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Am Fam Physician. 2009;80(5):525-530

Guideline source: Infectious Diseases Society of America

Literature search described? Yes

Evidence rating system used? Yes

Published source: Clinical Infectious Diseases, March 1, 2009

Available at: http://www.journals.uchicago.edu/doi/full/10.1086/596757

Since the Infectious Diseases Society of America (IDSA) published its clinical guideline on the management of candidiasis in 2004, several new antifungal agents have become available, and studies have provided new evidence on the treatment of candidemia; other forms of invasive candidiasis; and mucosal disease, including oropharyngeal and esophageal candidiasis. In light of these new findings, the IDSA has published updated recommendations. The most significant changes are discussed below, and the full recommendations (including dosing regimens) are summarized in Table 1.

ConditionTherapyComments
PrimaryAlternative
Candida isolated from respiratory secretionsTherapy not recommended (A-III)Lower respiratory tract infection with Candida is rare and requires histopathologic evidence to confirm diagnosis.
Candida osteoarticular infection
OsteomyelitisFluconazole (Diflucan), 400 mg (6 mg per kg) daily for six to 12 months; or LFAmB, 3 to 5 mg per k daily for several weeks, then fluconazole for six to 12 months (B-III)An echinocandin* or AmB-d, 0.5 to 1 mg per kg daily for several weeks, then fluconazole for six to 12 months (B-III)Duration of therapy is usually six to 12 months; surgical debridement may be necessary.
Septic arthritisFluconazole, 400 mg (6 mg per kg) daily for at least six weeks; or LFAmB, 3 to 5 mg per kg daily for several weeks, then fluconazole to completion (B-III)An echinocandin* or AmB-d, 0.5 to 1 mg per kg daily for several weeks, then fluconazole to completion (B-III)Duration of therapy is usually at least six weeks, but few data are available; surgical debridement is recommended; removal of infected prosthetic joints is usually recommended.
Central nervous system candidiasisLFAmB, 3 to 5 mg per kg, with or without flucytosine (Ancobon), 25 mg per kg, four times daily for several weeks, followed by fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily (B-III)Fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily for patients who cannot tolerate LFAmBTreat until all signs and symptoms, cerebrospinal fluid abnormalities, and radiologic abnormalities have resolved; removal of intraventricular devices is recommended.
Candida endophthalmitisAmB-d, 0.7 to 1 mg per kg, with flucytosine, 25 mg per kg, four times daily (A-III); or fluconazole, 6 to 12 mg per kg daily (B-III); surgical intervention in patients with severe endophthalmitis or vitreitis (B-III)LFAmB, 3 to 5 mg per kg daily; voriconazole (Vfend), 6 mg per kg every 12 hours for two doses, then 3 to 4 mg per kg every 12 hours; or an echinocandin* (B-III)Alternative therapy is recommended for patients who cannot tolerate or who fail therapy with amphotericin B or flucytosine; duration of therapy is at least four to six weeks, as determined by repeated examinations to verify resolution; diagnostic vitreal aspiration should be done if etiology is unknown.
Candida infection of the cardiovascular system
EndocarditisLFAmB, 3 to 5 mg per kg, with or without flucytosine, 25 mg per kg, four times daily; or AmB-d, 0.6 to 1 mg per kg daily, with or without flucytosine, 25 mg per kg four times daily; or an echinocandin† (B-III)Step-down therapy to fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily, for susceptible organism in stable patients with negative blood cultures (B-III)Valve replacement is strongly recommended; in patients who are unable to undergo surgical removal of the valve, chronic suppression with fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily, is recommended; lifelong suppressive therapy is recommended for prosthetic valve endocarditis if valve cannot be replaced.
