Candida vulvovaginitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Antifungal agents are indicated in candidiasis. Commonly used drugs include Amphotericin, Clotrimazole, Nystatin, Fluconazole and Ketoconazole. It is important to consider that Candida species are frequently part of the human body's normal oral and intestinal flora. Candidiasis is occasionally misdiagnosed by medical personnel as bacterial in nature, and treated with antibiotics against bacteria. This can lead to eliminating the yeast's natural competitors for resources, and increase the severity of the condition.

Medical Therapy

Acute Pharmacotherapy

In clinical settings, candidiasis is commonly treated with antimycotics - the antifungal drugs commonly used to treat candidiasis are topical clotrimazole, topical nystatin, fluconazole, and topical ketoconazole. In severe infections (generally in hospitalized patients), amphotericin B, caspofungin, or voriconazole may be used. Local treatment may include vaginal suppositories or medicated douches. Gentian violet can be used for breastfeeding thrush, but pediatrician recommends using it sparingly, since in large quantities it can cause mouth and throat ulcerations in nursing babies, and has been linked to mouth cancer in humans and to cancer in the digestive tract of other animals.

Dietary Therapy

One of the most potent nondrug or natural yeast-fighting substances is caprylic acid, a medium-chain fatty acid derived from coconut oil. Caprylic acid in capsule form is commonly sold as a dietary supplement in health food stores. It is very effective against Candida and other forms of fungi. It is even effective mixed with a little coconut oil or vitamin E oil as a topical application for fungal skin infections. Some cases of fungal infections that have lasted for months clear up in a matter of days using caprylic acid and a little coconut oil. It works just as effectively inside the body, killing fungi without the least bit of harm.

Polynesian women who eat their traditional coconut-based diet rarely, if ever, get yeast infections. Only in more temperate climates where processed vegetable oils are the main source of dietary fat are yeast infections, skin fungus, acne, and other skin infections big problems. Lauric acid, found in coconut oil, kills lipid-coated bacteria but does not appear to harm the friendly intestinal bacteria. Medium-Chain Fatty Acids (MCFA)s also have antifungal properties, so not only will they kill disease-causing bacteria and leave good bacteria alone but also they will kill Candida and other fungi in the intestinal tract, further supporting a healthy intestinal environment. Eating coconut oil on a regular basis, as the Polynesians do, helps to keep Candida and other harmful microorganisms at bay.

Some home remedies for candidiasis include the consumption or direct application of yogurt (which contains lactobacillus), probiotics, acidophilus tablets or salves, Pau d'arco tea, and even lightly crushed cloves of garlic, which yield allicin, an antifungal agent. Boric acid has also been used to treat yeast infections (by inserting gelcaps filled with boric acid powder into the vagina at bedtime for three to four consecutive nights). Eating a diet consisting primarily of green, fresh, raw vegetables also may give relief. Other alternative treatments consist in consuming a fermented beverage called Kefir.

While home remedies may offer relief in minor cases of infection (although a peer-reviewed study in Australia found yogurt ineffective as treatment for Candida albicans), seeking medical attention may be necessary, especially if the extent of the infection cannot be judged accurately by the patient. For instance, oral thrush is visible only at the upper digestive tract, but it may be that the lower digestive tract is likewise colonized by Candida species.

Treating candidiasis solely with medication may not give desired results, and other underlying causes require consideration. As an example, oral candidiasis is often linked to the use of inhaled corticosteroids in asthma medication. Patients on long-term inhaled corticosteroids should rinse their mouths after each dose of steroids to counteract this effect. Oral candidiasis can also be the sign of a more serious condition, such as HIV infection, or other immunodeficiency diseases. Following the health tips at vulvovaginal health can help prevent vaginal candidiasis.

Babies with diaper rash should have their diaper areas kept clean, dry, and exposed to air as much as possible. Sugars assist the overgrowth of yeast, possibly explaining the increased prevalence of yeast infections in patients with diabetes mellitus, as noted above. As many Candida spp. reside in the digestive tract, dietary changes may be effective for preventing or during a Candida infection. Due to its requirement for readily fermentable carbon sources, such as mono- or dimeric sugars (e.g., sucrose, glucose, lactose) and starch, avoiding foods that contain these nutrients in high abundance may help to prevent excessive Candida growth. Breast milk is a suitable growth substrate for yeasts, and both nursing mother and baby need to be treated (even if both are not symptomatic) to prevent thrush from being passed between mother and child.

