LAUSR

P resently, the Centers for Disease Control and Prevention and the World Health Organization recommend 2 g of metronidazole (MTZ) in a single dose for the treatment of trichomoniasis in women. For over three decades, 2-g single dose MTZ has been recommended as the first line treatment. These recommendations come largely from studies conducted in non-pregnant, symptomatic women. A randomized clinical trial among human immunodeficiency virus–infected women, another randomized clinical trial among human immunodeficiency virus–uninfected women published in the Lancet Infectious Diseases, and a meta-analysis of published studies consistently found that single-dose MTZ is less effective compared with multidose (500 mg orally twice daily for 7 days) therapy. Even with multidose therapy, early Trichomonas vaginalis repeat infection rates are high, and there are indications that these are mostly due to treatment failure rather than reinfection from untreated sexual partners. Interestingly, national T. vaginalis susceptibility testing has found a low prevalence (~4%) of MTZ resistance. Thus, other reasons for treatment failure, particularly regarding to the 2-g single dose, should be considered. Early pharmacokinetic studies of MTZ in healthy female volunteers have demonstrated that a single 2-g dose should maintain trichomonacidal concentrations for up to 48 hours. However, some patients receiving this dose experience treatment failure despite T. vaginalis being fully susceptible to MTZ in vitro. This suggests that in vivo pharmacokinetic and pharmacodynamics effects of MTZ may be playing a role in treatment failure. Here, we suggest two potential effects which may account for the superior efficacy of multidose MTZ versus single dose among womenwith trichomoniasis: competition for MTZ and inadequate accumulation of the metabolites of MTZ. Although serum MTZ concentrations are quite high after the single 2-gMTZ dose, the delivery of adequate drug concentration at the site of T. vaginalis infection may be insufficient. Microorganisms reduceMTZ inside cells and, under anaerobic conditions,