Pericarditis or myocarditisLFAmB, 3 to 5 mg per kg daily; or fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily; or an echinocandin† (B-III)After patient is stable, step-down therapy to fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily (B-III)Duration of therapy is often several months, but few data are available; a pericardial window or pericardiectomy is recommended.
Suppurative thrombophlebitisLFAmB, 3 to 5 mg per kg daily; or fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily; or an echinocandin† (B-III)After patient is stable, step-down therapy to fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily (B-III)Surgical incision and drainage or resection of the vein is recommended, if feasible; treat for at least two weeks after candidemia has resolved.
Infected pacemaker, ICD, or VADLFAmB, 3 to 5 mg per kg, with or without flucytosine, 25 mg per kg, four times daily; or AmB-d, 0.6 to 1 mg per kg daily, with or without flucytosine, 25 mg per kg four times daily; or an echinocandin† (B-III)Step-down therapy to fluconazole, 400 to 800 mg (6 to 12 mg per kg) daily, for susceptible organism in stable patients with negative blood cultures (B-III)Removal of pacemakers and ICDs is strongly recommended; treat for four to six weeks after the device is removed; in patients with VADs that cannot be removed, chronic suppressive therapy with fluconazole is recommended.
Candidemia
Neutropenic patientsAn echinocandin* or LFAmB, 3 to 5 mg per kg daily (A-II)Fluconazole, 800-mg (12-mg per kg) loading dose, then 400 mg (6 mg per kg) daily; or voriconazole, 400 mg (6 mg per kg) twice daily for two doses, then 200 mg (3 mg per kg) twice daily (B-III)An echinocandin or LFAmB is preferred for most patients; fluconazole is recommended for patients without recent azole exposure who are not critically ill; voriconazole is recommended when additional coverage for molds is desired; intravascular catheter removal is advised but controversial.
Nonneutropenic patientsFluconazole, 800-mg (12-mg per kg) loading dose, then 400 mg (6 mg per kg) daily; or an echinocandin* (A-I)LFAmB, 3 to 5 mg per kg daily; or AmB-d, 0.5 to 1 mg per kg daily; or voriconazole, 400 mg (6 mg per kg) twice daily for two doses, then 200 mg (3 mg per kg) twice daily (A-I)An echinocandin should be used in patients with moderately severe to severe illness and in those with recent azole exposure; transition to fluconazole after initial echinocandin may be appropriate; intravascular catheter removal is recommended, if possible; treat for 14 days after first negative blood culture and resolution of signs and symptoms of candidemia; ophthalmologic examination is recommended.
Chronic disseminated candidiasisFluconazole, 400 mg (6 mg per kg) daily, for stable patients (A-III); LFAmB, 3 to 5 mg per kg daily, or AmB-d, 0.5 to 0.7 mg per kg daily, for severely ill patients (A-III); after patient is stable, change to fluconazole (B-III)An echinocandin* for several weeks, followed by fluconazole (B-III)Transition from LFAmB or AmB-d to fluconazole is favored after several weeks in stable patients; duration of therapy is until lesions have resolved (usually months) and should continue through periods of immunosuppression (e.g., chemotherapy, transplantation).
Neonatal candidiasisAmB-d, 1 mg per kg daily (A-II); or fluconazole, 12 mg per k daily (B-II) for three weeksLFAmB, 3 to 5 mg per kg daily (B-III)Lumbar puncture and dilated retinal examination should be performed in all neonates with suspected invasive candidiasis; intravascular catheter removal is strongly recommended; duration of therapy is at least three weeks; LFAmB should be used only if there is no renal involvement; echinocandins should be used with caution if other agents cannot be used.
Nongenital mucocutaneous candidiasis
