Activity of micafungin (FK463) against an itraconazole-resistant strain of Aspergillus fumigatus and a strain of Aspergillus terreus demonstrating in vivo resistance to amphotericin B

• Published in: Journal of antimicrobial chemotherapy 2003-04, Vol.51 (4), p.913-919
• Main Authors: Warn, P. A., Morrissey, G., Morrissey, J., Denning, D. W.
• Format: Article
• Language: English
• Subjects: Amphotericin B - pharmacokinetics; Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - pharmacokinetics; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Aspergillosis - drug therapy; Aspergillosis - microbiology; Aspergillus; Aspergillus - drug effects; Aspergillus fumigatus - drug effects; Biological and medical sciences; Colony Count, Microbial; Drug Resistance, Fungal; Echinocandins; FK463; Immunosuppressive Agents - pharmacology; Itraconazole - blood; Itraconazole - pharmacology; Lipopeptides; Lipoproteins - pharmacokinetics; Lipoproteins - pharmacology; Lipoproteins - therapeutic use; Male; Medical sciences; micafungin; Mice; Microbial Sensitivity Tests; mouse; murine; Neutropenia - microbiology; Peptides, Cyclic - pharmacokinetics; Peptides, Cyclic - pharmacology; Peptides, Cyclic - therapeutic use; Pharmacology. Drug treatments
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkg185

We compared the activity of four doses of micafungin (FK463) with that of amphotericin B, liposomal amphotericin B and itraconazole in a murine model of disseminated aspergillosis. Temporarily neutropenic mice were infected with a lethal dose of either an itraconazole-resistant Aspergillus fumigatus isolate or Aspergillus terreus, a species that is less susceptible to amphotericin B. Treatment was started 24 h after infection and lasted for 7 days. Mice were treated with either amphotericin B (0.5 or 5 mg/kg), liposomal amphotericin (5 or 25 mg/kg), itraconazole (25 or 75 mg/kg) or FK463 (either 1, 2, 5 or 10 mg/kg). Treatment of the A. fumigatus model with either amphotericin B, liposomal amphotericin or FK463 prolonged survival. Doses of FK463 5 and 10 mg/kg had a 100% survival. Treatment of A. terreus infection with either itraconazole or FK463, but not amphotericin B, also prolonged survival. Doses of liposomal amphotericin of 5 and 25 mg/kg were ineffective against A. terreus infection. No treatment regime was able to totally clear the liver or kidneys in either model. The data indicate that FK463 may have a clinical role in the treatment of life-threatening invasive aspergillosis.