A systematic review of the literature on mechanisms of 5-nitroimidazole resistance in


Journal

Parasitology
ISSN: 1469-8161
Titre abrégé: Parasitology
Pays: England
ID NLM: 0401121

Informations de publication

Date de publication:
11 2020
Historique:
pubmed: 31 7 2020
medline: 16 6 2021
entrez: 31 7 2020
Statut: ppublish

Résumé

Trichomonas vaginalis is 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. PubMed, ScienceDirect and EMBASE databases were searched using keywords Trichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded. The search yielded 606 articles, of which 550 were excluded, leaving 58 articles. Trichomonas vaginalis resistance 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 vaginalis infection with Mycoplasma hominis or T. vaginalis virus has also been associated with resistance. Trichomonas vaginalis has two genotypes, with greater resistance seen in type 2 (vs type 1) populations. 5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the T. vaginalis genome. Alternative treatments outside of the 5-nitroimidazole class are needed.

Sections du résumé

BACKGROUND
Trichomonas vaginalis is 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.
METHODS
PubMed, ScienceDirect and EMBASE databases were searched using keywords Trichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded.
RESULTS
The search yielded 606 articles, of which 550 were excluded, leaving 58 articles. Trichomonas vaginalis resistance 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 vaginalis infection with Mycoplasma hominis or T. vaginalis virus has also been associated with resistance. Trichomonas vaginalis has two genotypes, with greater resistance seen in type 2 (vs type 1) populations.
DISCUSSION
5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the T. vaginalis genome. Alternative treatments outside of the 5-nitroimidazole class are needed.

Identifiants

pubmed: 32729451
doi: 10.1017/S0031182020001237
pii: S0031182020001237
pmc: PMC7677174
mid: NIHMS1626160
doi:

Substances chimiques

Antiprotozoal Agents 0
Tinidazole 033KF7V46H
Metronidazole 140QMO216E

Types de publication

Journal Article Research Support, N.I.H., Extramural Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1383-1391

Subventions

Organisme : NIAID NIH HHS
ID : U19 AI113212
Pays : United States

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Auteurs

Keonte J Graves (KJ)

Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Jan Novak (J)

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

W Evan Secor (WE)

Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Patricia J Kissinger (PJ)

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.

Jane R Schwebke (JR)

Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Christina A Muzny (CA)

Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

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