Effects of Empiric Antifungal Therapy for Septic Shock on Time to Appropriate Therapy for Candida Infection: A Pilot Study

Abstract

PurposeInappropriate initial therapy for Candida-related septic shock is common and associated with a high mortality rate. This before-after pilot study was conducted to determine the feasibility of using empiric therapy for reducing the time to appropriate antifungal therapy in patients with Candida-related septic shock. MethodsPatients aged 18–99years with septic shock presenting to Barnes-Jewish Hospital, St. Louis, Missouri, in 2012–2013 were assigned to 1 of 2 groups. Patients presenting between January 1, 2012, and December 31, 2012, were managed according to local standard of care for patients with septic shock, to include antifungal therapy at the discretion of the treating physician (standard therapy group). Patients presenting between January 1, 2013, and December 31, 2013, received empiric antifungal therapy (primarily micafungin 100 mg/d or fluconazole 800 mg on day 1, followed by 400 mg/d), facilitated by a clinical pharmacist in the medical intensive care unit, until microbiologic cultures were available to determine the cause of septic shock (empiric therapy group). The primary outcome was time to appropriate therapy after shock onset. FindingsA total of 28 patients were enrolled (mean age, 56.3 [15.1] years [range, 30–92 years]; 16 [57.1%] men). The time to appropriate therapy after shock onset was statistically shorter with empiric therapy (n = 13) compared with standard therapy (n = 15) (10.6 [15.8] vs 40.5 [26.0] hours; P = 0.001). Patients receiving empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%; P = 0.001) and within 24 hours (76.9% vs 40.0%; P = NS) of shock onset. In an analysis to determine the number of septic shock patients needed to be treated with empiric antifungal therapy for 1 patient with Candida-related septic shock to receive appropriate treatment, 256 patients without Candida infection received a total of 687 doses of empiric antifungal therapy (mean, 2.7 doses per patient) compared with 136 patients who received 382 doses of standard antifungal therapy (mean, 2.8 doses per patient); the number needed to treat was 19.6. ImplicationsThe present pilot study demonstrated that the use of empiric antifungal therapy for Candida-related septic shock was associated with a statistically shorter time to administration of appropriate treatment. ClinicalTrials.gov identifier.