title: Fluconazole MIC and the fluconazole dose/MIC ratio correlate with therapeutic response among patients with candidemia.
abstract: We tested 32 Candida isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients were treated with fluconazole doses now considered to be inadequate (</=200 mg), which contributed to high therapeutic failure rates (53% [17/32]). The geometric mean MIC and dose/MIC ratio for isolates associated with therapeutic failure (11.55 mug/ml and 14.3, respectively) differed significantly from values associated with therapeutic success (0.95 mug/ml and 219.36 [P = 0.0009 and 0.0004, respectively]). The therapeutic success rates among patients infected with susceptible (MIC </= 8 mug/ml), susceptible-dose dependent (S-DD) (MIC = 16 or 32 mug/ml), and resistant (MIC >/= 64 mug/ml) isolates were 67% (14/21), 20% (1/5), and 0% (0/6), respectively. A dose/MIC ratio >50 was associated with a success rate of 74% (14/19), compared to 8% (1/13) for a dose/MIC ratio </=50 (P = 0.0003). Our data suggest that both fluconazole MIC and dose/MIC ratio correlate with the therapeutic response to fluconazole among patients with candidemia. In clinical practice, dose/MIC ratio might prove easier to interpret than breakpoint MICs, since it quantitates the effects of increasing fluconazole doses that are alluded to in the S-DD designation.
authors.affiliation: University of Florida College of Medicine, P.O. Box 100277, JHMHC, Gainesville, FL 32610, USA. nguyemt@medicine.ufl.edu
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.forename: Victor L
authors.initials: VL
authors.lastname: Yu
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Morris
authors.forename: David R
authors.initials: DR
authors.lastname: Snydman
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002175:Candida / Q000145:classification / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016469:Fungemia / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000592:standards; D008875:Middle Aged; D011446:Prospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole