Resistance-guided testing targeting a single gene mutation could let clinicians safely reintroduce ciprofloxacin for the majority of gonorrhea cases still susceptible to it, sparing ceftriaxone as resistance climbs worldwide. Lao-Tzu Allan-Blitz, MD, MPH, offers insights into his work in this area.
This is the latest episode of our From Pathogen to Infectious Disease Diagnosis podcast, where we discuss the relationship between clinicians and laboratory professionals and detail the latest in diagnostics.
Neisseria gonorrhoeae has developed resistance to nearly every antibiotic used against it over the past several decades, says Lao-Tzu Allan-Blitz, MD, MPH, assistant clinical professor of medicine at the David Geffen School of Medicine at UCLA.
“We're facing more or less a crisis of how to treat gonorrhea effectively and prevent the downstream consequences, which include an increased risk for the acquisition of HIV, pelvic inflammatory disease among women, infertility, neonatal blindness, and extreme costs to the health system. We're talking about hundreds of millions of dollars over the lifetime of individuals who have been infected,” Allan-Blitz said.
Clinicians abandoned ciprofloxacin in the early 2000s once resistance reached 5% and moved to ceftriaxone, the current standard. Ceftriaxone resistance now exceeds 25% in some regions outside the US, raising concern about a treatment gap with no clear successor, acknowledges Allan-Blitz.
He and others have been studying this issue and looking for clinical management strategies. He points to resistance-guided therapy as a near-term solution. Allan-Blitz says the resistance-guided therapy approach is now a standard of care for Helicobacter pylori and they use it for methicillin-resistant Staphylococcus aureus treatment. Roughly 60% of N gonorrhoeae strains circulating in the US remain susceptible to ciprofloxacin.
“We have identified a single mutation in codon 91 of the gyrA gene in gonorrhea that is 98% sensitive and 98% specific for predicting ciprofloxacin resistance. So, rapid molecular assays that target this location have been developed and are now commercially available in the United States and elsewhere,” Allan-Blitz said. “And they allow clinicians within a number of hours up to a day to determine the gonorrhea genotype. And what's important to remember is that when a patient comes in with symptoms, they need to be treated then and there, but by and large we think more than half, maybe 60% of infections, are asymptomatic. And so for most people, you have some time where you take their swab or you take their urine sample, you send it to the laboratory, and you may not get their results back for a day. And if you can reflex the positive results to a gyrA genotyping assay, you can provide the gonorrhea results positive or negative, with the gyrA genotype results at the same time.”
Here are some studies Allan-Blitz has participated as an investigator as well as views as important references to this work.
Implementation of a Rapid Genotypic Assay to Promote Targeted Ciprofloxacin Therapy of Neisseria gonorrhoeae in a Large Health System
Beyond ciprofloxacin, Allan-Blitz's lab has identified genetic markers predicting susceptibility to cefixime, penicillin, and doxycycline, with the goal of building a full panel of resistance-guided diagnostics. He also emphasized that scaling this approach globally, not just in the US, is critical given how quickly resistant strains move across borders. Ceftriaxone-resistant cases have been imported into the US from regions with high resistance prevalence.
Insurance reimbursement remains a separate hurdle, but Allan-Blitz noted a recent CPT code approval for a Mycoplasma genitalium resistance assay as a potential precedent for a future gyrA codon 91 reimbursement code.
“CMS just set a reimbursement rate for that CPT code, and we're applying the same sort of logic to the gyrA codon 91 assay,” he said. “We don't have that code yet, so it's not in my hand, but once we have it in hand, I'm hoping that FDA-cleared tests, CPT code for reimbursement, commercially available assays, and high burden of need, we will start to really move the needle.”
