Commentary|Articles|September 15, 2026

Pathogen to Diagnosis: Using gyrA Genotyping to Revive Ciprofloxacin

Author(s)Matt Hoffman

New gyrA testing guides ciprofloxacin use for gonorrhea, cutting ceftriaxone reliance while tackling resistance, access, and FDA hurdles.

From Pathogen to Infectious Disease Diagnosis is a Contagion podcast hosted by Rodney E. Rohde, PhD, SV/SM/MB(ASCP)CM, FACSc, a University Distinguished and Regents' Professor at Texas State University, that connects laboratory professionals and infectious disease clinicians to discuss how the latest generation of diagnostic testing can help identify pathogens and guide treatment. Each episode brings a guest expert into conversation with Rohde to explore how emerging diagnostics are reshaping the relationship between the lab and the clinic.

The most recent episode focuses on how a single-gene diagnostic could let clinicians safely reintroduce a once-abandoned antibiotic for gonorrhea. In this episode, Lao-Tzu Allan-Blitz, MD, MPH, assistant clinical professor of medicine in the Division of Infectious Diseases at the David Geffen School of Medicine at UCLA, joins Rohde to discuss resistance-guided therapy for gonorrhea. Allan-Blitz's research focuses on infectious diseases, global health equity, and the development of low-cost molecular diagnostics for sexually transmitted infections, with clinical collaborations spanning multiple countries. The conversation centers on a single gene mutation that can predict which gonorrhea infections remain treatable with ciprofloxacin, a drug largely abandoned 2 decades ago.

"I'd like to look at this resistance-guided therapy with ciprofloxacin as the beginning, not the end."
—Lao-Tzu Allan-Blitz, MD, MPH

Neisseria gonorrhoeae has developed resistance to nearly every antibiotic used against it over the past several decades. Clinicians moved away from ciprofloxacin in the early 2000s once resistance reached 5%, shifting to ceftriaxone, the current standard treatment. Ceftriaxone resistance now exceeds 25% in some regions outside the United States, raising concern about a looming treatment gap with no clear successor. The downstream consequences of inadequately treated gonorrhea include an increased risk of HIV acquisition, pelvic inflammatory disease, infertility, neonatal blindness, and substantial costs to the health system.

gyrA genotyping enables real-time resistance-guided therapy

From Pathogen to Infectious Disease Diagnosis

[LISTEN TIME: 22 min, 20 seconds]

Listen to the full episode for more from Allan-Blitz on the future of resistance-guided diagnostics.

Resistance-guided therapy, already standard of care for Helicobacter pylori and methicillin-resistant Staphylococcus aureus, offers a near-term path back to ciprofloxacin for gonorrhea.1 Investigators have identified a single mutation in codon 91 of the gyrA gene that is 98% sensitive and 98% specific for predicting ciprofloxacin resistance, and rapid molecular assays targeting this mutation are now commercially available in the United States and elsewhere.1 Roughly 60% of N gonorrhoeae strains circulating in the US remain susceptible to ciprofloxacin, meaning most patients could avoid ceftriaxone if their strain's genotype is known. Across 3 clinical studies, ciprofloxacin achieved cure rates of 100% or greater than 98% across all anatomic sites, including the pharynx, where cure is notoriously difficult even with ceftriaxone.

"We have identified a single mutation in codon 91 of the gyrA gene that is 98% sensitive and 98% specific for predicting ciprofloxacin resistance."
—Lao-Tzu Allan-Blitz, MD, MPH

Because more than half of gonorrhea infections are asymptomatic, clinicians often have time between sample collection and treatment to reflex a positive result to gyrA genotyping, delivering both results simultaneously.1 When the assay was introduced in 2017, genotype turnaround took about 24 hours;1 a more recent study found it added closer to 2.5 days, though most surveyed patients said they would still wait the extra time to avoid an injection. Beyond the ecologic benefit of preserving ceftriaxone, an oral option eliminates the need for a return clinic visit and can be dispensed through a pharmacy or delivered to a patient's sex partner directly.

Treatment diversification looks beyond ciprofloxacin alone

Allan-Blitz was clear that resistance-guided therapy with ciprofloxacin is a beginning, not an endpoint, a point he has raised in prior conversations with Contagion about diversifying gonorrhea treatment. Relying on a single alternative antibiotic will eventually push resistance in the same direction, and in regions such as East Asia, where ciprofloxacin resistance already exceeds 99%, the approach is not viable. His lab has also developed CRISPR-based point-of-care assays for gonorrhea detection and resistance genotyping,2,3 including markers predicting susceptibility to cefixime,4 to build a full diagnostic panel that tailors treatment to the narrowest effective antibiotic. Scaling resistance-guided therapy to low-resource settings, where most gonorrhea is still managed syndromically without diagnostic infrastructure, remains a substantial hurdle, though Allan-Blitz pointed to field-deployable assays already piloted in Peru and planned trials in sub-Saharan Africa.

FDA clearance and reimbursement remain the final hurdles

FDA clearance and insurance reimbursement remain the primary barriers to routine use in the US. A large trial supporting 510(k) applications for 3 gyrA-testing devices is expected to conclude soon, with FDA-cleared devices anticipated in early 2027. On reimbursement, Allan-Blitz pointed to a recently approved CPT code for a Mycoplasma genitalium resistance assay as a precedent his group hopes to replicate for the gyrA codon 91 assay.

References
  1. Allan-Blitz LT, Humphries RM, Hemarajata P, Bhatti A, Pandori MW, Siedner MJ, Klausner JD. Implementation of a rapid genotypic assay to promote targeted ciprofloxacin therapy of Neisseria gonorrhoeae in a large health system. Clin Infect Dis. 2017;64(9):1268-1270. doi:10.1093/cid/ciw864
  2. Allan-Blitz LT, Shah P, Adams G, Branda JA, Klausner JD, Goldstein R, Sabeti PC, Lemieux JE. Development of Cas13a-based assays for Neisseria gonorrhoeae detection and gyrase A determination. mSphere. 2023;8(5):e0041623. doi:10.1128/msphere.00416-23
  3. Allan-Blitz LT, Adams G, Sanders G, et al. Preliminary clinical performance of a Cas13a-based lateral flow assay for detecting Neisseria gonorrhoeae in urine specimens. mSphere. 2024;10(1):e0067724. doi:10.1128/msphere.00677-24
  4. Nguyen THY, Garg S, Adams G, et al. Rapid Cas13a-based penA genotyping for cefixime susceptibility in Neisseria gonorrhoeae. mSphere. 2026;11(6):e0018226. doi:10.1128/msphere.00182-26

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