Pre-clinical development of antifungal susceptibility test methods for the testing of the novel antifungal agent E1210 versus Candida: comparison of CLSI and European Committee on Antimicrobial Susceptibility Testing methods

J Antimicrob Chemother. 2011 Nov;66(11):2581-4. doi: 10.1093/jac/dkr342. Epub 2011 Aug 25.

Abstract

Objectives: To compare European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI broth microdilution (BMD) methods for testing the novel antifungal E1210 against a recent collection of 102 clinical isolates of Candida spp.

Methods: Candida isolates (102) were tested by CLSI and EUCAST methods; 21 Candida albicans, 20 Candida glabrata, 25 Candida parapsilosis, 24 Candida tropicalis and 12 Candida krusei, including echinocandin- and azole-resistant isolates. CLSI and EUCAST MIC endpoints of 50% and 100% inhibition were determined using visual reading at 24 and 48 h of incubation and spectrophotometric reading at 24 h of incubation, respectively.

Results: E1210 CLSI MIC results ranged from ≤0.008 to only 1 mg/L (excluding C. krusei) depending on species, duration of incubation and endpoint criteria (EC). E1210 was not active against C. krusei (MIC(50) >16 mg/L). Overall essential agreement (EA; ±2 doubling dilutions) between the 24 and 48 h CLSI readings was 100% and 97.6% using the 50% and 100% inhibition EC, respectively. Slightly more trailing growth at 48 h was observed with the 100% inhibition EC. Comparison of the 50% and 100% endpoints at 24 h of incubation showed an overall EA of 100%. Comparison of CLSI and EUCAST read at 24 h of incubation and either 50% or 100% inhibition revealed an EA of 97.8% using the 50% inhibition EC and 88.9% using the 100% inhibition EC.

Conclusions: E1210 was found to have potent in vitro activity against Candida spp. when tested by both CLSI and EUCAST BMD methods, with the highest overall EA (97.8%) obtained when E1210 MIC results were read after 24 h of incubation using a partial inhibition EC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology*
  • Antifungal Agents / pharmacology*
  • Candida / drug effects*
  • Candida / growth & development
  • Candida / isolation & purification
  • Candidiasis / microbiology
  • Drug Discovery
  • Europe
  • Glycosylphosphatidylinositols / biosynthesis
  • Humans
  • Isoxazoles / pharmacology*
  • Microbial Sensitivity Tests / methods*

Substances

  • APX001A
  • Aminopyridines
  • Antifungal Agents
  • Glycosylphosphatidylinositols
  • Isoxazoles