Version May 2024
INTRODUCTION — Vulvovaginal candidiasis (VVC) is one of the most common causes of vulvovaginal itching and discharge. The disorder is characterized by inflammation in the setting of growth of Candida species. Treatment is indicated for the relief of symptoms and varies based on disease severity.
This topic will discuss treatment of acute VVC, including both uncomplicated and complicated infections. Related topics on the general approach to patients with abnormal vaginal discharge, diagnosis of VVC, and treatment of recurrent vulvovaginal candidiasis (RVVC) are presented separately:
●(See "Vaginitis in adults: Initial evaluation".)
●(See "Candida vulvovaginitis: Clinical manifestations and diagnosis".)
●(See "Candida vulvovaginitis in adults: Recurrent infection".)
In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. We encourage readers to consider the specific counseling and treatment needs of transgender and gender-diverse individuals.
WHOM TO TREAT — Treatment is indicated for patients with both symptoms and evidence of fungal vaginal infection on microscopy or laboratory tests. Asymptomatic patients with VVC identified for other reasons (ie, Pap smear) do not require treatment; 10 to 20 percent of reproductive-age females harbor Candida species [1]. Treatment approach is based on presence of uncomplicated infection (90 percent of patients) or complicated infection (10 percent of patients) (table 1).
UNCOMPLICATED INFECTION
Criteria — Criteria for uncomplicated infection include all of the following (table 1) [2]:
●Sporadic, infrequent episodes (<3 episodes/year)
●Nonpregnant individual
●Mild to moderate signs/symptoms (ie, minimal or localized erythema and/or edema, no fissures)
●Probable infection with Candida albicans (approximately 90 percent of patients with VVC have albicans-related infection)
●Immunocompetent individual
Treatment — Uncomplicated VVC can be treated with oral azoles, topical azoles, and triterpenoid drugs (table 2). As all drugs have established efficacy, use of any is reasonable [3-6]. After assessing patient preferences and prior response (if any), we generally proceed in the order presented below (algorithm 1). Other factors include drug interactions, use criteria, availability, and cost.
Oral fluconazole — We treat nonpregnant patients with oral fluconazole. Patients typically prefer oral rather than vaginal medications [4,7] and efficacy is similar for oral and topical azoles. (See 'Efficacy' below.)
●Dose – Fluconazole 150 mg orally given once or twice.
•Initial response is typically seen within 24 hours. In our experience, patients with mild symptoms respond with one dose but patients with moderate symptoms often need a second dose taken 72 hours after the first dose.
•Fluconazole maintains therapeutic concentrations in vaginal secretions for at least 72 hours after the ingestion of a single 150 mg tablet [8].
●Side effects and drug interactions – Side effects of single-dose fluconazole (150 mg) tend to be mild and infrequent. Oral fluconazole may cause gastrointestinal intolerance, headache, rash, and transient liver function abnormalities. Although fluconazole interacts with multiple drugs, interactions are rare at the dose used to treat VVC.
●Azole resistance – Azole resistance is uncommon for vaginitis caused by C. albicans [9,10]. In vitro susceptibility tests are typically not indicated unless compliant patients with a culture-proven diagnosis have no response to adequate therapy.
Oteseconazole is another oral azole but is indicated only for patients who are not of reproductive potential and have RVVC (ie, not for use in sporadic or acute VVC infections) [11]. (See "Candida vulvovaginitis in adults: Recurrent infection".)
Topical azoles — Multiple topical azole products are available (table 2). No regimen has demonstrated superiority over another; selection is based on patient preferences around duration of treatment, prior response history, and availability. While vulvar treatment can improve vulvar symptoms, vaginal therapy is necessary to eradicate the vaginal reservoir of organisms and fully treat the disease [12]. Topical therapy starts to relieve symptoms within hours.
In randomized trials, oral and topical antimycotic drugs achieved comparable clinical cure rates, which are in excess of 90 percent; short-term mycologic cure is slightly lower (70 to 80 percent) [4,13,14]. (See 'Efficacy' below.)
