Efficacy of high doses of liposomal amphotericin B in the treatment of experimental aspergillosis.

Abstract

OBJECTIVE:

Differences in efficacy between deoxycholate amphotericin B (d-AmB) and escalating doses of liposomal amphotericin B (L-AmB) were evaluated in a model of invasive pulmonary aspergillosis in persistently steroid-immunosuppressed rats.

METHODS:

Animals were infected intratracheally with a conidial suspension of a clinical isolate of Aspergillus fumigatus and randomized to receive intravenously 5% dextrose, 1 mg/kg/day of d-AmB or 3, 5 or 10 mg/kg/day of L-AmB.

RESULTS:

All the antifungal treatments improved survival, although no differences were found among the groups, perhaps because of treatment-related toxicity. In animals surviving long enough to receive at least five doses of antifungal treatment, there were significant reductions in paired lung weight in the 5 and 10 mg/kg/day L-AmB groups as compared with the controls (P=0.004 and 0.001, respectively) and with the 3 mg/kg/day L-AmB group (P=0.007 and 0.002, respectively). Significant decreases in fungal biomass, measured indirectly by chitin quantification, were found only in the 10 mg/kg/day L-AmB group as compared with controls (P=0.003), d-AmB (P=0.007) and 3 mg/kg/day L-AmB (P=0.001).

CONCLUSION:

Infusion of L-AmB doses as high as 10 mg/kg/day may be a good therapeutic option for the management of invasive pulmonary aspergillosis developing in the context of steroid immunosuppression, although further studies are needed to assess this approach.

• Authors: María Teresa Martín, Joan Gavaldà, Pedro López, Xavier Gomis, José Luís Ramírez, Dolors Rodríguez, Oscar Len, Queralt Jordano, Isabel Ruiz, Marta Rosal, Benito Almirante, Albert Pahissa
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 52 Issue 6 Pg. 1032-4 (Dec 2003) ISSN: 0305-7453 [Print] England
• PMID: 14613950 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Immunosuppressive Agents
• Liposomes
• Steroids
• Amphotericin B

Topics

• Amphotericin B (administration & dosage, therapeutic use)
• Animals
• Antifungal Agents (administration & dosage, therapeutic use)
• Aspergillosis, Allergic Bronchopulmonary (drug therapy, microbiology, pathology)
• Dose-Response Relationship, Drug
• Female
• Immunosuppressive Agents (pharmacology)
• Liposomes
• Lung (pathology)
• Organ Size (physiology)
• Rats
• Rats, Wistar
• Steroids (pharmacology)