Candiduria

Asymptomatic Candiduria

It is not recommended to treat asymptomatic candidiuria in otherwise healthy or predisposed patients because mostly it's self limited and resolves spontaneously,and to avoid recurrence and treatment complications. However, removal of the urine catheter is advised when possible. For patients with a risk of disseminated candidiasis or undergoing invasive urological procedure, antifungal therapy is required.

Antimicrobial Regimen

• Candidiasis

• 1. Candidemia

• 1.1. Nonneutropenic adults

• Preferred regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
• Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
• Preferred regimen (3): Micafungin 100 mg daily
• Preferred regimen (4): Anidulafungin 200 mg loading dose, THEN 100 mg daily
• Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
• Alternative regimen (2): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily
• Alternative regimen (3): Voriconazole 400 mg (6 mg/kg) PO/IV bid for 2 doses, THEN 200 mg (3 mg/kg) bid
• Note (1): Echinocandin includes Anidulafungin, Micafungin and Caspofungin.
• Note (2): Choose an echinocandin for moderately severe to severe illness and for patients with recent azole exposure.
• Note (3): Treat for 14 days after first negative blood culture result and resolution of signs and symptoms associated with candidemia.
• Note (4): Ophthalmological examination recommended for all patients.

• 1.2. Neutropenic patients

• Preferred regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily
• Preferred regimen (2): Micafungin 100 mg daily
• Preferred regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily
• Preferred regimen (4): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
• Alternative regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
• Alternative regimen (2): Voriconazole 400 mg (6 mg/kg) bid for 2 doses, THEN 200 mg (3 mg/kg) bid
• Note: Fluconazole is recommended for patients without recent azole exposure and who are not critically ill.

• 2. Suspected candidiasis treated with empiric antifungal therapy

• 2.1. Nonneutropenic patients

• Preferred regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
• Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
• Preferred regimen (3): Micafungin 100 mg daily
• Preferred regimen (4): Anidulafungin 200 mg loading dose, THEN 100 mg daily
• Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
• Alternative regimen (2): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily
• Note (1): Duration of therapy is uncertain, but should be discontinued if cultures and/or serodiagnostic tests have negative results.
• Note (2): Echinocandin includes Anidulafungin, Micafungin and Caspofungin.
• Note (3): Echinocandin is preferred for patients with recent azole exposure, patients with moderately severe to severe illness, or patients who are at high risk of infection due to C. glabrata or C. krusei.
• Note (4): Empirical antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever and should be based on clinical assessment of risk factors, serologic markers for invasive candidiasis, and/or culture data from nonsterile sites

• 2.2. Neutropenic patients

• Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
• Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
• Preferred regimen (3): Voriconazole 400 mg (6 mg/kg) bid for 2 doses, THEN 200 mg (3 mg/kg) bid
• Alternative regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
• Alternative regimen (2): Itraconazole 200 mg (3 mg/ kg) bid
• Note (1): In most neutropenic patients, it is appropriate to initiate empiric antifungal therapy after 4 days of persistent fever despite antibiotics.
• Note (2): Do not use an azole in patients with prior azole prophylaxis.

• 3. Urinary tract infection

• 3.1. Asymptomatic cystitis

• Preferred regimen: Therapy not usually indicated, unless patients are at high risk (e.g., neonates and neutropenic adults) or undergoing urologic procedures.
• Note (1): Elimination of predisposing factors recommended
• Note (2): For high-risk patients, treat as for disseminated candidiasis
• Note (3): For patients undergoing urologic procedures, fluconazole, 200–400 mg (3–6 mg/kg) daily or Amphotericin B deoxycholate(AmB-d) 0.3–0.6 mg/kg daily for several days before and after the procedure.

• 3.2. Symptomatic cystitis

• Preferred regimen: Fluconazole 200 mg (3 mg/kg) daily for 2 weeks
• Alternative regimen (1): Amphotericin B deoxycholate(AmB-d) 0.3–0.6 mg/kg for 1–7 days
• Alternative regimen (2): Flucytosine 25 mg/kg qid for 7–10 days
• Note: Amphotericin B deoxycholate(AmB-d) bladder irrigation is recommended only for patients with refractory fluconazole-resistant organisms (e.g., Candida krusei and Candida glabrata).

