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#179 Recurrent Vulvovaginal Candidiasis: Can the yeast be beat?


CLINICAL QUESTION
What is the most effective management for women with recurrent vulvovaginal candidiasis (four or more episodes within one year)?

BOTTOM LINE
Prophylaxis with six months of azole therapy (like fluconazole) will result in relapse in 9-19% of women compared to 50-64% on placebo (one fewer woman would relapse for every 2-4 treated). Efficacy, however, declines after therapy cessation and clinical cure remains elusive. Limited evidence suggests women may prefer episodic over maintenance therapy.  


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EVIDENCE
  • Two double blind, Randomized Controlled Trials (RCTs) of 3731 and 64 women2 with symptoms and culture confirmed recurrent vulvovaginitis, compared fluconazole  150 mg PO weekly for six months (after initial fluconazole 150 mg PO every 72 hours for 3 days) versus placebo: 
    • Significant difference in clinical relapse rate: 
      • Following six months treatment:1,2 9-19% versus 50-64%, Number Needed to Treat (NNT)=2-4.  
      • 12 month follow-up:1 57% versus 78%, NNT=5.  
        • Smaller study: No significant difference. 
        • No increase in resistance.1,2 
    • Adverse events: 
      • “Mild” elevation of liver enzymes in one patient, did not require discontinuation.1 
    • Limitations: Analysis only included compliant women.1 
  • Two RCTs examined monthly itraconazole 400 mg PO (114 women)3 or clotrimazole 500 mg vaginal suppository (62 women)4 versus placebo for six months:  
    • Significant difference in clinical relapse rate: 30-36% versus 64-79%, NNT=3-4.  
    • No longer significant at 12 month follow-up.3,4  
  • One observational study, 136 women, individualized decreasing dose (200 mg fluconazole three times/week, weekly x 2 months, biweekly x 4 months, then monthly x 6 months) based on clinical symptoms:5 
    • Clinical relapse during 12 months treatment: 30%. 
    • 18 month follow-up: 45%. 
Context: 
  • Studies of alternative therapies such as probiotics or homeopathy, are poor quality, and/or with mixed results.6-8 
  • Limited evidence suggests no significant difference between different azoles in Candida albicans acute or recurrent vulvovaginitis.9,10 
  • Candida albicans is responsible for 90% of vulvovaginal candidiasis; followed by Candida glabrata, which is azole-resistant.11 
  • One small trial (54 participants) demonstrated that treating male partner with antifungals does not reduce relapse rate.12 
  • A randomized cross-over trial of 23 women reported 74% versus 14% prefer to treat each episode empirically versus maintenance therapy.13 

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Author(s):

  • Christina Korownyk MD CCFP
  • Mathieos Belayneh BMSc

1. Sobel JD, Wiesenfeld HC, Martens M, et al. N Engl J Med. 2004; 351(9):876-83.

2. Bolouri F, Tabrizi NM, Tanha FD, et al. IJPR. 2009; 8(4):307-13.

3. Spinillo A, Colonna L, Piazzi G, et al. J Reprod Med. 1997; 42(2):83-7.

4. Roth AC, Milsom I, Forssman L, Wåhlén P. Genitourin Med. 1990; 66(5):357-60.

5. Donders G, Bellen G, Byttebier G, et al. Am J Obstet Gynecol. 2008; 199(6):613.e1-9.

6. Falagas ME, Betsi GI, Athanasiou S. J Antimicrob Chemother. 2006; 58(2):266-72.

7. Kumari A, Bishier MP, Naito Y, et al. J Biol Regul Homeost Agents. 2011; 25(4):543-51.

8. Witt A, Kaufmann U, Bitschnau M, et al. BJOG. 2009; 116(11):1499-505.

9. Pitsouni E, Iavazzo C, Falagas ME. Am J Obstet Gynecol. 2008; 198(2):153-60.

10. Fong IW. Genitourin Med. 1992 Dec; 68(6):374-7.

11. Sobel JD. Am J Obstet Gynecol. 2016; 214(1):15-21.

12. Fong IW. Genitourin Med. 1992 Jun; 68(3):174-6.

13. Fong IW.  Genitourin Med. 1994 Apr; 70(2):124-6.

Authors do not have any conflicts of interest to declare.