Reinfection and ceftriaxone tolerance in a clinical case of recurrent gonorrhoea: a case report supported byandmodels.

Abstract

BACKGROUND: Antibiotic tolerance slows bacterial killing during drug exposure without changing minimum inhibitory concentration (MIC) and is often missed by MIC-based testing in. OBJECTIVES: To quantify ceftriaxone tolerance using complementary laboratory assays and to integrate these readouts with genomic typing to interpret recurrent urethritis within one patient series. METHODS: Four clinical isolates obtained between 2022 and 2025 underwent tolerance disc testing. From the most recent isolate (25355), tolerant and non-tolerant variants were derived for functional study, including growth curves (logCFU/mL), minimum duration needed to kill 99% of cells (MDK99) across ceftriaxone concentrations, and ainfection model. Whole-genome sequencing with in silico typing compared strain type between episodes. RESULTS: Tolerance disc testing was positive for isolates 22073 and 25355. Across the growth trajectory, tolerant variants showed consistently lower bacterial counts than non-tolerant variants. Tolerant variants tended to exhibit longer MDK99 values, and inthey declined more slowly under ceftriaxone exposure. Sequencing revealed distinct sequence types across episodes, supporting reinfection rather than within-host persistence. CONCLUSIONS: Assays that capture killing kinetics detected ceftriaxone tolerance that was not captured by MIC-based testing. Genomic analysis distinguished reinfection from persistence. This integrated workflow may improve the evaluation of suspected treatment failure in gonorrhoea.