Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

suspected diagnosis

1st line – empiric antifungal therapy

Back
INITIAL
|
suspected diagnosis
|
non-neutropenic patients
1st line – 

empiric antifungal therapy

First-line choices are an echinocandin or fluconazole.

An echinocandin is preferred over azole agents for the initial treatment of candidemia if Candida krusei or C glabrata are suspected or documented, particularly in critically ill, hemodynamically unstable patients; those who have had recent exposure to an azole; and those colonized with azole-resistant Candida species.[22][43][44]​​ In addition, echinocandins are recommended as initial therapy for C auris species, as most strains in the US are susceptible.[16]​ Reports have suggested that echinocandin resistance among C glabrata isolates is increasing, although it is still uncommon.[46][47]

Fluconazole is an acceptable first-line option for patients who have had no recent azole exposure and are not colonized with azole-resistant Candida species.[22]

Fluconazole is preferred over echinocandins if infection is suspected in body compartments where echinocandins have poor penetration (e.g., central nervous system, eye, and urinary tract).

The lipid formulation of amphotericin-B is a recommended alternative if initial antifungals are not tolerated or are not available.

For patients who have no clinical response to empiric antifungal therapy at 4 to 5 days and who do not have subsequent evidence of invasive candidiasis after the start of empiric therapy or if cultures and surrogate markers are negative, consideration should be given to stopping antifungal therapy.[22]

Primary options

caspofungin: 70 mg intravenously as a loading dose, followed by 50 mg once daily

OR

anidulafungin: 200 mg intravenously as a loading dose, followed by 100 mg once daily

OR

micafungin: 100 mg intravenously once daily

OR

fluconazole: 800 mg intravenously as a loading dose, followed by 400 mg once daily

Secondary options

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

Consider – supportive care for sepsis

Back
INITIAL
|
suspected diagnosis
|
non-neutropenic patients
Consider – 

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

If patient is showing signs of sepsis, they may need to be admitted to the intensive care unit and given additional care such as vigorous fluid resuscitation. Vasopressors and inotropes can be considered if hypotension persists.

1st line – empiric antifungal therapy

Back
INITIAL
|
suspected diagnosis
|
neutropenic patients
1st line – 

empiric antifungal therapy

First-line choices are caspofungin, anidulafungin, micafungin, or lipid amphotericin-B.

Fluconazole or voriconazole are alternative agents.

An echinocandin is preferred over azole agents for the initial treatment of candidemia if Candida krusei or C glabrata are suspected or documented, particularly in critically ill, hemodynamically unstable patients; those who have had recent exposure to an azole; and those colonized with azole-resistant Candida species.[22][43][44]​​ In addition, echinocandins are recommended as initial therapy for C auris species, as most strains in the US are susceptible.[16]​ Reports have suggested that echinocandin resistance among C glabrata isolates is increasing, although it is still uncommon.[46][47]

Fluconazole is preferred over echinocandins if infection is suspected in body compartments where echinocandins have poor penetration (e.g., central nervous system, eye, and urinary tract). If patients have received an azole for prophylaxis, an azole should not be given as empiric therapy. Prophylactic antifungals are standard of care and routinely used in patients with neutropenia likely to persist longer than 7 days.

Primary options

caspofungin: 70 mg intravenously as a loading dose, followed by 50 mg once daily

OR

anidulafungin: 200 mg intravenously as a loading dose, followed by 100 mg once daily

OR

micafungin: 100 mg intravenously once daily

OR

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

Secondary options

fluconazole: 800 mg intravenously as a loading dose, followed by 400 mg once daily

OR

voriconazole: 6 mg/kg intravenously every 12 hours for 2 doses as a loading dose, followed by 3-4 mg/kg every 12 hours

Consider – supportive care for sepsis

Back
INITIAL
|
suspected diagnosis
|
neutropenic patients
Consider – 

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

Patients need to be admitted to the intensive care unit and given additional care such as vigorous fluid resuscitation. Vasopressors and inotropes can be considered if hypotension persists.

ACUTE

confirmed diagnosis: non-neutropenic patients (no complications)

1st line – antifungal therapy

Back
ACUTE
|
confirmed diagnosis: non-neutropenic patients (no complications)
|
not critically ill or no azole exposure or no fluconazole-resistant Candida species
1st line – 

antifungal therapy

An echinocandin is recommended as initial therapy. Fluconazole is an acceptable first-line alternative to an echinocandin in selected patients including those who are not critically ill and who are considered unlikely to have a fluconazole-resistant Candida species.

