title: Caspofungin susceptibility testing of isolates from patients with esophageal candidiasis or invasive candidiasis: relationship of MIC to treatment outcome.
abstract: The caspofungin clinical trial database offers an opportunity to assess susceptibility results for Candida pathogens obtained from patients with candidiasis and allows for correlations between efficacy outcomes and MICs. Candida isolates have been identified from patients enrolled in four studies of esophageal candidiasis and two studies of invasive candidiasis. The MICs of caspofungin for all baseline isolates were measured at a central laboratory using NCCLS criteria (document M-27A); MICs for caspofungin were defined as the lowest concentration inhibiting prominent growth at 24 h. MICs were then compared to clinical and microbiological outcomes across the two diseases. Susceptibility testing for caspofungin was performed on 515 unique baseline isolates of Candida spp. obtained from patients with esophageal candidiasis. MICs for caspofungin ranged from 0.008 to 4 microg/ml; the MIC50 and MIC90 were 0.5 and 1.0 microg/ml, respectively. Susceptibility testing was also performed on 231 unique baseline isolates of Candida spp. from patients with invasive candidiasis. The majority (approximately 96%) of MICs were between 0.125 and 2 microg/ml, with MIC50 and MIC90 for caspofungin being 0.5 and 2.0 microg/ml, respectively. Overall, caspofungin demonstrated potent in vitro activity against clinical isolates of Candida species. A relationship between MIC for caspofungin and treatment outcome was not seen for patients with either esophageal candidiasis or invasive candidiasis. Patients with isolates for which the MICs were highest (>2 microg/ml) had better outcomes than patients with isolates for which the MICs were lower (<1 microg/ml). Additionally, no correlation between MIC and outcome was identified for specific Candida species.
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., BL 3-4, P.O. Box 4, West Point, PA 19486-0004, USA. nicholas_kartsonis@merck.com
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kartsonis
authors.forename: John
authors.initials: J
authors.lastname: Killar
authors.forename: Lori
authors.initials: L
authors.lastname: Mixson
authors.forename: Chao-Min
authors.initials: CM
authors.lastname: Hoe
authors.forename: Carole
authors.initials: C
authors.lastname: Sable
authors.forename: Kenneth
authors.initials: K
authors.lastname: Bartizal
authors.forename: Mary
authors.initials: M
authors.lastname: Motyl
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology*; D002180:Candidiasis, Oral / Q000188:drug therapy / Q000382:microbiology*; D000077336:Caspofungin; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D016208:Databases, Factual; D054714:Echinocandins; D004947:Esophagus / Q000382:microbiology; D006801:Humans; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D000077336:Caspofungin