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Case Report

Metronidazole-Resistant Trichomoniasis: Beneficial Pharmacodynamic Relationship With High-Dose Oral Tinidazole and Vaginal Paromomycin Combination Therapy

Henien, Mira BS; Nyirjesy, Paul MD; Smith, Katharine PhD, CRNP

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Sexually Transmitted Diseases: January 2019 - Volume 46 - Issue 1 - p e1-e2
doi: 10.1097/OLQ.0000000000000903
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Vaginal trichomoniasis is one of the most prevalent curable sexually transmitted infections in the United States.1 Similar to bacterial vaginosis, trichomoniasis has been associated with significant morbidities, including pelvic inflammatory disease, low birth weight, preterm delivery, and increased susceptibility to human immunodeficiency virus.1,2 Nitroimidazoles, bactericidal antibiotics which act on anaerobic protozoa by reduction of a 5-nitro group that produces reactive intermediates destructive to DNA, are the mainstay of treatment for trichomoniasis.1 A one-time oral 2-g dose of metronidazole is often effective. However, recent reports describe emerging metronidazole-refractory trichomoniasis. In case reports and series of metronidazole-resistant trichomoniasis, high-dose oral tinidazole,3 intravaginal paromomycin cream,4 or a combination of tinidazole and paromomycin cream,5 has been used successfully. Given the small number of described cases, it is unclear whether the combination of tinidazole and paromomycin works better than either medication singly. We hereby present a case of failure to single-agent therapy with high-dose oral tinidazole followed by single-agent therapy with intravaginal paromomycin cream. Although consecutive use of oral tinidazole and intravaginal paromomycin cream resulted in treatment failure, subsequent therapy with the same 2 agents used together resulted in a cure.

CASE REPORT

We report a case of a 49-year-old woman with a 5-month history of unrelenting trichomonas infection. She denied any sexual activity after the initial diagnosis. She was previously seen at an outpatient clinic and treated with 6 regimens of oral metronidazole and oral tinidazole. She stated that she had been compliant with all of her previous treatment courses. This patient also had sexually transmitted infection testing, including human immunodeficiency virus testing, all of which were negative. Susceptibility tests were not performed for this patient because of difficulty in obtaining them. In addition, it was decided that it would not change treatment course and add to therapy in a meaningful way. Therapy included both 1- and 7-day regimens, the highest dose of tinidazole being 2 g daily for a week. After completing 6 courses of oral metronidazole and high-dose oral tinidazole without relief, the patient was referred to the Drexel Vaginitis Center. After confirmation of the diagnosis by nucleic acid amplification testing, combination high-dose oral tinidazole (1 g, 3 times daily) and 4 g of 6.25% intravaginal paromomycin cream nightly for 2 weeks was prescribed. At the 1-month follow-up, the patient remained positive for trichomonas. However, upon review of medication adherence, the patient reported misunderstanding initial instructions and using oral tinidazole (500 mg, 3 times daily) followed by 2 weeks of 4 g of 6.25% intravaginal paromomycin cream instead of the combination which had been prescribed. After additional counseling, the patient used high-dose oral tinidazole in conjunction with the intravaginal paromomycin cream. This paromomycin cream was obtained from a compounding pharmacy. She experienced no adverse events, and the cost to the patient was US $10 after an authorization process. After treatment with the combination regimen, the patient remained clinically asymptomatic and trichomonas nucleic acid amplification tests were negative at 1- and 4-month visits.

DISCUSSION

Metronidazole-resistant trichomonas infection is an uncommon problem which presents a significant therapeutic challenge when it occurs. Standard of care for metronidazole-resistant trichomonas infection is currently oral tinidazole, which produces a reactive intermediate by reduction of a 5-nitro group that is toxic to bacterial DNA similar to other nitroimidazoles used to treat trichomoniasis.1 Paromomycin has also been used in cases of metronidazole-resistant trichomoniasis as it has a different mechanism of action from nitroimidazoles. Paromomycin intravaginal cream is an aminoglycoside that exerts its action by destruction of ribosomal RNA.6 It should be noted that in rare cases, paromomycin has led to vaginal ulcerations.7 Currently, there are 3 described cases of patients that have been cured with oral tinidazole and intravaginal paromomycin cream together.2,4 It is unclear from these cases if a cure was obtained by single-therapy tinidazole or paromomycin or a combination of the two, as the patients did not demonstrate failure to each individual medication. This case clearly demonstrates strong evidence that there is an additive or possibly even a synergistic effect between the 2 drugs, as a cure was only obtained with combination therapy. Clinically, this case adds evidence that using the combination therapy should be strongly considered in cases of tinidazole-resistant or paromomycin-resistant trichomoniasis. Researchers working with Trichomonas vaginalis in vitro should consider developing MIC testing standards for paromomycin and exploring whether a synergistic effect exists between these 2 drugs. We remain unaware of any cases of resistance to combination therapy with oral tinidazole and paromomycin cream in the world literature.

REFERENCES

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