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 (e.g., caspofungin, anidulafungin, micafungin) or fluconazole.

An echinocandin is preferred over azoles for the initial treatment when candidemia secondary to a Candida species known to have azole resistance is 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.[32][68][69]​​​ In addition, echinocandins are recommended as initial therapy for Candida auris species, as most strains in the US are susceptible.[19]​ Reports have suggested that echinocandin resistance among Candida glabrata isolates is increasing, although it is still uncommon.[71][72]

Fluconazole is an acceptable first-line option for clinically stable patients who have had no recent azole exposure and are not colonized with azole-resistant Candida species such as Candida krusei, C glabrata, or C auris.[32]

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 or liposomal 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.[32]

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

OR

amphotericin B liposomal: 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 the 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 an echinocandin (e.g., caspofungin, anidulafungin, micafungin), or lipid or liposomal amphotericin-B.

Fluconazole or voriconazole are alternative agents in patients who are not critically ill, have not had azole exposure, and are not suspected or known to have an azole-resistant Candida species.

An echinocandin is preferred over azoles for the initial treatment of candidemia when azole-resistant Candida species 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 such as Candida krusei, Candida glabrata, or Candida auris.[19][32][68][69]​​​ ​ Reports have suggested that echinocandin resistance among C glabrata isolates is increasing, although it is still uncommon.[71][72]

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

OR

amphotericin B liposomal: 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

If the 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.

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 azole-resistant Candida species
1st line – 

antifungal therapy

An echinocandin (e.g., caspofungin, anidulafungin, micafungin) 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 or liposomal 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.[32]

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. In all cases of candidemia, repeat blood cultures should be obtained daily until clearance of candidemia is documented.

Echinocandins are recommended as initial therapy for Candida auris species, as most strains in the US are susceptible.​[19]

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

OR

amphotericin B liposomal: 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 azole-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., Candida albicans, Candida parapsilosis, and Candida tropicalis).[32]

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.[32]

Primary options

fluconazole: 400 mg orally once daily

Consider – source control

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

source control

Treatment recommended for SOME patients in selected patient group

Source control is an essential part of therapy; in addition to central venous catheter removal when the central venous catheter is thought to be the source of infection, drainage of any abscess or removal of infected material should be attempted.

Consider – supportive care for sepsis

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

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

If the 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 – antifungal therapy

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

antifungal therapy

An echinocandin (e.g., caspofungin, anidulafungin, micafungin) is preferred for patients who are critically ill, who have had recent azole exposure, or in whom the infection is caused by a species expected to be azole-resistant, such as Candida glabrata, Candida krusei, or Candida auris.[19][32][68][69]​​ Reports have suggested that echinocandin resistance among C glabrata isolates is increasing, although it is still uncommon.[71][72]

Lipid or liposomal 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. In all cases of candidemia, repeat blood cultures should be obtained daily until clearance of candidemia is documented.

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

amphotericin B liposomal: 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 azole-resistant Candida species
Consider – 

transition to high-dose fluconazole or voriconazole

Treatment recommended for SOME patients in selected patient group

For infection due to Candida glabrata, Candida krusei, or Candida auris, transition to higher-dose fluconazole or voriconazole should only be considered among patients with fluconazole-susceptible or voriconazole-susceptible isolates.[32]

Primary options

fluconazole: 800 mg intravenously/orally once daily

OR

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

Consider – source control

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

source control

Treatment recommended for SOME patients in selected patient group

Source control is an essential part of therapy; in addition to central venous catheter removal when the central venous catheter is thought to be the source of infection, drainage of any abscess or removal of infected material should be attempted.

Consider – supportive care for sepsis

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

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

If the 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.

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 azole-resistant Candida species
1st line – 

antifungal therapy

Initial therapy is with an echinocandin (e.g., caspofungin, anidulafungin, micafungin).

Lipid or liposomal 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.

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. In all cases of candidemia, repeat blood cultures should be obtained daily until clearance of candidemia is documented.

Echinocandins are recommended as initial therapy for C auris species, as most strains in the US are susceptible.[19]​​

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

OR

amphotericin B liposomal: 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 – source control

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

source control

Treatment recommended for SOME patients in selected patient group

Source control is an essential part of therapy; in addition to central venous catheter removal when the central venous catheter is thought to be the source of infection, drainage of any abscess or removal of infected material should be attempted.

One possible exception is in some instances in neutropenic patients where translocation from the gastrointestinal tract is suspected to be the source of candidemia rather than a true catheter infection; catheter removal should therefore be considered on an individual basis in those with neutropenia.[32]​ 

Consider – supportive care for sepsis

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

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

If the 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 – antifungal therapy

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

antifungal therapy

Initial therapy for most patients should be with an echinocandin (e.g., caspofungin, anidulafungin, micafungin).[19]​ Reports have suggested that echinocandin resistance among Candida glabrata isolates is increasing, although it is still uncommon.[71][72]

Lipid or liposomal 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. In all cases of candidemia, repeat blood cultures should be obtained daily until clearance of candidemia is documented.

