The early systemic prophylaxis of infection after stroke study - A randomized clinical trial

Background and Purpose - Early infection after stroke is frequent but the clinical value of antibiotic prophylaxis in acute stroke has never been explored. Objective and Methods - The Early Systemic Prophylaxis of Infection After Stroke (ESPIAS) is a randomized, double-blind, placebo-controlled study of antibiotic prophylaxis in patients older than 18 years with nonseptic ischemic or hemorrhagic stroke enrolled within 24 hours from clinical onset. Interventions included intravenous levofloxacin (500 mg/100 mL/d, for 3 days) or placebo (0.9 % physiological serum) in addition to optimal care. A sample size of 240 patients was calculated to identify a 15 % absolute risk reduction of the primary outcome measure, which was the incidence of infection at day 7 after stroke. Secondary outcome measures were neurological outcome and mortality at day 90. Results - Based on a preplanned futility analysis, the study was interrupted prematurely when 136 patients had been included. Levofloxacin and placebo patients had a cumulative rate of infection of 6 % and 6 % (P = 0.96) at day 1; 10 % and 12 % (P = 0.83) at day 2; 12 % and 15 % (P = 0.66) at day 3; 16 % and 19 % (P = 0.82) at day 7; and 30 % and 33 % (P = 0.70), at day 90. Using logistic regression, favorable outcome at day 90 was inversely associated with baseline National Institutes of Health Stroke Scale (OR, 0.72; 95 % CI, 0.59 to 0.89; P = 0.002) and allocation to levofloxacin (OR, 0.19; 95 % CI, 0.04 to 0.87; P = 0.03). Conclusions - Prophylactic administration of levofloxacin (500 mg/ 100 mL/day for 3 days) is not better than optimal care for the prevention of infections in patients with acute stroke.