Abnormal vaginal discharge: What does and does not work in treating underlying causes

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Applied Evidence

Abnormal vaginal discharge: What does and does not work in treating underlying causes

J Fam Pract. 2004 November;53(11):890-894

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References

1. Hillier SL, Lipinski C, Briselden AM, Eschenbach DA. Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis. Obstet Gynecol 1993;81:963-967.

2. Hanson JM, McGregor JA, Hillier SL, et al. Metronidazole for bacterial vaginosis. A comparison of vaginal gel vs. oral therapy. J Reprod Med 2000;45:889-896.

3. Lugo-Miro VI, Green M, Mazur L. Comparison of different metronidazole therapeutic regimens for bacterial vaginosis. A meta-analysis. JAMA 1992;268:92-95.

4. Ferris DG, Litaker MS, Woodward L, Mathis D, Hendrich J. Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J Fam Pract 1995;41:443-449.

5. Fischbach F, Petersen EE, Weissenbacher ER, Martius J, Hosmann J, Mayer H. Efficacy of clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis. Obstet Gynecol 1993;82:405-410.

6. Hillier S, Krohn MA, Watts DH, Wolner-Hanssen P, Eschenbach D. Microbiologic efficacy of intravaginal clindamycin cream for the treatment of bacterial vaginosis. Obstet Gynecol 1990;76:407-413.

7. Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial. Lancet 2003;361:983-988.

8. Mikamo H, Kawazoe K, Izumi K, Watanabe K, Ueno K, Tamaya T. Comparative study on vaginal or oral treatment of bacterial vaginosis. Chemotherapy 1997;43:60-68.

9. Ahmed-Jushuf IH, Shahmanesh M, Arya OP. The treatment of bacterial vaginosis with a 3 day course of 2% clindamycin cream: results of a multicentre, double blind, placebo controlled trial. B V Investigators Group. Genitourin Med 1995;71:254-256.

10. Schmitt C, Sobel JD, Meriwether C. Bacterial vaginosis: treatment with clindamycin cream versus oral metronidazole. Obstet Gynecol 1992;79:1020-1023.

11. Paavonen J, Mangioni C, Martin MA, Wajszczuk CP. Vaginal clindamycin and oral metronidazole for bacterial vaginosis: a randomized trial. Obstet Gynecol 2000;96:256-260.

12. Puapermpoonsiri S, Watanabe K, Kato N, Ueno K. In vitro activities of 10 antimicrobial agents against bacterial vaginosis-associated anaerobic isolates from pregnant Japanese and Thai women. Antimicrob Agents Chemother 1997;41:2297-2299.

13. Sobel JD. Vaginitis. N Engl J Med 1997;337:1896-1903.

14. Shalev E, Battino S, Weiner E, Colodner R, Keness Y. Ingestion of yogurt containing Lactobacillus acidophilus compared with pasteurized yogurt as prophylaxis for recurrent candidal vaginitis and bacterial vaginosis. Arch Fam Med 1996;5:593-596.

15. Lamont RF, Jones BM, Mandal D, Hay PE, Sheehan M. The efficacy of vaginal clindamycin for the treatment of abnormal genital tract flora in pregnancy. Infect Dis Obstet Gynecol 2003;11:181-189.

16. Marrazzo J. Vulvovaginal candidiasis. BMJ 2002;325:586.

17. Emele FE, Fadahunsi AA, Anyiwo CE, Ogunleye O. A comparative clinical evaluation of econazole nitrate, miconazole, and nystatin in the treatment of vaginal candidiasis. West Afr J Med 2000;19:12-15.

18. Stein GE, Mummaw N. Placebo controlled trial of itraconazole for treatment of acute vaginal candidiasis. Antimicrob Agents Chemother 1993;37:89-92.

19. Van der Pas H, Peeters F, Janssens D, Snauwaert E, Van Cutsem J. Treatment of vaginal candidosis with oral ketoconazole. Eur J Obstet Gynecol Reprod Biol 1983;14:399-404.

20. Sanz Sanz F, del Palacio Hernanz A. Randomized comparative trial of three regimens of itraconazole for treatment of vaginal mycoses. Rev Infect Dis 1987;9 Suppl 1:S139-S142.

21. Silva-Cruz A, Andrade L, Sobral L, Francisca A. Itraconazole versus placebo in the management of vaginal candidiasis. Int J Gynaecol Obstet 1991;36:229-232.

22. Watson MC, Grimshaw JM, Bond CM, Mollison J, Ludbrook A. Oral versus intravaginal imidazole and triazole anti-fungal agents for the treatment of uncomplicated vulvovaginal candidiasis (thrush): a systematic review. BJOG 2002;109:85-95.

