Surface response modeling to examine the combination of amphotericin B deoxycholate and 5-fluorocytosine for treatment of invasive candidiasis

J Infect Dis. 2005 Aug 15;192(4):673-80. doi: 10.1086/432069. Epub 2005 Jul 7.

Abstract

The strategy of combining antifungal drugs in a treatment regimen may improve the outcome of invasive candidiasis. Using a well-validated pharmacodynamic murine model of invasive candidiasis, we defined the effect of the combination of amphotericin B deoxycholate (AmB) and 5-fluorocytosine (5FC) by use of the Greco model of drug interaction. The combination was additive, meaning that the experimental effect did not deviate in a statistically significant manner from the null reference model (or additive surface) of the combined effect. From a clinical perspective, the addition of 5FC to a regimen of AmB may enable the near-maximum effect to be reached in circumstances in which the administration of a given dose of AmB alone produces a submaximum effect but an increase in the dose is not possible, because of dose-related toxicity. Our methods provide a way in which some of the complex issues surrounding antifungal combination treatment can be addressed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / administration & dosage*
  • Animals
  • Antifungal Agents / administration & dosage*
  • Candidiasis / drug therapy*
  • Deoxycholic Acid / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Synergism
  • Drug Therapy, Combination
  • Flucytosine / administration & dosage*
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Models, Biological

Substances

  • Antifungal Agents
  • Drug Combinations
  • Deoxycholic Acid
  • Amphotericin B
  • amphotericin B, deoxycholate drug combination
  • Flucytosine