Enabling Ciprofloxacin Resistance-Guided Therapy for Neisseria gonorrhoeae : Aligning Diagnostics, Regulation, Guidelines, and Reimbursement
Betsy Wonderly Trainor, Jennifer L Osborn, Jeffrey D Klausner, Michael J Satlin, Sarah N Buss, Alicia Scheffer-Wong, Annette Harris, Barbara Van Der Pol, Carolyn Deal, Ashley Nenninger, Elisa Mokany, Kyung Moon, Joseph D Yao, Lindley A Barbee, Yonatan H Grad, Richard Alm, Lao-Tzu Allan-Blitz, Deborah Godes, Elizabeth M Marlowe, Scott R Evans, Lauren Komarow, Stephanie E McLaughlin, Brooke E Nichols, Robin PatelAbstract
Gonorrhea treatment in the United States relies on empirically administered intramuscular ceftriaxone. Diagnostics to predict Neisseria gonorrhoeae ciprofloxacin susceptibility/resistance could enable use of ciprofloxacin, a low-cost, single-dose oral antibiotic, to treat ciprofloxacin-susceptible gonorrhea. Ciprofloxacin resistance in N. gonorrhoeae is overwhelmingly mediated by a single mutation in gyrA at codon 91. Molecular interrogation of this site reliably predicts ciprofloxacin resistance and susceptibility. The Antibacterial Resistance Leadership Group (ARLG) is performing a multicenter, multicompany study to generate regulatory-grade clinical performance data to support Food and Drug Administration submissions of multiple nucleic acid amplification tests to predict ciprofloxacin susceptibility in N. gonorrhoeae. In December 2025, a multidisciplinary group was convened by the ARLG and Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator to discuss a coordinated pathway to enable individualized ciprofloxacin resistance-guided gonorrhea therapy in the United States, acknowledging this will require integration across diagnostics, regulation, guidelines, reimbursement, and implementation. Meeting highlights are presented.