The Invisible Tide of Neisseria gonorrhoeae Treatment Failures: A Review and Commentary

Neisseria gonorrhoeae has developed resistance to every class of antibiotics historically used in its treatment, undermining current therapeutic options. This review systematically assessed documented treatment failures with ceftriaxone, the recommended antibiotic in many settings. Thirty-three cases of probable or confirmed ceftriaxone treatment failure were identified, with only 8 meeting the European Centre for Disease Prevention and Control criteria for confirmed failure. All confirmed cases were in heterosexuals and most involved pharyngeal infections; a site associated with limited drug penetration and reduced diagnostic sensitivity. Although ceftriaxone-resistant strains are increasingly prevalent globally-particularly in Asia-confirmed failures were reported almost exclusively from high-income countries with robust surveillance and diagnostics, suggesting significant under-reporting elsewhere. Inconsistent treatment regimens, heterogeneous definitions of treatment failures, and limited access to culture diagnostics hamper accurate detection of true clinical failures. These findings underscore the urgent need for standardized definitions, improved global reporting infrastructure, and measures to preserve ceftriaxone efficacy while new treatments are developed.