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Mensagem  Renato de Oliveira em Seg Jan 21, 2013 1:48 pm


Treatment is indicated for relief of symptoms. Ten to 20 percent of reproductive age women who harbor candida are asymptomatic; they do not require therapy. The patient may resume sexual intercourse when her discomfort resolves.

Women with candidal vaginitis are classified as having uncomplicated infection (90 percent of patients) or complicated infection (10 percent of patients). Criteria are listed in the table.

Uncomplicated infections usually respond to treatment within a couple of days. Complicated infections require a longer course of therapy and may take two weeks to fully resolve.

Uncomplicated infection — Criteria for uncomplicated infection are:

Sporadic, infrequent episodes
Mild to moderate signs/symptoms
Probable infection with Candida albicans
Healthy, nonpregnant woman

A variety of oral and vaginal preparations, many available over the counter and in single-dose regimens, are available for the treatment of uncomplicated vulvovaginal candidiasis (table 3). Randomized trials have shown that oral and topical antimycotic drugs achieve comparable clinical cure rates, which are in excess of 90 percent; short-term mycologic cure is slightly lower (70 to 80 percent). Topical treatments may cause local burning or irritation, while oral medication may cause gastrointestinal intolerance, headache, rash, and transient liver function abnormalities. Oral medications take a day or two longer than topical therapy to relieve symptoms. However, studies that assessed patient preference consistently reported a preference for the convenience of oral treatment.

Treatment of uncomplicated vaginal candidiasis
Drug and trade name(s) Requires a prescription in US Preparation Intravaginal* dose for adult
Gyne-Lotrimin®• No 1 percent cream 1 applicatorful (~5 g) daily for 7 days
Gyne-Lotrimin 3®• No 2 percent cream 1 applicatorful (~5 g) daily for 3 days
Gyne-Lotrimin®Δ Not applicable (not available in US) 100 mg vaginal tabletΔ Insert 1 vaginal tablet daily for 7 days or 2 tablets daily for 3 days
Monistat® 7 No 2 percent cream 1 applicatorful (~5 g) daily for 7 days
Monistat® 3 No 4 percent cream 1 applicatorful (~5 g) daily for 3 days
Monistat® 7 No 100 mg vaginal suppository 1 suppository daily for 7 days
Monistat® 3, Vagistat-3® Yes (except kit) 200 mg vaginal suppository (combination kit may include 2 percent miconazole cream for external use) 1 suppository daily for 3 days
Monistat® 1 Day Ovule® No 1200 mg vaginal suppository (combination kit may include 2 percent miconazole cream for external use) 1 suppository for 1 day
Nystatin vaginal(former US trade name Mycostatin®) Yes 100,000 unit vaginal tablet Insert 1 vaginal tablet daily for 14 days
Terazole 7®, Zazole®• Yes 0.4 percent cream 1 applicatorful (~5 g) daily at bedtime for 7 days
Terazole 3®, Zazole®• Yes 0.8 percent cream 1 applicatorful (~5 g) daily at bedtime for 3 days
Terazole 3®, Zazole®• Yes 80 mg vaginal suppository 1 suppository daily at bedtime for 3 days
Vagistat-1®, 1-Day No 6.5 percent ointment 1 applicatorful (~5 g) at bedtime as a single dose
Femstat®Δ, Gynazole-1®Δ Not applicable (not available in US) 2 percent creamΔ 1 applicatorful (~5 g) as a single dose


Diflucan®• Yes 150 mg oral tablet Single dose by mouth
There are no significant differences
inefficacy among topical and systemic azoles (cure rates >80 percent
for uncomplicated vulvovaginal candidiasis).* Except fluconazole (oral administration)
• Generic equivalent preparation(s) are available in US
Δ Not available in US
◊ Cure rate with nystatin is 70 to 80 percent.

The absence of superiority of any formulation, agent, or route of administration suggests that cost, patient preference, and contraindications are the major considerations in the decision to prescribe an anti-fungal for oral or intravaginal administration. We suggest use of oral fluconazole, given that most women consider oral drugs more convenient than those applied intravaginally. Fluconazole maintains therapeutic concentrations in vaginal secretions for at least 72 hours after the ingestion of a single 150 mg tablet. Side effects of single-dose fluconazole (150 mg) tend to be mild and infrequent. However, fluconazole interacts with multiple drugs; therefore, the potential for drug interactions should be addressed when prescribing this agent. Since fluconazole is now available in a generic form, a single dose regimen of fluconazole is less expensive than over the counter topical antifungals.