Triterpenoid (ibrexafungerp) — Ibrexafungerp (commercial name Brexafemme) is a single-day multi-dose oral triterpenoid antifungal for use in nonpregnant patients with uncomplicated VVC [15]. Unlike fluconazole, which inhibits fungal growth, ibrexafungerp kills Candida species by inhibiting formation of the fungal cell wall and is the first in its class (glucan synthase inhibitor) [16,17].
●Prescribing information – Ibrexafungerp is prescribed as four tablets of 150 mg each [15]. The patient should take two tablets by mouth twice in one day (ie, two in the morning and two at night).
●Patient selection – Patients who may benefit from this therapy include those who are allergic to fluconazole and other triazoles, do not tolerate fluconazole or other triazoles, and/or have Candida infections that are resistant to fluconazole.
●Drug interactions – Individuals using strong CYP3A inhibitors should reduce the dose to 150 mg twice in one day because of increased exposure to ibrexafungerp. Individuals taking strong or moderate CYP3A inducers may have significantly reduced exposure and are advised to use another antifungal treatment or avoid cotreatment with ibrexafungerp and CYP3A inducers.
●Pregnancy and lactation – The drug should not be given to pregnant individuals because of concern for fetal harm based on animal studies [15]. Human data for both pregnancy and lactation are lacking.
While the single-day regimen and oral dosing are appealing, the cost may be prohibitive for many. Discussion of extended ibrexafungerp treatment for RVVC is presented separately. (See "Candida vulvovaginitis in adults: Recurrent infection", section on 'Ibrexafungerp'.)
Efficacy
●Comparison of azoles – Both oral and topical azole treatment result in symptom relief and resolution of infection in approximately 80 to 90 percent of patients who complete therapy [4,5]. Rates vary by definition of cure and duration of follow-up, among other variables [4].
A meta-analysis of 26 trials, including 5007 participants, reported the following outcome data for oral (mainly fluconazole) compared with topical azoles [4]:
•Clinical cure – Defined as absence of symptoms.
-Short-term (5 to 15 days) clinical cure rates: Oral 79 percent, topical 77 percent, odds ratio (OR) 1.14, 95% CI 0.91-1.43, n = 1859.
-Long-term cure (2 to 12 weeks) clinical rates: Oral 85 percent, topical 84 percent, OR 1.07, 95% CI 0.77-1.50, n = 1042.
•Mycological cure – Defined as no evidence of vulvovaginal candidiasis by either mycological culture or microscopy.
-Short-term (5 to 15 days) mycological cure rates: Oral 83 percent, topical 80 percent, OR 1.24, 95% CI 1.03-1.50, n = 3057.
-Long-term cure (2 to 12 weeks) mycological rates: Oral 72 percent, topical 66 percent, OR 1.29, 95% CI 1.05-1.60, n = 1661.
●Ibrexafungerp – Ibrexafungerp is more effective than placebo and, in one small trial, oral fluconazole [3,18,19]. Larger trials are required to determine superiority of one drug treatment compared with the other.
•Placebo comparison – Clinical trials have demonstrated ibrexafungerp results in higher clinical cure rates compared with placebo [18,19].
•Oral fluconazole comparison – A trial comparing ibrexafungerp (300 mg bid for one day) with single-dose oral fluconazole in 62 patients reported [3]:
-10-day test of cure – Clinical cure rates of 52 versus 58 percent, respectively, and mycological cure rates of 63 percent for both. Clinical cure was defined as "complete resolution of vulvovaginal signs and symptoms" and mycological cure indicated negative fungal cultures. Differences in patient entry and assessment criteria likely contributed to lower clinical and mycological cure rates compared with the azole meta-analysis discussed above [4].
-25-day follow-up of clinical responders – Continued response rates of 41 versus 42 percent and mycological eradication rates of 48 versus 38 percent, respectively.
In post-hoc analysis, rates of clinical improvement were similar at 10-day test of cure (70 versus 71 percent) but at 25 days were 82 percent for ibrexafungerp and 58 percent for oral fluconazole. Rescue medication was used less often in the ibrexafungerp group compared with oral fluconazole (4 versus 29 percent).