• 3.3 Pyelonephritis

• Preferred regimen (1): Fluconazole 200–400 mg (3–6 mg/kg) daily for 2 weeks
• Alternative regimen (1): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily ± Flucytosine (5-FC) 25 mg/kg qid
• Alternative regimen (2): Flucytosine (5-FC) 25 mg/kg qid for 2 weeks
• Note: For patients with pyelonephritis and suspected disseminated candidiasis, treat as for candidemia.

• 4. Urinary fungus balls

• Preferred regimen (1): Surgical removal strongly recommended
• Preferred regimen (2): Fluconazole 200–400 mg (3–6 mg/kg) daily
• Preferred regimen (3): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily ± Flucytosine (5-FC) 25 mg/kg qid
• Note (1): Local irrigation with Amphotericin B deoxycholate(AmB-d) may be a useful adjunct to systemic antifungal therapy.
• Note (2): Treatment duration should be until symptoms have resolved and urine cultures no longer yield Candida species.

• 5. Vulvovaginal candidiasis

• Preferred regimen (1): Butoconazole 2% cream 5 g intravaginally for 3 days
• Preferred regimen (2): Butoconazole 2% cream 5 g (butoconazole1-sustained release), single intravaginal application
• Preferred regimen (3): Clotrimazole 1% cream 5 g intravaginally for 7–14 days
• Preferred regimen (4): Clotrimazole 100-mg vaginal tablet for 7 days
• Preferred regimen (5): Clotrimazole 100-mg vaginal tablet, 2 tablets for 3 days
• Preferred regimen (6): Miconazole 2% cream 5 g intravaginally for 7 days
• Preferred regimen (7): Miconazole 100-mg vaginal suppository, 1 suppository for 7 days
• Preferred regimen (8): Miconazole 200-mg vaginal suppository, 1 suppository for 3 days
• Preferred regimen (9): Miconazole 1200-mg vaginal suppository, 1 suppository for 1 day
• Preferred regimen (10): Nystatin 100,000-unit vaginal tablet, 1 tablet for 14 days
• Preferred regimen (11): Tioconazole 6.5% ointment 5 g intravaginally in a single application
• Preferred regimen (12): Terconazole 0.4% cream 5 g intravaginally for 7 days
• Preferred regimen (13): Terconazole 0.4% cream 5 g intravaginally for 3 days
• Preferred regimen (14): Terconazole 80-mg vaginal suppository, 1 suppository for 3 days
• Preferred regimen (15): Fluconazole 150 mg single dose for uncomplicated vaginitis
• Note: For recurring Candida Vulvovaginal candidiasis (VVC), 10–14 days of induction therapy with a topical or oral azole, followed by fluconazole at a dosage of 150 mg once per week for 6 months, is recommended

• 6. Chronic disseminated candidiasis

• Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) daily for stable patients
• Preferred regimen (2): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily for severely ill patients
• Preferred regimen (3): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily for severely ill patients
• Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily, followed by oral Fluconazole when clinically appropriate
• Alternative regimen (2): Micafungin 100 mg daily, followed by oral Fluconazole when clinically appropriate
• Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily, followed by oral Fluconazole when clinically appropriate
• Note (1): Transition from Lipid formulation of amphotericin B(LFAmB) or Amphotericin B deoxycholate(AmB-d) to fluconazole is favored after several weeks in stable patients.
• Note (2): Duration of therapy is until lesions have resolved (usually months) and should continue through periods of immunosuppression (e.g., chemotherapy and transplantation).
• Note (3): Therapy should be continued for weeks to months, until calcification occurs or lesions resolve.

• 7. Candida osteoarticular infection

• 7.1. Osteomyelitis

• Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) daily for 6–12 months
• Preferred regimen (2): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily for at least 2 weeks, then Fluconazole 400 mg daily for 6–12 months
• Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
• Alternative regimen (2): Micafungin 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
• Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
• Alternative regimen (4): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
• Note (1): Duration of therapy usually is prolonged (6–12 months)
• Note (2): Surgical debridement is frequently necessary

• 7.2. Septic arthritis

• Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) for at least 6 weeks
• Preferred regimen (2): Lipid formulation of amphotericin B (LFAmB) 3–5 mg/kg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
• Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
• Alternative regimen (2): Micafungin 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
• Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
• Note (1): Duration of therapy usually is for at least 6 weeks, but few data are available.
• Note (2): Surgical debridement is recommended for all cases.
• Note (3): For infected prosthetic joints, removal is recommended for most cases.

