What is the coverage of Micafungin for invasive fungal infections?

Micafungin Antifungal Coverage

Micafungin provides fungicidal activity against all major Candida species (including fluconazole-resistant C. glabrata and C. krusei) and fungistatic activity against Aspergillus species, but has no clinically established efficacy against other invasive fungal pathogens such as Mucorales, Cryptococcus, or endemic fungi. 1, 2

Spectrum of Activity Against Candida Species

Micafungin demonstrates excellent coverage for invasive candidiasis:

• All clinically relevant Candida species are covered, including C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei 3, 4
• Particularly valuable for fluconazole-resistant C. glabrata isolates, making it especially relevant in oncohematological patients receiving fluconazole prophylaxis 4, 5
• Demonstrated non-inferiority to liposomal amphotericin B (90% success rate in both arms) and caspofungin (74% vs 71% success rates) in large randomized controlled trials for invasive candidiasis 3, 5
• Effective for candidemia and deep-seated Candida infections including peritoneal and pleural space infections 1

Activity Against Aspergillus Species

Micafungin has fungistatic activity against Aspergillus but limited clinical evidence:

• Demonstrates in vitro and in vivo activity against Aspergillus species 3, 6
• FDA-approved for empirical treatment of fungal infections in neutropenia where Aspergillus coverage may be needed 1
• Approved for prophylaxis in hematopoietic stem cell transplant recipients where it showed trends toward fewer invasive aspergillosis episodes compared to fluconazole 3, 1
• Not FDA-approved for treatment of established invasive aspergillosis - efficacy has not been established in controlled trials 1, 6
• Clinical evidence limited to prospective non-randomized studies (492 patients) and case reports suggesting possible effectiveness, but randomized controlled trials are lacking 6

Coverage Limitations - Critical Gaps

Micafungin has NO established efficacy against:

• Mucorales (Rhizopus, Mucor, Lichtheimia) - echinocandins are not active against mucormycosis 3
• Cryptococcus species - no clinically relevant activity 2
• Endemic fungi (Histoplasma, Blastomyces, Coccidioides) - not covered 2
• Fusarium and Scedosporium species - no established activity 2

FDA-Approved Indications Defining Coverage

Treatment indications:

• Candidemia and invasive candidiasis in adults and pediatrics (including neonates): 100 mg/day IV in adults, 2 mg/kg/day IV in pediatrics (max 100 mg) 1
• Esophageal candidiasis: 150 mg/day IV in adults 1

Prophylaxis indications:

• HSCT recipients: 50 mg/day IV in adults, 1 mg/kg/day IV in pediatrics from conditioning through day +30 or neutrophil recovery 3, 1
• Profound neutropenia (ANC <500 for ≥10 days): 1 mg/kg/day IV in pediatrics, approved for prophylaxis of Candida infections 3

Clinical Efficacy Data Supporting Coverage

For invasive candidiasis:

• 83% overall response rate in 126 patients with candidemia treated with micafungin 5
• 90% success rate comparable to liposomal amphotericin B in 531-patient randomized trial 3, 5
• 74% success rate with 100 mg/day dose, non-inferior to caspofungin in phase III trial 3

For prophylaxis in HSCT:

• 80.7% successful prophylaxis vs 73.7% with fluconazole (7% absolute difference, 95% CI 1.5-12.5%) in 882 patients 1
• Only 4 proven breakthrough Candida infections with micafungin vs 2 with fluconazole 1

Important Caveats for Clinical Use

• Resistance is rare but has been reported; consider susceptibility testing for treatment failures 4
• C. parapsilosis may have higher MICs to echinocandins compared to other Candida species, though clinical significance remains uncertain 3
• Micafungin provides no oral step-down option - must transition to azole if oral therapy desired 2
• Peripheral IV administration may cause phlebitis/thrombophlebitis more frequently than central administration 1