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Few data exist on successes at reducing pediatric catheter-associated bloodstream infections (CA-BSI). The objective was to eradicate CA-BSI with a multifaceted pediatric-relevant intervention proven effective in adult patients.Prospective cohort of pediatric intensive care (PICU) patients with historical controls.Multidisciplinary PICU.PICU patients with intervention targeting PICU providers.Multifaceted intervention involving preintervention staff surveys, provider educational program, creation of central catheter procedure cart, guideline-supported central catheter insertion checklist, nursing staff empowerment to stop procedures that breached guidelines, and real-time data feedback to PICU leadership.We measured rate of CA-BSI per 1000 catheter days from August 2001 through September 2006. Reliable use of evidence-based best practices for insertion of central catheters in our PICU was associated with a statistically and clinically significant decrease in our CA-BSI rate for 24 months postintervention (p < .05). During a portion of this postintervention period, we experienced a dramatic increase in our CA-BSI rate that was ultimately found to be due to the introduction of a new positive displacement mechanical valve intravenous port in April 2004. After removal of this positive displacement mechanical valve, our CA-BSI rate dropped from 5.2 ± 4.5 CA-BSI per 1000 central catheter days to a rate of 3.0 ± 1.9 CA-BSI per 1000 central catheter days. Chart review of postintervention CA-BSI cases revealed that these patients acquired CA-BSI weeks after both PICU admission and after insertion of the most recent central catheter.Our data show that improving practices for insertion of central catheters leads to a reduction of CA-BSI among pediatric patients but not elimination of CA-BSI. More research is needed to identify best practices for maintenance of central catheters for children. In addition, our experience shows that even despite good interventions to control CA-BSI, institutions must remain vigilant to factors such as new technology with apparent advantages but short track records of use.