COMPLICATED INFECTION — Patients with complicated infection includes those who are pregnant, have severe symptoms or immunocompromise, have infection with non-albicans Candida (NAC) species, or have recurrent infection (≥3 test-confirmed infections per year) (table 1) [2,5]. Treatment of recurrent infection is discussed in detail in related content (algorithm 2). (See "Candida vulvovaginitis in adults: Recurrent infection".)
Pregnancy — Treatment of pregnant people is primarily indicated for relief of symptoms; vaginal candidiasis is not associated with adverse pregnancy outcomes [20]. Beyond symptom relief, one European guideline advises treating all colonized pregnant persons in the third trimester to reduce the rates of oral thrush and diaper dermatitis in newborns [21]. VVC occurring during pregnancy is considered a complicated infection because pregnancy impacts choice of treatment based on concerns for adverse fetal outcomes and longer courses of therapy are typically needed, rather than the disease being inherently more severe or complicated in pregnant persons.
●Initial treatment – We suggest application of a topical imidazole vaginally for seven days rather than treatment with oral antifungal agents (azoles or ibrexafungerp) because of potential risks with these drugs (algorithm 3) [5,11,15,22-26]. While we typically use clotrimazole or miconazole, others are reasonable.
•Clotrimazole 1% cream – One applicatorful (approximately 5 g) in the vagina daily for seven days
Or
•Miconazole 2% cream – One applicatorful (approximately 5 g) in the vagina daily for seven days
Or
•Nystatin suppository 100,000 units – One suppository in the vagina nightly for 14 nights [27]. Suppositories can be prepared by a compounding pharmacy if not commercially available. Potential side effects include burning, redness, and irritation.
●Treatment duration – We begin with the treatment durations listed above, but some pregnant patients may require longer treatment courses of 10 to 14 days to fully resolve symptoms.
●RVVC in pregnancy – Pregnant patients with RVVC (defined as ≥3 test-confirmed infections per year) use an induction regimen and then begin maintenance therapy for continued suppression of symptoms (algorithm 4). Detailed discussion of RVVC in pregnancy is presented in related content. (See "Candida vulvovaginitis in adults: Recurrent infection", section on 'Pregnant'.)
●Drugs to avoid in pregnancy
•Oral fluconazole – We avoid oral fluconazole during pregnancy, particularly in the first trimester, because it may increase the risk of miscarriage and its impact on congenital anomalies is unclear [15,22,24]. Oral fluconazole therapy does not appear to increase the risk of stillbirth or neonatal death [24,28].
-Pregnancy loss – Two large observational studies reported an association between oral fluconazole and pregnancy loss [22,24]. While two earlier observational studies totaling just over 1500 patients did not report an association [29,30], the larger studies likely had greater power to detect an increase in miscarriage risk.
A cohort study comparing 3315 pregnant persons who received oral fluconazole (150 to 300 mg between 7 and 22 weeks) with matched control patients reported increased risk of pregnancy loss with fluconazole exposure, although the absolute risk remained low (4.4 versus 4.2 percent, respectively, hazard ratio 0.14, 95% CI 1.23-1.77) [22]. Stillbirth risk did not differ among the groups, although stillbirth was a relatively rare outcome.
A subsequent larger population cohort study that evaluated over 320,000 pregnancies reported increased risk of pregnancy loss with fluconazole exposure during early pregnancy [24]. While the absolute risk remained small, a dose-dependent relationship was reported (≤150 mg: pregnancy loss rates 1.2 versus 0.5 percent, adjusted odds ratio [aOR] 2.23, 95% CI 1.96-2.54 and >150 mg: pregnancy loss rates 0.9 versus 0.2 percent, aOR 3.20, 95% CI 2.73-3.75).
