Recalcitrant Vaginal Trichomoniasis Sex Transm Infect: First Published As 10.1136/Sti.75.2.127 on 1 April 1999

Sex Transm Inf 1999;75:127–128 127

Recalcitrant vaginal trichomoniasis Sex Transm Infect: first published as 10.1136/sti.75.2.127 on 1 April 1999. Downloaded from Clinical R S Pattman knots

As Trichomonas vaginalis infects the urethra, successes are prejudiced by the possibility of a Bartholin’s and Skene’s glands, as well as the coincidental spontaneous resolution. vagina systemic treatment for trichomoniasis is The size of the problem is diYcult to estab- recommended. The only group of drugs with lish although in 1989 a British Cooperative safe, proved, systemic eYcacy is the imidazoles Clinical Group study identified 24 contempo- and the most widely used agent is metronida- rary resistant cases from 18 diVerent centres in zole. When antimicrobial resistance arises it is the United Kingdom (although not all centres likely to be shared across the group.1 Metroni- participated).4 A variety of therapeutic regi- dazole resistant strains have only been reported mens were described. In the same year in the in patients who have already received treatment United States the Centers for Disease Control5 with this drug. It is therefore most important estimated that 5% of all T vaginalis isolates dis- that at presentation women are given a regimen played some level of resistance to metronida- which maximises the likelihood of achieving zole. The largest recent series (three cases) was 6 therapeutic levels supported by thorough part- reported in 1997 by Lewis et al, all with diVer- ner notification to limit the need to provide ent therapeutic outcomes. further treatment. As resistance may be relative rather than The failure of women with vaginal trichomo- absolute most clinicians would persist with niasis to respond to metronidazole is not imidazoles in high dosage which may include uncommon and in most cases probably results oral, topical, and intravenous preparations, from a failure to take the medication as advised often in combination. Some success has been or reinfection from an untreated, usually reported by using metronidazole in this way asymptomatic, male sexual partner. The although changing imidazoles is generally disulfiram-like reaction with alcohol is likely to favoured. Tinidazole appears to be the pre- compromise adherence so the 2 g single dose ferred option although niridazole has been postulated as being a useful alternative as it is treatment may achieve better results in cases of unaVected by oxygen in aerobic assays. How- poor compliance, whereas the 7 day treatment ever, in clinical practice the results have been (400 mg or 500 mg twice a day) is better if disappointing. reinfection is likely to arise before a contact can The management of persistent cases there-

be treated. Therapeutic levels of the drug may http://sti.bmj.com/ after tends to be idiosyncratic and lacks be related to the patient’s weight so considera- consistency. For every report of apparent tion should be given to higher dosage regimens success, assuming that spontaneous resolution in the obese patient. In early cases of has not occurred, there are documented cases persistence the possibility of metronidazole of failure using similar regimens and no one inactivation by vaginal aerobic and anaerobic 2 has collected enough cases to draw any mean- bacteria should be covered by prescribing a ingful conclusions. There are also no systemic on October 2, 2021 by guest. Protected copyright. combination of either amoxycillin or erythro- alternatives so the eVect of the available topical mycin with high dose metronidazole or by sub- medications will be limited. Experimental in stituting an alternative imidazole such as vitro eYcacy does not mean that an agent will tinidazole. Although rare the possibility of a 3 have any beneﬁt in resistant cases. low plasma zinc level should also be consid- Clinicians faced with the problem of intran- ered as imidazole re-treatment with an oral zinc sigent vaginitis unresponsive to high dose imi- supplement may be curative. dazoles have reported some apparent success Metronidazole resistance is the most likely with treatments used before the introduction of cause of treatment failure thereafter and strains metronidazole. These include paromomycin, sent for sensitivity testing from such cases are which needs to be prepared in a cream for invariably resistant to metronidazole in aerobic intravaginal administration at a dose of 250 mg culture (personal communication, no longer daily for 5–14 days, arsenic pessaries (acetar- routinely available through the Public Health sol) 500 mg daily for 10 days, zinc sulphate Laboratory Service). Unlike other infections douches (1%) in combination with metronida- metronidazole resistant trichomoniasis has zole, and povidone iodine as a douche or in never been reported arising in population clus- combination with metronidazole as a pessary. Department of ters and always appears to be preceded by prior Genitourinary The serendipitous resolution of resistant infec- Medicine, Newcastle imidazole medication, usually on several occa- tion after a woman started using condoms with General Hospital, sions. The resistance mechanism is unclear but a single 100 mg nonoxynol-9 pessary suggests Newcastle upon Tyne may have an idiosyncratic basis. This means that this may be a further therapeutic option. In NE4 6BE that no single author or centre has suYcient other studies both nonoxynol-9 and povidone R S Pattman experience to recommend satisfactory evi- iodine have provided symptomatic relief to Accepted for publication denced based measures to manage such cases women with trichomonal vulvovaginitis with- 11 February 1999 and many case reports of alleged treatment out eradicating the infection (see ﬁg 1). 128 Pattman

