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

Abstract: 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).