-Congenital anomalies – The impact of fluconazole on congenital anomalies is difficult to assess, in part because of the variability across studies for drug dose, gestational age, duration of exposure, method of exposure assessment, and the lack of consistency across the reported congenital anomalies. Overall, the data appear reassuring for people who took low-dose fluconazole (150 mg) before realizing that they were pregnant [29-36], although an increased risk of cardiac and musculoskeletal anomalies cannot be definitively excluded, especially at higher doses [24,37,38]. In the United States Medicaid Analytic eXtract database including over 1.9 million pregnancies, the reported overall association would result in approximately 12 additional musculoskeletal anomalies per 10,000 exposed pregnancies [37]. Additionally, case reports have described a pattern of congenital anomalies (abnormalities of cranium, face, bones, and heart) after first-trimester exposure to high-dose fluconazole therapy (400 to 800 mg/day) [39,40].
•Oteseconazole – Oteseconazole, an oral azole, is not for use in patients who are pregnant, could become pregnant, or are lactating because animal data suggest potential for fetal and/or infant harm [11].
•Ibrexafungerp – Ibrexafungerp is not for use in pregnancy because of concerns for fetal harm based on animal data [15].
•Terconazole – Terconazole is a triazole drug used topically that is absorbed through the vagina. Based on concerns for embryotoxicity in rabbits and rats, terconazole labelling states "it should not be in the first trimester" unless use is essential to the welfare of the patient and it "may be used during the second and third trimester if potential benefits outweigh the possible risks to the fetus" [41].
•Vaginal boric acid – We do not use vaginal boric acid in pregnancy as risk of harm is unknown. Boric acid can cause death if ingested orally.
Severe symptoms or immunocompromise — Individuals with severe symptoms (eg, extensive vulvovaginal involvement, skin fissures, and/or tissue edema) or immunocompromise (eg, immunosuppressive drugs, poorly controlled diabetes) generally need longer courses of oral or topical antimycotic drugs [5]. It is unknown whether one route is more effective than the other (algorithm 2).
●Preferred – For treatment of complicated infections, we suggest treatment with oral fluconazole 150 mg for two to three sequential doses, 72 hours apart; patients with more severe infections receive three doses (table 3) [5,6]. In our clinical practice, patients do well with this approach and generally prefer oral to vaginal therapy, as topical therapies may exacerbate vulvovaginal discomfort. Additionally, oral fluconazole is more readily available and lower cost than ibrexafungerp. However, treatment with topical azoles for 7 to 14 days (table 2) or ibrexafungerp is reasonable.
●Alternates
•Ibrexafungerp – Ibrexafungerp (150 mg tablets, two tablets taken orally twice in one day) may be prescribed for individuals with severe VVC [18,19]. The need for repeat dosing, or optimal dosing interval for repeat therapy, is not yet known. Full discussion of ibrexafungerp dosing and contraindications is presented above. (See 'Triterpenoid (ibrexafungerp)' above.)
•Topical azole therapy – Observational series report that patients who choose topical azole therapy benefit from 7 to 14 days of treatment (eg, clotrimazole, miconazole, terconazole) rather than a one- to three-day course [5].
●Adjunct topical steroids – For severe Candida vulvar inflammation (ie, extensive tissue erythema and/or edema), topical corticosteroids can be applied to the vulva for 48 hours until the antifungals exert their effect. Topical corticosteroids can be given as a separate agent (eg, hydrocortisone, betamethasone) or as combination therapy (eg, clotrimazole-betamethasone or nystatin-triamcinolone).
●HIV infection – Treatment of patients with HIV is the same as for those without infection; the approach is based on presence of uncomplicated or complicated disease. Individuals with HIV infection generally respond to short-course therapy and do not need extended treatment unless symptoms are particularly severe or recurrent [5,42].
●Efficacy – While both single and two-dose fluconazole treatment improve symptoms, the two-dose regimen results in higher clinical cure rates. In a trial that randomized 556 patients with severe or RVVC to single dose or two sequential doses of fluconazole (150 mg), the two-dose regimen resulted in significantly higher clinical cure/improvement rates on day 14 (85 versus 94 percent) and day 35 (67 versus 80 percent) in those with severe, but not recurrent, disease [42]. However, the response to therapy was lower in the 8 percent infected with NAC.
