Preventive antibiotic therapy in acute stroke

Stroke is the second most common cause of death and the third most common cause of disability worldwide. Infections complicate stroke in about one-third of patients and they are associated with unfavourable disease outcome and mortality. This thesis is focused on the ‘Preventive Antibiotics in Stroke Study’ (PASS), a multicenter randomised clinical trial aimed at prevention of infections with antibiotic therapy to improve functional outcome in stroke patients. 2550 stroke patients were randomised to ceftriaxone in addition to standard therapy, or standard therapy alone. Preventive antibiotic therapy did not improve functional outcome at 3 months. It did prevent infections, but this was merely due to prevention of urinary tract infection, pneumonia was not prevented. We also described the cost-effectiveness analysis of the PASS in this thesis. This showed that preventive antibiotic therapy was likely to be a cost-effective treatment, although the possible costs of future antimicrobial resistance were not included in this analysis. Patients are vulnerable for infection after stroke due to immune suppression, partly mediated by the sympathetic nervous system. We also investigated whether pre-stroke use of beta-blockers could decrease infection rate, but found that infection rates were increased in patients with pre-stroke beta-blocker use. Finally, we describe a prediction rule for pneumonia and infection after stroke. This prediction rule can be used to select the patients at the highest risk for these infections for future trials. Future trials should be focused on diagnosis of post-stroke infection and combined treatment approaches for fever, infection and aspiration.