Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.
There have been several significant changes in the management of candidiasis since the last publication of these guidelines in January 2004. Most of these changes relate to the appropriate use of echinocandins and expanded spectrum azoles in the management of candidemia, other forms of invasive candidiasis, and mucosal candidiasis. For some of the less common forms of invasive candidiasis (e.g., chronic disseminated candidiasis, osteomyelitis, and CNS disease), there are few new treatment data since 2004, with only anecdotal experience, case reports, or small series providing some evidence to support new approaches to therapy. Each section of the Guideline begins with a specific clinical question and is followed by numbered recommendations and a summary of the most-relevant evidence in support of the recommendations. The most significant changes and/or additions to existing recommendations are described below in the Executive Summary. The remaining topics are discussed in greater detail in the main body of the guidelines.
Fluconazole (loading dose of 800 mg [12 mg/kg], then 400 mg [6 mg/kg] daily) or an echinocandin (caspofungin: loading dose of 70 mg, then 50 mg daily; micafungin: 100 mg daily; anidulafungin: loading dose of 200 mg, then 100 mg daily) is recommended as initial therapy for most adult patients (A-I). The Expert Panel favors an echinocandin for patients with moderately severe to severe illness or for patients who have had recent azole exposure (A-III). Fluconazole is recommended for patients who are less critically ill and who have had no recent azole exposure (A-III). The same therapeutic approach is advised for children, with attention to differences in dosing regimens.
Transition from an echinocandin to fluconazole is recommended for patients who have isolates that are likely to be susceptible to fluconazole (e.g., Candida albicans) and who are clinically stable (A-II).
For infection due to Candida glabrata, an echinocandin is preferred (B-III). Transition to fluconazole or voriconazole therapy is not recommended without confirmation of isolate susceptibility (B-III). For patients who have initially received fluconazole or voriconazole, are clinically improved, and whose follow-up culture results are negative, continuing use of an azole to completion of therapy is reasonable (B-III).
For infection due to Candida parapsilosis, treatment with fluconazole is recommended (B-III). For patients who have initially received an echinocandin, are clinically improved, and whose follow-up culture results are negative, continuing use of an echinocandin is reasonable (B-III).
Amphotericin B deoxycholate (AmB-d) administered at a dosage of 0.5–1.0 mg/kg daily or a lipid formulation of AmB (LFAmB) administered at a dosage of 3–5 mg/kg daily are alternatives if there is intolerance to or limited availability of other antifungals (A-I). Transition from AmB-d or LFAmB to fluconazole is recommended for patients who have isolates that are likely to be susceptible to fluconazole (e.g., C. albicans) and who are clinically stable (A-I).
Voriconazole administered at a dosage of 400 mg (6 mg/kg) twice daily for 2 doses and then 200 mg (3mg/kg) twice daily thereafter is effective for candidemia (A-I), but it offers little advantage over fluconazole and is recommended as step-down oral therapy for selected cases of candidiasis due to Candida krusei or voriconazole-susceptible C. glabrata (B-III).
The recommended duration of therapy for candidemia without obvious metastatic complications is for 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms attributable to candidemia (A-III).
Intravenous catheter removal is strongly recommended for nonneutropenic patients with candidemia (A-II).
An echinocandin (caspofungin: loading dose of 70 mg, then 50 mg daily; micafungin: 100 mg daily [A-II]; anidulafungin: loading dose of 200 mg, then 100 mg daily [A-III]) or LFAmB (3–5 mg/kg daily [A-II]) is recommended for most patients.
For patients who are less critically ill and who have no recent azole exposure, fluconazole (loading dose of 800 mg [12 mg/kg], then 400 mg [6 mg/kg] daily) is a reasonable alternative (B-III). Voriconazole can be used in situations in which ad ditional mold coverage is desired (B-III).
For infections due to C. glabrata, an echinocandin is preferred (B-III). LFAmB is an effective but less attractive alternative (B-III). For patients who were already receiving voriconazole or fluconazole, are clinically improved, and whose follow-up culture results are negative, continuing use of the azole to completion of therapy is reasonable (B-III).
For infections due to C. parapsilosis, fluconazole or LFAmB is preferred as initial therapy (B-III). If the patient is receiving an echinocandin, is clinically stable, and follow-up culture results are negative, continuing the echinocandin until completion of therapy is reasonable. For infections due to C. krusei, an echinocandin, LFAmB, or voriconazole is recommended (B-III).