Non-albicans Candida species
Microbiology and clinical significance — NAC species include C. glabrata (most common), C. krusei, C. tropicalis, S. cerevisiae, and C. parapsilosis, among others [43]. Azole treatment of C. glabrata is often unsuccessful, and C. krusei and S. cerevisiae are generally inherently resistant to fluconazole. C. tropicalis is typically azole sensitive. As azole therapy is unlikely to treat NAC, infection with NAC species have been associated with increased office visits for recurring vulvovaginal complaints when compared with C. albicans [44] and have been observed in 10 to 20 percent of patients with RVVC [5].
Candida glabrata — C. glabrata is a frequent vaginal colonizer that has low vaginal virulence and rarely causes symptoms, even when identified by culture. Therefore, we make every effort to exclude other causes of symptoms and only treat C. glabrata vaginitis when all other potential sources of the vaginal symptoms have been addressed [5]. When treatment is elected, C. glabrata does not respond to typical first-line therapies because of inherent resistance or low-level drug susceptibility [43,45-47].
●Preferred – Although studies specific to treatment of C. glabrata are limited, we prefer treatment with vaginal boric acid or vaginal nystatin as these drugs are reasonably available, generally well tolerated, and have some supporting evidence.
•Vaginal boric acid – Vaginal boric acid 600 mg capsule nightly for two to three weeks resolves symptoms in roughly 70 percent of patients with confirmed C. glabrata (table 3) [5,48-50]. We prefer initial treatment with vaginal boric acid for nonpregnant persons because it is reasonably effective, low cost, and accessible. However, we do not use vaginal boric acid in pregnant patients as safety has not been established. Boric acid capsules can be fatal if swallowed.
•Nystatin – Nystatin suppository 100,000 units in vagina at night for 14 to 30 nights (duration varies with disease severity) [27,49,51]. At least one consensus guideline advises topical nystatin for C. glabrata [21]. Although there are limited data to support nystatin treatment of C. glabrata, advantages include that nystatin is generally well tolerated, low cost, and accessible. Potential side effects include burning, redness, and irritation.
●Minimal data – As there are minimal supporting data for the treatments below, selection is mainly based on availability (ie, access, cost) and adverse effects.
•Topical flucytosine cream – Topical flucytosine cream 16%, 5 g dose, intravaginally at night for 14 nights. A retrospective review of patients with culture-confirmed C. glabrata reported 27 of 30 patients (90 percent) had a successful outcome after they had not responded to vaginal boric acid and azole therapy [49]. Flucytosine cream may require a compounding pharmacy to construct a cream from oral capsules, which limits access and increases cost. Highest efficacy is seen when used in combination with topical amphotericin B, as below [50,52].
•Amphotericin B suppository – Amphotericin B, 50 mg suppository, intravaginally at night for 14 nights. An observational study of 10 patients with persistent NAC infection despite conventional treatment reported that seven patients were successfully treated with 50 mg vaginal suppository at night for 14 nights [52]. While combined treatment with both amphotericin B and nystatin 100,000 mg suppositories has been reported, both drugs are polyene compounds and their combined use is of unclear benefit [50,51]. Amphotericin B suppositories are not commercially available and require manufacture by a compounding pharmacy, which limits access and increases cost [50].
•Ibrexafungerp – Ibrexafungerp is single-day oral triterpenoid antifungal for use in postmenarchal females with VVC [15]. While it may be a treatment option for C. glabrata, supporting data for this population are lacking and the optimal drug dose and duration are uncertain. If used, the dosing regimen would be the same as for uncomplicated infection. Ibrexafungerp is not for use during pregnancy or lactation. (See 'Triterpenoid (ibrexafungerp)' above.)
