Reply: Evidence of Recent Genomic Evolution in Gonococcal Strains With Decreased Susceptibility to Cephalosporins or Azithromycin in the United States, 2014–2016

To the Editor—We would like to extend our gratitude to Drs. Deng and Klausner for their interest in our article, in which we phylogenetically characterized gonococcal isolates collected through national sentinel surveillance and circulating in the United States, between 2014 and 2016 [1]. We identified 2 major subpopulations of strains associated with reduced susceptibility to either azithromycin (multilocus sequence typing [MLST] ST9363) or cephalosporins (MLST ST1901), and we detailed the evolution of several strains that possessed mutations that were not observed in the United States in 2000–2013.

Antimicrobial resistance (AMR) in the gonococcus represents a major public health threat, chiefly due to its rapidly evolving nature and the increasingly limited number of available treatment options. Although routine surveillance of AMR in circulating strains is essential in monitoring this threat, an equally important practice involves the promotion of antibiotic stewardship in limiting the spread of resistance. It is notable that the Centers for Disease Control and Prevention’s Gonococcal Isolate Surveillance Project, a historic sentinel surveillance program, has tracked AMR trends for over 30 years and, more recently, included whole-genome sequencing (WGS) of a subset of isolates [2]. As a result, the implementation of WGS has generated massive quantities of genomic data that can be used in tandem with data from traditional antimicrobial susceptibility testing to examine AMR trends. In addition, the release of these data to the public repositories has facilitated the ability of other investigators to conduct a myriad of follow-up studies.

We read with great interest the article by Deng et al [3], a follow-up to their recently published review of 415 international isolates with reduced cefixime susceptibility, describing a 6-codon algorithm that accurately predicts decreased cefixime susceptibility from penA alleles, and we believe it may provide a promising next step in the development of molecular assays for use in clinical settings. Diagnostic point-of-care tests could represent a potential paradigm shift in patient diagnosis and treatment, by providing clinicians with the simultaneous ability to rapidly screen gonococcal infections of concern and provide personalized patient care. Although unlikely to return to generally recommended usage, historically recommended drugs for empiric treatment (eg, ciprofloxacin, cefixime) could be effective treatments in patients identified with susceptible gonococcal infections. Work such as described by Deng et [3] al greatly contributes to the exploration of this approach.

Notes

Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, the Department of Veterans Affairs or the National Institutes of Health.

Financial support. This work was funded by the Centers for Disease Control and Prevention (CDC) and in part made possible through support from the CDC’s Advanced Molecular Detection and Combating Antibiotic Resistant Bacteria programs. This project was also supported in part by an appointment to the Research Participation Program at the CDC administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the CDC. W. M. S. was supported by National Institutes of Health Grant R37AI21150-33 and funds from an Intergovernmental Personnel Act from the CDC and a Senior Research Career Scientist Award from the Biomedical Laboratory Research and Development Service of the US Department of Veterans Affairs.

Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.