OBJECTIVE We describe the use of implementation science at the unit level and organizational level to guide an intervention to reduce central-line-associated bloodstream infections (CLABSIs) in a high-volume, regional, burn intensive care unit (BICU). DESIGN A single center observational quasi-experimental study. SETTING A regional BICU in Maryland serving 300-400 burn patients annually. INTERVENTIONS In 2011, an organizational-level and unit-level intervention was implemented to reduce the rates of CLABSI in a high-risk patient population in the BICU. At the organization level, leaders declared a goal of zero infections, created an infrastructure to support improvement efforts by creating a coordinating team, and engaged bedside staff. Performance data were transparently shared. At the unit level, the Comprehensive Unit-based Safety Program (CUSP)/ Translating Research Into Practice (TRIP) model was used. A series of interventions were implemented: development of new blood culture procurement criteria, implementation of chlorhexidine bathing and chlorhexidine dressings, use of alcohol impregnated caps, routine performance of root-cause analysis with executive engagement, and routine central venous catheter changes. RESULTS The use of an implementation science framework to guide multiple interventions resulted in the reduction of CLABSI rates from 15.5 per 1,000 central-line days to zero with a sustained rate of zero CLABSIs over 3 years (rate difference, 15.5; 95% confidence interval, 8.54-22.48). CONCLUSIONS CLABSIs in high-risk units may be preventable with the a use a structured organizational and unit-level paradigm. Infect Control Hosp Epidemiol 2017;38:1306-1311.

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