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Amphotericin B lipid complex in the treatment of experimental cryptococcal meningitis and disseminated candidosis.

Abstract
In the quest for safer and more effective antifungal agents, amphotericin B (AMB) has been placed in a variety of lipid preparations. In this study, we examined the efficacy of amphotericin B lipid complex (ABLC) on experimental cryptococcal meningitis and disseminated candidosis. This formulation is relatively safe compared to the parent compound, and therefore doses ten times greater than the commercial amphotericin B deoxycholate can be given to rabbits. Although at equal doses the ABLC preparation is less potent than AMB, a higher dose of ABLC was rapidly fungicidal in the contexts of both a central nervous system infection with Cryptococcus neoformans during immune suppression, and a heart and kidney infection with Candida albicans. Rapid sterilization of tissue should be a goal of antifungal drug therapy, particularly in the immune compromised host. From these studies, this AMB lipid formulation has the ability to produce rapid fungicidal activity in vivo, but it requires higher doses than AMB deoxycholate. Clinical trials in humans must examine carefully the therapeutic-toxic ratio in dose-escalation protocols to determine the optimal dosage strategy for this agent.
AuthorsJ R Perfect, K A Wright
JournalThe Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 33 Issue 1 Pg. 73-81 (Jan 1994) ISSN: 0305-7453 [Print] England
PMID8157577 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drug Combinations
  • Liposomes
  • Deoxycholic Acid
  • Amphotericin B
  • amphotericin B, deoxycholate drug combination
Topics
  • Amphotericin B (administration & dosage, therapeutic use)
  • Animals
  • Blood Vessels (microbiology)
  • Candidiasis (drug therapy, microbiology)
  • Colony Count, Microbial
  • Cryptococcus neoformans
  • Deoxycholic Acid (administration & dosage, therapeutic use)
  • Drug Combinations
  • Endocarditis (drug therapy, microbiology)
  • Kidney (microbiology)
  • Liposomes
  • Male
  • Meningitis, Cryptococcal (drug therapy, microbiology)
  • Rabbits

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