Codon 91 Gyrase A Testing Is Necessary and Sufficient to Predict Ciprofloxacin Susceptibility in Neisseria gonorrhoeae

To the Editor—We read with great interest the article by Grad et al [1]. We agree with their conclusion that gyrase A (gyrA) genotype testing of Neisseria gonorrhoeae is a valuable means of resistance testing; however, we believe that gyrA testing, specifically of codon 91, is both necessary and sufficient for predicting susceptibility to ciprofloxacin. There have been 11 studies (N=4777 specimens) comparing real-time polymerase chain reaction (RT-PCR) genotype results with conventional antimicrobial susceptibility testing methods, all of which have demonstrated high sensitivity and specificity (93.8%–100% and 93.2%–100%, respectively). Positive and negative predictive values were similarly impressive (94.4%–100% and 87.5%–100%, respectively). Furthermore, 4 studies found that mutation at codon 91 of the gyrA gene as determined by RT-PCR was 100% specific for N. gonorrhoeae compared with other Neisseria species [2–5].

Other mutations have been shown to contribute to ciprofloxacin resistance, but previous studies have shown that other mutations in general occur in conjunction with a mutation in the gyrA gene [6, 7]. In addition, it is estimated that approximately 80% of N. gonorrhoeae infections in the United States are susceptible to ciprofloxacin [8]. Those 2 facts support the implementation of gyrA genotype testing to promote the use of targeted ciprofloxacin therapy. That may in turn reduce overuse of ceftriaxone. A recent article showed that treatment may be a major driver of ceftriaxone resistance in Neisseria gonorrhoeae [9], which has been called one of the top 3 urgent threats to public health by the Centers for Disease Control and Prevention [10].

We developed a rapid codon 91 gyrA genotypic assay using RT-PCR techniques [6], and we verified the assay in accordance with Clinical Laboratory Improvement Amendments [2]. UCLA Health introduced that assay into routine clinical practice for all N. gonorrhoeae–positive specimens in November 2015. Further studies are underway to characterize the impact of that implementation.

Notes

Financial support. This research was supported by the National Institutes of Health (grants R21AI117256 and R21AI109005).

Potential conflicts of interest. Both authors: No reported conflicts.

Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.