title: Efficacy of caspofungin in the treatment of esophageal candidiasis resistant to fluconazole.
abstract: Caspofungin is a new echinocandin drug with comparable in vitro activity against azole-susceptible and -resistant isolates of that could provide a less toxic alternative to amphotericin B for the management of esophageal candidiasis with clinical or laboratory evidence of decreased susceptibility to fluconazole. The authors retrospectively analyzed its efficacy in adults with endoscopically documented esophagitis from four Phase II and III studies using two definitions of resistance to fluconazole: 1) clinically refractory infection based on failure of esophageal symptoms to improve despite at least 1 week of >or=200 mg/d of fluconazole; or 2) microbiologically resistant infection with either "susceptible dose-dependent" or "resistant" isolates based on MICs of 16 to 32 and >or=64 microg fluconazole/mL, respectively. A favorable response required resolution of all symptoms and substantial improvement in endoscopic findings. Seven of 11 patients (64%) who had been clinically refractory to fluconazole had favorable responses to caspofungin. Eleven of 14 patients (79%) whose isolates had decreased susceptibility to fluconazole had favorable responses to caspofungin, including 5 (83%) of 6 patients infected by isolates with MICs of >or=64 microg fluconazole/mL. Caspofungin appeared to be efficacious therapy for some patients with esophageal candidiasis who were clinically refractory to fluconazole or infected by with reduced susceptibility to fluconazole in vitro.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kartsonis
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Ken
authors.initials: K
authors.lastname: Bartizal
authors.forename: Patricia Scott
authors.initials: PS
authors.lastname: Hicks
authors.forename: Desmond
authors.initials: D
authors.lastname: Ryan
authors.forename: Carole A
authors.initials: CA
authors.lastname: Sable
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy*; D000077336:Caspofungin; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal; D054714:Echinocandins; D004935:Esophageal Diseases / Q000188:drug therapy* / Q000382:microbiology; D004945:Esophagoscopy; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use; D006801:Humans; D007263:Infusions, Parenteral; D055666:Lipopeptides; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010455:Peptides; D010456:Peptides, Cyclic; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D015725:Fluconazole; D000077336:Caspofungin