Clinical and economic impact of methicillin resistance in patients with Staphylococcus aureus bacteremia

Abstract

We performed a retrospective cohort study to determine the morbidity, mortality, and hospital costs attributable to methicillin resistance in patients with S. aureus bacteremia (SAB). Episodes of SAB occurring at the Detroit Receiving Hospital in 1999–2001 were evaluated. Controlling for confounding variables, patients with methicillin-resistant Staphylococcus aureus (MRSA) had a 1.5-fold longer length of stay (19.1 versus 14.2 days, P = 0.005) and a 2-fold increased cost of hospitalization ($21 577 versus $11 668, P = 0.001) compared with methicillin-susceptible S. aureus (MSSA). MRSA patients were at increased risk for delayed treatment, and delayed therapy was an independent predictor of mortality. Efforts should be made to ensure that appropriate therapy is initiated promptly in patients at risk for MRSA. Infection control policies must be strictly enforced to limit the spread of MRSA and potentially minimize excess hospital expenditures incurred with MRSA. With the advent of new treatment options, the impact of MRSA will need to be revisited to determine if these therapies can remedy the increased morbidity associated with MRSA.

Introduction

Staphylococcus aureus is a predominant human pathogen and is associated with considerably morbidity and mortality (McGowan et al., 1975, Mylotte et al., 1987, National Noscocomial Infections Surveillance report, 1996, Weinstein et al., 1983). Treatment of S. aureus infections has been complicated by the persistent rise in rates of S. aureus isolates with methicillin resistance. Methicillin-resistant Staphylococcus aureus (MRSA) was first described in 1961 and has since become endemic in many hospitals. In some institutions, MRSA accounts for more than 50% of all S. aureus infections (Pfaller et al., 1999).

The contribution of methicillin resistance to the morbidity and mortality associated with S. aureus bacteremia (SAB) is controversial (Abramson and Sexton, 1999, Blot et al., 2002, Collopy et al., 1984, Conterno et al., 1998, Cosgrove et al., 2003, Engemann et al., 2003, French et al., 1990, Gonzalez et al., 1999, Graffunder and Venezia, 2002, Harbarth et al., 1998, Hershow et al., 1992, Ibelings and Bruining, 1998, Lewis and Saravolatz, 1985, Lodise et al., 2003a, Lodise et al., 2003b, Mylotte and Tayara, 2000, Roghmann, 2000, Romero-Vivas et al., 1995, Rubin et al., 1999, Selvey et al., 2000, Soriano et al., 2000, Wakefield et al., 1988). It is well-known that patients with MRSA bloodstream infections are more likely than patients with methicillin-susceptible S. aureus (MSSA) infections to have serious underlying medical conditions and higher severity-of-illness scores (Abramson and Sexton, 1999, Asensio et al., 1996, Collopy et al., 1984, Conterno et al., 1998, Cosgrove et al., 2003, Engemann et al., 2003, French et al., 1990, Gonzalez et al., 1999, Graffunder and Venezia, 2002, Harbarth et al., 1998, Hershow et al., 1992, Ibelings and Bruining, 1998, Law and Gill, 1988, Lewis and Saravolatz, 1985, Lodise et al., 2003a, Lodise et al., 2003b, Mylotte and Tayara, 2000, Pujol et al., 1994, Rello et al., 1994, Roghmann, 2000, Romero-Vivas et al., 1995, Rubin et al., 1999, Selvey et al., 2000, Soriano et al., 2000, Wakefield et al., 1988, Warshawsky et al., 2000). These underlying characteristics make it difficult to determine if methicillin resistance specifically contributes to inferior outcomes in these patients. In addition, different antibiotics are used to treat MRSA and MSSA infections, and the variable antibacterial activity of these agents may further impact patient outcomes. Previous studies examining the impact of MRSA on outcomes have focused on the association between MRSA and mortality and findings have varied (Collopy et al., 1984, Conterno et al., 1998, Cosgrove et al., 2003, Engemann et al., 2003, French et al., 1990, Graffunder and Venezia, 2002, Harbarth et al., 1998, Hershow et al., 1992, Ibelings and Bruining, 1998, Lewis and Saravolatz, 1985, Melzer et al., 2003, Mylotte and Tayara, 2000, Roghmann, 2000, Romero-Vivas et al., 1995, Rubin et al., 1999, Selvey et al., 2000, Soriano et al., 2000). Little information exists on the relationship between MRSA and intermediate endpoints, such as length of stay, rate of improvement, and cost of hospitalization.(Abramson and Sexton, 1999, Collopy et al., 1984, Engemann et al., 2003, Graffunder and Venezia, 2002, Rubin et al., 1999, Wakefield et al., 1988). Furthermore, previous studies have not always adequately adjusted for disease severity and comorbid conditions when evaluating the influence of MRSA on both primary and intermediate outcomes. Adjustment of confounders is critical to minimize the contribution of baseline differences between MRSA and MSSA patients to the observed outcomes. Therefore, the objective of this study was to determine the independent influence of methicillin resistance on the primary and intermediate outcomes associated with SAB while appropriately controlling for confounding variables.