PROJECT SUMMARY Cerebrospinal fluid (CSF) shunt placement allows children with hydrocephalus, a common cause of neurological disability in children, to survive and avoid ongoing brain injury. However, CSF shunts can frequently require surgical revision; and with each subsequent CSF shunt surgery, the risk of CSF shunt infection increases. The burden to children, families, and the healthcare system of over 2,000 CSF shunt infections annually in terms of costs, morbidity over the life span, and quality of life are substantial and preventable. Two novel peri-operative techniques have emerged as recent advances to prevent CSF shunt infections: intrathecal instillation of broad spectrum antibiotics into the shunt during surgery, and the use of antibiotic impregnated shunt tubing, a more widespread, but expensive and controversial technique. The overall objective of this proposal is to determine the comparative effectiveness of intrathecal antibiotics and antibiotic impregnated shunt tubing in the prevention of CSF shunt infection. Compared to a clinical trial, use of large databases to study relatively uncommon events permits us to capitalize upon the existence of comprehensive information about large numbers of diverse patients for efficient analyses. The Pediatric Health Information System + (PHIS+) database includes detailed administrative, laboratory, microbiology, and radiology data for 6 large pediatric neurosurgical centers from 2007 to 2012; and PHIS+ includes over 6,900 CSF shunt surgeries, with over 1,600 receiving intrathecal antibiotics, over 1,245 receiving antibiotic-impregnated shunt tubing, and over 2,700 receiving prophylactic intravenous antibiotics alone (standard care). Specific Aim 1 will compare the risk of infection following the use of intrathecal antibiotics, antibiotic impregnated shunt tubing, and standard care during CSF shunt surgery. The independent association of each novel technique compared to standard care, after adjusting for patient and procedure risk factors, with subsequent CSF shunt infection will be determined. We will also examine complications, length of stay, and readmissions. Specific Aim 2 will determine the changes in infecting organism and patterns of antimicrobial resistance following the use of intrathecal antibiotics, antibiotic impregnated shunt tubing, and standard care during CSF shunt surgery. Specific Aim 3 will evaluate the cost-effectiveness of using intrathecal antibiotics, antibiotic impregnated shunt tubing, and standard care during CSF shunt surgery for the prevention of CSF shunt infection using cost data from PHIS+. This proposal will rapidly fill a critical knowledge gap in prevention of CSF shunt infection, addresses a critical healthcare-associated infection, and its findings will rapidly be available for widespread dissemination.