Lipid formulations of amphotericin-B are considered alternatives if initial antifungal agents are not tolerated or not available.

Voriconazole is effective for candidemia but offers little advantage over fluconazole as initial therapy. It is recommended as step-down oral therapy for selected cases of candidemia due to C krusei or for C glabrata that has been shown to be susceptible.

Treatment course: 2 weeks from clearance of Candida from the blood and when clinical symptoms have resolved. If patients have complications (e.g., endophthalmitis, endocarditis, osteomyelitis), more prolonged therapy is required depending upon the site involved.

Echinocandins are recommended as initial therapy for C auris species, as most strains in the US are susceptible.​[16]

Primary options

caspofungin: 70 mg intravenously as a loading dose, followed by 50 mg once daily

OR

anidulafungin: 200 mg intravenously as a loading dose, followed by 100 mg once daily

OR

micafungin: 100 mg intravenously once daily

OR

fluconazole: 800 mg intravenously/orally as a loading dose, followed by 400 mg once daily

Secondary options

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

Tertiary options

voriconazole: 6 mg/kg intravenously every 12 hours for 2 doses as a loading dose, followed by 3 mg/kg every 12 hours

Consider – transition to oral fluconazole once stable

Back
ACUTE
|
confirmed diagnosis: non-neutropenic patients (no complications)
|
not critically ill or no azole exposure or no fluconazole-resistant Candida species
Consider – 

transition to oral fluconazole once stable

Treatment recommended for SOME patients in selected patient group

Transition from an echinocandin to fluconazole is recommended for patients who are clinically stable (usually within 5-7 days), who have documented clearance of Candida from the bloodstream, and who are infected with an organism that is susceptible to fluconazole (e.g., C albicans, C parapsilosis, and C tropicalis).[22]

Transition from amphotericin-B to fluconazole is recommended after 5-7 days for patients who have fluconazole-susceptible isolates, who are clinically stable, and in whom repeat cultures on antifungal therapy are negative.[22]

Primary options

fluconazole: 400 mg orally once daily

Consider – intravascular catheter removal

Back
ACUTE
|
confirmed diagnosis: non-neutropenic patients (no complications)
|
not critically ill or no azole exposure or no fluconazole-resistant Candida species
Consider – 

intravascular catheter removal

Treatment recommended for SOME patients in selected patient group

If the patient has an intravascular catheter present, removal is recommended.

Consider – supportive care for sepsis

Back
ACUTE
|
confirmed diagnosis: non-neutropenic patients (no complications)
|
not critically ill or no azole exposure or no fluconazole-resistant Candida species
Consider – 

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

Patients need to be admitted to the intensive care unit and given additional care such as vigorous fluid resuscitation. Vasopressors and inotropes can be considered if hypotension persists.

1st line – antifungal therapy

Back
ACUTE
|
confirmed diagnosis: non-neutropenic patients (no complications)
|
critically ill or recent azole exposure or infection due to C glabrata
1st line – 

antifungal therapy

An echinocandin is preferred for patients who are critically ill, who have had recent azole exposure, or in whom the infection is caused by C glabrata. In addition, echinocandins are recommended as initial therapy for C auris species, as most strains in the US are susceptible.[16]​ Reports have suggested that echinocandin resistance among C glabrata isolates is increasing, although it is still uncommon.[46][47]

Lipid formulations of amphotericin-B are considered alternatives if initial antifungal agents are not tolerated or not available.

Treatment course: 2 weeks from clearance of Candida from the blood and when clinical symptoms have resolved. If patients have complications (e.g., endophthalmitis, endocarditis, osteomyelitis), more prolonged therapy is required depending upon the site involved.