Azole resistance has only been reported in one case of vaginitis caused by C. albicans. Thus, in vitro susceptibility tests are rarely indicated unless compliant patients with a culture-proven diagnosis have no response to adequate therapy.

Complicated infections — Characteristics of complicated infections include:

Poorly controlled diabetes, immunosuppression, debilitation
Severe signs/symptoms
Candida species other than C. albicans, particularly C. glabrata
History of recurrent (≥4/year) vulvovaginal candidiasis

Severe symptoms or compromised host — Women with severe inflammation or host factors suggestive of complicated infection are less likely to respond to short courses of oral or topical antimycotic drugs. Observational series have reported that these patients require 7 to 14 days of topical azole therapy, rather than a one to three day course. A randomized trial demonstrated that two doses of oral therapy was more effective than one dose. Comparative trials of topical versus oral treatment of complicated infection have not been performed.

Given the convenience of oral therapy, we suggest fluconazole (150 mg orally) for two to three sequential doses 72 hours apart for treatment of complicated infections, depending on the severity of the infection (table 4). The efficacy of this approach was illustrated in a prospective study that randomly assigned 556 women with severe or recurrent candidiasis to therapy with a single dose of fluconazole (150 mg) or two sequential doses given three days apart [46]. Severity of disease was based upon a scoring system involving degree of pruritus and physical signs (erythema, edema, excoriation/fissure formation). The two dose regimen resulted in significantly higher clinical cure/improvement rates at evaluation on day 14 (94 versus 85 percent) and day 35 (80 versus 67 percent) in women with severe, but not recurrent, disease. However, the response to therapy was lower in the 8 percent of women infected with nonalbicans Candida.

Treatment complicated vaginal candidiasis

Severe vaginitis

No short course therapy
Oral fluconazole 150 mg every 72 h for 2 or 3 doses (depending on severity)
Topical antifungal therapy daily for 7 d, some patients may
respond better if a topical corticosteroid is also administered to the

Recurrent vulvovaginal candidiasis

Induction (3 doses of fluconazole 150 mg every 72 h until
asymptomatic) followed by maintenance fluconazole 150 mg once per week
for 6 months. If fluconazole is not feasible, options include 10-14 days
of a topical or oral azole followed by maintenance therapy for 6 months
(eg, clotrimazole (200 mg vaginal cream twice weekly or 500 mg vaginal
suppository once weekly)

Non-albicans Candida vaginitis

Therapy depends upon species identified
C. glabrata: intravaginal boric acid 600 mg daily for 14 d
If failure occurs: 17 percent flucytosine, 5 g nightly for 14 d
C krusei: intravaginal boric acid 600 mg daily for 14 d or clotrimazole 2 percent cream for 7-14 d
All other species: Conventional dose fluconazole

Abnormal host/susceptible Candida isolates

Oral or topical therapy for 7-14 d

For severe Candida vulvar inflammation (vulvitis), some experts suggest additional low potency topical corticosteroids for 48 hours until the antifungals exert their effect.

C. glabrata — C. glabrata has low vaginal virulence and rarely causes symptoms, even when identified by culture. Every effort should be made to exclude other co-existent causes of symptoms and only then treat for yeast vaginitis. Treatment failure with azoles is common (around 50 percent) in patients with C. glabrata vaginitis. Moderate success (65 to 70 percent) in women infected with this organism can be achieved with intravaginal boric acid (600 mg capsule once daily at night for two weeks) [20]. Better results (>90 percent cure) have been achieved with intravaginal flucytosine cream (5 g nightly for two weeks). Neither boric acid capsules nor flucytosine cream is available commercially and must be made by a compounding pharmacy. Boric acid capsules can be fatal if swallowed.

There are no good data regarding use of oral voriconazole for C. glabrata vaginitis. Anecdotal reports suggest poor response and rare on cure rate success, and the potential for toxicity. There are also no good data on the efficacy of nystatin, which is available as a pessary in some parts of the world. One or two pessaries of 100,000 units nystatin are inserted into the vagina nightly for 14 days. Alternatively, a suppository can be prepared by a compounding pharmacy. Potential side effects include burning, redness, and irritation.

