Comparative resistance of Candida albicans clinical isolates to fluconazole and itraconazole in vitro and in vivo in a murine model

Antimicrob Agents Chemother. 1996 Jun;40(6):1342-5. doi: 10.1128/AAC.40.6.1342.

Abstract

Relationships between azole susceptibility and in vivo response to antifungal therapy in a murine model of candidiasis were investigated for Candida albicans isolates sampled from human immunodeficiency virus type 1-positive patients with oropharyngeal candidiasis. The susceptibilities of seven clinical isolates and two reference strains to fluconazole (FCZ) and itraconazole (ITZ) were determined in vitro by the broth microdilution method. Four isolates were resistant to FCZ and ITZ, two were susceptible to both azoles, and three were resistant to FCZ and susceptible to ITZ (dissociated resistance). CD1 mice were inoculated with each isolate and treated with either FCZ or ITZ (drug regimen, 5 mg/kg of body weight twice daily for 5 days). Quantitative cultures of kidneys were performed at the end of the treatment. On the other hand, the survival rates of the mice were followed daily. These two parameters were clearly correlated with in vitro susceptibility. Thus, the phenomenon of a dissociation of resistance to FCZ and ITZ may be found in vivo as well as in vitro.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Candida albicans / classification
  • Candida albicans / drug effects*
  • Candida albicans / isolation & purification
  • Candidiasis / mortality
  • Candidiasis / prevention & control*
  • Drug Resistance, Microbial
  • Female
  • Fluconazole / pharmacology*
  • Fluconazole / therapeutic use
  • Humans
  • Itraconazole / pharmacology*
  • Itraconazole / therapeutic use
  • Mice
  • Mice, Inbred Strains
  • Microbial Sensitivity Tests
  • Survival Rate

Substances

  • Antifungal Agents
  • Itraconazole
  • Fluconazole