23. van Heusden AM, Merkus HM, Corbeij RS, et al. Single-dose oral fluconazole versus single-dose topical miconazole for the treatment of acute vulvovaginal candidosis. Acta Obstet Gynecol Scand 1990;69:417-422.

24. Sobel JD. Vulvovaginitis. When Candida becomes a problem. Dermatol Clin 1998;16:763-768,xii.-

25. Sobel JD, Kapernick PS, Zervos M, et al. Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole. Am J Obstet Gynecol 2001;185:363-369.

26. Creatsas GC, Charalambidis VM, Zagotzidou EH, Anthopoulou HN, Michailidis DC, Aravantinos DI. Chronic or recurrent vaginal candidosis: short-term treatment and prophylaxis with itraconazole. Clin Ther 1993;15:662-671.

27. Horowitz BJ, Giaquinta D, Ito S. Evolving pathogens in vulvovaginal candidiasis: implications for patient care. J Clin Pharmacol 1992;32:248-255.

28. del Palacio A, Sanz F, Sanchez-Alor G, et al. Double-blind randomized dose-finding study in acute vulvovaginal can-didosis. Comparison of flutrimazole site-release cream (1, 2 and 4%) with placebo site-release vaginal cream. Mycoses 2000;43:355-365.

29. Singh S, Sobel JD, Bhargava P, Boikov D, Vazquez JA. Vaginitis due to Candida krusei: epidemiology, clinical aspects, and therapy. Clin Infect Dis 2002;35:1066-1070.

30. Cross EW, Park S, Perlin DS. Cross-Resistance of clinical isolates of Candida albicans and Candida glabrata to over-the-counter azoles used in the treatment of vaginitis. Microb Drug Resist 2000;6:155-161.

31. Sobel JD, Chaim W. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy. Clin Infect Dis 1997;24:649-652.

32. Forna F, Gulmezoglu AM. Interventions for treating trichomoniasis in women. Cochrane Database Syst Rev 2003(2);CD000218.

33. duBouchet L, McGregor JA, Ismail M, McCormack WM. A pilot study of metronidazole vaginal gel versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis. Sex Transm Dis 1998;25:176-179.

34. Tidwell BH, Lushbaugh WB, Laughlin MD, Cleary JD, Finley RW. A double-blind placebo-controlled trial of single-dose intravaginal versus single-dose oral metronidazole in the treatment of trichomonal vaginitis. J Infect Dis 1994;170:242-246.

35. Spence MR, Harwell TS, Davies MC, Smith JL. The minimum single oral metronidazole dose for treating trichomoniasis: a randomized, blinded study. Obstet Gynecol 1997;89:699-703.

36. Petrin D, Delgaty K, Bhatt R, Garber G. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev 1998;11:300-317.

37. Lossick JG, Kent HL. Trichomoniasis: trends in diagnosis and management. Am J Obstet Gynecol 1991;165:1217-1222.

38. Dombrowski MP, Sokol RJ, Brown WJ, Bronsteen RA. Intravenous therapy of metronidazole-resistant Trichomonas vaginalis. Obstet Gynecol 1987;69:524-525.

39. Pearlman MD, Yashar C, Ernst S, Solomon W. An incremental dosing protocol for women with severe vaginal trichomoniasis and adverse reaction to metronidazole. Am J Obstet Gynecol 1996;174:934-936.

40. Nyirjesy P, Sobel JD, Weitz MV, Leaman DJ, Gelone SP. Difficult-to-treat trichomoniasis: results with paromomycin cream. Clin Infect Dis. 1998;26:986-988.

41. Sobel JD, Nyirjesy P, Brown W. Tinidazole therapy for metronidazole resistant vaginal trichomoniasis. Clin Infect Dis 2001;33:1341-1346.

Oral treatments are popular, most commonly a single dose of fluconazole. Oral itraconazole and ketoconazole have also been used successfully (SOR: A).^18-21 A systematic review of oral vs vaginal azoles showed similar efficacy, but more side effects occurred with oral therapy (SOR: A).²² Gastrointestinal side effects occur in up to 15% of women.²³

