A Systematic Review of the Literature on Mechanisms of 5-Nitroimidazole Resistance in Trichomonas vaginalis

BackgroundTrichomonas vaginalisis the most common non-viral sexually transmitted infection. 5-Nitroimidazoles [metronidazole (MTZ) and tinidazole (TDZ)] are FDA-approved treatments. To better understand treatment failure, we conducted a systematic review on mechanisms of 5-nitroimidazole resistance.MethodsPubMed, ScienceDirect and EMBASE databases were searched using keywordsTrichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded.ResultsThe search yielded 606 articles, of which 550 were excluded, leaving 58 articles.Trichomonas vaginalisresistance varies and is higher with MTZ (2.2–9.6%) than TDZ (0–2%). Resistance can be aerobic or anaerobic and is relative rather than absolute. Differential expression of enzymes involved in trichomonad energy production and antioxidant defenses affects 5-nitroimidazole drug activation; reduced expression of pyruvate:ferredoxin oxidoreductase, ferredoxin, nitroreductase, hydrogenase, thioredoxin reductase and flavin reductase are implicated in drug resistance.Trichomonas vaginalisinfection withMycoplasma hominisorT. vaginalisvirus has also been associated with resistance.Trichomonas vaginalishas two genotypes, with greater resistance seen in type 2 (vstype 1) populations.Discussion5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in theT. vaginalisgenome. Alternative treatments outside of the 5-nitroimidazole class are needed.