Data Sources   For estimation of attributable costs, we conducted a systematic review of the literature using PubMed for the years 1986 through April 2013. For HAI incidence estimates, we used the National Healthcare Safety Network of the Centers for Disease Control and Prevention (CDC).
Study Selection   Studies performed outside the United States were excluded. Inclusion criteria included a robust method of comparison using a matched control group or an appropriate regression strategy, generalizable populations typical of inpatient wards and critical care units, methodologic consistency with CDC definitions, and soundness of handling economic outcomes.
Data Extraction and Synthesis   Three review cycles were completed, with the final iteration carried out from July 2011 to April 2013. Selected publications underwent a secondary review by the research team.
Main Outcomes and Measures   Costs, inflated to 2012 US dollars.
Results   Using Monte Carlo simulation, we generated point estimates and 95% CIs for attributable costs and length of hospital stay. On a per-case basis, central line–associated bloodstream infections were found to be the most costly HAIs at $45 814 (95% CI, $30 919-$65 245), followed by ventilator-associated pneumonia at $40 144 (95% CI, $36 286-$44 220), surgical site infections at $20 785 (95% CI, $18 902-$22 667), Clostridium difficile infection at $11 285 (95% CI, $9118-$13 574), and catheter-associated urinary tract infections at $896 (95% CI, $603-$1189). The total annual costs for the 5 major infections were $9.8 billion (95% CI, $8.3-$11.5 billion), with surgical site infections contributing the most to overall costs (33.7% of the total), followed by ventilator-associated pneumonia (31.6%), central line–associated bloodstream infections (18.9%), C difficile infections (15.4%), and catheter-associated urinary tract infections (<1 span="">
Conclusions and Relevance   While quality improvement initiatives have decreased HAI incidence and costs, much more remains to be done. As hospitals realize savings from prevention of these complications under payment reforms, they may be more likely to invest in such strategies.