Primary options

caspofungin: 70 mg intravenously as a loading dose, followed by 50 mg once daily

OR

micafungin: 100 mg intravenously once daily

OR

anidulafungin: 200 mg intravenously as a loading dose, followed by 100 mg once daily

Secondary options

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

Consider – transition to high-dose fluconazole or voriconazole

Back
ACUTE
|
confirmed diagnosis: non-neutropenic patients (no complications)
|
critically ill or recent azole exposure or infection due to C glabrata
Consider – 

transition to high-dose fluconazole or voriconazole

Treatment recommended for SOME patients in selected patient group

For infection due to C glabrata, transition to higher-dose fluconazole or voriconazole should only be considered among patients with fluconazole-susceptible or voriconazole-susceptible isolates.[22]

Primary options

fluconazole: 800 mg intravenously/orally once daily

OR

voriconazole: 3-4 mg/kg intravenously/orally every 12 hours

Consider – intravascular catheter removal

Back
ACUTE
|
confirmed diagnosis: non-neutropenic patients (no complications)
|
critically ill or recent azole exposure or infection due to C glabrata
Consider – 

intravascular catheter removal

Treatment recommended for SOME patients in selected patient group

If the patient has an intravascular catheter present, removal is recommended.

Consider – supportive care for sepsis

Back
ACUTE
|
confirmed diagnosis: non-neutropenic patients (no complications)
|
critically ill or recent azole exposure or infection due to C glabrata
Consider – 

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

Patients need to be admitted to the intensive care unit and given additional care such as vigorous fluid resuscitation. Vasopressors and inotropes can be considered if hypotension persists.

confirmed diagnosis: neutropenic patients (no complications)

1st line – antifungal therapy

Back
ACUTE
|
confirmed diagnosis: neutropenic patients (no complications)
|
not critically ill or no recent azole exposure or no fluconazole-resistant Candida species
1st line – 

antifungal therapy

Initial therapy is with an echinocandin.

Lipid formulations of amphotericin-B are considered an alternative therapy in this patient group.

Fluconazole is an alternative for patients who are not critically ill and who have had no prior azole exposure.

Voriconazole can be used if mold coverage is required. It 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 course: 2 weeks from clearance of Candida from the blood and when clinical symptoms have resolved. If patients have complications (e.g., endophthalmitis, endocarditis, osteomyelitis), more prolonged therapy is required depending upon the site involved.

Echinocandins are recommended as initial therapy for C auris species, as most strains in the US are susceptible.[16]​​

Primary options

caspofungin: 70 mg intravenously as a loading dose, followed by 50 mg once daily

OR

anidulafungin: 200 mg intravenously as a loading dose, followed by 100 mg once daily

OR

micafungin: 100 mg intravenously once daily

Secondary options

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

Tertiary options

fluconazole: 800 mg intravenously as a loading dose, followed by 400 mg once daily

OR

voriconazole: 6 mg/kg intravenously every 12 hours for 2 doses as a loading dose, followed by 3-4 mg/kg every 12 hours

Consider – intravascular catheter removal

Back
ACUTE
|
confirmed diagnosis: neutropenic patients (no complications)
|
not critically ill or no recent azole exposure or no fluconazole-resistant Candida species
Consider – 

intravascular catheter removal

Treatment recommended for SOME patients in selected patient group

If the patient has an intravascular catheter present, removal should be considered.

Consider – supportive care for sepsis

Back
ACUTE
|
confirmed diagnosis: neutropenic patients (no complications)
|
not critically ill or no recent azole exposure or no fluconazole-resistant Candida species
Consider – 

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

Patients need to be admitted to the intensive care unit and given additional care such as vigorous fluid resuscitation. Vasopressors and inotropes can be considered if hypotension persists.

1st line – antifungal therapy

Back
ACUTE
|
confirmed diagnosis: neutropenic patients (no complications)
|
critically ill or recent azole exposure or infection due to C glabrata
1st line – 

antifungal therapy

Initial therapy for most patients should be with an echinocandin, especially if infection is caused by Candida glabrata. In addition, echinocandins are recommended as initial therapy for C auris species, as most strains in the US are susceptible.[16]​ Reports have suggested that echinocandin resistance among C glabrata isolates is increasing, although it is still uncommon.[46][47]

Lipid formulations of amphotericin-B are considered an alternative therapy in this patient group.

Voriconazole can be used if mold coverage is required.

Treatment course: 2 weeks from clearance of Candida from the blood and when clinical symptoms have resolved. If patients have complications (e.g., endophthalmitis, endocarditis, osteomyelitis), more prolonged therapy is required depending upon the site involved.

