Sustained Transmission of Neisseria gonorrhoeae with High-Level Resistance to Azithromycin, Indianapolis, Indiana 2017-2018

Background Since 2014, Neisseria gonorrhoeae (Ng) azithromycin (AZM) susceptibility has declined in the United States, but high-level azithromycin resistance (HL-AZMR) has been infrequent and sporadic. We describe a cluster of 14 Ng isolates with HL-AZMR identified in Indianapolis over 13 months. Methods Ng culture specimens (genital and extragenital) were collected from attendees of the Bell Flower Clinic. Isolates underwent antimicrobial susceptibility testing (AST) by Etest ®. AZM minimum inhibitory concentrations ≥256 µg/ml were classified as HL-AZMR. Local disease intervention specialists interviewed patients whose isolates demonstrated HL-AZMR and conducted partner services. Relatedness of isolates was investigated by genomic analyses. Results During 2017-2018, 1,016 Ng isolates collected at the Bell Flower Clinic underwent AST. Fourteen isolates (1.4%) from 12 men collected over 13 months demonstrated HL-AZMR; all were cephalosporin-susceptible. Of the 12 men, nine were white and reported male sex partners. Nine of the men were able to be re-tested; all were cured with 250 mg ceftriaxone plus 1g azithromycin. Two men named each other as partners; no other partners in common were reported. Genomic analysis demonstrated close relatedness of the HL-AZMR isolates and a novel combination of a mosaic-mtrR promoter along with 23S rRNA mutations that appear to have emerged from circulating strains. Conclusions The close genetic relatedness with limited epidemiological linkages between patients highlights the challenges of gonorrhea partner investigations and suggests undetected local transmission. Local AST, rapid public health action, and epidemiologic investigations combined with genomic analysis provides a multi-pronged approach to understanding an STD outbreak.