Intravenous metronidazole,liquid tinidazole,and intra-vaginal boric acid to cure trichomonas in a patient with gastric bypass surgery

Abstract

This study presents a case report of a female patient with symptomatic refractory Trichomonas vaginalis infection who was not able to clear her infection with high-dose oral metronidazole, oral tinidazole, intra-vaginal zinc sulfate, intra-vaginal metronidazole, intra-vaginal tinidazole, and intra-vaginal boric acid. She was unable to tolerate intra-vaginal paromomycin. A combination of intravenous metronidazole, oral tinidazole liquid suspension, and intra-vaginal boric acid for 14 days subsequently achieved a complete symptomatic and laboratory cure.

Keywords

Protozoal disease

Introduction

Trichomoniasis is the most prevalent non-viral sexually transmitted infection (STI) in the United States.¹ It affects more than 3.7 million people,¹ and since 70% of the patients are asymptomatic, routine testing is prudent in high-risk populations (human immunodeficiency virus [HIV], women in STI clinics, correctional facilities, multiple sex partners, exchanging sex for payment, history of STIs, and illicit drug use).¹ Trichomonas vaginalis (TV) increases the risk of HIV, pelvic inflammatory disease, and pre-term birth in women.¹ The only recommended and approved treatment consists of 5-nitroimidazoles (metronidazole or tinidazole).¹ All the other drug recommendations are anecdotal and based on case reports and case series only. We present a challenging case of refractory TV with high-level resistance to metronidazole and tinidazole, hoping it may help others facing a similar case.

Case report

A 37-year-old Caucasian woman, presented to our clinic with persistent TV. She was HIV negative, non-pregnant and had a medical history of obesity treated with gastric bypass surgery. She was not sexually active at the time of presentation. In the recent past, she had been monogamous with one male partner for a month but had lost contact with him. Initially, her vaginal wet mount was positive for TV, and she was treated with oral metronidazole 2 g single dose with no symptomatic improvement. This was followed by oral metronidazole 2 g daily for seven days. She continued to be symptomatic with vaginal discharge, and her vaginal nucleic acid amplification test (NAAT) was positive for TV. She had a negative urine chlamydia and gonorrhea NAAT, and her serum rapid plasma reagin (RPR) was non-reactive. A Center for Disease Control and Prevention (CDC) kit (TV InPouch™) was sent, by a previous clinician, which showed TV with high-level resistance to metronidazole (MIC 400 µg/ml) and tinidazole (MIC 200 µg/ml). Per CDC recommendations, she was treated with a course of oral metronidazole 2 g daily for 14 days. She continued to have vaginal discharge, and her vaginal TV NAAT was positive; therefore, she was given oral tinidazole 2 g daily plus intra-vaginal metronidazole 0.75% daily and was referred to our clinic. At the time of her clinic visit with us, she was on day 6 of this treatment. She complained of intense nausea and intermittent vomiting with tinidazole. On examination, she had copious thin yellow vaginal discharge with no odor and mild vulvar irritation. She was given promethazine as needed for nausea. Post 14 days of high-dose oral tinidazole plus intra-vaginal metronidazole, she continued to have vaginal discharge, and her vaginal TV NAAT was positive. Oral nitazoxanide was prescribed,² but the patient was unable to afford it. She was given zinc sulfate 1% with tinidazole topical vaginal paste^3,4 and was advised to use it along with another course of oral tinidazole 2 g daily for 14 days. Post high-dose tinidazole plus topical zinc sulfate, she remained symptomatic and her vaginal TV NAAT was positive, so another CDC kit (TV InPouch™) was sent six weeks after the first one. This test revealed TV with very high-level resistance to metronidazole (MIC >400 µg/ml) and tinidazole (MIC >200 µg/ml). CDC recommended a higher dose of tinidazole and intra-vaginal paromomycin.⁵ She was already taking higher-dose tinidazole, and hence we added intra-vaginal paromomycin 500 mg daily for 21 days. This resulted in severe vaginal irritation after two days of use, and hence paromomycin was stopped. She was prescribed intra-vaginal boric acid suppositories 600 mg daily for three months.⁶ At follow-up, her vaginal discharge had decreased on boric acid but not completely resolved. Her vaginal TV NAAT was still positive. Given her history of gastric bypass surgery, there was concern of decreased oral absorption of medications. Intravenous (IV) metronidazole is considered to achieve higher serum and tissue concentrations.^7,8 She was given IV metronidazole 500 mg every 8 h for 14 days along with intra-vaginal boric acid 600 mg daily.^7,8 The patient reported that she became symptom free while on IV metronidazole, but once the course finished, her vaginal discharge came back. Her vaginal TV NAAT was still positive. The patient always had nausea with tinidazole pills, despite taking anti-nausea medications, and she was not willing to try another course of pills. We continued IV metronidazole for another week, continued intra-vaginal boric acid 600 mg daily and added liquid tinidazole 2 g daily for 14 days. A 67 mg/mL tinidazole suspension can be made with tablets and cherry syrup, by crushing four 500 mg tablets to a fine powder and adding 10 mL cherry syrup to form a uniform paste. On completion of this regimen, she was asymptomatic and her vaginal NAAT and TV InPouch test finally became negative. At two-month follow-up, she remained asymptomatic and had negative urine and vaginal TV NAAT (Table 1).