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

amphotericin B liposomal: 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 – source control

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

source control

Treatment recommended for SOME patients in selected patient group

Source control is an essential part of therapy; in addition to central venous catheter removal when the central venous catheter is thought to be the source of infection, drainage of any abscess or removal of infected material should be attempted.

One possible exception is in some instances in neutropenic patients where translocation from the gastrointestinal tract is suspected to be the source of candidemia rather than a true catheter infection; catheter removal should therefore be considered on an individual basis in those with neutropenia.[32]

Consider – supportive care for sepsis

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

supportive care for sepsis

Treatment recommended for SOME patients in selected patient group

If the 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.

confirmed diagnosis: with complications

1st line – prolonged antifungal therapy

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

prolonged antifungal therapy

For endocarditis, initial treatment should be with a high-dose echinocandin (e.g., caspofungin, anidulafungin, micafungin), or lipid or liposomal amphotericin-B with or without flucytosine.[32]​ 

In all cases of candidemia, repeat blood cultures should be obtained daily until clearance of candidemia is documented.

Primary options

caspofungin: 150 mg intravenously once daily

OR

anidulafungin: 200 mg intravenously once daily

OR

micafungin: 150 mg intravenously once daily

OR

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

OR

amphotericin B liposomal: 3-5 mg/kg/day intravenously

OR

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

or

amphotericin B liposomal: 3-5 mg/kg/day intravenously

-- AND --

flucytosine: 25 mg/kg orally four times daily

Consider – azole step-down therapy

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

azole step-down therapy

Treatment recommended for SOME patients in selected patient group

Fluconazole can be used as step-down therapy in patients with fluconazole-susceptible Candida, after clinical improvement and clearance of candidemia is documented. Other azoles (e.g., voriconazole) can be used for step-down therapy if isolates are resistant to fluconazole but susceptible to other azoles. Total duration of treatment is at least 6 weeks, although it can be much longer, especially if there is no surgical intervention or in cases complicated by perivalvular abscesses.[32]​ In patients not able to undergo valve replacement, long-term suppression with fluconazole may be considered after completion of 6 weeks of therapy.

Primary options

fluconazole: 400-800 mg orally once daily

Secondary options

voriconazole: 200-300 mg orally twice daily

Consider – surgery

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

surgery

Treatment recommended for SOME patients in selected patient group

Despite the lack of powered randomized studies, most literature suggests improved outcomes and decreased mortality in patients treated with surgical intervention in addition to antifungal therapy. Surgical intervention (valve replacement/repair or vegetectomy) is therefore recommended when possible.[81]

Antifungals should be continued 6 weeks after surgery. In patients with native valve endocarditis not able to undergo valve replacement, long-term suppression with fluconazole may be considered after completion of 6 weeks of therapy. In patients with prosthetic valve candida endocarditis, chronic suppressive therapy is recommended.

1st line – prolonged antifungal therapy

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

prolonged antifungal therapy

Endophthalmitis should be treated with lipid or liposomal amphotericin-B with flucytosine for azole-resistant isolates. Fluconazole or voriconazole is preferred for azole-susceptible isolates. Treatment should be continued for 4-6 weeks or longer, depending on clinical response as determined by serial ophthalmologic exams. For cases of chorioretinitis without vitreal involvement, systemic antifungals for 4-6 weeks are recommended.

In all cases of candidemia, repeat blood cultures should be obtained daily until clearance of candidemia is documented.

Primary options

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

or

amphotericin B liposomal: 3-5 mg/kg/day intravenously

-- AND --

flucytosine: 25 mg/kg orally four times daily

Secondary options

fluconazole: 800 mg intravenously/orally as a loading dose, followed by 400-800 mg 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.[32]

Intravitreal injection of amphotericin-B or voriconazole should be considered for vitritis or macular involvement.[32]

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 candida pyelonephritis
1st line – 

prolonged antifungal therapy

Candida pyelonephritis can be secondary to ascending infection from the urinary tract or hematogenous spread. Fluconazole is the only azole with good concentration in the urine. Pyelonephritis should be treated with fluconazole for at least 2 weeks, with amphotericin-B deoxycholate as an alternative. Another option is flucytosine in combination with amphotericin-B.[20]

In all cases of candidemia, repeat blood cultures should be obtained daily until clearance of candidemia is documented.

Primary options

fluconazole: 200-400 mg intravenously/orally once daily

Secondary options

amphotericin B deoxycholate: 0.3 to 0.6 mg/kg/day intravenously

OR

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

or

amphotericin B liposomal: 3-5 mg/kg/day intravenously

-- AND --

flucytosine: 25 mg/kg orally four times daily

Consider – source control

Back
ACUTE
|
confirmed diagnosis: with complications
|
with candida pyelonephritis
Consider – 

source control

Treatment recommended for SOME patients in selected patient group

Surgical intervention may be indicated for source control, especially in the setting of fungal balls. Removal or replacement of nephrostomy tubes or stents should be attempted when these are present.

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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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