Timing of Susceptibility-Based Antifungal Administration in Patients with Candida Bloodstream Infection

We sought to determine the impact of timing of appropriate antifungal therapy, as assessed by susceptibility results, on patient survival after candidemia. Patients 16 years of age or older with first episodes of candidemia from 2001–2009 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 candidemia, 380 (85%) of whom had antifungal susceptibility data. Candida albicans was the most common pathogen (221, 50%) followed by C. glabrata (99, 22%), C. parapsilosis (59, 13%), C. tropicalis (48,11%), and C. krusei (6,1%). Thirty-day mortality was 34% (151 out of 446 patients) and there was not a clear relationship between time from positive culture to receipt of appropriate antifungal therapy and 30-day survival. On multivariable Cox regression, increased Acute Physiology and Chronic Health Evaluation (APACHE) II score (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.09–1.13, p≤0.001), cirrhosis (HR 2.15, 95% CI 1.48–3.13, p≤0.001), and Human Immunodeficiency Virus (HIV) infection (HR 2.03, 95% CI 1.11–3.72, p=0.02), were independent predictors of mortality. A secondary analysis requiring patients in the early treatment group to have received at least 24 hours of effective antifungal therapy did show a significant mortality benefit to receiving antifungal treatment within 72 hours of a positive blood culture being drawn (30-day mortality for early treatment: 27% versus 40%, p=0.004; HR for mortality with delayed treatment on multivariable analysis: 1.41, 95% CI 1.01–1.98, p=0.045). Candida bloodstream infection is associated with high mortality, despite timely receipt of appropriate antifungal therapy.