Recommended duration of therapy for candidemia without persistent fungemia or metastatic complications is for 2 weeks after documented clearance of Candida from the bloodstream, resolution of symptoms attributable to candidemia, and resolution of neutropenia (A-III).
Intravenous catheter removal should be considered (B-III).
Empirical therapy for suspected candidiasis in nonneutropenic patients is similar to that for proven candidiasis. Fluconazole (loading dose of 800 mg [12mg/kg], then 400 mg [6 mg/kg] daily), caspofungin (loading dose of 70 mg, then 50 mg daily), anidulafungin (loading dose of 200 mg, then 100 mg daily), or micafungin (100 mg daily) is recommended as initial therapy (B-III). An echinocandin is preferred for patients who have had recent azole exposure, whose illness is moderately severe or severe, or who are at high risk of infection due to C. glabrata or C. krusei (B-III).
AmB-d (0.5–1.0 mg/kg daily) or LFAmB (3–5 mg/kg daily) are alternatives if there is intolerance to other antifungals or limited availability of other antifungals (B-III).
Empirical antifungal therapy should be considered for critically ill patients with risk factors for invasive candidiasis and no other known cause of fever, and it should be based on clinical assessment of risk factors, serologic markers for invasive candidiasis, and/or culture data from nonsterile sites (B-III).
LFAmB (3–5 mg/kg daily), caspofungin (loading dose of 70 mg, then 50 mg daily) (A-I), or voriconazole (6 mg/kg administered intravenously twice daily for 2 doses, then 3 mg/kg twice daily) are recommended (B-I).
Fluconazole (loading dose of 800 mg [12 mg/kg], then 400 mg [6 mg/kg] daily) and itraconazole (200 mg [3mg/kg] twice daily) are alternative agents (B-I).
AmB-d is an effective alternative, but there is a higher risk of toxicity with this formulation than with LFAmB (A-I).
Azoles should not be used for empirical therapy in patients who have received an azole for prophylaxis (B-II).
AmB-d (1 mg/kg daily) is recommended for neonates with disseminated candidiasis (A-II). If urinary tract involvement is excluded, LFAmB (3–5 mg/kg daily) can be used (B-II). Fluconazole (12 mg/kg daily) is a reasonable alternative (B-II). The recommended length of therapy is 3 weeks (B-II).
A lumbar puncture and a dilated retinal examination, preferably by an ophthalmologist, are recommended in neonates with sterile body fluid and/or urine cultures positive for Candida species (B-III). Imaging of the genitourinary tract, liver, and spleen should be performed if the results of sterile body fluid cultures are persistently positive (B-III).
Echinocandins should be used with caution and are generally limited to situations in which resistance or toxicity precludes the use of fluconazole or AmB-d (B-III).
Intravascular catheter removal is strongly recommended (A-II).
In nurseries with high rates of invasive candidiasis, fluconazole prophylaxis may be considered in neonates whose birth weight is <1000 g (A-I). Antifungal drug resistance, drug-related toxicity, and neurodevelopmental outcomes should be observed (A-III).
For solid-organ transplant recipients, fluconazole (200–400 mg [3–6 mg/kg] daily) or liposomal AmB (L-AmB) (1–2 mg/kg daily for 7–14 days) is recommended as postoperative antifungal prophylaxis for liver (A-I), pancreas (B-II), and small bowel (B-III) transplant recipients at high risk of candidiasis.
For patients hospitalized in the ICU, fluconazole (400 mg [6 mg/kg] daily) is recommended for high-risk patients in adult units that have a high incidence of invasive candidiasis (B-I).
For patients with chemotherapy-induced neutropenia, fluconazole (400 mg [6 mg/kg} daily) (A-I), posaconazole (200 mg 3 times daily) (A-I), or caspofungin (50 mg daily) (B-II) is recommended during induction chemotherapy for the duration of neutropenia. Oral itraconazole (200 mg twice daily) is an effective alternative (A-1), but it offers little advantage over other agents and is less well tolerated.
For stem cell transplant recipients with neutropenia, fluconazole (400 mg [6 mg/kg] daily), posaconazole (200 mg 3 times daily), or micafungin (50 mg daily) is recommended during the period of risk of neutropenia (A-I).