Critical Considerations on the Proposed In Vitro Secnidazole Susceptibility Breakpoint for Trichomonas vaginalis

This correspondence calls into question the research by Graves et al. that determines an in vitro minimal lethal concentration (MLC) of 12.5 μg/ml for secnidazole (SEC) as linked to clinical resolution in Trichomonas vaginalis [1]. Recognizing the significance of establishing SEC susceptibility thresholds with increasing metronidazole (MTZ) resistance, we highlight several critical limitations: (1) No pharmacokinetic-pharmacodynamic (PK-PD) validation correlating the MLC with attainable drug concentrations in genital tissue; (2) Omission of isolates from males even with their roles in morbidity/reservoirs; (3) Neglect of the impact of vaginal microbiota on drug-parasite dynamics; (4) Absence of analysis on molecular resistance mechanisms; and (5) Possible selection bias due to the low representation of clinical SEC failures (n = 5) and MTZ-resistant isolates (n = 1).