance Among Persons Diagnosed With Neisseria gonorrhoeae Infection at a Sexual Health Clinic: 2012-2019

Background There is conflicting evidence on whether prior azithromycin (AZM) exposure is associated with reduced susceptibility to AZM (AZM(RS)) among persons infected with Neisseria gonorrhoeae (NG). Methods The study population included Public Health-Seattle and King County Sexual Health Clinic (SHC) patients with culture-positive NG infection at >= 1 anatomic site whose isolates were tested for AZM susceptibility in 2012-2019. We used multivariate logistic regression to examine the association of time since last AZM prescription from the SHC in <= 12 months with subsequent diagnosis with AZM(RS) NG (minimum inhibitory concentration [MIC], >= 2.0 mu g/mL) and used linear regression to assess the association between the number of AZM prescriptions in <= 12 months and AZM MIC level, controlling for demographic, behavioral, and clinical characteristics. Results A total of 2155 unique patients had 2828 incident NG infections, 156 (6%) of which were caused by AZM(RS) NG. AZM(RS) NG was strongly associated with receipt of AZM from the SHC in the prior 29 days (adjusted odds ratio, 6.76; 95% confidence interval [CI], 1.76 to 25.90) but not with receipt of AZM in the prior 30-365 days. Log AZM MIC level was not associated with the number of AZM prescriptions within <= 12 months (adjusted correlation, 0.0004; 95% CI, -.04 to .037) but was associated with number of prescriptions within <30 days (adjusted coefficient, 0.56; 95% CI, .13 to .98). Conclusions Recent individual-level AZM treatment is associated with subsequent AZM(RS) gonococcal infections. The long half-life and persistence of subtherapeutic levels of AZM may result in selection of resistant NG strains in persons with recent AZM use. Among sexual health clinic patients with culture-positive Neisseria gonorrhoeae at >= 1 anatomic site, azithromycin exposure in the prior 30 days was associated with azithromycin-resistant infection.