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To better understand treatment failure, we conducted a systematic review on mechanisms of 5-nitroimidazole resistance.<\/jats:p><\/jats:sec><jats:sec id=\"S0031182020001237_sec_a2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>PubMed, ScienceDirect and EMBASE databases were searched using keywords<jats:italic>Trichomonas vaginalis<\/jats:italic>, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded.<\/jats:p><\/jats:sec><jats:sec id=\"S0031182020001237_sec_a3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>The search yielded 606 articles, of which 550 were excluded, leaving 58 articles.<jats:italic>Trichomonas vaginalis<\/jats:italic>resistance varies and is higher with MTZ (2.2\u20139.6%) than TDZ (0\u20132%). 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.<jats:italic>Trichomonas vaginalis<\/jats:italic>infection with<jats:italic>Mycoplasma hominis<\/jats:italic>or<jats:italic>T. vaginalis<\/jats:italic>virus has also been associated with resistance.<jats:italic>Trichomonas vaginalis<\/jats:italic>has two genotypes, with greater resistance seen in type 2 (<jats:italic>vs<\/jats:italic>type 1) populations.<\/jats:p><\/jats:sec><jats:sec id=\"S0031182020001237_sec_a4\" sec-type=\"discussion\"><jats:title>Discussion<\/jats:title><jats:p>5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the<jats:italic>T. vaginalis<\/jats:italic>genome. Alternative treatments outside of the 5-nitroimidazole class are needed.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0031182020001237","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T10:32:57Z","timestamp":1596105177000},"page":"1383-1391","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":63,"title":["A systematic review of the literature on mechanisms of 5-nitroimidazole resistance in<i>Trichomonas vaginalis<\/i>"],"prefix":"10.1017","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8646-3801","authenticated-orcid":false,"given":"Keonte J.","family":"Graves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Novak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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