• 8. CNS candidiasis

• Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid for several weeks followed by Fluconazole 400–800 mg (6–12 mg/kg) daily
• Alternative regimen (1): Fluconazole 400–800 mg (6–12 mg/ kg) daily for patients unable to tolerate Lipid formulation of amphotericin B (LFAmB)
• Note (1): Treat until all signs and symptoms, CSF abnormalities, and radiologic abnormalities have resolved.
• Note (2): Removal of intraventricular devices is recommended.

• 9. Candida endophthalmitis

• Preferred regimen (1): Amphotericin B deoxycholate(AmB-d) 0.7–1 mg/kg AND Flucytosine 25 mg/ kg qid
• Preferred regimen (2): Fluconazole 400–800 mg daily (loading dose of 12 mg/kg then 6–12 mg/kg daily) is an acceptable alternative for less severe endophthalmitis
• Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily
• Alternative regimen (2): Voriconazole 6 mg/kg q12h for 2 doses, then 3–4 mg/kg q12h
• Alternative regimen (3): Caspofungin 70 mg loading dose, THEN 50 mg daily
• Alternative regimen (4): Micafungin 100 mg daily
• Alternative regimen (5): Anidulafungin 200 mg loading dose, THEN 100 mg daily
• Note (1): Alternative therapy is recommended for patients intolerant of or experiencing failure of Amphotericin B and Flucytosine therapy
• Note (2): Duration of therapy is at least 4–6 weeks as determined by repeated examinations to verify resolution.
• Note (3): Diagnostic vitreal aspiration should be done if etiology unknown.
• Note (4): Fluconazole at a dosage of 400–800 mg daily (loading dose of 12 mg/kg then 6–12 mg/kg daily) is an acceptable alternative for less severe endophthalmitis
• Note (5): Surgical intervention for patients with severe endophthalmitis or vitreitis

• 10. Candida infection of the cardiovascular system

• 10.1. Endocarditis

• Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid
• Preferred regimen (2): Amphotericin B deoxycholate AmB-d 0.6–1 mg/kg daily ± Flucytosine 25 mg/kg qid
• Preferred regimen (3): Caspofungin 50–150 mg daily
• Preferred regimen (4): Micafungin 100–150 mg daily
• Preferred regimen (5): Anidulafungin 100–200 mg daily
• Alternative regimen (1): Step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily for susceptible organism in stable patient with negative blood culture results
• Note (1): Valve replacement is strongly recommended.
• Note (2): For those who are unable to undergo surgical removal of the valve, chronic suppression with fluconazole 400–800 mg (6–12 mg/kg) daily is recommended.
• Note (3): Lifelong suppressive therapy for prosthetic valve endocarditis if valve cannot be replaced is recommended.

• 10.2. Pericarditis or myocarditis

• Preferred regimen (1): Lipid formulation of amphotericin B (LFAmB) at a dosage of 3–5 mg/kg daily
• Preferred regimen (2): Fluconazole 400–800 mg (6–12 mg/kg) daily
• Preferred regimen (3): Caspofungin 50–150 mg daily
• Preferred regimen (4): Micafungin 100–150 mg daily
• Preferred regimen (5): Anidulafungin 100–200 mg daily
• Alternative regimen (1): After stable, step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily
• Note(1): Therapy is often for several months, but few data are available
• Note(2): A pericardial window or pericardiectomy is recommended.

• 10.3. Suppurative thrombophlebitis

• Preferred regimen (1): Lipid formulation of amphotericin B (LFAmB) at a dosage of 3–5 mg/kg daily
• Preferred regimen (2): Fluconazole 400–800 mg (6–12 mg/kg) daily
• Preferred regimen (3): Caspofungin 50–150 mg daily
• Preferred regimen (4): Micafungin 100–150 mg daily
• Preferred regimen (5): Anidulafungin 100–200 mg daily
• Alternative regimen (1): After stable, step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily
• Note(1): Surgical incision and drainage or resection of the vein is recommended if feasible.
• Note(2): Treat for at least 2 weeks after candidemia has cleared.

