Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study

Abstract

Background Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. Methods Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5–10 days post-treatment. Results Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5–100%). Conclusions Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. Clinical Trials Registration NCT02961751.

Characterization of a Neisseria gonorrhoeae Ciprofloxacin panel for an antimicrobial resistant Isolate Bank

“…With the advancement of newer, faster rapid molecular tests, there is a potential for clinicians to choose antibiotics discontinued for gonorrhea treatment based on the presence or absence of known genetic markers. This kind of targeted treatment potentially has the advantages of allowing physicians to select common and still effective antibiotics based on testing results [ 27 – 29 ].…”

“…This notion is especially facilitated by the fact that the ciprofloxacin resistance mechanisms utilized by N . gonorrhoeae are well defined and there are clear targets to be selected for developing rapid molecular tests [ 28 , 29 ]. To this end, to conserve the usage of current first line antibiotics and in considering re-use of previously favored first line antibiotics, ciprofloxacin is an ideal candidate.…”

Clinical Microbiology in 2021: My Favorite Studies about Everything Except My Least Favorite Virus

“…The Centers for Disease Control and Prevention (CDC) now recommends ceftriaxone with or without azithromycin, abandoning the previously recommended ciprofloxacin due to increased resistance. Klausner et al developed a molecular assay that can reliably predict ciprofloxacin susceptibility by targeting a single point mutation in N. gonorrhoeae gyrA that is responsible for >95% of ciprofloxacin resistance in the organism [ 27 ]. Among 211 enrolled subjects for whom remnant specimens were available, 106 subjects had culture-positive infections (some with multiple sites of infection) that tested positive for wild-type gyrA serine 91 and were subsequently treated with ciprofloxacin and tested for microbiologic cure 5 to 10 days later.…”

Reflex Detection of Ciprofloxacin Resistance in Neisseria gonorrhoeae by Use of the SpeeDx ResistancePlus GC Assay

“…With recent reports of increasing resistance, individualized therapy based on the molecular detection of resistance determinants (resistance-guided therapy [RGT]) has been suggested as a way of improving antimicrobial stewardship and delaying the emergence of AMR ( 2 , 3 ). In particular, RGT for ciprofloxacin has been incorporated into gonorrhea treatment guidelines in the United Kingdom and was shown to be feasible and effective in a recent multisite clinical study in the United States ( 4 , 5 ).…”