In Vitro Drug Susceptibility and Doses of Metronidazole Required for Cure in Cases of Refractory Vaginal Trichomoniasis

Abstract

There are currently no laboratory or clinical guidelines for the identification and treatment of disease caused by metronidazole-resistant strains of Trichomonas vaginalis. Fifty-three isolates of T. vaginalis from cases of refractory vaginitis in the United States (26 states) and Canada were tested for aerobic and anaerobic metronidazole susceptibility, and after various dosages of metronidazole, the therapeutic outcomes were evaluated for 31 of these cases. The mean aerobic metronidazole susceptibility of these isolates was 195.5 micrograms/ml (range, 12.5-greater than 1,000), which was about eightfold higher than that seen in isolates that were not resistant to metronidazole. The mean anaerobic susceptibility was 5 micrograms/ml (range, 1.6-25), which was about threefold higher than that of isolates from nonresistant strains. The average aerobic-to-anaerobic ratio of metronidazole susceptibility in the highly resistant isolates was more than 3.5-fold greater than that seen in the nonresistant isolates. White women accounted for 88% of the resistant infections. Of 31 cases that were re-treated and monitored, the highest average dose that failed to achieve a cure was 2.1 g of metronidazole/day given over an eight-day period; 27 (87%) of 31 cases were ultimately cured with an average dosage of 2.6 g of metronidazole/day given over a mean period of nine days. Resistance to treatment with metronidazole varied from mild to severe, and the resistance was occasionally more severe than the susceptibility values indicate.

Trichomoniasis

“…This resistance is relative and can usually be overcome with higher doses of oral metronidazole (67). For example, marginal resistance, defined as an aerobic minimal lethal concentration (MLC) of metronidazole of 50 g/ml, requires a total treatment dose of 10 g administered over several days for cure wheareas high-level resistance (MLC, Ն400 ug/ml) requires 40 g. Intravenous formulations offer no advantage over the oral drug.…”

Current Issues and Considerations Regarding Trichomoniasis and Human Immunodeficiency Virus in African-Americans

“…However, since recent data indicate that resistance to metronidazole is rising (9.6% of isolates in a recent study), judicious drug use is extremely important (83). Resistance to metronidazole is thought to be relative and can often be overcome with higher doses of the drug (54). Additionally, resistance to tinidazole, a drug that was recently approved for the treatment of T. vaginalis, has been reported, but this drug is in the same drug class as metronidazole (23).…”

Genetic Relatedness of Trichomonas vaginalis Reference and Clinical Isolates

“…† = Data from prior study. 13 ATCC = American Type Culture Collection; U = data unknown; NT = not tested; NT # = not tested but presumed sensitive as patients responded to therapy and cleared infection . 14 Numbers at the upper left of each node show the operational taxonomic unit (OUT) jackknifing percent values based on 10,000 resampled datasets, which estimate statistical support for the existence of those branches.…”