Treatment of Trichomonas vaginalis Infections

Lossick, Joseph G.

doi:10.1093/clinids/4.supplement_4.s801

Cited by 37 publications

(7 citation statements)

References 84 publications

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“…It has a longer half-life than metronidazole and is eliminated at a significantly lower rate (86). It shows superior tissue distribution to that of metronidazole, and concentrations of the drug found in vaginal secretions are close to the levels found in serum, showing that it is delivered more effectively to this area than is metronidazole (73). MLCs of tinidazole for various T. vaginalis strains are consistently lower than MLCs for metronidazole, and this is reflected clinically: tinidazole is curative at lower doses then metronidazole.…”

Section: Tinidazolementioning

confidence: 99%

Treatment of Infections Caused by Metronidazole-ResistantTrichomonas vaginalis

et al. 2004

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Infections with the sexually transmitted protozoan Trichomonas vaginalis are usually treated with metronidazole, a 5-nitroimidazole drug derived from the antibiotic azomycin. Metronidazole treatment is generally efficient in eliminating T. vaginalis infection and has a low risk of serious side effects. However, studies have shown that at least 5% of clinical cases of trichomoniasis are caused by parasites resistant to the drug. The lack of approved alternative therapies for T. vaginalis treatment means that higher and sometimes toxic doses of metronidazole are the only option for patients with resistant disease. Clearly, studies of the treatment and prevention of refractory trichomoniasis are essential. This review describes the mechanisms of metronidazole resistance in T. vaginalis and provides a summary of trichomonicidal and vaccine candidate drugs

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Section: Tinidazolementioning

confidence: 99%

Treatment of Infections Caused by Metronidazole-ResistantTrichomonas vaginalis

et al. 2004

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“…A few T. vaginalis strains with lowered susceptibility to 5-nitroimidazoles were also developed in experimental studies. Clinical and laboratory aspects of metronidazole resistance have been previously reviewed (8,16,19).Lowered metronidazole susceptibility of such isolates of T. vaginalis can be observed in tests on mice. The same property is detected in in vitro tests only under specific conditions, among which aerobiosis seems critical (13,19).…”

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confidence: 99%

mentioning

confidence: 99%

Metabolism and metronidazole uptake in Trichomonas vaginalis isolates with different metronidazole susceptibilities

Müller¹,

Gorrell²

1983

Antimicrob Agents Chemother

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Three Trichomonas vaginalis isolates with low in vivo susceptibilities to metronidazole (95% curative dose, >3 x 100 mg kg-' in subcutaneous infections in mice) were compared with strain ATCC 30001 and with four isolates exhibiting high in vivo susceptibilities (95% curative dose, <3 x 15 mg kg-1). Activity of pyruvate:ferredoxin oxidoreductase, anaerobic fermentation, and anaerobic intracellular accumulation of [14C]metronidazole label showed no significant isolatedependent differences which could be correlated with drug susceptibility. The results suggest that processes providing electrons for metronidazole activation are not defective in the resistant strains. Aerobiosis, known to inhibit the antimicrobial action of metronidazole, inhibited accumulation of label more strongly in resistant isolates than in susceptible ones. No differences were detected, however, between resistant and susceptible isolates in respiration, aerobic fermentation, and the specific activity of NADH and NADPH oxidases, the main terminal oxidases of T. vaginalis. These findings suggest that the production of electrons is not diminished under aerobic conditions. The inhibitory effect of aerobic conditions on metronidazole activation, possibly due to competition for the electrons, is markedly enhanced in the resistant isolates compared to the susceptible ones. The mechanism of this effect, however, remains unknown.Metronidazole and other 5-nitroimidazoles are effective in the treatment of human trichomoniasis and in infections caused by other anaerobic protozoa as well as bacteria. The possibility of metronidazole resistance in Trichomonas vaginalis has been repeatedly suggested and dismissed in the past. In recent studies, however, several cases of therapeutic failure were attributed to resistance of the parasite because, compared with random isolates, isolates obtained from these cases showed lower metronidazole susceptibility in certain assays. A few T. vaginalis strains with lowered susceptibility to 5-nitroimidazoles were also developed in experimental studies. Clinical and laboratory aspects of metronidazole resistance have been previously reviewed (8,16,19).Lowered metronidazole susceptibility of such isolates of T. vaginalis can be observed in tests on mice. The same property is detected in in vitro tests only under specific conditions, among which aerobiosis seems critical (13,19). Beaulieu et al. (1) noted that the effect of aerobiosis on metronidazole metabolism in a susceptible isolate is different from that in a resistant isolate of T. vaginalis. A 5-nitroimidazole-resistant strain of Tritrichomonas foetus developed in mice also shows similar properties (10,11).These findings demonstrate that resistance is related to the effect of aerobiosis.The action of 5-nitroimidazoles in anaerobic microorganisms consists of several steps (5, 15): (i) entry of the drug into the cell; (ii) reductive metabolic activation to short-lived cytotoxic intermediates, a process inhibited by aerobiosis; (iii) interaction of the cytotoxic intermedia...

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“…It has been suggested that resis tance is not absolute but involves moderate increases in the minimum inhibition concen tration for most 'resistant' strains [3]. It is thus essential to ascertain the levels attain able in the vaginal fluid after oral therapy.…”

Section: Discussionmentioning

confidence: 99%

Implications of Metronidazole Pharmacodynamics for Therapy of Trichomoniasis

Larsen

Wilson²,

Glover³

et al. 1986

Gynecol Obstet Invest

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A liquid chromatographic technique for the detection of metronidazole (MDZ) and its major metabolites, combined with a vaginal sampling technique employing extraction of the drug from vaginal swabs, was used to evaluate the concentration of MDZ in the vaginal fluid during therapy. Wide variation in the absolute concentration of unchanged drug was noted, although the average vaginal levels were about half the serum concentration 2 h after treatment had been initiated and comparable to the serum levels 6 and 24 h after treatment. Oral administration of MDZ invariably resulted in the presence of the drug in the serum and urine but the drug was not always detected in the vaginal secretions. The presence of the relatively inactive acetyl metabolite in the vaginal fluid of patients who failed to respond to therapy for trichomoniasis suggested the possible role of drug modification as a contributing factor in the lack of therapeutic success. The presence of MDZ in women in whom the cervix had previously been surgically removed attests to the transport or transudation of the drug across the vaginal epithelium without involvement of the secretory activity of the cervix.

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Treatment of Trichomonas vaginalis Infections

Cited by 37 publications

References 84 publications

Treatment of Infections Caused by Metronidazole-ResistantTrichomonas vaginalis

Treatment of Infections Caused by Metronidazole-ResistantTrichomonas vaginalis

Metabolism and metronidazole uptake in Trichomonas vaginalis isolates with different metronidazole susceptibilities

Implications of Metronidazole Pharmacodynamics for Therapy of Trichomoniasis

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