Timing of susceptibility-based antifungal drug administration in patients with Candida bloodstream infection: correlation with outcomes

We sought to determine the impact of timing of appropriate antifungal therapy, as assessed by susceptibility results, on patient survival. Patients epsilon 16 years of age with first episodes of candidaemia during 200109 were included. Clinical data were collected retrospectively, including time to appropriate antifungal therapy and patient survival. The study population included 446 patients [243 (54) female, mean age 53 years] with candidaemia, 380 (85) of whom had antifungal susceptibility data. Candida albicans was the most common pathogen (221, 50) followed by Candida glabrata (99, 22), Candida parapsilosis (59, 13), Candida tropicalis (48, 11) and Candida krusei (6, 1). Appropriate antifungal therapy consisted of fluconazole (177, 40), an echinocandin (125, 28), amphotericin B (41, 9) and voriconazole (6, 1); 97 (22) failed to receive appropriate antifungal therapy. The 30 day mortality was 34 (151/446) and there was no clear relationship between time from positive culture to receipt of appropriate antifungal therapy and 30 day survival. On multivariable Cox regression, increased APACHE II score [hazard ratio (HR) 1.11, 95 CI 1.091.13, P0.001], cirrhosis (HR 2.15, 95 CI 1.483.13, P0.001) and HIV infection (HR 2.03, 95 CI 1.113.72, P0.02) were independent predictors of mortality. A secondary analysis requiring patients in the early treatment group to have received epsilon 24 h of effective antifungal therapy did show a significant mortality benefit to receiving antifungal treatment within 72 h of a positive blood culture being drawn (30 day mortality for early treatment: 27 versus 40, P0.004; HR for mortality with delayed treatment on multivariable analysis: 1.41, 95 CI 1.011.98, P0.045). Candida bloodstream infection is associated with high mortality, despite timely receipt of appropriate antifungal therapy.