Background The emergence of azithromycin-resistant Neisseria gonorrhoeae threatens recommended first-line treatment regimens.

Methods We investigated cases of azithromycin-resistant gonorrhoea detected at Public Health – Seattle and King County STD Clinic between January 2014 and February 2015. In 2012–2013, zero of 237 MSM urethral isolates were azithromycin-resistant. The US Centres for Disease Control and Prevention (CDC) and Clinical and Laboratory Standards Institute (CLSI) do not define an azithromycin-resistance breakpoint. CDC uses ≥2 mcg/mL as an “Alert Value” minimal inhibitory concentration (MIC) (here called resistant). We used agar dilution to determine MICs.

Results Of 179 urethral, 83 pharyngeal and 87 rectal isolates from MSM, 11 (6.1%), 6 (7.2%) and 5 (5.7%) had azithromycin MIC ≥2 mcg/mL, respectively. We identified no cases of azithromycin-resistance among 56 heterosexuals. Overall, 19 (6.9%) of 276 MSM with culture-positive gonorrhoea had an azithromycin-resistant isolate. The median azithromycin MIC was 4.0 mcg/mL (range 2 to >256 mcg/mL). Eight patients’ isolates also demonstrated tetracycline resistance (MIC ≥2 mcg/mL); one was ciprofloxacin-resistant (MIC 16.0 mcg/mL). None exhibited reduced susceptibility to cefixime or ceftriaxone. Clinicians treated thirteen (68%) cases with ceftriaxone and azithromycin, one (5.3%) with ceftriaxone and doxycycline, two (10.6%) with study drug, and three (15.8%) with 2g of azithromycin. Two of three men treated with azithromycin-monotherapy had a test of cure (TOC) and both had persistent infection; their isolates demonstrated azithromycin MICs of 32 mcg/mL and 4.0 mcg/mL. One rectal treatment-failure was cured with 360 mg of gentamicin intramuscularly; the other (urethra/pharynx positive), was treated with ceftriaxone and doxycycline. He did not undergo repeat TOC. The individual with high-level azithromycin-resistance (MIC >256 mcg/mL) was an international traveller and not locatable for TOC.

Conclusions Clinically important azithromycin-resistant Neisseria gonorrhoeae now are found in >5% of MSM with gonorrhoea in Seattle. These findings support new CDC recommendations to avoid treating gonorrhoea with azithromycin alone.

Disclosure of interest statement This work was funded by the US National Institutes of Health and CDC. No pharmaceutical grants were received in the development of this study.