• 10.4. Infected pacemaker, ICD, or VAD

• Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid
• Preferred regimen (2): Amphotericin B deoxycholate (AmB-d) 0.6–1 mg/kg daily ± Flucytosine 25 mg/kg qid
• Preferred regimen (3): Caspofungin 50–150 mg daily
• Preferred regimen (4): Micafungin 100–150 mg daily
• Preferred regimen (5): Anidulafungin 100–200 mg daily
• Alternative regimen (1): Step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily for susceptible organism in stable patient with negative blood culture results
• Note(1): Removal of pacemakers and ICDs strongly recommended.
• Note(2): Treat for 4–6 weeks after the device removed.
• Note(3): For VAD that cannot be removed, chronic suppressive therapy with fluconazole is recommended.

• 11. Neonatal candidiasis

• Preferred regimen (1): Amphotericin B deoxycholate (AmB-d) 1 mg/kg daily for 3 weeks
• Preferred regimen (2): Fluconazole 12 mg/kg daily for 3 weeks
• Alternative regimen (1): Lipid formulation of amphotericin B (LFAmB) 3–5 mg/kg daily for 3 weeks
• Note (1): A lumbar puncture and dilated retinal examination should be performed on all neonates with suspected invasive candidiasis.
• Note (2): Intravascular catheter removal is strongly recommended.
• Note (3): Duration of therapy is at least 3 weeks.
• Note (4): Lipid formulation of amphotericin B (LFAmB) used only if there is no renal involvement.
• Note (5): Echinocandins should be used with caution when other agents cannot be used.

• 12. Candida isolated from respiratory secretions

• Preferred regimen (1): Therapy not recommended
• Note (1): Candida lower respiratory tract infection is rare and requires histopathologic evidence to confirm a diagnosis.

• 13. Nongenital mucocutaneous candidiasis

• 13.1. Oropharyngeal

• Preferred regimen (1): Clotrimazole troches 10 mg 5 times daily
• Preferred regimen (2): Nystatin suspension at a concentration of 100,000 U/mL and a dosage of 4–6 mL qid OR 1–2 Nystatin pastilles (200,000 U each) administered qid for 7–14 days
• Preferred regimen (3): Fluconazole 100–200 mg PO (3 mg/kg) daily for 7–14 days
• Alternative regimen (1): Itraconazole solution 200 mg daily
• Alternative regimen (2): Posaconazole suspension at a dosage of 400 mg twice daily for 3 days, THEN 400 mg daily for up to 28 days
• Alternative regimen (3): Voriconazole 200 mg bid
• Alternative regimen (4): Amphotericin B deoxycholate (AmB-d) 1-mL oral suspension administered at a dosage of 100 mg/mL qid
• Alternative regimen (5): Caspofungin 70 mg IV loading dose, THEN 50 mg daily
• Alternative regimen (6): Micafungin 100 mg IV daily
• Alternative regimen (7): Anidulafungin 200 mg IV loading dose, THEN 100 mg daily
• Alternative regimen (8): Amphotericin B deoxycholate (AmB-d) 0.3 mg/kg daily
• Note(1): Fluconazole is recommended for moderate-to-severe disease, and topical therapy with clotrimazole or nystatin is recommended for mild disease.
• Note(2): Treat uncomplicated disease for 7–14 days.
• Note(3): For refractory disease, itraconazole, voriconazole, posaconazole, or AmB suspension is recommended.

• 13.2. Esophageal

• Preferred regimen (1): Fluconazole 200–400 mg (3–6 mg/kg) PO daily
• Preferred regimen (2): Caspofungin 70 mg IV loading dose, THEN 50 mg daily
• Preferred regimen (3): Micafungin 100 mg IV daily
• Preferred regimen (4): Anidulafungin 200 mg IV loading dose, THEN 100 mg daily
• Preferred regimen (4): AmB-d 0.3–0.7 mg/kg daily
• Alternative regimen (1): Itraconazole oral solution 200 mg daily
• Alternative regimen (2): Posaconazole 400 mg bid
• Alternative regimen (3): Voriconazole 200 mg bid
• Note(1): Oral fluconazole is preferred.
• Note(2): For patients unable to tolerate an oral agent, IV fluconazole, an echinocandin, or AmB-d is appropriate.
• Note(3): Treat for 14–21 days.
• Note(4): For patients with refractory disease, the alternative therapy as listed or AmB-d or an echinocandin is recommended.