What are the symptoms and treatment options for systemic yeast infections?

Symptoms and Treatment of Systemic Yeast Infection

Clinical Presentation of Systemic Candidiasis

Systemic yeast infections (invasive candidiasis) present with signs and symptoms of sepsis syndrome that are clinically indistinguishable from bacterial bloodstream infections, including fever, hypotension, tachycardia, and organ dysfunction. 1

Key Clinical Features:

• Persistent fever unresponsive to broad-spectrum antibacterial therapy is the hallmark presentation 1
• Septic shock may develop, particularly in critically ill patients, with mortality rates exceeding 60% without adequate source control 1
• Signs of hematogenous dissemination to organs including eyes (endophthalmitis), heart (endocarditis), kidneys, liver, and spleen may occur 1
• Skin lesions can manifest as erythematous papules or nodules in disseminated disease, particularly in neutropenic patients 1
• The infection is frequently associated with high attributable mortality even with treatment 1, 2

Diagnostic Challenges:

• Blood cultures have poor sensitivity (21-71%) even in autopsy-proven invasive candidiasis 2
• Clinical presentation is nonspecific and overlaps with bacterial sepsis 1, 3
• Beta-D-glucan testing combined with procalcitonin shows high sensitivity (98%) and negative predictive value (95%) for excluding invasive candidiasis 2

Treatment Approach

Initial Empiric Therapy for Critically Ill Patients

For suspected systemic candidiasis in critically ill or neutropenic patients, initiate empiric antifungal therapy immediately without waiting for culture confirmation, as delayed treatment significantly worsens outcomes. 1

First-Line Treatment Options:

Echinocandins are the preferred initial therapy for most patients with suspected invasive candidiasis: 1

• Anidulafungin: 200 mg loading dose, then 100 mg daily IV
• Micafungin: 100 mg daily IV
• Caspofungin: 70 mg loading dose, then 50 mg daily IV

Alternative regimens based on patient stability and risk factors: 1

• Fluconazole 800 mg loading dose, then 400 mg daily (6 mg/kg) IV or oral for clinically stable, non-critically ill patients without recent azole exposure 1
• Amphotericin B deoxycholate 0.5-0.7 mg/kg/day IV or lipid formulation amphotericin B (liposomal 3-5 mg/kg/day) for acutely ill patients or azole-resistant species 1

Critical Management Steps:

Remove all central venous catheters whenever feasible, especially in non-neutropenic patients, as catheter retention significantly increases mortality. 1

• Catheter removal combined with antifungal therapy is more effective than antifungal therapy alone 1
• Source control of intra-abdominal infections is essential; absence of adequate source control results in mortality >60% regardless of antifungal therapy 1

Species-Specific Considerations:

• C. albicans, C. tropicalis, C. parapsilosis: Respond to fluconazole or echinocandins 1
• C. glabrata: Often azole-resistant; echinocandins preferred 1
• C. krusei: Intrinsically fluconazole-resistant; use amphotericin B 1.0 mg/kg/day or echinocandin 1
• C. parapsilosis: If isolated, lipid formulation amphotericin B preferred over echinocandins due to higher MICs 1

Treatment Duration:

Continue antifungal therapy for at least 2 weeks after the last positive blood culture AND complete resolution of signs and symptoms of infection. 1

• For deep-seated infections (endocarditis, osteomyelitis, CNS involvement), extend therapy for weeks to months based on site 1
• Step-down from IV amphotericin B to oral fluconazole is appropriate once patient is clinically stable 1

High-Risk Populations Requiring Prophylaxis

Neutropenic Patients:

Fluconazole 400 mg daily or itraconazole solution 2.5 mg/kg every 12 hours during neutropenia is recommended for high-risk patients including those with acute myelogenous leukemia or allogeneic bone marrow transplant. 1

Critically Ill ICU Patients:

• Empiric antifungal therapy justified in patients with septic shock and multiple Candida colonization sites, prolonged ICU stay, broad-spectrum antibiotics, central lines, and recent abdominal surgery 1, 3
• Risk stratification using clinical prediction rules helps identify appropriate candidates 3

Common Pitfalls to Avoid:

• Do not delay antifungal therapy while awaiting culture results in critically ill patients with high clinical suspicion 1, 2
• Do not rely solely on blood cultures for diagnosis given their poor sensitivity 2
• Do not use fluconazole empirically in critically ill patients or those with recent azole exposure due to risk of resistant species 1
• Do not continue central venous catheters when candidemia is documented, as this significantly impairs treatment success 1
• Do not use inadequate doses: Fluconazole requires 400-800 mg daily (not 200 mg) for invasive disease 1

Monitoring and Follow-up:

• Obtain ophthalmologic examination to exclude endophthalmitis in all patients with candidemia 1
• Monitor for late-appearing symptoms of focal hematogenous spread (endocarditis, osteomyelitis, abscess formation) 1
• Repeat blood cultures every 24-48 hours until clearance is documented 1
• Monitor renal function, electrolytes (particularly potassium and magnesium), and liver function during amphotericin B therapy 4