Skin and soft tissue infections (SSTIs) are common reasons for seeking medical care, and can have significant morbidity including hospitalization [1, 2]. In patients hospitalized due to SSTI, Staphylococcus aureus (S. aureus) is the most common bacterial pathogen identified [3–5].

In the past, methicillin-resistant S. aureus (MRSA) infections were mostly confined to patients with risk factors such as hospitalization or recent healthcare contact [6]. More recently however, there has been a dramatic increase in community-associated MRSA (CA-MRSA) infections which often present as SSTIs, affecting individuals without prior risk factors^3;6. The emergence of MRSA in SSTIs has challenged treatment, as this bacterium is resistant to beta-lactam antibiotics that were previously the standard of care for S. aureus-SSTI treatment [5].

In the U.S.A. between 1997 and 2005, the overall annual rate of visits for SSTIs to physician offices, hospital outpatient departments, and emergency departments increased from 32.1 to 48.1 visits per 1,000 people, which at the U.S. population level, equated to 14.2 million total SSTI visits in 2005 [7]. S. aureus hospitalizations also increased in parallel with the increase in SSTIs. Between 1999 and 2005, the estimated number of S. aureus–related hospitalizations across infection types increased by 62%, from 294,570 to 477,927 and the estimated number of MRSA-related hospitalizations more than doubled, from 127,036 in 1999 to 278,203 in 2005 [8]. The increase in S. aureus hospitalizations has occurred coincidentally with the emergence of the USA300 clone as a primary cause of CA-MRSA infections, which mostly manifest as SSTIs [9].

In terms of management of S. aureus-SSTIs, treatment costs can be substantial. Cost estimates vary by populations studied, cost perspective, and antibiotic therapy chosen, among other factors [10, 11]. In a U.S.A. study of 1997 inpatients and outpatients, Marton, et al., reported that mean overall SSTI episode costs among adults were $8,865 (with 12.6% of the episodes resulting in hospitalization) [10]. Menzin, et al., studied over 13,000 S. aureus-SSTI inpatient episodes from 2005 to 2006 and found that the mean associated hospitalization costs were $6,800 per patient [12]. Itani, et al., studied 5,156 patients hospitalized with SSTIs and found that the median charge among the 3,079 with gram positive-associated SSTIs (which includes S. aureus) was $19,894 with a mean of $40,046 [2].

The above investigations were limited by relatively small sample size and/or relatively short study time frames. To address these data limitations, we performed a retrospective observational study to evaluate the US national trend of the incidence and cost of hospitalizations associated to S. aureus-SSTIs from 2001 through 2009.

Based on HCUP data, which is comprised of 20% of all US hospitalizations between 2001 and 2009, we found an increase in S. aureus associated hospitalizations consistent with prior reports [8, 9, 18]. Importantly, we found that among S. aureus infection the proportion of hospitalizations with a diagnosis code for SSTI also increased, indicating that the rise in S. aureus infections was at least in part driven by SSTIs. By 2009, half of all S. aureus -hospitalizations were associated with a SSTI code.

We also found that between 2001 and 2009 costs associated with S. aureus-SSTI hospitalizations increased 26%, which would imply an increase of national cost from $3.36 to $4.22 billion in constant dollars. Trends in S. aureus-SSTI hospitalization cost increases may be explained, at least in part, by changes in the age group demographics of hospitalization, hospital length of stay, and/or average hospitalization cost. For example, by 2009, patients aged 0–44 years accounted for a larger proportion of hospitalizations than in 2001 (36% vs. 26%, respectively). Furthermore, the average length of stay and cost of hospitalization dropped within these age groups more than in the older age strata (Table 2). Therefore, the fact that the national annual cost of S. aureus-SSTI hospitalizations did not increase even higher was because the higher S. aureus-SSTI hospitalization rates were attenuated by increasingly lower age of those hospitalized (who have less expensive hospitalizations) as well as shorter length of stay in all age groups over time. We found a mean cost of S. aureus-SSTI of $11,622 in 2009, which falls into the cost/charge range found in the literature from $6,800 to $40,046 [12].

The increase in SA-SSTIs seen disproportionately in the younger age groups has occurred at a time of an increased incidence of infections due to CA-MRSA caused by the USA 300 strain, which has also been noted in the younger age groups [18, 19].

Our findings on the increased incidence of S. aureus-SSTI hospitalizations are generally in agreement with prior studies. Klein, et al., showed a 62% increase in the incidence of S. aureus hospitalization between 1999 and 2005 [8], which is similar to the 55% increase between 2001 and 2005 we have found. Interestingly, there are recent data demonstrating decreases in invasive MRSA infections between 2005 and 2011 [20]. However, we did not see decreases, most likely because the decreases noted by Dantes, et al., appear to be driven largely by decreases in healthcare-associated MRSA infections, likely due to hospital-based infection prevention efforts [20], whereas our data focused on SSTIs, which are typically community associated and thus less likely to be affected by hospital-based prevention efforts.

Our study has several limitations. First, we calculated the estimated costs of S. aureus-SSTIs using associated cost estimates, rather than excess cost estimates. Thus, we have likely overestimated the cost of S. aureus associated SSTIs because our analysis includes the costs of concomitant treatment of comorbidities. On the other hand, we may have underestimated the S. aureus-SSTI associated hospitalization cost because HCUP provides information on direct hospital costs only, and not costs associated with physicians and other medical professionals that provided care but which are billed separately. Second, diagnoses of S. aureus-SSTI were based solely on ICD-9 codes and were not validated with chart reviews. Overall, our estimates of S. aureus-SSTI hospitalization incidence was (~30%) higher than those of Klein, et al. [8], during the overlapping periods of the two studies. This difference may be due to the databases used (we used HCUP while Klein, et al., used the National Hospital Discharge Survey). In addition, we adopted a previous ICD-9 coding method [8] that included some diagnoses which are not universally classified as SSTIs, such as device infections and wound infections.

Another limitation is that the incidence of S. aureus-SSTI hospitalizations is only a fraction of all the burden of S. aureus-SSTIs in the population. For example, SSTIs are a major reason for emergency department (ED) visits [4, 21]. Even though ED visits are associated with a lower cost than hospitalizations, they are high in volume, and may still account for a large national cost associated with S. aureus-SSTIs. Therefore, as suggested above, our methods could have led to an underestimate of total costs attributable to S. aureus-SSTIs. Finally, it should be noted that contemporary data from NIS are typically 3 years old making descriptions of current or past year trends impossible.

In summary, between 2001 and 2009, the overall incidence of S. aureus hospitalizations increased by 57%, with the peak incidence in 2008. This increase was driven by S. aureus-SSTI hospitalizations, which rose by 105%. Children 0–17 years experienced the highest growth in S. aureus-SSTI hospitalizations (316%). However, the highest incidence of S. aureus-SSTI hospitalizations was observed in the population ≥ 75 years old across all the study years, and in 2009 the incidence in this age group was still about 7 times higher than in children. The national annual cost of S. aureus-SSTI hospitalizations increased by 26%. This increase could have been more dramatic if it were not for the counterbalancing shift in the demographics of S. aureus-SSTI hospitalizations to younger patients who have less expensive hospitalizations, and to the trend for shorter hospital stays for S. aureus-SSTIs. Efforts to prevent S. aureus-SSTIs and MRSA-associated SSTIs could have a meaningful impact on healthcare costs for this common infection.