•Voriconazole – As there are scant data regarding use of oral voriconazole for C. glabrata vaginitis, it should not be used to treat VVC unless all other topical and systemic antifungal therapies have failed [51]. Animal data (mice) and anecdotal reports suggest occasional cures, but there is potential for hepatic toxicity, arrhythmias, and QT prolongation [53,54]. When used to treat VVC, oral voriconazole 200 mg is given orally twice daily for two weeks [55]. Dose adjustments are required for hepatic impairment. Treatment duration depends on patient response. The drug should be taken at least one hour before or after a meal [54].
•Combined drug therapy – Multi-drug treatment has been reported using both sequential and simultaneous therapies. Supporting data are limited to small case reports [50,56].
●Generally avoided – Azole therapy commonly results in treatment failure (around 50 percent) for patients with C. glabrata vaginitis [43,48].
Candida krusei — C. krusei is mostly resistant to fluconazole [43,57] but is usually susceptible to topical azole creams and suppositories, such as clotrimazole, miconazole, and terconazole (table 3) [51]. We treat with any of these topical azoles for 7 to 14 days (table 2). It is also likely to respond to oral itraconazole or ketoconazole (itraconazole 200 mg orally twice daily for 7 to 14 days or ketoconazole 400 mg orally daily for 7 to 14 days), but these oral agents have variable toxicity, so topical therapy is advised for first-line therapy. Idiosyncratic hepatotoxicity secondary to ketoconazole therapy is a concern but rare in this setting. 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 nonfluconazole therapies. For patients who have not responded adequately to azole treatment, oral ibrexafungerp may be tried, but the optimal dose and duration are not known.
Other non-albicans species — The optimal treatment of other NAC species is unknown. Treatment options include topical clotrimazole (100 mg in vagina daily for 14 days), nystatin (as above), or vaginal boric acid (as above) [43]. Other combination therapies have also been reported [50]. We prefer vaginal boric acid for patients who have not responded to azole treatments [43].
Recurrent infection — RVVC is defined as three or more episodes of confirmed symptomatic fungal infection within one year [5,58]. Discussion of RVVC management, including azole-resistant infection, is presented in detail in related content. (See "Candida vulvovaginitis in adults: Recurrent infection".)
FOLLOW-UP CARE AND SYMPTOM RECURRENCE
●Treatment response – Uncomplicated infections usually respond to treatment within a couple of days; complicated infection may require one to two weeks. There is no medical contraindication to sexual intercourse during treatment, but it may be uncomfortable until inflammation improves. Treatment of sexual partners is not indicated. (See 'Sex partners' below.)
●Symptom recurrence – Patients with symptom recurrence undergo repeat evaluation and testing to confirm fungal infection and exclude other causes and/or mixed infection. Correct and consistent treatment of the initial infection is also confirmed. (See "Candida vulvovaginitis: Clinical manifestations and diagnosis", section on 'Diagnostic approach'.)
●Repeat treatment – Patients with confirmed symptomatic VVC are again treated based on presence of uncomplicated or complicated infection. Patients who are candidates for ibrexafungerp may prefer this drug as an alternate to fluconazole. Patients with ≥3 confirmed VVC episodes in 12 months are treated for RVVC. (See "Candida vulvovaginitis in adults: Recurrent infection".)
PREVENTIVE AND COMPLEMENTARY TREATMENTS — Multiple VVC preventive treatments have been tried with little success, including oral nystatin, lactobacillus (oral or vaginal), other probiotics, and garlic [51,59-61]. Tea tree oil or vapor may have anti-Candida activity but clinical correlation is needed [62,63].
One exception is the patient who develops symptomatic yeast infection during or immediately after antibiotic therapy. For these patients, fluconazole (150 mg orally) at the start and end of antibiotic therapy may prevent post-antibiotic vulvovaginitis [64]. (See "Candida vulvovaginitis: Clinical manifestations and diagnosis", section on 'Risk factors'.)
UNIQUE POPULATIONS
Sex partners — Although sexual transmission of Candida species can occur, we and others do not recommend treatment of asymptomatic sex partners since sexual activity is not a significant cause of infection or reinfection [5,65]. The bulk of evidence from randomized trials does not support treatment of sexual partners [66-68], although this approach is somewhat controversial in individuals with confirmed recurrent VVC. One organization states no recommendation can be made for treating sex partners of patients with complicated (including recurrent) VVC as data specific to this population are lacking [5]. Treatment of recurrent VVC is presented in detail separately. (See "Candida vulvovaginitis in adults: Recurrent infection".)
