Is there literature supporting the administration of metronidazole 2000 mg IV once for the treatment of Trichomoniasis?

Comment by InpharmD Researcher

No clinical literature was identified supporting administration of metronidazole 2000 mg intravenous (IV) once for the treatment of trichomoniasis. Available evidence consistently describes the 2 g dose in the context of oral single-dose therapy, while IV use is derived from older descriptive literature or utilized in multidose salvage regimens or desensitization protocols rather than as a single-dose strategy.

Background

Metronidazole and tinidazole are the primary agents used for treatment of trichomoniasis, with standard regimens consisting of either a single 2 g dose or multidose therapy administered orally. Intravenous (IV) administration is noted as a potential alternative route when oral therapy is not feasible; however, specific IV dosing strategies or the clinical circumstances under which IV use should be employed are not described. [1], [2]

A 2004 narrative review on the microbiology, pharmacology, and treatment of Trichomonas vaginalis infection describes metronidazole as the primary systemic therapy, typically administered as oral single-dose or multidose regimens. Within this discussion, IV administration is noted, including doses of 500 mg to 2 g infused over approximately 20 minutes, with reported cure rates of 85% to 95% for both oral and IV regimens; however, these IV dosing details are derived from older referenced literature rather than contemporary treatment data. [3], [4]

Studies describe IV use of metronidazole within desensitization protocols. IV metronidazole has been administered using incremental dosing at 15 to 20 minute intervals, beginning at 0.005 mg and increasing stepwise (0.005 mg, 0.015 mg, 0.05 mg, 0.15 mg, 0.5 mg, 1.5 mg, 5 mg, 15 mg, 30 mg, 60 mg, 125 mg, 250 mg, 500 mg) to a final cumulative dose of 2 g, with reported clinical and microbiologic cure following completion of therapy. Importantly, these protocols involve gradual dose increases under close monitoring rather than administration of a single 2 g dose. [5], [6]

Although not specific to an intravenous single dose for trichomoniasis, available evidence from oral regimens and pharmacokinetic data may provide relevant context. A randomized trial demonstrated that a single 2 g oral dose resulted in higher rates of persistent infection compared with multidose therapy (19% vs 11%; risk ratio [RR] 0.55), and a meta-analysis found treatment failure was approximately 1.8 to 1.9 times more likely with single-dose therapy. Of note, metronidazole administered orally or intravenously has a bioavailability of approximately 93% to 100% and a half-life of approximately 8.7 hours with linear elimination. A single 2 g dose achieves concentrations above the minimum lethal concentration for up to 24 to 48 hours, followed by declining concentrations, whereas multidose regimens maintain concentrations above this threshold with each subsequent dose; however, these data are derived from in vitro pharmacodynamic studies and do not evaluate clinical outcomes for IV use. [7], [8], [9]

References: [1] Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015 Aug 28;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137.
[2] Meites E, Gaydos CA, Hobbs MM, et al. A Review of Evidence-Based Care of Symptomatic Trichomoniasis and Asymptomatic Trichomonas vaginalis Infections. Clin Infect Dis. 2015;61 Suppl 8(Suppl 8):S837-S848. doi:10.1093/cid/civ738
[3] Cudmore SL, Delgaty KL, Hayward-McClelland SF, Petrin DP, Garber GE. Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis. Clin Microbiol Rev. 2004;17(4):783-793. doi:10.1128/CMR.17.4.783-793.2004
[4] Lossick JG. Treatment of sexually transmitted vaginosis/vaginitis. Rev Infect Dis. 1990;12 Suppl 6:S665-S681. doi:10.1093/clinids/12.supplement_6.s665
[5] Van Gerwen OT, Camino AF, Bourla LN, Legendre D, Muzny CA. Management of Trichomoniasis in the Setting of 5-Nitroimidazole Hypersensitivity. Sex Transm Dis. 2021;48(8):e111-e115. doi:10.1097/OLQ.0000000000001326
[6] Helms DJ, Mosure DJ, Secor WE, Workowski KA. Management of trichomonas vaginalis in women with suspected metronidazole hypersensitivity. Am J Obstet Gynecol. 2008;198(4):370.e1-370.e3707. doi:10.1016/j.ajog.2007.10.795
[7] Kissinger P, Muzny CA, Mena LA, et al. Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis in women: an open-label, randomised controlled trial. Lancet Infect Dis. 2018;18(11):1251-1259. doi:10.1016/S1473-3099(18)30423-7
[8] Howe K, Kissinger PJ. Single-Dose Compared With Multidose Metronidazole for the Treatment of Trichomoniasis in Women: A Meta-Analysis. Sex Transm Dis. 2017;44(1):29-34. doi:10.1097/OLQ.0000000000000537
[9] Cudmore SL, Delgaty KL, Hayward-McClelland SF, Petrin DP, Garber GE. Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis. Clin Microbiol Rev. 2004;17(4):783-793. doi:10.1128/CMR.17.4.783-793.2004
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there literature supporting the administration of metronidazole 2000 mg IV once for the treatment of Trichomoniasis?

