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Wild-Type Gyrase A Genotype of Neisseria gonorrhoeae Predicts In Vitro Susceptibility to Ciprofloxacin: A Systematic Review of the Literature and Meta-Analysis

Allan-Blitz, Lao-Tzu; Wang, Xiaoyan PhD; Klausner, Jeffrey D. MD, MPH

Sexually Transmitted Diseases: May 2017 - Volume 44 - Issue 5 - p 261–265
doi: 10.1097/OLQ.0000000000000591

Multidrug-resistant Neisseria gonorrhoeae infections have been declared 1 of the top 3 urgent threats to public health. Approaches to combat resistance include targeted therapy with antibiotics previously thought to be ineffective, made possible by rapid molecular assays to predict susceptibility. Previous studies have associated the gyrase A (gyrA) gene of N. gonorrhoeae with in vitro resistance to ciprofloxacin. We conducted a systematic review of studies comparing N. gonorrhoeae gyrA genotype results with conventional antimicrobial susceptibility testing results. We identified 31 studies meeting inclusion criteria, among which 7 different loci for mutations in the gyrA gene were identified, from 16 countries between the years of 1996 and 2016. We then performed a meta-analysis among those studies stratifying by use of real-time polymerase chain reaction (PCR) or non–real-time PCR technique, and compared the summary receiver operating characteristic curves between the 2 PCR methods. Among studies using real-time PCR, the pooled estimate of sensitivity and specificity of gyrA genotype results for the prediction of N. gonorrhoeae susceptibility to ciprofloxacin were 98.2% (95% confidence interval [CI], 96.5–99.1%) and 98.6% (95% CI, 97.0–99.3%), respectively. The summary operating characteristic curves for studies using real-time PCR techniques were well separated from those using non–real-time PCR techniques, with only slight overlap in the CIs, suggesting that real-time PCR techniques were a more accurate approach. GyrA genotype testing is a novel approach to combating the emergence of multidrug-resistant N. gonorrhoeae and is a sensitive and specific method to predict in vitro ciprofloxacin susceptibility.

A review of studies comparing gyrase A genotype of Neisseria gonorrhoeae to conventional susceptibility testing methods suggests strong evidence for use of rapid genotypic assays to predict in vitro susceptibility.

From the *David Geffen School of Medicine, †Department of General Internal Medicine and Health Services Research, ‡Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine and §Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA

Acknowledgments: This research was supported by the United States National Institutes of Health grants R21AI117256 and R21AI109005.

Conflict of interest: None declared.

Correspondence: Lao-Tzu Allan-Blitz, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095. E-mail:; Jeffrey Klausner, MD, MPH, Department of Medicine: Infectious Disease, UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095. E-mail:

Received for publication September 30, 2016, and accepted January 4, 2017.

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© Copyright 2017 American Sexually Transmitted Diseases Association