Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: A patient-level quantitative review of randomized trials

Background. Invasive candidiasis (IC) is an important healthcare-related infection, with increasing incidence and a crude mortality exceeding 50%. Numerous treatment options are available yet comparative studies have not identified optimal therapy.Methods.We conducted an individual patient-level quantitative review of randomized trials for treatment of IC and to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Studies were identified by searching computerized databases and queries of experts in the field for randomized trials comparing the effect of ≥2 antifungals for treatment of IC. Univariate and multivariable analyses were performed to determine factors associated with patient outcomes. Results. Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, and the rate of treatment success was 67.4%. Logistic regression analysis for the aggregate data set identified increasing age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P =. 02), the Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08-1.14; P =. 0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18-2.44; P =. 001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P =. 01) as predictors of mortality. Conversely, removal of a central venous catheter (CVC) (OR, 0.50; 95% CI,. 35-.72; P =. 0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI,. 45-.94; P =. 02) were associated with decreased mortality. Similar findings were observed for the clinical success end point. Conclusions. Two treatment-related factors were associated with improved survival and greater clinical success: use of an echinocandin and removal of the CVC.