Management of Trichomonas vaginalis in women with suspected metronidazole hypersensitivity

Results 

Provider characteristics 

From September 1, 2003-September 30, 2006, 127 providers requested consultation in managing women with trichomonas infection and suspected metronidazole hypersensitivity. The women were seen by a variety of providers in a variety of clinical settings and diverse geographic areas (Table 2). Fifty percent of providers requesting consultation had witnessed a hypersensitivity reaction. Fifty-nine of the 127 providers (47%) returned follow-up information (Table 2). Providers were more likely to return follow-up information on women in whom they had directly observed the suspected hypersensitivity reaction than from women who had self-reported or were referred after experiencing a hypersensitivity reaction (59% vs 35%).

TABLE 2. Characteristics of providers who requested consultation on management of Trichomonas vaginalis and possible metronidazole allergy and characteristics of their patients, 2003-2006

		Initial call		Follow-upa
		n	(%)b	n	n/N (%)
	Total	127	100.0	59	46.5
	Provider characteristics
	Provider
	Physician	56	44.1	26	46.4
	Nurse practitioner	28	22.0	15	53.6
	Nurse	6	4.7	2	33.3
	Physician’s assistant	5	3.9	3	60.0
	Other	32	25.2	13	40.6
	Type of facility
	Corrections	4	3.1	3	75.0
	Hospital	16	12.6	6	37.5
	Infectious disease	5	3.9	3	60.0
	Obstetrics/gynecology	30	23.6	10	33.3
	Private practice	38	29.9	22	57.9
	Public clinic	26	20.5	11	42.3
	Other	8	6.3	4	50.0
	Regionc
	Midwest	28	22.0	11	39.3
	Northeast	10	7.9	7	70.0
	South	69	54.3	30	43.5
	West	19	15.0	10	52.6
	Referrald
	Yes	63	49.6	22	34.9
	No	64	50.4	37	59.1
	Patient characteristics
	Reported hypersensitive reactionse
	Anaphylaxis	11	6.9	2	18.2
	Erythematous rash	10	6.3	7	70.0
	Facial edema	18	11.3	8	44.4
	Gastrointestinal intolerance	9	5.7	5	55.6
	Pruritus	16	10.0	10	62.5
	Urticaria	74	46.5	31	41.9
	Otherf	21	13.2	9	42.9

Helms. Management of Trichomonas vaginalis in metronidazole hypersensitivity. Am J Obstet Gynecol 2008.

a Follow-up refers to whether a provider returned any follow-up information on the patient after assistance from the CDC. b Percentages may not always add to 100, based on missing data. c Based on U.S. census regions. d Woman self-reported hypersensitivity or was referred to provider after initial hypersensitive reaction. e Can have more than 1 reported reaction. f Other includes flushing, shortness of breath, general swelling, dizziness, Stevens-Johnson syndrome, and seizure.

Response to metronidazole desensitization 

Fifty-nine women had follow-up information available; 41 women were treated following consultation, and 18 women were not treated (Figure). Reasons that were provided for not receiving treatment included initial treatment cure, being transferred or released from a correctional facility, the cost associated with the desensitization procedure, or the lack of resources to monitor the patient during the desensitization procedure.

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FIGURE. Flow chart of women for whom follow-up information was provided Final treatment outcome information was available for 34 of the women (58%). Microbiologic cure indicates that women were negative for T. vaginalis by wet mount or culture on the follow-up visit after treatment. Clinical cure indicates that women had no symptoms of trichomoniasis at the follow-up visit. Helms. Management of Trichomonas vaginalis in metronidazole hypersensitivity. Am J Obstet Gynecol 2008.

Fifteen of the 41 women (37%) were treated using either the oral (8 women) or IV (7 women) metronidazole desensitization regimens (Figure). All fifteen of these women (100%) were cured (3 microbiologic, 9 suspected microbiologic, 3 clinical) with minimal to no side effects. One woman who received oral metronidazole desensitization experienced a pruritic rash on the final day and was administered steroids with resolution of the rash. One woman who received IV metronidazole desensitization experienced mild urticaria and pruritus 45 minutes following the final 2-g dose and was managed with Benadryl and displayed prompt resolution of symptoms.

