Publications

The epidemic character of community-associated methicillin-resistant Staphylococcus aureus, especially the geographically widespread clone USA300, is poorly understood. USA300 isolates carry a type IV staphylococcal chromosomal cassette mec (SCCmec) element conferring beta-lactam antibiotic class resistance and a putative pathogenicity island, arginine catabolic mobile element (ACME). Physical linkage between SCCmec and ACME suggests that selection for antibiotic resistance and for pathogenicity may be interconnected. We constructed isogenic mutants containing deletions of SCCmec and ACME in a USA300 clinical isolate to determine the role played by these elements in a rabbit model of bacteremia. We found that deletion of type IV SCCmec did not affect competitive fitness, whereas deletion of ACME significantly attenuated the pathogenicity or fitness of USA300. These data are consistent with a model in which ACME enhances growth and survival of USA300, allowing for genetic "hitchhiking" of SCCmec. SCCmec in turn protects against exposure to beta-lactams.

BACKGROUND

Methicillin-resistant Staphylococcus aureus (MRSA) infections have become a major public health problem in both the community and hospitals. Few studies have characterized the incidence and clonal composition of disease-causing strains in an entire population. Our objective was to perform a population-based survey of the clinical and molecular epidemiology of MRSA disease in San Francisco, California.

METHODS

We prospectively collected 3985 MRSA isolates and associated clinical and demographic information over a 12-month period (2004-2005) at 9 San Francisco-area medical centers. A random sample of 801 isolates was selected for molecular analysis.

RESULTS

The annual incidence of community-onset MRSA disease among San Francisco residents was 316 cases per 100,000 population, compared with 31 cases per 100,000 population for hospital-onset disease. Persons who were aged 35-44 years, were men, and were black had the highest incidence of community-onset disease. The USA300 MRSA clone accounted for 234 cases of community-onset disease and 15 cases of hospital-onset disease per 100,000 population, constituting an estimated 78.5% and 43.4% of all cases of MRSA disease, respectively. Patients with community-onset USA300 MRSA versus non-USA300 MRSA disease were more likely to be male, be of younger age, and have skin and soft-tissue infections. USA300 strains were generally more susceptible to multiple antibiotics, although decreased susceptibility to tetracycline was observed in both community-onset (P = .008) and hospital-onset (P = .03) USA300 compared to non-USA300 strains.

CONCLUSIONS

The annual incidence of community-onset MRSA disease in San Francisco is substantial, surpassing that of hospital-onset disease. USA300 is the predominant clone in both the community and hospitals. The dissemination of USA300 from the community into the hospital setting has blurred its distinction as a community-associated pathogen.

OBJECTIVES

We sought to determine whether chronic conditions and functional limitations are equally predictive of mortality among older adults.

METHODS

Participants in the 1998 wave of the Health and Retirement Study (N=19430) were divided into groups by decades of age, and their vital status in 2004 was determined. We used multivariate Cox regression to determine the ability of chronic conditions and functional limitations to predict mortality.

RESULTS

As age increased, the ability of chronic conditions to predict mortality declined rapidly, whereas the ability of functional limitations to predict mortality declined more slowly. In younger participants (aged 50-59 years), chronic conditions were stronger predictors of death than were functional limitations (Harrell C statistic 0.78 vs. 0.73; P=.001). In older participants (aged 90-99 years), functional limitations were stronger predictors of death than were chronic conditions (Harrell C statistic 0.67 vs. 0.61; P=.004).

CONCLUSIONS

The importance of chronic conditions as a predictor of death declined rapidly with increasing age. Therefore, risk-adjustment models that only consider comorbidities when comparing mortality rates across providers may be inadequate for adults older than 80 years.