Economic value of resistance-guided gonorrhea treatment: cost-neutrality thresholds for resistance test pricing in the United States

Background: Rising antimicrobial resistance in Neisseria gonorrhoeae threatens the effectiveness of existing therapies. Resistance-guided treatment (RGT) may reduce treatment failures, complications, and inappropriate use of last-line agents while slowing resistance emergence. Methods and Findings: We developed an individual-level stochastic simulation model of gonorrhea diagnosis and treatment in the United States, incorporating infection prevalence, symptom status, diagnostic accuracy, resistance profiles, treatment pathways, and partner management (costs in 2025 USD). We evaluated three resistance testing strategies, ciprofloxacin-only, ciprofloxacin+ceftriaxone, and triple-target (including a novel drug A), across a wide range of resistance scenarios. We quantified economic value across three dimensions: (1) per-episode direct medical cost savings, (2) system-level costs attributable to ceftriaxone resistance emergence among MSM, and (3) avoided costs of new antibiotic development, estimating the maximum per-test price at which RGT remains cost-neutral. Per-episode cost-neutrality thresholds ranged from near $0 when ceftriaxone resistance was absent to up to $45/test at 15% ceftriaxone resistance. At 50% ciprofloxacin and 5% ceftriaxone resistance, the population-weighted threshold was $4 (95% UI:$3-$8) for a CIP-only test and $11 (95% UI:$5-$14) for a triple-target test. Among MSM, incorporating system-level resistance emergence costs and avoided antibiotic development costs increased the total per-test value to $35-$145 for a single-target test and $84-$128 for a triple-target test, depending on whether prescribing practices shift when ceftriaxone resistance reaches 5%. Conclusions: Resistance-guided therapy offers economic benefits across multiple dimensions even at relatively high diagnostic prices, supporting investment in gonorrhea resistance testing to improve partner outcomes, delay resistance emergence, and enhance the long-term cost-efficiency of gonorrhea management.