Primary options

caspofungin: 70 mg intravenously as a loading dose, followed by 50 mg once daily

OR

micafungin: 100 mg intravenously once daily

OR

anidulafungin: 200 mg intravenously as a loading dose, followed by 100 mg once daily

Secondary options

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

OR

voriconazole: 6 mg/kg intravenously every 12 hours for 2 doses as a loading dose, followed by 3-4 mg/kg every 12 hours

Consider – intravascular catheter removal

Back
ACUTE
|
confirmed diagnosis: neutropenic patients (no complications)
|
critically ill or recent azole exposure or infection due to C glabrata
Consider – 

intravascular catheter removal

Treatment recommended for SOME patients in selected patient group

If the patient has an intravascular catheter present, removal should be considered.

Consider – supportive care for sepsis

Back
ACUTE
|
confirmed diagnosis: neutropenic patients (no complications)
|
critically ill or recent azole exposure or infection due to C glabrata
Consider – 

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

Patients need to be admitted to intensive care unit and given additional care such as vigorous fluid resuscitation. Vasopressors and inotropes can be considered if hypotension persists.

confirmed diagnosis: with complications

1st line – prolonged antifungal therapy

Back
ACUTE
|
confirmed diagnosis: with complications
|
with endocarditis
1st line – 

prolonged antifungal therapy

For endocarditis, the combination of lipid amphotericin-B ± flucytosine is preferred, with high-dose echinocandins as an alternative. Fluconazole can be used as step-down therapy. Total duration of treatment is at least 6 weeks, although in patients not able to undergo valve replacement, long-term suppression with fluconazole may be considered.

Primary options

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

OR

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

and

flucytosine: 25 mg/kg/day orally given in 4 divided doses

Secondary options

caspofungin: 70 mg intravenously as a loading dose, followed by 50 mg once daily

OR

anidulafungin: 200 mg intravenously as a loading dose, followed by 100 mg once daily

OR

micafungin: 100 mg intravenously once daily

Plus – fluconazole step-down therapy

Back
ACUTE
|
confirmed diagnosis: with complications
|
with endocarditis
Plus – 

fluconazole step-down therapy

Treatment recommended for ALL patients in selected patient group

Fluconazole can be used as step-down therapy. Total duration of treatment is at least 6 weeks, although in patients not able to undergo valve replacement, long-term suppression with fluconazole may be considered.

Primary options

fluconazole: 400 mg intravenously/orally once daily

1st line – prolonged antifungal therapy

Back
ACUTE
|
confirmed diagnosis: with complications
|
with endophthalmitis
1st line – 

prolonged antifungal therapy

Endophthalmitis should be treated with lipid amphotericin-B with flucytosine for azole-resistant isolates. Fluconazole or voriconazole may be considered for azole-susceptible isolates. Treatment should be continued for 4-6 weeks or longer, depending on clinical response as determined by serial ophthalmologic examinations.

Primary options

amphotericin B lipid complex: 3-5 mg/kg/day intravenously

and

flucytosine: 25 mg/kg/day orally given in 4 divided doses

Secondary options

fluconazole: 400 mg intravenously/orally once daily

OR

voriconazole: 6 mg/kg intravenously every 12 hours for 2 doses as a loading dose, followed by 4 mg/kg every 12 hours

Consider – vitrectomy + intravitreal amphotericin-B or intravitreal voriconazole

Back
ACUTE
|
confirmed diagnosis: with complications
|
with endophthalmitis
Consider – 

vitrectomy + intravitreal amphotericin-B or intravitreal voriconazole

Treatment recommended for SOME patients in selected patient group

Early surgical intervention with a partial vitrectomy is an important adjunctive consideration in more advanced cases and can be a sight-saving procedure.[22]

Intravitreal injection of amphotericin-B or voriconazole should be considered for vitritis or macular involvement.[22]

Primary options

amphotericin B deoxycholate: consult specialist for guidance on intravitreal dose

OR

voriconazole: consult specialist for guidance on intravitreal dose

1st line – prolonged antifungal therapy

Back
ACUTE
|
confirmed diagnosis: with complications
|
with renal candidiasis
1st line – 

prolonged antifungal therapy

Therapy for renal candidiasis varies depending on the clinical syndrome; pyelonephritis should be treated with fluconazole for 2 weeks, with amphotericin-B as an alternative.

Primary options

fluconazole: 400 mg intravenously/orally once daily

Secondary options

amphotericin B deoxycholate: 0.5 to 0.7 mg/kg/day intravenously

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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