Reliability of Genetic Alterations in Predicting Ceftriaxone Resistance in Neisseria gonorrhoeae Globally

Abstract

ABSTRACT Antimicrobial resistance in N. gonorrhoeae is increasing globally, and ceftriaxone is the recommended treatment for empirical therapy in most settings. Developing molecular assays to detect decreased ceftriaxone susceptibility is critical. Using PathogenWatch, a public database of N. gonorrhoeae genomes, antibiotic susceptibility data and DNA sequences of different genes associated with ceftriaxone resistance were extracted. That information was used to determine the sensitivity and specificity of different molecular markers and algorithms to predict decreased susceptibility to ceftriaxone. A total of 12,943 N. gonorrhoeae genomes were extracted from the PathogenWatch database, of which 9,540 genomes were used in the analysis. The sensitivity and specificity of specific molecular markers and algorithms were largely consistent with prior reports. Small variation (<10%) in either sensitivity or specificity occurred. Certain algorithms using different molecular markers at various prevalence of decreased ceftriaxone susceptibility identified a potentially clinically useful range of positive and negative predictive values. We validated previously described mutations and algorithms in a large public database containing a global collection of N. gonorrhoeae genomes. Certain mutations and algorithms resulted in sensitivity and specificity values consistent with those of prior studies. Further research is needed to integrate these markers and algorithms into the development of molecular assays to predict decreased ceftriaxone susceptibility. IMPORTANCE Antimicrobial resistance in Neisseria gonorrhoeae (N. gonorrhoeae), the causative agent of gonorrhea, is rising globally. Ceftriaxone is the last remaining antibiotic for empirical treatment of gonorrhea. Developing molecular tests to predict ceftriaxone resistance can help to improve detection and surveillance of ceftriaxone resistance. Here, we utilized PathogenWatch, a public global online database of N. gonorrhoeae genomes, to evaluate different genetic markers in predicting decreased susceptibility to ceftriaxone. We compiled MICs for ceftriaxone from the PathogenWatch database and used a computational approach to extract all the genetic markers from the genomic data. We determined the sensitivity and specificity for predicting decreased ceftriaxone susceptibility among several combinations of genetic markers. We identified several combinations of genetic markers with high predictive values for decreased susceptibility to ceftriaxone. These combinations of genetic markers might be promising candidates for future molecular tests to predict ceftriaxone resistance.

Keywords

• Neisseria gonorrhoeae
• algorithms
• assays
• ceftriaxone
• antimicrobial resistance
• genetic markers