OropharyngealClotrimazole troche (formerly Mycelex Troche), 10 mg five times daily; nystatin suspension or pastilles four times daily (B-II); or fluconazole, 100 to 200 mg daily (A-I)Itraconazole (Sporanox) solution, 200 mg daily; or posaconazole (Noxafil), 400 mg daily (A-II); or voriconazole, 200 mg twice daily; or amphotericin B oral suspension (B-II); IV echinocandin* or AmB-d, 0.3 mg per kg daily (B-II)Fluconazole is recommended for patients with moderate to severe disease, and topical therapy with clotrimazole or nystatin is recommended for those with mild disease; uncomplicated disease should be treated for one to two weeks; for patients with refractory disease, itraconazole, voriconazole, posaconazole, or amphotericin B suspension is recommended.
EsophagealFluconazole, 200 to 400 mg (3 to 6 mg per kg) daily (A-I); an echinocandin*; or AmB-d, 0.3 to 0.7 mg per kg daily (B-II)Itraconazole solution, 200 mg daily; or posaconazole, 400 mg twice daily; or voriconazole, 200 mg twice daily (A-III)Oral fluconazole is preferred; an echinocandin or AmB-d is appropriate for patients who cannot tolerate an ral agent; duration of therapy is two to three weeks; for patients with refractory disease, the alternative therapy, AmB-d, or an echinocandin is recommended.
Suspected candidiasis treated with empiric antifungal therapy
Neutropenic patientsLFAmB, 3 to 5 mg per kg daily; caspofungin (Cancidas), 70-mg loading dose, then 50 mg daily (A-I); or voriconazole, 400 mg (6 mg per kg) twice daily for two doses, then 200 mg (3 mg per kg) twice daily (B-I)Fluconazole, 800-mg (12-mg per kg) loading dose, then 400 mg (6 mg per kg) daily; or itraconazole, 200 mg (3 mg per kg) twice daily (B-I)In most neutropenic patients, it is appropriate to initiate empiric antifungal therapy after four days of persistent fever despite antibiotic use; serodiagnostic tests and computed tomography imaging may be helpful; azoles should not be used in patients with previous azole prophylaxis.
Nonneutropenic patientsFluconazole, 800-mg (12-mg per kg) loading dose, then 400 mg (6 mg per kg) daily; or an echinocandin* (B-III)LFAmB, 3 to 5 mg per kg daily, or AmB-d, 0.5 to 1 mg per kg daily (B-III)An echinocandin is preferred for patients with moderately severe to severe illness and/or recent azole exposure; selection of appropriate patients should be based on clinical risk factors, serologic tests, and culture data; duration of therapy is uncertain, but treatment should be discontinued if cultures or serodiagnostic tests are negative.
Urinary tract infection
Asymptomatic cystitisTherapy not usually indicated, unless patient is at high risk (e.g., neonates, neutropenic adults) or is undergoing urologic procedures (A-III)Elimination of predisposing factors is recommended; for high-risk patients, treat as for disseminated candidiasis; for patients undergoing urologic procedures, use fluconazole, 200 to 400 mg (3 to 6 mg per kg) daily, or AmB-d, 0.3 to 0.6 mg per kg daily, for several days before and after the procedure.
Symptomatic cystitisFluconazole, 200 mg (3 mg per kg) daily for two weeks (A-III)AmB-d, 0.3 to 0.6 mg per kg for one to seven days; or flucytosine, 25 mg per kg four times daily for seven to 10 days (B-III)Alternative therapy is recommended for patients with fluconazole-resistant organisms; AmB-d bladder irrigation is recommended only for patients with refractory fluconazole-resistant organisms (e.g., Candida krusei, Candida glabrata).
PyelonephritisFluconazole, 200 to 400 mg (3 to 6 mg per kg) daily for two weeks (B-III)AmB-d, 0.5 to 0.7 mg per kg daily, with or without flucytosine, 25 mg per kg four times daily; or flucytosine alone for two weeks (B-III)For patients with pyelonephritis and suspected disseminated candidiasis, treat as for candidemia.
Urinary fungus ballsSurgical removal strongly recommended (B-III); fluconazole, 200 to 400 mg (3 to 6 mg per kg) daily; or AmB-d, 0.5 to 0.7 mg per kg daily, with or without flucytosine, 25 mg per kg four times daily (B-III)Local irrigation with AmB-d may be a useful adjunct to systemic antifungal therapy.
Vulvovaginal candidiasisTopical agents or fluconazole, 150-mg single dose, for uncomplicated vaginitis (A-I)Recurrent vulvovaginal candidiasis is managed with fluconazole, 150 mg weekly for six months after initial control of the recurrent episode.

