What is the recommended treatment for a patient suspected of having a fungal infection?

Treatment of Suspected Fungal Infection

For patients with suspected fungal infections, initiate empiric antifungal therapy immediately based on risk stratification: echinocandins (caspofungin, micafungin, or anidulafungin) for critically ill or neutropenic patients with suspected invasive candidiasis; voriconazole for suspected invasive aspergillosis; and fluconazole 400-800 mg daily for hemodynamically stable patients with suspected candidiasis who have not had recent azole exposure. 1, 2

Risk Stratification Determines Treatment Urgency

High-risk patients requiring immediate empiric therapy include: 1, 2

• Neutropenic patients (especially <100 cells/mm³ for >10-15 days) 1
• Solid organ or hematopoietic stem cell transplant recipients 2
• Patients on high-dose corticosteroids or other immunosuppressants 3, 2
• ICU patients with prolonged stays and central venous catheters 1
• Persistent fever after 4-7 days of broad-spectrum antibiotics in high-risk patients 1, 2

Low-risk patients (brief neutropenia <7 days expected, no prior antifungal exposure, clinically stable) may not require routine empiric antifungal therapy. 1

Treatment Algorithm by Clinical Scenario

Suspected Invasive Candidiasis in Critically Ill/Neutropenic Patients

First-line therapy: 1

• Echinocandin (preferred): Caspofungin 70 mg loading dose, then 50 mg daily; OR micafungin 100 mg daily; OR anidulafungin 200 mg loading dose, then 100 mg daily 1
• These agents are fungicidal and have superior outcomes in critically ill patients 1

Alternative therapy: 1

• Lipid formulation amphotericin B 3-5 mg/kg daily (if echinocandin unavailable or resistant species suspected) 1
• Fluconazole 800 mg loading dose, then 400 mg daily ONLY if patient is not critically ill and has no prior azole exposure 1

Step-down therapy after clinical stabilization (5-7 days): 1

• Transition to fluconazole 400 mg daily if isolate is susceptible (e.g., Candida albicans), patient is clinically stable, and repeat blood cultures are negative 1

Suspected Invasive Aspergillosis

First-line therapy: 1, 2, 4

• Voriconazole (preferred): 6 mg/kg IV every 12 hours for 2 doses (Day 1), then 4 mg/kg IV every 12 hours; OR 400 mg PO every 12 hours for 2 doses, then 200 mg PO every 12 hours 1, 4
• Voriconazole has the strongest evidence for invasive aspergillosis 2

Alternative therapy: 1

• Lipid formulation amphotericin B 3-5 mg/kg daily 1
• Echinocandin (caspofungin, micafungin) 1
• Itraconazole (less preferred due to absorption variability) 1

Suspected Mucormycosis (Zygomycosis)

Mandatory first-line therapy: 1, 2

• Lipid formulation amphotericin B 5 mg/kg daily (high dose) 1
• Azoles and echinocandins are NOT effective against mucormycetes 2
• Aggressive surgical debridement is mandatory when feasible 1

Candidemia with Identified Species

For Candida albicans (fluconazole-susceptible): 1

• Fluconazole 800 mg loading dose, then 400 mg daily is appropriate after initial echinocandin therapy or as primary therapy in non-critically ill patients 1

For Candida glabrata: 1

• Continue echinocandin OR transition to high-dose fluconazole 800 mg daily or voriconazole 200-300 mg twice daily ONLY if susceptibility testing confirms susceptibility 1

For Candida krusei: 1

• Echinocandin (intrinsically resistant to fluconazole) 1
• Voriconazole is an alternative for step-down oral therapy 1

Site-Specific Considerations

CNS involvement (meningitis, brain abscess): 1

• Voriconazole (preferred for aspergillosis) 1
• Fluconazole 400-800 mg daily (for candidiasis) 1
• Amphotericin B formulations (alternative) 1
• Echinocandins have inadequate CNS penetration 5

Endophthalmitis: 1

• Fluconazole, voriconazole, or amphotericin B (echinocandins have poor ocular penetration) 1, 5
• Dilated fundoscopic examination mandatory within first week for all candidemia patients 1

Urinary tract candidiasis: 1

• Fluconazole 200-400 mg daily for 14 days (preferred due to excellent urinary concentration) 1
• Amphotericin B 0.3-0.6 mg/kg daily (alternative) 1

Duration of Therapy

Candidemia: 1

• Continue for 2 weeks after documented clearance of bloodstream and resolution of symptoms 1
• Obtain follow-up blood cultures daily or every other day until clearance documented 1

Invasive aspergillosis: 1

• Continue until resolution or stabilization of all clinical and radiographic manifestations (typically several months) 1
• Median duration in clinical trials: 10 days IV, then 76 days oral therapy 4

Esophageal candidiasis: 1

• Treat for 14-21 days until clinical improvement 1

Critical Monitoring Parameters

Clinical response assessment: 1, 3, 2

• Monitor for clinical improvement within 4-5 days; if no improvement, consider switching antifungal class 3
• Repeat blood cultures to document clearance 1, 2
• Fundoscopic examination for all candidemia patients 1

Therapeutic drug monitoring: 5

• Consider for voriconazole (target trough 1-5.5 mcg/mL), itraconazole, and posaconazole due to pharmacokinetic variability 5
• Voriconazole metabolism affected by CYP2C19 polymorphisms 5

Toxicity monitoring: 4, 6

• Voriconazole: visual disturbances, liver transaminase elevations, skin rashes 4, 6
• Amphotericin B: renal function, electrolytes (especially potassium and magnesium) 6
• Echinocandins: minimal adverse effects, generally well-tolerated 6

Common Pitfalls to Avoid

Premature discontinuation of therapy: 1, 3

• Continuing therapy throughout periods of immunosuppression is essential to prevent relapse 1, 3
• Chronic disseminated candidiasis requires several months of therapy 1

Inappropriate fluconazole use: 1, 7

• Do NOT use fluconazole as first-line therapy in critically ill patients 1
• Do NOT use fluconazole for C. krusei (intrinsically resistant) or empirically for C. glabrata without susceptibility data 1, 7

Failure to remove central venous catheters: 1

• CVC removal is strongly recommended as early as possible in candidemia when safe to do so 1

Using azoles or echinocandins for suspected mucormycosis: 2

• These agents are ineffective; amphotericin B is mandatory 2

Drug-drug interactions with azoles: 4, 5

• Voriconazole dose must be increased when co-administered with phenytoin or efavirenz 4
• Triazoles have extensive drug interactions requiring careful medication review 5

Inadequate dosing for protected sites: 5

• Echinocandins do not achieve adequate concentrations in CNS or eye 5
• Use fluconazole, voriconazole, or amphotericin B for these sites 5