Comment 

This evaluation sought to better document the effectiveness of treatment options used for management of women with metronidazole hypersensitivity. There are few published alternatives for treatment of trichomonas infection, and there have been only a few case reports of effective metronidazole desensitization for women with metronidazole hypersensitivity.13, 14 Intravaginal alternatives have not been well studied and can be associated with adverse reactions.15, 17, 18, 19, 20 Thus, to evaluate the quality of our treatment recommendations for metronidazole-hypersensitive women with trichomoniasis, we collected data on treatment outcomes from their health providers. We found that the oral and IV metronidazole desensitization regimens were 100% effective (15 of 15) in the management of trichomonas infection in women with nitroimidazole hypersensitivity. Nitroimidazole desensitization was associated with minor adverse reactions in 2 women but was effectively managed with antihistamines and steroids, similar to the limited adverse reaction previously described in the oral desensitization case study.13

Many of the providers who sought consultation chose not to utilize the desensitization regimens. The providers’ decisions to use alternative therapies included the cost of IV desensitization, lack of facilities to monitor desensitization, and the inability to obtain approval from the supervisory physician to authorize the procedure. Treatment effectiveness was achieved in only 5 of 12 women (42%) who received alternative intravaginal treatment regimens, all of whom had suspected microbiologic cure. Of these, 3 of the 4 of the women treated with Betadine douches were cleared of infection. However, no standard dose or duration of the topical Betadine was used. Previous reports documented some effectiveness of Betadine douche or povidone-iodine pessaries.15, 21 There is also evidence that Betadine may be effective against T vaginalis in vitro (W. E. Secor, unpublished data).

In this evaluation, intravaginal paromomycin was effective in eradicating trichomonas infection in only 1 of 4 women but was associated with vaginal ulceration, consistent with the adverse reaction described in a previous case report.22 Paromomycin is an aminocyclitol antibiotic that is applied intravaginally because it is not absorbed by the gastrointestinal tract. Nyirjesy et al22 reported that using paromomycin intravaginally for 2 weeks in women with metronidazole hypersensitivity was effective in 6 of 9 women, although 1 woman experienced a relapse 2 weeks after treatment.

Only 1 of the 3 women treated with clotrimazole demonstrated suspected microbiologic cure of her trichomonas infection, which is similar to other studies.19, 23, 24 A recent multicenter trial documented a 11% success rate in women treated with clotrimazole.23

Neither furazolidone (2 patients) nor acetarsol (1 patient) appeared effective for treatment of trichomoniasis in women with metronidazole hypersensitivity in the current evaluation. Furazolidone is a nitrofuran and a potent monoamine oxidase inhibitor, and its in vitro effectiveness against T vaginalis has been documented.25, 26 Our findings were inconsistent with another study in which treatment with intravaginal furazolidone demonstrated clearance of trichomonas infection within 72 hours in 45 of 48 women, with only 3 patients experiencing further symptoms in the following 1-3 months.27 Acetarsol is an arsenical compound and has demonstrated effectiveness as well as treatment failure.20, 28 Acetarsol has been associated with vaginal irritation and a generalized rash.

A limitation to this evaluation is the inconsistent method used for the diagnostic testing to define cure. This evaluation had to rely heavily on what diagnostic methods clinicians had available. Wet mount has a sensitivity of 40-80% and is the most commonly used method of diagnosis in the clinic setting. It relies on visual detection of viable organisms with characteristic motility, size, and morphology.29 Few providers had the availability to perform culture. Currently culture is the gold standard for diagnosis because of its higher sensitivity (up to 95%).29 Only 3 women’s cures were based on a negative culture. It is possible that as many as 50% of the women with apparent microbiologic cures may not have been completely cleared of infection because of the insensitivity of wet mount to define treatment outcome.

We were unable to obtain information on time between treatment and follow-up. Although we recommended clinical assessment occur 3 weeks following treatment, few clinicians provided this information. If the assessment of cure was performed too early, it may be that some women with apparent microbiologic cure may have had a residual infection. Nevertheless, the incremental dosing protocols consistently achieved clinical and/or apparent microbiologic cure in a manner that was safe for women with suspected hypersensitivity to metronidazole.

This evaluation most likely underrepresents the number of women experiencing metronidazole hypersensitivity and is limited by its passive inclusion strategy. The evaluation began as a response to consultation requests from providers caring for women with suspected metronidazole hypersensitivity. Because of a small sample size of women in this evaluation, the success rate may not be generalizable to a larger population. However, this evaluation appears to be the largest case series that examines the treatment options for women with suspected metronidazole hypersensitivity. In addition, the success of the desensitization for women shows that it is a safer method for treating women with hypersensitivity to metronidazole.

Overall, this evaluation confirmed that the oral and IV metronidazole incremental dosing protocols are effective in the management of trichomonas infection in women with hypersensitivity to nitroimidazoles. Although treatment with alternative drugs had some success, topical therapies appear less effective than metronidazole desensitization. Nevertheless, the development of new, nonnitroimidazole oral alternatives for the management of women with trichomoniasis and metronidazole hypersensitivity remains a need for the effective management of the disease.