Level of evidence

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Please see Tables 1-2 for your response.


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

Design

Case report

Case Presentation

A 37-year-old female presented to the clinic with persistent Trichomonas vaginalis (TV). She was HIV negative, not pregnant, and had a medical history of obesity treated with gastric bypass surgery.

Due to her history of gastric bypass surgery, there was a concern of decreased oral absorption of medications. She was given IV metronidazole 500 mg every 8 hours for 14 days along with intravaginal boric acid 600 mg daily. The patient reported that she became symptom-free while on IV metronidazole, but once the course finished, her vaginal discharge came back. Her vaginal nucleic acid amplification test (NAAT) was positive for TV. She reported being nauseous with tinidazole pills, despite taking anti-nausea medications, and not willing to try another course of pills.

IV metronidazole was continued for another week along with continued intravaginal boric acid 600 mg daily, and liquid tinidazole 2 g daily for 14 days was added. A 67 mg/mL tinidazole suspension was 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.

Once this regimen was completed, she was asymptomatic and her vaginal NAAT was negative. At two month follow-up, she remained asymptomatic and had a negative urine and vaginal TV NAAT.

Study Author Conclusions

Intravenous 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 treatment, but this can be offered as an alternative regimen in refractory trichomoniasis cases.

The authors report that a tinidazole suspension can be made by crushing four 500 mg tablets and adding them to 10 mL of cherry syrup.

References:
[1] Butt S, Tirmizi A. Intravenous metronidazole, liquid tinidazole, and intra-vaginal boric acid to cure trichomonas in a patient with gastric bypass surgery. Int J STD AIDS. 2018;29(8):825-827

Resistance of Trichomonas vaginalis to metronidazole: report of the first three cases from Finland and optimization of in vitro susceptibility testing under various oxygen concentrations

Design

Case series

Case presentation

The 2000 study reports three cases of metronidazole-resistant Trichomonas vaginalis infection in Finland and includes both in vitro susceptibility testing and clinical treatment data. While the primary focus of the study was characterization of resistance using minimum inhibitory concentrations (MICs) and minimum lethal concentration (MLC) measurements under varying oxygen conditions, it also describes patient-level treatment outcomes.

In all three cases, patients experienced persistent infection despite multiple courses of oral metronidazole and were subsequently treated with intravenous (IV) metronidazole using multidose regimens (e.g., 1 g/day for 3 days, 500 mg four times daily for 7 days, and 750 mg three times daily for 5 days), resulting in symptom resolution and negative follow-up cultures. These findings demonstrate that IV metronidazole has been used as a salvage approach in refractory trichomoniasis.

Study Author Conclusions

It appears that the metronidazole resistance of T. vaginalis is an emerging threat in Europe. Thus, testing for metronidazole susceptibility in vitro and introduction of rapid and intense medication should be implemented more often.
References:
[1] [1] Meri T, Jokiranta TS, Suhonen L, Meri S. Resistance of Trichomonas vaginalis to metronidazole: report of the first three cases from Finland and optimization of in vitro susceptibility testing under various oxygen concentrations. J Clin Microbiol. 2000;38(2):763-767. doi:10.1128/JCM.38.2.763-767.2000