C. krusei — Candida krusei is usually resistant to fluconazole, but is highly susceptible to topical azole creams and suppositories, such as clotrimazole, miconazole, and terconazole. It is also likely to respond to oral itraconazole or ketoconazole, but these oral agents have variable toxicity so topical therapy is advised for first-line therapy. In vitro susceptibility testing is indicated in compliant patients with culture-proven diagnosis of C krusei and no response to a conventional course of one of these non-fluconazole therapies.

Pregnancy — Treatment of pregnant women is only indicated for relief of symptoms. Vaginal candidiasis is not associated with adverse pregnancy outcomes. We suggest application of a topical imidazole (clotrimazole, miconazole) vaginally for seven days. Vaginal nystatin is another option, but requires prolonged therapy (7 to 14 days).

Administration of oral azoles during the first trimester is contraindicated as case reports have described a set of birth defects (abnormalities of cranium, face, bones, and heart) after first trimester exposure to high dose therapy (400 to 800 mg/day). The magnitude of the teratogenic risk is unknown. Although first trimester use of a single, low dose of fluconazole 150 mg to treat vaginal yeast infection has not been associated with an increased risk of embryopathy, most epidemiologic studies were too small to detect an increased risk of major birth defects or rare syndromes [52].

Recurrent infection — The treatment of women with recurrent infections can be difficult and frustrating. Attempts should be made to eliminate or reduce risk factors for infection (eg, improve glycemic control, switch to lower dose oral contraceptive). Although not based upon data from randomized studies, a trial of one or more behavioral changes may rarely be beneficial for some women (eg, avoidance of panty liners, pantyhose, cranberry juice). Treatment should also be directed at the sexual dysfunction and marital discord that frequently accompany chronic vaginitis.

Azoles — Randomized trials comparing different therapeutic regimens have not been performed. Some specialists treat each recurrent episode in these women with the regimens described above for uncomplicated infections (table 3), while others prescribe longer initial therapy (7 to 14 days of a topical azole or three doses of fluconazole 150 mg orally on day 1 with repeat doses on day 4 and 7). The Infectious Diseases Society of America recommends 10 to 14 days of induction therapy with a topical or oral azole, followed by fluconazole 150 mg once per week for six months (clotrimazole 200 mg vaginal cream twice weekly is a nonoral alternative). Given the safety profile of low dose fluconazole, most experts do not suggest any laboratory monitoring; however, if other oral imidazoles (ketoconazole, itraconazole) are used, particularly if taken daily, then monitoring liver function tests is recommended.

Multiple observational studies of nonpregnant women with recurrent vulvovaginal candidiasis have shown that antifungal maintenance suppressive therapy taken for six months after an initial induction regimen resulted in negative cultures. The best available option in nonpregnant women is fluconazole 150 mg orally once per week for six months. However, maintenance therapy is only effective for preventing recurrent infection as long as the medication is being taken. This was illustrated in a trial of 387 women with recurrent vulvovaginal candidiasis treated with open-label fluconazole (150 mg orally at 72-hour intervals for three doses) and then randomly assigned to weekly doses of fluconazole (150 mg) or placebo for six months. The maintenance therapy phase was begun two weeks after initiation of treatment in patients who were clinically cured. Study drugs were discontinued in patients diagnosed with recurrent candidal infection during follow-up visits.

The proportion of women who remained disease-free was significantly higher in the fluconazole group (91 versus 36 percent at six months, 73 versus 28 percent at nine months, and 43 versus 22 percent at 12 months).
The mean time to recurrence in the fluconazole and placebo groups was 10.2 and 4.0 months, respectively.
Resistant isolates of Candida albicans or superinfection with C. glabrata were not observed.

Although this regimen of maintenance fluconazole was convenient, safe, and as effective as other therapies, long-term cure of recurrent vulvovaginal candidiasis was not achieved in one-half of the women studied. Episodes of recurrent candidiasis resumed when maintenance therapy was discontinued.

Based on the data cited above and personal experience, we believe that the optimal therapy for recurrent vulvovaginal candidiasis in nonpregnant women consists of initial induction therapy with fluconazole 150 mg every 72 hours for three doses, followed by maintenance fluconazole therapy once per week for six months. Therapy is then discontinued, at which point some patients achieve a prolonged remission, while others relapse. A short-term relapse, with culture confirmation of the diagnosis, merits reinduction therapy with three doses of fluconazole, followed by repeat weekly maintenance fluconazole therapy, this time for one year. A minority of women persist in relapsing as soon as fluconazole maintenance is withdrawn (fluconazole dependent recurrent vulvovaginal candidiasis). Symptoms in these patients can be controlled by months or years of weekly fluconazole.

