Effect of Antifungal Therapy Timing on Mortality in Cancer Patients with Candidemia

Abstract

Prior studies have shown that delays in treatment are associated with increased mortality in patients with candidemia. The purpose of this study was to measure three separate time periods comprising the diagnosis and treatment of candidemia and to determine which one(s) is associated with hospital mortality. Patients with blood cultures positive for Candida spp. were identified. Subjects were excluded if no antifungal therapy was given or if there was preexisting antifungal therapy. Collected data included the time from blood culture collection to positivity (incubation period), the time from blood culture positivity to provider notification (provider notification period), and the time from provider notification to the first dose of antifungal given (antifungal initiation period). These times were assessed as predictors of inpatient mortality. A repeat analysis was done with adjustments for age, sex, race, underlying cancer, catheter removal, APACHE III score, acute renal failure, neutropenia, and non-Candida albicans species. A total of 106 episodes of candidemia were analyzed. The median incubation time was 32.1 h and was associated with mortality (univariate hazard ratio per hour, 1.025; P ‫؍‬ 0.001). The median provider notification and antifungal initiation periods were 0.3 and 7.5 h, respectively, and were not associated with mortality. Adjusted analysis yielded similar results. For cancer patients with candidemia, the incubation period accounts for a significant amount of time, compared with the provider notification and antifungal initiation times, and is associated with in-hospital mortality. Strategies to shorten the incubation time, such as utilizing rapid molecularly based diagnostic methods, may help reduce in-hospital mortality.

Diagnostic Issues, Clinical Characteristics, and Outcomes for Patients with Fungemia

“…Several studies have shown that early treatment improves overall survival (20,34,50). To our surprise, we were not able to detect any difference in outcome dependent on the timing of therapy.…”

Invasive fungal infections in acute leukemia

“…For cancer patients with candidemia, the incubation length i.e. the time to a positive culture (median, 32.1 hours) is an independent risk factor for inhospital mortality, which increases an estimated 1.025-fold for every additional hour [Taur et al 2010]. The early use of diagnostic tests in the face of possible fungal infection can contribute to the early identification of IFI and initiation of antifungal therapy.…”

“…Predictors of unfavorable outcome for IC include old age (>6065 years) [Hahn-Ast et al 2010;Horn et al 2010;Chen et al 2006;Uzun and Anaissie, 2000], the presence and persistence of neutropenia [Horn et al 2010;Uzun and Anaissie, 2000;Anaissie et al 1998], multiorgan yeast dissemination [Uzun and Anaissie, 2000;Anaissie et al 1998], corticosteroid therapy [Horn et al 2010;Labelle et al 2008;Chen et al 2006], high Acute Physiology and Chronic Health Evaluation (APACHE) II or III scores [Horn et al 2010;Labelle et al 2008;Anaissie et al 1998], and delayed treatment [Taur et al 2010;Garey et al 2006;Morrell et al 2005 [Uzun and Anaissie, 2000] are also associated with increased risk of death. In some studies removal of vascular catheters improved patient outcome [Horn et al 2010;Labelle et al 2008;Anaissie et al 1998], but in another study removal of vascular access devices was not associated with better outcome except for a subset of patients with device-related candidemia [Chen et al 2006].…”

Comparison between the Biflex III-Biotyper and the Axima-SARAMIS Systems for Yeast Identification by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

“…Candida species are the 4th cause of nosocomial bloodstream infection and are associated with a high mortality rate (2). Many studies demonstrated that rapid initiation of appropriate antifungal therapy is crucial to reducing mortality (3,4). The susceptibility to antifungal molecules varies depending on the genus and the species.…”