Abstract
Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in a vulvo-vaginitis and altered vaginal discharge in symptomatic women. Since its introduction in the 1960 s, metronidazole has been the first-line drug for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or reinfection, although metronidazole resistance has previously been documented. Sensitivity testing is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. This case looks at a patient with refractory disease over an 18-month period, where intravenous infusion of metronidazole resulted in cure after multiple previous therapy failures. There is limited evidence to endorse the use of intravenous metronidazole, and this case report provides further support for its efficacy.
Treatment history.
IV: Intravenous.
Subsequent treatment regimens included azithromycin followed by a further two-week course of metronidazole at 400 mg PO TDS with 1 g OD per rectum, and then metronidazole gel PV (40 g nocte five days), alongside oral treatment of 2 g for five days. Following no improvement, tinidazole 2 g BD was given for 14 days, preceded by a two-week course of doxycycline (100 mg BD). This led to a brief, four-day resolution in symptoms after which time a recurrence occurred as confirmed by wet mount microscopy. A repeat course of tinidazole for two weeks (2 g BD) was given alongside a two-week course of erythromycin (500 mg BD) and fluconazole (150 mg weekly). This was followed by a further four-week course of tinidazole at 500 mg QDS, with amoxicillin (500 mg TDS one week) preceding this. During this period she also used lactic acid pessaries on a nightly basis.
Understandably at this time, a year after her initial presentation, the patient was frustrated by her poor response to treatment. Factors implicated in resistant TV include low serum zinc concentrations, inactivation of metronidazole by vaginal bacteria and ineffective delivery of drug to the vagina. Vaginal preparations achieve lower cure rates, which may be due to poor absorption into the serum thus leading to sub-therapeutic delivery to infected glands. 3 In this patient, zinc levels were found to be within normal limits, and empirical antibiotics were given prior to nitroimidazole treatment to minimise the influence of other vaginal bacteria.
Further expert opinion was sought nationally, and alternative approaches were considered. Literature for the prolonged use of high-dose tinidazole (3 g BD for two weeks) was limited, and concerns were raised with possible adverse outcomes of seizures, peripheral neuropathy and blood dyscrasia. Evidence supporting the use of nitazoxanide, an anti-protozoal agent used in the treatment of Cryptosporidium parvum or Giardia lamblia, was in vitro only. 3 Diloxanide, a luminal amoebicide used in the treatment of amoebiasis, was another agent considered. However, there was no literature supporting its use in trichomoniasis and, therefore, funding was not warranted. Intravaginal boric acid has been used in patients with TV infection who are either unable to take first-line medication due to severe nitroimidazole allergy 4 or are resistant to standard treatment. 5 In these cases, extended topical treatment was given for 1–2 months resulting in cure. Prolonged use of boric acid pessaries has been associated with a number of side effects including seizures, anaemia, hair loss and anorexia, 6 and following discussion with the patient was not deemed appropriate as the next line of treatment. A literature review revealed some success in patients using povidone-iodine (Betadine) douches,7,8 and these appeared to be generally well tolerated. They were subsequently prescribed at a dose of 30 ml PV OD for 30 days. This was followed by a repeat course over 60 days. Disappointingly, this led to no improvement, and microscopy and culture remained positive.
With options now limited, the decision was taken to admit to hospital to receive IV metronidazole at a dose of 500 mg TDS, along with metronidazole vaginal gel BD for one week. Side effects from treatment included nausea and migraine, for which propranolol was prescribed. After one day in hospital, the patient was tolerating the treatment, and the rest of the IV metronidazole was administered at home by trained nurses (outpatient parenteral antibiotic therapy).
At review, there had been a significant improvement in symptoms and negative microscopy and culture for TV on four occasions up until three months’ post treatment.
IV treatment and hospital admission in this case were not ideal due to difficult social circumstances but were deemed necessary after failing to find an effective oral or topical alternative. Although rare, refractory TV poses a difficult clinical challenge and IV metronidazole may be successful in achieving cure where other regimens have failed.
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.