Preventive antibiotic therapy in patients with acute stroke

This thesis describes the effect of preventive antibiotic therapy on functional outcome after stroke. Infection is a common complication in the acute phase, affecting 30% of the patients; most often pneumonia and urinary tract infections. Many studies report a negative effect of the occurrence of an infection on stroke outcome. It therefore seems plausible that by reducing the post-stroke infection rate, functional outcome following stroke will improve. We performed a large phase-three multicentre, prospective, randomised, open-label, blinded endpoint trial investigating whether the preventive use of ceftriaxone improves stroke outcome. The intervention did neither improve functional outcome, nor reduce mortality. The number of post-stroke infections, however, were significantly and safely reduced. In none of the predefined subgroups a beneficial effect of the intervention was found. A post-hoc analysis suggested that patients treated with intravenous thrombolysis might benefit, despite a trend towards an increased rate of intracerebral haemorrhage. After the subsequent publication of two similar studies, a Cochrane meta-analysis showed that also the ‘overall’ use of preventive antibiotics does neither reduce the risk of dependency nor death, despite a significant reduction in the post-stroke infection rate. This reduction is highly significant for urinary tract infections, whereas pneumonia is not affected. We conclude that preventive antibiotic therapy should currently not be applied in standard stroke care. This insight might change in the future, since data is too limited to consider specific antibiotic regimens or subgroups of patients. New implications for future research include the background of post-stroke pneumonia and immunological alterations following stroke