The Early Systemic Prophylaxis of Infection After Stroke Study

Abstract

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.

Stroke-Induced Immunodepression

“…In an animal model of stroke, prophylaxis against bacterial infection dramatically improved mortality and reduced infarct sizes. 18 In a recently published randomized clinical trial (ESPIAS trial 19 ), the fluochinolone levofloxacin did not prevent infections in patients with acute stroke. In the PANTHERIS trial (http://controlled-trials.com/isrctn/ trial/PANTHERIS/0/74386719.html), we are currently testing whether another fluochinolone, moxifloxacin, prevents infections in patients with severe stroke.…”

Superiority of Preventive Antibiotic Treatment Compared with Standard Treatment of Poststroke Pneumonia in Experimental Stroke: A Bed to Bench Approach

“…Whereas the PANTHERIS and MISS trials suggest superiority of a preventive antiinfective therapy over current standard therapy in terms of infection control, ESPIAS is questioning this approach. [15][16][17] A metanalysis on these trials suggests that PAT reduces the occurrence of poststroke infections, but remains ineffective in terms of outcome. 18 Consequently, the current 'gold standard' by stroke guidelines is treatment immediately after diagnosis of infections.…”

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

“…The choice of the optimum antibiotic drug for infections in patients with acute stroke remains hypothetical. Chamorro et al [45] hypothesized that harmful central nervous system effects of levofloxacin may have been responsible for the negative results of their study. To date, there have been no controlled studies on the potentially differential effects of antibiotic drugs in patients with acute stroke.…”

“…The first study using a design complying with modern standards was the BEarly Systemic Prophylaxis of Infection After Stroke^(ESPIAS) study [45]. This was a large, welldesigned controlled study.…”

“…This was a large, welldesigned controlled study. Perhaps unwisely, Chamorro et al [45] used levofloxacin, a third-generation, extended-spectrum (Brespiratory^) fluoroquinolone antibiotic, an antibiotic that was new at the time when this study was being planned. Interestingly, its primary outcome was the difference in infection rate between the 2 groups.…”