Treatment of symptomatic males is reviewed separately. (See "Balanitis in adults".)
Lactating patients — Both topical azoles and oral fluconazole are compatible with breastfeeding but not all drugs have been studied.
●Nystatin – Nystatin is very poorly absorbed with oral ingestion (ie, the amount absorbed by the milk-fed infant is minimal) and thus the drug is compatible for use by lactating individuals [69,70].
●Fluconazole – Fluconazole is considered acceptable for use in lactating patients as the "amount excreted into breastmilk is less than the neonatal fluconazole dosage," and no adverse effects have been reported in breastfed infants or infants treated with parenteral fluconazole [71-73].
●Other topical azoles – Miconazole and clotrimazole are minimally absorbed from the vagina and thus are considered reasonable for use in lactating patients [74,75]. As butoconazole, tioconazole, and terconazole have not been studied during lactation, other drugs may be preferred [76-78].
Ibrexafungerp and oteseconazole are not used in pregnant or lactating patients because of concern for fetal and/or infant harm based on animal studies [11,15].
Allergy to fluconazole — Fluconazole allergy is uncommon in our practice the but the overall prevalence of fluconazole allergy in patients with acute VVC is unknown [51]. Fluconazole allergy can present with typical allergic symptoms that range in severity and include rash and, occasionally, angioedema. It is difficult to distinguish between isolated fluconazole allergy versus allergy to the entire azole class. Therefore, other oral azoles such as ketoconazole (commercial name Nizoral) or itraconazole (commercial name Sporanox) should not be prescribed to patients with true fluconazole allergy. Discussion with an allergist is recommended. There are no data on the efficacy of fluconazole desensitization, which is theoretically possible.
Treatment for patients with fluconazole allergy (severe rash and/or angioedema) and acute confirmed VVC include:
●Topical azole drugs – Either miconazole or clotrimazole can be prescribed, 500 to 1500 mg, in the vagina once (table 2). In general, miconazole is available as 100 mg or 200 mg vaginal suppositories while clotrimazole is available as 100 mg vaginal tablet; total dose of 500 to 1500 mg per treatment.
●Nystatin – Nystatin suppository 100,000 units in the vagina daily for seven days. Nystatin is a polyene antifungal.
●Ibrexafungerp – Ibrexafungerp is an oral triterpenoid antifungal for use in nonpregnant patients. Dosing is described above. (See 'Triterpenoid (ibrexafungerp)' above.)
●Vaginal boric acid – Vaginal boric acid 600 mg capsule in vagina daily for seven days. Boric acid can cause death if consumed orally.
Females taking tamoxifen — Tamoxifen is an estrogen receptor blocker and is widely used in patients with breast cancer. Paradoxically, tamoxifen may result in "agonist" or estrogen-like benign manifestations in the vagina, characterized by mild discharge and increased risk of VVC. We treat individuals taking tamoxifen who also have recurrent VVC, which is discussed separately, with maintenance fluconazole therapy. (See "Candida vulvovaginitis in adults: Recurrent infection".)
Male partners with postcoital hypersensitivity reaction — Uncommonly, male partners of individuals with vaginal Candida colonization can develop immediate postcoital itching and burning with redness and a rash of the penis. This postcoital syndrome probably represents an acute hypersensitivity reaction to Candida organisms or antigens in the partner's vagina, even in the absence of symptomatic vulvovaginitis.
●Condoms – Condom use (internal or external) typically prevents symptoms. (See "External (formerly male) condoms" and "Internal (formerly female) condoms".)
●Antifungal treatment for female sex partner – Males with recurrent postcoital symptoms benefit from immediate topical antimycotic therapy but symptoms will recur with next exposure to Candida organisms from the lower genital tract of the female sexual partner. This often requires the female partner to follow a long-term maintenance antimycotic regimen. (See "Candida vulvovaginitis in adults: Recurrent infection", section on 'Fluconazole'.)
