Effects of prophylactic antibiotic therapy with Mezlocillin plus sulbactam on the incidence and height of fever after severe acute ischemic stroke: The Mannheim infection in stroke study (MISS)

Background and Purpose - Fever after stroke is a strong predictor for a negative outcome with infections as the most common cause. The aim of this pilot study was to evaluate the effects of prophylactic antibiotic therapy on the incidence and height of fever after acute ischemic stroke. Methods - This is a randomized, controlled study of antibiotic prophylaxis in patients with ischemic stroke enrolled within 24 hours from clinical onset who presented bedridden ( modified Rankin score > 3) with no significant infection. Interventions included prophylactic mezlocillin plus sulbactam ( 3 X 2 g/ 1 g for 4 days) or conventional management. Over 10 days, body temperature was continuously monitored, and the presence of infection was daily assessed. Primary end points were incidence and height of fever; secondary end points included rate of infection and clinical outcome. Results - Sixty patients were included ( mean, 75 years; median National Institutes of Health Stroke Scale score, 16). Over the first 3 days, patients in the intervention group showed lower mean body temperatures as well as lower daily peak temperatures ( P < 0.05). Throughout the observation period, 15 of 30 patients in the intervention group but 27 of 30 patients in the conventionally treated group developed an infection ( P < 0.05). Mean interval until the diagnosis of infection was 5.1 days in the intervention group and 3.3 days in the control group ( P < 0.05). Clinical outcome was more favorable in patients with prophylactic therapy ( P = 0.01). Conclusions - In patients with acute severe stroke, prophylactic administration of mezlocillin plus sulbactam over 4 days decreases body temperature, lowers the rate of infection, and may be associated with a better clinical outcome.