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

Abstract

Background: Since 2014, Neisseria gonorrhoeae azithromycin (AZM) susceptibility has declined in the United States, but high-level AZM resistance (HL-AZMR) has been infrequent and sporadic. We describe a cluster of 14 N. gonorrhoeae isolates with HL-AZMR identified in Indianapolis over 13 months. Methods: N. gonorrhoeae culture specimens (genital and extragenital) were collected from attendees of the Bell Flower Clinic. Isolates underwent antimicrobial susceptibility testing (AST) using 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, AST was performed in 1016 N. gonorrhoeae isolates collected at the Bell Flower Clinic. Fourteen isolates (1.4%) from 12 men collected over 13 months demonstrated HL-AZMR; all were cephalosporin susceptible. Of the 12 men, 9 were white and reported male sex partners. Nine of the men were able to be retested; all were cured with 250-mg ceftriaxone plus 1-g AZM. 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 ribosomal RNA mutations that appear to have emerged from circulating strains. Conclusions: The close genetic relatedness with limited epidemiologic 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 multipronged approach to understanding an outbreak of sexually transmitted disease.