Candidemia

NONNEUTROPENIC PATIENTS

Initial therapy for most nonneutropenic adults with candidemia should be fluconazole (Diflucan) or an echinocandin (e.g., caspofungin [Cancidas], anidulafungin [Eraxis], micafungin [Mycamine]). Echinocandins are preferred in patients with moderately severe to severe illness and in patients who have had recent azole exposure. Fluconazole is recommended for patients who are less critically ill and who have not been recently exposed to azoles. The same approach, with differences in dosing regimens, is advised for children.

An echinocandin is also preferred for patients infected with Candida glabrata; transitioning to fluconazole or voriconazole (Vfend) is not recommended without confirmation of isolate susceptibility. Patients who initially received fluconazole or voriconazole can continue azole therapy if they are clinically improved and have negative follow-up cultures.

Fluconazole is recommended for patients with Candida parapsilosis infection. Patients who initially received an echinocandin can continue therapy if they are clinically improved and have negative follow-up cultures.

Patients who cannot tolerate other antifungals can be given amphotericin B deoxycholate or a lipid formulation of amphotericin B (LFAmB). Transitioning to fluconazole is recommended if the isolates are likely to be susceptible to f luconazole.

Voriconazole is effective for candidemia, but offers little advantage over fluconazole and is recommended as step-down oral therapy for select patients with candidiasis from Candida krusei or voriconazolesusceptible C. glabrata.

In patients without obvious metastatic complications, therapy should continue for two weeks after resolution of symptoms and documented evidence of clearance of Candida from the bloodstream. Intravenous catheter removal is strongly recommended for nonneutropenic patients with candidemia.

NEUTROPENIC PATIENTS

An echinocandin is recommended for most neutropenic patients with candidemia. Those who are less critically ill and who have not been recently exposed to azoles can be given fluconazole as an alternative. Voriconazole can be used if additional mold coverage is desired.

Patients with infections from C. glabrata should be treated with an echinocandin. LFAmB is an effective but less desirable alternative. Patients who initially received fluconazole or voriconazole can continue azole therapy if they are clinically improved and have negative follow-up cultures.

Patients with infections from C. parapsilosis should be treated initially with fluconazole or LFAmB. Patients who initially received an echinocandin can continue therapy if they are clinically improved and have negative follow-up cultures. An echinocandin, LFAmB, or voriconazole is recommended for infections from C. krusei.

In patients without persistent fungemia or metastatic complications, therapy should continue for two weeks after resolution of symptoms and neutropenia, and documented evidence of clearance of Candida from the bloodstream. Intravenous catheter removal should be considered.

Empiric Treatment for Suspected Invasive Candidiasis

NONNEUTROPENIC PATIENTS

Empiric therapy for suspected candidiasis is similar to that for proven candidiasis. Fluconazole or an echinocandin is recommended as initial therapy. An echinocandin is preferred for patients who have been recently exposed to azoles, whose illness is moderately severe to severe, or who are at high risk of C. glabrata or C. krusei infection. Amphotericin B deoxycholate or LFAmB is an alternative for patients who cannot tolerate other antifungals.

Empiric therapy should be considered for critically ill patients with risk factors for invasive candidiasis and no other known cause of fever. It should be based on clinical assessment of risk factors, serologic markers for invasive candidiasis, and/or cultures from nonsterile sites.

NEUTROPENIC PATIENTS

LFAmB, caspofungin, or voriconazole is recommended for empiric treatment of suspected candidiasis in neutropenic patients. Fluconazole and itraconazole (Sporanox) are alternatives. Amphotericin B deoxycholate is an effective alternative, but confers a higher risk of toxicity than LFAmB.

Azoles should not be used for empiric therapy in patients who have received an azole for prophylaxis.

Neonatal Candidiasis

Amphotericin B deoxycholate is recommended for neonates with disseminated candidiasis. LFAmB can be used if urinary tract involvement is excluded. Fluconazole is a reasonable alternative.

A lumbar puncture and dilated retinal examination, preferably by an ophthalmologist, are recommended in neonates with sterile body fluid and/or urine cultures that are positive for Candida. Imaging of the genitourinary tract, liver, and spleen should be performed if the results of sterile body fluid cultures are persistently positive.

Echinocandins should be used with caution and are generally limited to situations in which resistance or toxicity precludes the use of fluconazole or amphotericin B deoxycholate.

Intravascular catheter removal is strongly recommended in this population. In nurseries with high rates of invasive candidiasis, fluconazole prophylaxis can be considered in neonates whose birth weight is less than 1,000 g. Antifungal drug resistance, drug-related toxicity, and neurodevelopmental outcomes should be observed.

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