Evaluation of the correlation of caspofungin MICs and treatment outcome in murine infections by wild type strains of Candida parapsilosis

Diagn Microbiol Infect Dis. 2013 Sep;77(1):41-5. doi: 10.1016/j.diagmicrobio.2013.05.011. Epub 2013 Jun 24.

Abstract

We have evaluated the in vitro activity of caspofungin against 36 wild-type strains of Candida parapsilosis sensu stricto using 3 techniques: broth microdilution, disk diffusion, and the determination of minimal fungicidal concentration (MFC). The first 2 methods showed a good in vitro activity of caspofungin, but the MFCs were ≥2 dilutions above their corresponding MICs. In a murine model of disseminated infection, we evaluated the efficacy of caspofungin at 5 mg/kg against 8 strains of C. parapsilosis representing different degrees of in vitro susceptibility (0.12-1 μg/mL). All the isolates responded to treatment and (1→3)-β-D-glucan levels were reduced in all the cases; however, the study revealed differences among isolates, since caspofungin reduced the tissue burden of mice infected with isolates with MICs ≤0.5 μg/mL but was less effective against those with MICs of 1 μg/mL.

Keywords: Animal models; C. parapsilosis; Caspofungin; Fungal infections.

MeSH terms

  • Animals
  • Candida / drug effects*
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Caspofungin
  • Colony Count, Microbial
  • Disease Models, Animal
  • Echinocandins / pharmacology*
  • Echinocandins / therapeutic use*
  • Lipopeptides
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Proteoglycans
  • Treatment Outcome
  • beta-Glucans / blood

Substances

  • Echinocandins
  • Lipopeptides
  • Proteoglycans
  • beta-Glucans
  • polysaccharide-K
  • Caspofungin