Our study represents the largest study to date of outcomes due to SSI due to MRSA. Our findings confirm that SSIs due to MRSA lead to significant patient suffering and provide quantitative estimates of the staggering costs of these infections. SSI due to MRSA led to a 7-fold increased risk of death, a 35-fold increased risk of hospital readmission, more than 3 weeks of additional hospitalization, and more than $60,000 of additional charges compared to uninfected controls.
Numerous studies have evaluated the impact of methicillin-resistance in patients with bloodstream infection (BSIs), yet many of these studies have come to conflicting results 
. An array of confounding factors have been cited as potential causes for these conflicting conclusions, including patient mix and co-morbid conditions, treatment, severity of illness, and even methods for analysis 
. The authors of two meta-analyses analyzed data from many of the studies cited above; both concluded that, on the whole, available data suggested that methicillin-resistance is associated with higher mortality among patients with S. aureus
The issue is less clear regarding the impact of methicillin-resistance among patients with S. aureus
SSI. To our knowledge, only three other studies directly compared patients with SSI due to MRSA to patients with SSI due to MSSA in an attempt to determine the attributable impact of methicillin-resistance on outcomes among patients with S. aureus
The first study compared 15 patients with mediastinitis due to MRSA to 26 patients with mediastinitis due to MSSA at a single center in France 
. Patient follow-up was continued for four years. Using multivariable analytic statistical techniques, the authors of this small study concluded that mediastinitis due to MRSA led to a 4.6-fold increase in risk of mortality compared to mediastinitis due to MSSA. No other outcomes were analyzed.
The second study compared 73 patients with mediastinitis due to MRSA to 145 patients with mediastinitis due to MSSA in a single center in France 
. Outcomes of patients admitted to the ICU with S. aureus
mediastinitis were analyzed. Methicillin resistance was not an independent predictor of ICU mortality using multivariable analyses. However, mediastinitis due to MRSA was a predictor of a longer duration of mechanical ventilation and ICU stay compared to mediastinitis due to MSSA in an unadjusted statistical analysis.
The third study compared 127 patients with SSI due to MRSA to 173 patients with SSI due to MSSA in two centers (one tertiary care and one community hospital) in North Carolina, USA 
. Several different types of surgical procedures were included in the analysis, though the majority of procedures were cardiothoracic. In multivariable analyses, methicillin resistance was associated with a 3-fold increase in 90-day mortality, 3 additional days of hospitalization, and $14,000 of additional charges per SSI.
Our multi-center study demonstrated that methicillin-resistance led to longer hospitalization and higher charges among patients with S. aureus SSI. Of note, patients with SSI due to MRSA had higher baseline proportions of co-morbid illness than both uninfected controls and patients with SSI due to MSSA. Our outcomes analyses controlled for these differences. Although methicillin resistance led to higher risk of mortality among patients with S. aureus SSI in unadjusted analyses, SSI due to MRSA was no longer an independent predictor for risk of mortality compared to SSI due to MSSA after controlling for variables for co-morbid illness, severity of infection, and appropriateness of treatment. These results did not change in our sensitivity analysis limited to patients who received appropriate therapy. However, our Kaplan-Meier analysis suggests that differences may have existed if other time points had been selected, as the mortality curves for patients with SSI due to MRSA and patients with SSI due to MSSA quickly diverged. Nevertheless, the impact of methicillin resistance on outcome of patients who survived was substantial. Our adjusted analyses also demonstrated that methicillin-resistance among patients with S. aureus SSI led to approximately 6 additional days of hospitalization and more than $24,000 of additional charges.
Our estimates of the financial burden of SSI due to MRSA are unique. On the whole, SSI due to MRSA led to charges in excess of $19 million for the group of study hospitals. We believe our estimate for the attributable impact of a single SSI due to MRSA of more than $61,000 can be used by administrators and infection control personnel to design and evaluate specific preventative interventions. For example, if an intervention (e.g., decolonization, screening, hiring of one FTE) costs less than $61,000 and leads to the prevention of only one SSI due to MRSA, then this intervention will likely be cost effective for the institution.
Our study has limitations. First, our study included only deep incisional and organ/space infections. Thus, our findings cannot be generalized to superficial incisional SSIs due to MRSA. Deep incisional and organ/space SSIs, however, are more severe and clinically important than superficial SSI. In fact, cost estimates would have been even higher had we included superficial incisional infections in our analysis. Second, our charge estimates only included indirect in-hospital costs. As a result, our charge estimates are likely underestimations of the true financial impact of these devastating infections. Third, this study included procedures that were performed prior to 2003. Since this time, greater emphasis has been placed on appropriate peri-operative antibiotic administration; thus, rates of SSI due to MRSA or MSSA may have changed since 2003. Finally, most of the surgical procedures we examined were cardiothoracic and orthopedic procedures. Thus, our results may be more reflective of the outcomes of SSI due to MRSA in these types of procedures. In fact, patients with orthopedic procedures were less likely to have adverse outcomes than patients that underwent other types of procedures. Thus, inclusion of a high number of orthopedic procedures may have biased our results towards the null and led to an underestimation of the impact of SSI due to MRSA on adverse clinical outcomes.
In summary, our study provides novel and interesting data regarding the clinical and financial impact of SSI due to MRSA and the impact of methicillin resistance among patients with SSI due to S. aureus. Not surprisingly, SSI due to MRSA led to incredibly poor outcomes compared to uninfected controls. Of particular interest, methicillin-resistance led to a longer duration of hospitalization and increased healthcare costs but did not increase the risk of mortality among patients with SSI due to S. aureus. Our estimates for the financial impact of SSI due to MRSA can be used to determine the cost-effectiveness of preventative strategies.