Community-associated methicillin-resistant S. aureus (CA-MRSA) is increasingly common in hospitals, with potentially serious consequences. The aim of this study was to assess the impact of antibiotic prescription patterns on the selection of CA-MRSA within hospitals, in a context of competition with other circulating staphylococcal strains, including methicillin-sensitive (MSSA) and hospital-associated methicillin-resistant (HA-MRSA) strains. We developed a computerized agent-based model of S. aureus transmission in a hospital ward in which CA-MRSA, MSSA, and HA-MRSA strains may cocirculate. We investigated a wide range of antibiotic prescription patterns in both intensive care units (ICUs) and general wards, and we studied how differences in antibiotic exposure may explain observed variations in the success of CA-MRSA invasion in the hospitals of several European countries and of the United States. Model predictions underlined the influence of antibiotic prescription patterns on CA-MRSA spread in hospitals, especially in the ICU, where the endemic prevalence of CA-MRSA carriage can range from 3% to 20%, depending on the simulated prescription pattern. Large antibiotic exposure with drugs effective against MSSA but not MRSA was found to promote invasion by CA-MRSA. We also found that, should CA-MRSA acquire fluoroquinolone resistance, a major increase in CA-MRSA prevalence could ensue in hospitals worldwide. Controlling the spread of highly communityprevalent CA-MRSA within hospitals is a challenge. This study demonstrates that antibiotic exposure strategies could participate in this control. This is all the more important in wards such as ICUs, which may play the role of incubators, promoting CA-MRSA selection in hospitals.

iInterventions designed to reduce antibiotic consumption are under way worldwide. While overall reductions are often achieved, their impact on the selection of antibiotic-resistant selection cannot be assessed accurately from currently available data. We developed a mathematical model of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) transmission inside and outside the hospital. A systematic simulation study was then conducted with two objectives: to assess the impact of antibiotic class-specific changes during an antibiotic reduction period and to investigate the interactions between antibiotic prescription changes in the hospital and the community. The model reproduced the overall reduction in MRSA frequency in French intensive-care units (ICUs) with antibiotic consumption in France from 2002 to 2003 as an input. However, the change in MRSA frequency depended on which antibiotic classes changed the most, with the same overall 10% reduction in antibiotic use over 1 year leading to anywhere between a 69% decrease and a 52% increase in MRSA frequency in ICUs and anywhere between a 37% decrease and a 46% increase in the community. Furthermore, some combinations of antibiotic prescription changes in the hospital and the community could act in a synergistic or antagonistic way with regard to overall MRSA selection. This study shows that class-specific changes in antibiotic use, rather than overall reductions, need to be considered in order to properly anticipate the impact of an antibiotic reduction campaign. It also highlights the fact that optimal gains will be obtained by coordinating interventions in hospitals and in the community, since the effect of an intervention in a given setting may be strongly affected by exogenous factors.