Abstract
Background. Treatment of Neisseria gonorrhoeae infection is empirical and based on population-wide susceptibilities. Increasing antimicrobial resistance underscores the potential importance of rapid diagnostic tests, including sequence-based tests, to guide therapy. However, the usefulness of sequence-based diagnostic tests depends on the prevalence and dynamics of the resistance mechanisms.Methods. We define the prevalence and dynamics of resistance markers to extended-spectrum cephalosporins, macrolides, and fluoroquinolones in 1102 resistant and susceptible clinical N. gonorrhoeae isolates collected from 2000 to 2013 via the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project.Results. Reduced extended-spectrum cephalosporin susceptibility is predominantly clonal and associated with the mosaic penA XXXIV allele and derivatives (sensitivity 98% for cefixime and 91% for ceftriaxone), but alternative resistance mechanisms have sporadically emerged. Reduced azithromycin susceptibility has arisen through multiple mechanisms and shows limited clonal spread; the basis for resistance in 36% of isolates with reduced azithromycin susceptibility is unclear. Quinolone-resistant N. gonorrhoeae has arisen multiple times, with extensive clonal spread.Conclusions. Quinolone-resistant N. gonorrhoeae and reduced cefixime susceptibility appear amenable to development of sequence-based diagnostic tests, whereas the undefined mechanisms of resistance to ceftriaxone and azithromycin underscore the importance of phenotypic surveillance. The identification of multidrug-resistant isolates highlights the need for additional measures to respond to the threat of untreatable gonorrhea.
Highlights
Treatment of Neisseria gonorrhoeae infection is empirical and based on population-wide susceptibilities
Quinolone-resistant N. gonorrhoeae and reduced cefixime susceptibility appear amenable to development of sequence-based diagnostic tests, whereas the undefined mechanisms of resistance to ceftriaxone and azithromycin underscore the importance of phenotypic surveillance
The identification of multidrug-resistant isolates highlights the need for additional measures to respond to the threat of untreatable gonorrhea
Summary
We define the prevalence and dynamics of resistance markers to extended-spectrum cephalosporins, macrolides, and fluoroquinolones in 1102 resistant and susceptible clinical N. gonorrhoeae isolates collected from 2000 to 2013 via the Centers for Disease Control and Prevention’s Gonococcal Isolate Surveillance Project. We obtained isolates of N. gonorrhoeae from the Centers for Disease Control and Prevention’s Gonococcal Isolate Surveillance Project (GISP), with samples collected as described [6]. Antimicrobial susceptibility was interpreted according to Clinical and Laboratory Standards Institute for ciprofloxacin [7], and according to Centers for Disease and Control and Prevention’s guidelines for cefixime, ceftriaxone, and azithromycin, for which Clinical and Laboratory Standards Institute resistance criteria have not been established [8]. Single-nucleotide polymorphisms (SNPs) were called (ie, filtered to determine the working set of SNPs from all candidate sites) according to previous parameters [1]. See the Supplementary Methods for further details of analysis of NG-MAST, recombination, and population structure
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