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A characterization of mean inhibitory concentrations and patient outcomes in patients failing to respond to fluconazole treatment of severe infections caused by Candida sp.

Abstract number: P834

Objectives: The goal of this study was to determine if fluconazole failures are more frequently associated with fluconazole-resistant or fluconazole-susceptible strains of Candida, and to compare the calculated AUIC values of patients with fluconazole-susceptible verses fluconazole-resistant isolates.

Methods: This study was a retrospective, case series of adult patients (>18 years) with an index Candida bloodstream infection and sufficient demographic, laboratory and microbiologic data to calculate serial AUICs and determine clinical and microbiologic outcome. Patients had to have received at least three days of fluconazole and organism susceptibility had to be available prior to enrolment. Although all had to initially fail fluconazole, both failures and successes were enrolled and analysed.

Results: 97 cases were enrolled with 52 (54%) being culture positive for Candida albicans. Although 98% of C. albicans isolates were susceptible, clinical success was achieved in only 58% of cases and the organism persisted at day 10 in 27% of the cases. 8 cases (15%) were found to have an AUIC < 100. The AUIC < 100 group tended to have a higher median MIC compared to the AUIC > 100 (0.56 vs. 0.19, p = 0.47). Compared to C. albicans, more intermediate and resistant organisms were observed in the non-albicans species group as 80% of isolates were susceptible (p = 0.005). Clinical success rates differed significantly between susceptible and non-susceptible isolates (53% vs. 11%, p = 0.039), while bacterial eradication tended to occur less often in nonsusceptible compared to susceptible organisms (44% vs. 61%, p = 0.461). A total of 18 cases (40%) had AUICs <100 with median MICs in those cases being higher compared to cases with AUIC > 100 (2.26 vs. 0.29, p = 0.058).

Conclusion: Fluconazole failure is almost always associated with susceptible organisms, particularly for C. albicans. For non-albicans species more intermediate or resistant organisms were observed, and the overall MIC was higher than for C. albicans. Failure in susceptible organisms occurs because fluconazole dosing does not achieve a blood concentration high enough to eradicated organisms with susceptible but somewhat higher MICs. Lowering the breakpoint would rationalize failure in some but not all of these patients. If the breakpoints are not lowered, further research is needed to determine the fluconazole dosing necessary to achieve success in those patients with susceptible but higher MICs.

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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