T vaginalis.7 Furazolidone is available in Oral metronidazole Germany as a vaginal pessary but information Retreat, alter 2 g single dose regimen if on its value in resistant trichomoniasis is or necessary. limited. Mebendazole, when prepared as a Sex Transm Infect: first published as 10.1136/sti.75.2.127 on 1 April 1999. Downloaded from 400 or 500 mg twice Treat partners(s) vaginal preparation, has proved unsuccessful in daily for 5—7 days established metronidazole resistant cases. Other measures documented include the use of inactivated lactobacilli as a vaccine, with Adherence failure generally a poor response and the withdrawal Reinfection of oestrogen replacement treatment in a post menopausal woman. Hydrogen peroxide pro- ducing lactobacilli have no protective ability Exclude low plasma zinc against trichomoniasis unlike bacterial vagino- sis so local measures aimed at altering the local Oral metronidazole 400 mg three times daily for 7—10 days bacterial ﬂora are unlikely to be successful. or 2 g daily for 3—5 days. Consider combining with: Finally, researchers have examined other oral amoxycillin 250 mg three times daily for 5—7 days or agents in animal and in vitro experiments oral erythromycin 250 mg four times daily for 5—7 days although there do not appear to be any practi- cal developments. These agents include pyrazoles,8 geneticin9 (an aminoglycoside lethal to swine at minimum therapeutic doses), and Azole alternative usually at increased dosage hamycin10 (a polyene with cytotoxic side eVects). Tinidazole systemic and topical (various regimens) ? Niridazole (unaffected by oxygen in aerobic assay) The problem of antibiotic resistance, so well recognised in bacterial infection, does not receive the same prominence when dealing with protozoan infections, where basic therapeutic options are much more limited. For Documented "cures" people with metronidazole resistant trichomoniasis or who are unable to take this group of Acetarsol pessaries Theoretical or ameliorating Nonoxynol-9 pessaries remedies drugs there is a clear need for a safe, systemic, Paromomycin in cream non-imidazole based alternative. Povidone iodine douches Fenticonazole pessaries Zinc sulphate douches with Furazolidone pessaries 1 Meingassner JG, Thurner J. Strain of Trichomonas vagina- oral/topical metronidazole Nonoxynol-9 pessaries lis resistant to metronidazole and other 5-nitromidazoles. Inactivated Lactobacillus Povidone iodine pessaries Antimicrob Agents Chemother 1979;15:254–7. vaccination 2 Ralph ED, Clarke DA. Inactivation of metronidazole by anaerobic and aerobic bacteria. Antimicrob Agents Chemo- Cessation of oestrogen ther 1978;14:377–83. replacement therapy 3 Willmott F, Say J, Downey D, et al. Zinc and recalcitrant trichomoniasis. Lancet 1983;i:1053. http://sti.bmj.com/ 4 British Co-operative Clinical Group. An investigation, by Figure 1 Management of recalcitrant vaginal trichomoniasis. questionnaire, of cases of recalcitrant vaginal trichomoniasis seen in genitourinary medicine clinics in the United Topical azoles (clotrimazole, butaconazole, Kingdom. Int J STD AIDS 1992;3:24–7. 5 Centers for Disease Control website. www.cdc.gov and fenticonazole), marketed for yeast and 6 Lewis DA, Habgood L, White R, et al. Managing vaginal tri- fungal infections, have been suggested as they chomoniasis resistant to high-dose metronidazole therapy. Int J STD AIDS 1997;8:780–4. have shown some activity in non-resistant 7 Sears SD, O’Hare J. In vitro susceptibility of Trichomonas trichomoniasis. However, when used in resist- vaginalis to 50 antimicrobial agents. Antimicrob Agents on October 2, 2021 by guest. Protected copyright. Chemother 1988;32:144–6. ant cases the response has been generally poor 8 Escario JA, Igea AM, Contreras M, et al. Antiparasitic activ- although they may provide some symptomatic ity of nine pyrazole derivatives against Trichomonas vaginalis, Entamoeba invadens and Plasmodium berghei. relief. Annals Trop Med Parasitol 1988;82:257–62. Mebendazole and furazolidone are antipro- 9 Riley DE, Krieger JN. Kinetics of killing or growth of Trichomonas vaginalis in the presence of aminoglycosides, tozoal agents used primarily for bowel infec- neomycin and geneticin (G418). Int J Antimicrob Agents tions as they are not absorbed by the 1996;7:257–9. 10 Lushbaugh WB, Cleary JD, Finley RW. Cytotoxicity of gastrointestinal tract. In vitro studies have hamycin for Trichomonas vaginalis, HeLa and BHK-21. J shown eYcacy against metronidazole resistant Antimicrob Chemother 1995;36:795–802.