Drug library screening against metronidazole-sensitive and metronidazole-resistant Trichomonas vaginalis isolates.

Abstract

OBJECTIVES:

Metronidazole and tinidazole are effective treatments for most patients with trichomoniasis but not for individuals who are infected with very resistant strains of Trichomonas vaginalis or persons with hypersensitivity to the 5-nitroimidazole drugs. Thus, there is a need for additional oral therapies to treat trichomoniasis.

METHODS:

We screened the US Drug Collection Library against metronidazole-susceptible and resistant strains of T vaginalis. Activity was measured by incubating parasites and drugs for 48 h in the presence of tritiated thymidine. Growth inhibition was determined by the reduction of incorporated radioactivity by compounds at 20 μM in comparison to media control. Drugs that showed good initial activity were further tested to calculate IC50 values. Drugs with the most promise were tested together with metronidazole to see if there was any combinatorial effect.

RESULTS:

Of the 1040 drugs in the library, 83 (8%) reduced growth of a metronidazole-susceptible T vaginalis strain by at least 20%. Of these, IC50 values were calculated for 27 compounds and 8 drugs were evaluated in combination with metronidazole. Disulfiram and nithiamide were non-5-nitroimidazole drugs that showed the best activity against parasites when used alone. Albendazole and coenzyme B12 were the most promising compounds to boost the efficacy of metronidazole.

CONCLUSIONS:

No one drug was as effective as any of the 5-nitroimidazole compounds. However, disulfiram and nithiamide may be useful to treat individuals with hypersensitivity to 5-nitroimidazole drugs and albendazole and coenzyme B12 may be helpful in combination with metronidazole or tinidazole for treatment of persons with highly resistant T vaginalis infections.

• Authors: E Brook Goodhew, W Evan Secor
• Journal: Sexually transmitted infections (Sex Transm Infect) Vol. 89 Issue 6 Pg. 479-84 (Sep 2013) ISSN: 1472-3263 [Electronic] England
• PMID: 23794105 (Publication Type: Journal Article)

Chemical References

• Antiprotozoal Agents
• Metronidazole

Topics

• Antiprotozoal Agents (isolation & purification, pharmacology)
• Drug Evaluation, Preclinical
• Drug Resistance
• Humans
• Inhibitory Concentration 50
• Metronidazole (pharmacology)
• Parasitic Sensitivity Tests
• Trichomonas vaginalis (drug effects)
• United States