In women with recurrent vulvovaginal candidiasis, there is some evidence that frequent and prolonged use of fluconazole can infrequently select for fluconazole resistance in C albicans strains previously susceptible to fluconazole, which limits the options available for treating these women. In a study of 25 women with refractory Candida vaginitis and a C albicans isolate with fluconazole minimum inhibitory concentration (MIC) ≥2 micrograms/mL, those with fluconazole MIC values of 2 and 4 micrograms/mL were treated successfully by increasing fluconazole dosage to 200 mg twice weekly. In the authors’ experience, a higher dose of fluconazole was not effective for women with MIC ≥8 micrograms/mL. These women should be evaluated for cross-resistance to itraconazole and ketoconazole, as some patients can be treated effectively with long-term maintenance daily imidazole therapy. However, use of itraconazole or ketoconazole requires intermittent hepatic function testing. Women with severe recurrent vulvovaginal candidiasis infection and high-level pan azole resistance do not have options other than topical boric acid (see 'Boric acid' below) or nystatin suppositories.

In women with refractory vulvovaginal candidiasis with persistently positive C albicans cultures, MICs to various antifungals can be tested by using the broth microdilution method conducted in accordance with Clinical and Laboratory Standards Institution (CLSI) criteria and breakpoints.

Probiotics — There is no evidence that women with recurrent vulvovaginal candidiasis have vaginal flora deficient in lactobacilli. Although there is a popular belief that ingestion or vaginal administration of yogurt or other agents containing live lactobacilli decreases the rate of candidal colonization and symptomatic relapse, the few studies in this area have a number of methodologic flaws (eg, no control group, short follow-up) and small numbers of subjects. The value of administering live lactobacilli to women with recurrent infection has been refuted in other studies and this approach should be considered unproven. In addition, the quality of commercially available probiotics varies worldwide. In the United States, the content of these products is not standardized and often of poor quality.

Immunotherapy — Local vaginal hypersensitivity to Candida albicans has been proposed as the cause of recurrent infection in some women. Immunotherapy of candidal vaginitis is a novel therapeutic approach under investigation, but no effective prophylactic or therapeutic vaccine has been developed for this purpose.

Boric acid — Boric acid has not been proven to be an effective treatment of recurrent vulvovaginitis and has no role in treatment of recurrent vulvovaginitis due to Candida albicans, unless azole resistance is demonstrated by in vitro tests. There are no safety data on long-term use of boric acid, which causes significant local irritation and has the potential for toxicity (including death) if ingested by accident. A course of boric acid (600 mg intravaginal boric acid vaginal

suppositories daily for two weeks) should be considered only in cases of proven azole-resistant infection; these cases are rare.

Treatment of partners — Although sexual transmission of Candida can occur, most experts do not recommend treatment of sexual partners of women with recurrent vulvovaginal candidiasis since sexual activity is not a significant cause of infection or reinfection. However, this issue remains controversial.

Breastfeeding women — Nystatin does not enter breast milk and is compatible with breastfeeding. Fluconazole is excreted in human milk, but the American Academy of Pediatrics considers the use of fluconazole compatible with breastfeeding, as no adverse effects on the infant have been reported. There is no information on use of butoconazole, clotrimazole, ticonazole, terconazole on nursing infants, but systemic absorption after vaginal administration is minimal, hence topical use of all antimycotics in nursing mothers is reasonable.

Post-coital hypersensitivity reaction in male partner — In a variant syndrome, males develop immediate post-coital itching and burning with redness and a rash of the penis. This post-coital syndrome probably represents an acute hypersensitivity reaction to Candida organisms or antigens in the partner's vagina, even in the absence of symptomatic vulvovaginitis.

Males with recurrent post-coital symptoms do not benefit from topical antimycotic therapy since the key to eradicating symptoms lies in eliminating Candida organisms from the lower genital tract of female sexual partners. This often requires the female partner to follow a long-term maintenance antimycotic regimen.

A post-coital shower and application of a topical low potency corticosteroid to the penis may provide symptomatic relief within 12 to 24 hours. Penile cultures may remain positive for Candida despite normal physical findings

Renato de Oliveira

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Mensagem  Renato de Oliveira em Seg Jan 21, 2013 1:49 pm

REFERÊNCIA: UpToDate - Candida vulvovaginitis

Renato de Oliveira

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Data de inscrição : 01/12/2012

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