Date Published: February 28, 2013
Publisher: Public Library of Science
Author(s): Roger Kouyos, Eili Klein, Bryan Grenfell, Bruce R. Levin.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of morbidity and mortality in both hospitals and the community. Traditionally, MRSA was mainly hospital-associated (HA-MRSA), but in the past decade community-associated strains (CA-MRSA) have spread widely. CA-MRSA strains seem to have significantly lower biological costs of resistance, and hence it has been speculated that they may replace HA-MRSA strains in the hospital. Such a replacement could potentially have major consequences for public health, as there are differences in the resistance spectra of the two strains as well as possible differences in their clinical effects. Here we assess the impact of competition between HA- and CA-MRSA using epidemiological models which integrate realistic data on drug-usage frequencies, resistance profiles, contact, and age structures. By explicitly accounting for the differing antibiotic usage frequencies in the hospital and the community, we find that coexistence between the strains is a possible outcome, as selection favors CA-MRSA in the community, because of its lower cost of resistance, while it favors HA-MRSA in the hospital, because of its broader resistance spectrum. Incorporating realistic degrees of age- and treatment-structure into the model significantly increases the parameter ranges over which coexistence is possible. Thus, our results indicate that the large heterogeneities existing in human populations make coexistence between hospital- and community-associated strains of MRSA a likely outcome.
Over the past ten years community-associated strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) have emerged and spread rapidly, accounting for large increases in disease both in the community and in the hospital , . While originally thought to be primarily a hospital-associated pathogen (HA-MRSA), the emergence of a community-associated strain, which has a different genetic background  and drug susceptibility profile , , has raised questions about how the epidemiology and the ecology of the disease will evolve, particularly with respect to which strain will predominate.
In order to explore the possibility of coexistence between HA-MRSA and CA-MRSA, we consider a series of epidemiological models of increasing complexity. The simplest, basic model ignores all population structure beyond the distinction between hospital and community. We then extend this basic model by incorporating age- and treatment-heterogeneities in accordance with published data (see Methods).
We examined how differences in age-structured patterns of antibiotic use and hospitalization rates can promote coexistence of CA- and HA-MRSA. Overall, our results show that hospital and community-associated strains of MRSA can coexist if the broader resistance spectrum of the hospital-associated strains is balanced by intermediate fitness-disadvantages in the absence of treatment. For such intermediate fitness costs, the hospital-associated strains have higher fitness in the hospital, where treatment rates are high, whereas community-associated strains have a higher fitness in the community were treatment rates are low. Despite opposite directions of selection, both strains are present in both environments if there is coexistence at all (see Figure S3 for example runs). This occurs because of the high rates of discharge and hospitalization, which cycle individuals between the hospital and the community. Moreover, our results also indicate that opposite directions of selection are not sufficient for maintaining coexistence. This is especially true for our basic model describing well-mixed populations in the hospital and community, in which we found coexistence only for a very narrow range of HA-MRSA fitness-costs.