Table 1.

List of consecutive TV treatments.

Oral metronidazole 2 g × 1

Oral metronidazole 2 g daily × 14 days

Oral tinidazole 2 g daily PLUS intra-vaginal metronidazole 0.75% daily × 14 days

Oral tinidazole 2 g daily PLUS intra-vaginal zinc sulfate 1% with tinidazole paste daily × 14 days

Oral tinidazole 2 g daily PLUS intra-vaginal paromomycin 500 mg daily × 14 days (intra-vaginal paromomycin stopped after 2 days of use due to vaginal irritation)

Intra-vaginal boric acid 600 mg daily × 90 days

Intravenous metronidazole 500 mg every eight hours PLUS intra-vaginal boric acid 600 mg daily × 14 days

Intravenous metronidazole 500 mg every eight hours × 7 days PLUS oral liquid tinidazole 2 g daily PLUS intra-vaginal boric acid 600 mg daily × 14 days

Discussion

Failure with traditional treatment regimens for TV is generally due to lack of routine testing, partner’s non-compliance with medication or acquisition of new infection and drug resistance.⁹ Metronidazole resistance occurs in 4%–10% of isolates and tinidazole resistance in 1%.^10,11 Generally, in vitro resistance to metronidazole correlates poorly with clinical response. In a study of TV isolates from females who failed standard therapy twice, 66% of strains had some metronidazole resistance, and 32% of these strains had high-level resistance.¹² Tinidazole resistance is similar to metronidazole resistance. Treatment options for metronidazole- and tinidazole-resistant TV are high-dose tinidazole 2 g daily and tinidazole vaginal tablets for 14 days. Some studies show benefit with intra-vaginal paromomycin and boric acid.¹³ Our patient had reliable compliance with medication and had no new sexual partners. She had taken high-dose tinidazole and intra-vaginal paromomycin and boric acid but continued to be symptomatic and tested positive for TV. She had history of Roux-en-Y gastric bypass, which could potentially decrease intestinal absorption. We used IV metronidazole 500 mg every eight hours for better efficacy.^7,8 Liquid oral tinidazole 2 g daily was used to avoid intense nausea and vomiting caused by the pills. IV metronidazole along with liquid oral tinidazole for 14 days plus intra-vaginal boric acid can be a treatment option in patients with highly-resistant TV with gastric bypass surgery. Data are lacking, as there is no current study with this combination of treatment, but we think this can be offered as an alternative regimen in refractory trichomoniasis cases. Further clinical trials are imperative.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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