Uncomplicated Vulvovaginal Candidiasis
Terconazole is used intravaginally for the treatment of vulvovaginal candidiasis. Prior to initial use of miconazole in a woman who has signs and symptoms of uncomplicated vulvovaginal candidiasis, the diagnosis should be confirmed either by demonstrating yeast or pseudohyphae with direct microscopic examination of vaginal discharge (saline or 10% potassium hydroxide [KOH] wet mount or Gram stain) or by culture; identifying Candida by culture in the absence of symptoms is not an indication for antifungal treatment since approximately 10-20% of women harbor Candida or other yeasts in the vagina. When an adequate response is not achieved following a course of terconazole therapy for vulvovaginal candidiasis or if there is recurrence of symptoms within 2 months, appropriate microbiologic studies should be performed to confirm the diagnosis and identify unusual Candida species (e.g., C. glabrata).
Up to 75% of women reportedly have at least one episode of vulvovaginal candidiasis and 40-45% have 2 or more episodes during their lifetime, but a small percentage of women (up to 5%) have recurrent vulvovaginal candidiasis (i.e., 4 or more episodes of symptomatic vulvovaginal candidiasis in a year). While certain factors may precipitate a sporadic attack of vulvovaginal candidiasis and have been associated with an increased risk for recurrent vulvovaginal candidiasis (e.g., uncontrolled diabetes mellitus, pregnancy, oral contraceptive use, corticosteroid or other immunosuppressive therapy, immunodeficiency, use of intravaginal sponges or devices, repeated courses of topical or systemic antibacterial agents), these factors are not present in most women who have recurrent episodes.
Azole antifungals (imidazole and triazole derivatives) are considered the drugs of choice for the treatment of vulvovaginal candidiasis. The US Centers for Disease Control and Prevention (CDC) and other clinicians generally recommend that uncomplicated vulvovaginal candidiasis (defined as vulvovaginal candidiasis that is mild to moderate, sporadic or infrequent, most likely caused by Candida albicans, and occurring in immunocompetent women) should be treated with an intravaginal azole antifungal (e.g., butoconazole, clotrimazole, miconazole, terconazole, tioconazole) given in appropriate single-dose or short-course regimens or, alternatively, oral fluconazole given in a single-dose regimen. These regimens generally have been associated with clinical and mycologic cure rates of 80-90% in otherwise healthy, nonpregnant women with uncomplicated infections, and there is no clear evidence that any one intravaginal azole antifungal regimen is superior to any other intravaginal azole regimen available for the treatment of these infections. While intravaginal nystatin also can be used for the treatment of uncomplicated vulvovaginal candidiasis, it generally is less effective than intravaginal azole antifungals. A longer duration of therapy (i.e., 7-14 days) with an intravaginal or oral azole antifungal generally is necessary for the treatment of complicated vulvovaginal candidiasis, including recurrent and severe disease. Complicated vulvovaginal candidiasis is defined as infections that are recurrent or severe, caused by Candida other than C. albicans, or occurring in women who have underlying medical conditions such as pregnancy, uncontrolled diabetes, debilitation, or immunosuppression.
(See Complicated and Recurrent Vulvovaginal Candidiasis under Uses: Vulvovaginal Candidiasis.)
Vulvovaginal candidiasis usually is not acquired through sexual activity, and treatment of sexual partner(s) is not recommended but may be considered in women who have recurrent infections. However, male sexual partners who have symptomatic balanitis or penile dermatitis may benefit from treatment with a topical antifungal to relieve symptoms.
Terconazole given once daily for 7 days as a 0.4% vaginal cream or once daily for 3 days as a 0.8% vaginal cream or as 80-mg vaginal suppositories produces clinical cures (i.e., complete absence of vulvovaginal burning, itching, swelling, erythema, excoriation, and/or ulceration and substantial decreases in vaginal discharge) in approximately 84-96% and mycologic cures in 79-97% of nonpregnant and pregnant patients with vulvovaginal candidiasis 7 days after completion of therapy. The relapse rate 3-4 weeks after therapy is 3-15%.
Terconazole has been used with good results in women with vulvovaginal candidiasis during oral contraceptive use. Although oral contraceptive use has been associated with an increased incidence of vulvovaginal candidiasis and frequently recurring infection, cure rates reported with terconazole in patients using oral contraceptive agents concomitantly do not differ substantially from those in women using other methods of contraception or not practicing contraception. Because vulvovaginal candidiasis may be more difficult to cure during pregnancy, many experts prefer the use of 7-day regimens in pregnant patients. However, terconazole has been used with good results in pregnant women when given as a 3-day regimen using 80-mg vaginal suppositories or as a 7-day regimen using the 0.4% vaginal cream.
