Infectious Diseases Society of America 2016 [6]

European Society of Clinical Microbiology and Infectious Diseases 2019 [25]

IC in non-neutropenic patients

Initial therapy

Echinocandin recommended as initial therapy.

Fluconazole acceptable as alternative to echinocandin in patients who not critically ill and considered unlikely to have a fluconazole-resistant Candida species.

AmB 3-5 mg/kg daily is a reasonable alternative if there is intolerance, limited availability, or resistance to other antifungal agents.

AmB-d should not be used as a first-line treatment in critically ill patients with documented or suspected IC because of its significant nephrotoxicity

Transition (Switch)

Transition from an echinocandin to fluconazole (usually within 5-7 days) for patients who are clinically stable, have isolates that are susceptible to fluconazole (e.g., C. albicans), and negative repeat blood cultures.

Transition from AmB to fluconazole after 5-7 days in patients with isolates susceptible to fluconazole, who are clinically stable, and in whom repeat cultures on antifungal therapy are negative.

Voriconazole is recommended as step-down oral therapy for selected cases of candidemia due to C. krusei.

De-escalation from echinocandin to fluconazole when the patient is clinically stable, and the isolate is susceptible to fluconazole.

Echinocandins should not be de-escalated if central venous catheter or any other foreign material has not been removed or if an intravascular device (e.g., pacemaker) must be left in place because echinocandins have enhanced activity against biofilm.

Resistance

Among patients with suspected azole- and echinocandin-resistant Candida infections, lipid formulation AmB (3-5 mg/kg daily) is recommended.

Treatment duration and follow-up

Follow-up blood cultures should be performed every day or every other day to establish the time point at which candidemia has been cleared.

Recommended duration of therapy for candidemia without obvious metastatic complications is for 2 weeks after documented clearance of Candida species from the bloodstream and resolution of symptoms attributable to candidemia

IC should be treated for at least 14 days after the first negative blood culture.

IC without positive blood cultures should be treated for 10-14 days.

Neutropenic patients

Initial therapy

Echinocandin is recommended as initial therapy.

Lipid formulation AmB, 3-5 mg/kg daily, is an effective but less attractive alternative because of the potential for toxicity.

Fluconazole 800 mg (12 mg/kg) loading dose then 400 mg (6 mg/kg) daily, is an alternative for patients who are not critically ill and have had no prior azole exposure.

For infections due to C. krusei, an echinocandin, lipid formulation AmB, or voriconazole is recommended.

Transition (Switch)

Fluconazole, 400 mg (6 mg/kg) daily, can be used for step-down therapy during persistent neutropenia in clinically stable patients who have susceptible isolates and documented bloodstream clearance.

Voriconazole can also be used as step-down therapy during neutropenia in clinically stable patients who have had documented bloodstream clearance and isolates that are susceptible to voriconazole.

Treatment duration and follow-up

Recommended minimum duration of therapy for candidemia without metastatic complications is 2 weeks after documented clearance of Candida from the bloodstream, provided neutropenia and symptoms attributable to candidemia have resolved.

Prophylaxis in ICU settings

Fluconazole could be used in high-risk patients in adult ICUs with a high rate (> 5%) of IC.

An alternative is to give an echinocandin.

The panel recommends against the routine and universal administration of antifungal pre-emptive therapy or prophylaxis in critically ill patients.

Empirical therapy in non-neutropenic patients in the ICU

Should be considered in critically ill patients with risk factors for IC and no other known cause of fever. It should be based on clinical assessment of risk factors, surrogate markers for IC, and/or culture report from nonsterile sites.

Preferred empirical therapy is echinocandin.

Fluconazole is an acceptable alternative for patients with no recent azole exposure and without azole-resistant Candida species colonization.

Lipid formulation AmB, 3-5 mg/kg daily, can be used if there is intolerance to other antifungal agents.

Recommended duration of empirical therapy is the same as for treatment of documented candidemia.

For patients with no clinical response to empirical antifungal therapy at 4-5 days and no subsequent evidence of IC after the start of empirical therapy or a negative non-culture-based diagnostic assay with a high negative predictive value, stopping antifungal therapy should be considered.

Might be considered only in patients with septic shock and MOF with more than 1 extra-digestive site (i.e., urine, mouth, throat, upper and lower respiratory tracts, skin folds, drains, or operative site) with proven Candida species colonization.

Not recommended in patients without septic shock and MOF.

Echinocandins should be used as the first-line treatment in critically ill patients with septic shock and MOF with IC.

Fluconazole should be considered as first-line treatment for critically ill patients with low severity of disease (i.e., without septic shock and/or MOF) in settings with low fluconazole resistance.

Liposomal AmB should be preferred over other lipid formulations when previous treatment with echinocandins and azoles has failed.

Antifungal treatment should be stopped in patients with suspected (but not proven) IC with negative blood cultures and/or other negative culture specimens taken from suspected infectious foci before starting antifungal therapy.

Neonatal candidiasis

AmB deoxycholate, 1 mg/kg daily, is recommended.

Fluconazole, 12 mg/kg intravenous or oral daily, is a reasonable alternative in patients who have not been on fluconazole prophylaxis.

Echinocandins should be used with caution and limited to salvage therapy or situations in which resistance or toxicity preclude the use of AmB deoxycholate or fluconazole.

The recommended duration of therapy for candidemia without obvious metastatic complications is 2 weeks after documented clearance of Candida species from the bloodstream and resolution of signs attributable to candidemia

Central nervous system candidiasis

For initial treatment, liposomal AmB, 5 mg/kg daily, with or without oral flucytosine, 25 mg/kg 4 times daily is recommended.

For step-down therapy after the patient has responded to initial treatment, fluconazole, 400-800 mg (6-12 mg/kg) daily, is recommended