●Symptom reduction – A postcoital shower and application of a topical low-potency corticosteroid to the penis may provide symptomatic relief within 12 to 24 hours (table 4). Penile cultures may remain positive for Candida despite normal physical findings.
Incidental finding — Treatment of Candida identified on a Pap smear of an asymptomatic person is not indicated because up to 20 percent of reproductive-aged women will be colonized with Candida species [79,80]. Similarly, individuals with Candida noted on an intrauterine device (IUD) that was cultured after removal do not require treatment in the absence of symptoms.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gynecologic infectious diseases (non-sexually transmitted)".)
SUMMARY AND RECOMMENDATIONS
●Whom to treat – The goal of treatment is to relieve symptoms. Asymptomatic individuals and sex partners do not require treatment. (See 'Whom to treat' above.)
●Uncomplicated infection in nonpregnant patients – For nonpregnant individuals with uncomplicated vulvovaginal candidiasis (VVC) (table 1), we suggest a single dose of oral fluconazole (150 mg) rather than other oral, multidose, or topical azole regimens (algorithm 1) (Grade 2C). While topical agents or ibrexafungerp are reasonable alternatives, patients generally prefer single-dose therapy for simplicity and prefer oral to vaginal treatment. Additionally, ibrexafungerp may be limited by availability and cost. (See 'Treatment' above.)
●Pregnancy – For pregnant persons, we suggest a topical azole vaginally for seven days (algorithm 3) (Grade 2C). Longer duration of topical therapy is typically needed to fully resolve the infection. Nystatin suppositories are a reasonable alternative if available. Oral azoles are not typically used because case reports have described a pattern of congenital anomalies (abnormalities of cranium, face, bones, and heart) after first-trimester exposure to high-dose oral azole therapy (400 to 800 mg/day) and cohort studies have reported conflicting data on risk of miscarriage. Ibrexafungerp and oteseconazole are contraindicated in pregnancy based on animal data. (See 'Pregnancy' above.)
●Severe symptoms or immunocompromise – For people with severe symptoms or immunocompromise, we suggest oral fluconazole (150 mg) in two sequential doses given three days apart rather than single-dose oral fluconazole, ibrexafungerp, or topical regimens (Grade 2C). While clinical trial data addressing these populations are limited, the rationale for the two-dose regimen rather than single-dose is that these patients have more severe infection and/or greater risk for recurrence. (See 'Severe symptoms or immunocompromise' above.)
●Non-albicans Candida infections – In most cases, the species is not known and treatment of Candida albicans is assumed. In some patients, such as those who have not responded to previous azole treatment, species information is available.
•For individuals with Candida glabrata infection who do not respond to azole therapy, we suggest intravaginal boric acid (600 mg capsule once daily at night for two weeks) (Grade 2C). Alternative treatments include intravaginal nystatin suppository 100,000 units daily, intravaginal amphotericin B suppository, flucytosine cream, ibrexafungerp, or voriconazole; selection is driven by availability. (See 'Candida glabrata' above.)
•For individuals with Candida krusei infection, we suggest treatment with a topical azole (cream or suppository) other than fluconazole (table 3) (Grade 2C). C. krusei is often resistant to fluconazole but is usually susceptible to clotrimazole, miconazole, and terconazole and intermittently susceptible to oral itraconazole and oral ketoconazole. (See 'Candida krusei' above.)
●Fluconazole allergy – The incidence of fluconazole allergy in patients with acute VVC is unknown but uncommon. Individuals with fluconazole allergy, including angioedema and severe rash, can receive topical azoles such as miconazole or clotrimazole. (See 'Allergy to fluconazole' above.)
●Sex partners – We do not treat sex partners of patients with acute VVC since treatment has not been shown to improve cure or reduce recurrence rates. However, for patients with confirmed recurrent vulvovaginal candidiasis (RVVC), treatment of sex partners is controversial. (See 'Sex partners' above.)
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