Intravaginal terconazole appears to be at least as effective as intravaginal clotrimazole or miconazole in the treatment of vulvovaginal candidiasis. In several studies, 7 days of therapy with terconazole 0.4% vaginal cream given once daily or 3 days of therapy with terconazole 80-mg vaginal suppositories given once daily was as effective as 3 days of therapy with clotrimazole 200-mg vaginal tablets given once daily. In studies in pregnant and nonpregnant women who received 7 days of therapy with terconazole 0.4% vaginal cream or clotrimazole 1% vaginal cream, mycologic cure rates 1 week after therapy were 90-94.6 and 84.4-95%, respectively, and relapse rates 4 weeks later were 3.3 and 16.7%, respectively. In controlled studies comparing terconazole 0.4% vaginal cream and miconazole 2% vaginal cream applied once daily for 7 days, clinical cure rates 7-10 days after therapy were 92 and 91%, respectively, and mycologic cure rates were 86 and 83%, respectively.
Complicated and Recurrent Vulvovaginal Candidiasis
Optimum regimens for the treatment of recurrent vulvovaginal candidiasis (usually defined as 4 or more episodes of symptomatic vulvovaginal candidiasis in a year) have not been established. Although each individual episode caused by C. albicans may respond to usual short-course intravaginal antifungal regimens or a single-dose of oral fluconazole, a longer duration of initial therapy may be necessary to achieve mycologic remission and chronic maintenance therapy may be necessary to prevent relapse. The CDC recommends use of an initial intensive regimen consisting of 7-14 days of an intravaginal azole antifungal or a 3-dose regimen of oral fluconazole (100-, 150-, or 200-mg doses given every third day for a total of 3 doses) followed by a maintenance antifungal regimen (given for 6 months). For the maintenance regimen, the CDC recommends oral fluconazole (100-, 150-, or 200-mg doses once weekly). If this oral regimen cannot be used, some clinicians recommend intravaginal clotrimazole (200 mg twice weekly or 500 mg once weekly) or other intravaginal treatments used intermittently. These maintenance regimens can be effective in reducing recurrent infections; however, 30-50% of women will have recurrent disease once maintenance therapy is discontinued.
The response rate to short-course antifungal regimens is lower in patients with severe vulvovaginal candidiasis (i.e., extensive vulvar erythema, edema, excoriation, and fissure formation) and either a 2-dose regimen of oral fluconazole (150 mg repeated 3 days later) or 7-14 days therapy with an intravaginal azole antifungal is recommended for these infections. These more prolonged regimens may also be necessary for the treatment of vulvovaginal candidiasis in women with underlying debilitating medical conditions (e.g., those with uncontrolled diabetes or those receiving corticosteroid therapy).
For the treatment of vulvovaginal candidiasis during pregnancy, the CDC recommends use of a 7-day regimen of an intravaginal azole antifungal.
Vulvovaginal candidiasis may occur more frequently and may be more severe in women with human immunodeficiency virus (HIV) infection than in women without HIV infection and these infections have been recognized as an early manifestation of acquired immunodeficiency syndrome (AIDS) in women. While optimum therapy for recurrent vulvovaginal candidiasis in HIV-infected women has not been established, there is no evidence to date that these women have a lower response rate to the intravaginal or oral antifungal regimens usually recommended for the treatment of vulvovaginal candidiasis. Therefore, the CDC and other clinicians recommend that treatment of vulvovaginal candidiasis in HIV-infected women be the same as that in women without HIV infection.
Recurrent vulvovaginal candidiasis rarely may be caused by resistant strains of C. albicans or, more commonly, by other Candida with reduced susceptibility to azole antifungals (e.g., C. glabrata). It has been suggested that repeated treatment of recurrent vulvovaginal candidiasis with intravaginal azole antifungals and widespread and/or injudicious use of these agents for self-medication of vulvovaginal candidiasis may favor the selection of Candida resistant to azole antifungals. Optimum therapy for the treatment of vulvovaginal candidiasis caused by Candida with reduced susceptibility to azole antifungals has not been determined to date. For the treatment of vulvovaginal candidiasis caused by Candida other than C. albicans, the CDC and other clinicians recommend 7-14 days of therapy with an antifungal agent other than fluconazole; if recurrence occurs, a 14-day regimen of intravaginal boric acid (not commercially available in the US) is recommended. Referral to a specialist is advised.