In Vitro and In Vivo Exposure-Effect Relationship of Liposomal Amphotericin B against Aspergillus fumigatus

Antimicrob Agents Chemother. 2019 May 24;63(6):e02673-18. doi: 10.1128/AAC.02673-18. Print 2019 Jun.

Abstract

In vitro pharmacokinetic/pharmacodynamic data of liposomal amphotericin B (L-AMB) were compared with animal data from neutropenic and nonneutropenic models of azole-susceptible and azole-resistant invasive aspergillosis. L-AMB was equally effective. The in vitro fC max (maximum concentration of free drug)/MIC ratio associated with 50% of maximal activity was 0.31 (0.29 to 0.33), similar to that in neutropenic but not nonneutropenic mice (0.11 [0.06 to 0.20]). Simulation analysis indicated that standard L-AMB doses (1 to 3 mg/kg) are adequate for nonneutropenic patients, but higher doses (7.5 to 10 mg/kg) may be required for neutropenic patients for Aspergillus fumigatus isolates with MICs of 0.5 to 1 mg/liter.

Keywords: Aspergillus fumigatus; azole resistance; dose optimization; liposomal amphotericin B; neutropenia.

MeSH terms

  • Amphotericin B / pharmacology*
  • Animals
  • Antifungal Agents / pharmacology*
  • Aspergillosis / microbiology
  • Aspergillus fumigatus / drug effects*
  • Azoles / pharmacology
  • Drug Resistance, Fungal / drug effects
  • Female
  • Mice
  • Microbial Sensitivity Tests

Substances

  • Antifungal Agents
  • Azoles
  • liposomal amphotericin B
  • Amphotericin B