TABLE

Antifungal medications used to treat vulvovaginal candidiasis

Generic name	Trade name	Dose	Duration	Cost per course of treatment*
Over the counter
Butoconazole 2% cream	Femstat-3 Mycelex-3 generic	5 g every night	3 days	$5–$34
Clotrimazole 1% cream	Mycelex-7 generic	5 g every night	7–10 days	$2–$7
Clotrimazole 200 mg suppository	Gyne-Lotrimin generic	1 every night	3 days	$2–$9
Miconazole 100 mg suppository	Monistat generic	1 every night	7 days	$2–$14
Miconazole 2% cream	Monistat generic	5 g every night	7–10 days	$2–$11
Miconazole 200 mg suppository	Monistat-3	1 every night	3 days	$3–$22
Miconazole 100 mg suppository plus 2% external cream	Gyne-Lotrimin generic	1 every night	5 days	$5–$12
Tioconazole 6.5% ointment	Vagistat-1 generic	4.6 g	1 day	$2–$19
Prescription
Econazole 1% cream	Spectazole	5 g	3–6 days	$18 for 15 g $31 for 30 g
Terconazole 0.4% cream	Terazol-7	5 g	7 days	$41
Terconazole 0.8% cream	Terazol-3	5 g	3 days	$41
Terconazole 80 mg suppository	Terazol-3	1 every night	3 days	$41
Nystatin 100,000 U vaginal tablets	Generic	1 every night	7–14 days	$14–$35
Fluconazole 150 mg tablet	Diflucan	1 orally daily	1 day	$14
Itraconazole 100 mg tablet	Sporonox	2 orally daily 4 orally	3 days 1 day	$56 $37 ($281 for 30 tablets)
Ketoconazole 200 mg tablet	Nizoral generic	2 orally daily	5 days	$32–$43 ($95 for 30 generic tablets)
*Average wholesale price for entire regimen in US dollars.

Treating complicated VVC

About 5% of women diagnosed with VVC will have frequent recurrences, 4 or more per year.²⁴ Current therapies are fungistatic rather than fungicidal, so the yeast are reduced but not eradicated. Hypersensitivity and allergic reactions to topical preparations may be confused with recurrences. Experts recommend that, if wet mount or culture results confirm recurrent vaginitis, topical therapy should be increased from 5 to 7 days up to 10 to 14 days, or that a second oral fluconazole tablet be given 3 days after the first (SOR: C).²⁴ Women with severe cases of VVC also benefit from 2 sequential doses of fluconazole given 3 days apart (SOR: B).²⁵

Suppressive therapy may be used after initial treatment for 6 months or more (SOR: B). Suppressive therapy options include oral fluconazole 150 mg or vaginal clotrimazole 500 mg once a week, oral or intravaginal nystatin twice weekly, and oral itraconazole 200 mg monthly.^24,26

Non-albicans species tend to be more resistant to oral and topical azoles (SOR: B).^27-29 If this species is detected on culture, a long course of suppressive therapy should be attempted (SOR: C).²⁴ If imidazole therapy fails to control symptoms, suspect resistance.

Resistance to azoles may be demonstrated by in vitro susceptibility testing. Cross-resistance to topical and oral (fluconazole) azoles has been documented.³⁰ There have been few studies of alternatives to azoles for treatment of resistant yeast vaginitis. One little-studied alternative is intravaginal boric acid, which may be used as a 14-day course of 600 mg daily in gelatin capsules (SOR: C).³¹ Nystatin and flucytosine (Ancoban) for 7 to 14 days are other alternatives (SOR: C).²⁴

Candida in pregnancy

Commonly used topical imidazoles are classified as category C in pregnancy and have not been associated with increased risk of birth defects.

Trichomoniasis

Current treatment for trichomoniasis is oral metronidazole, given as a 2-g single dose, 250 mg 3 times daily for 7 days or 500 mg twice a day for 7 days. Treatment should also be given to the woman’s partner (SOR: A).³² Intravaginal therapy is not effective, probably due to the parasite’s presence in inaccessible areas such as the vaginal glands and urethra.^33,34 Short-term treatment is comparable with long-term treatment, with similar rates of nausea and vomiting (SOR: A).³² A 1.5-g single-dose treatment has been shown to be equivalent to 2 g (SOR: B).³⁵

The incidence metronidazole-resistant trichomoniasis has been estimated at 5%.³⁶ In such cases, higher-dose therapy may be still be effective. For low to moderate resistance, 2 too 2.5 g daily for 3 to 10 days has been recommended (SOR: B).³⁷ Intravenous high-dose metronidazole, 2 g every 8 hours for 3 days, has been reported to successfully treat highly resistant trichomonas (SOR: C).³⁸ Another case report of 2 women with presumed allergy to metronidazole were successfully treated with incremental dosing of IV metronidazole (SOR: C).³⁹ A small case series of women with metronidazole allergy or resistance treated with paromomycin cream intravaginally showed cure in 6 of 9 cases (SOR: C).⁴⁰ Oral tinidazole has been approved in 2004 for use in the treatment of metronidazole-resistant trichomoniasis (SOR: B).⁴¹

Corresponding author
Linda French, MD, Associate Professor, Department of Family Practice, College of Human Medicine, Michigan State University, B101 Clinical Center, East Lansing, MI 48824. E-mail: Linda.French@ht.msu.edu.