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Hospital-community interactions foster coexistence between methicillin-resistant strains of Staphylococcus aureus.

Kouyos R, Klein E, Grenfell B - PLoS Pathog. (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America. roger.kouyos@uzh.ch

ABSTRACT
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.

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A) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the basic model.The red area indicates coexistence in the age-structured model. B) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the treatment-structured model. The red area indicates co-existence in the treatment- and age-structured model. The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the community in the absence of effective therapy. The y-axis corresponds to ratio between the fitness costs of HA-MRSA in hospital and community.
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ppat-1003134-g006: A) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the basic model.The red area indicates coexistence in the age-structured model. B) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the treatment-structured model. The red area indicates co-existence in the treatment- and age-structured model. The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the community in the absence of effective therapy. The y-axis corresponds to ratio between the fitness costs of HA-MRSA in hospital and community.

Mentions: HA-MRSA is most likely adapted to the hospital environment in other ways than by its broad antibiotic resistance spectrum (e.g. tolerance to disinfectants, smaller requirements of invasibility, etc.) [2], [22]. Accordingly, it is likely better able to compete against CA-MRSA (in the absence of therapy) in the hospital as opposed to the community. Taking this effect into account, we find that as the fitness-cost of HA-MRSA in the hospital decreases relative to CA-MRSA, the maximal fitness cost of HA-MRSA for which coexistence occurs is strongly increased. By contrast the minimal cost for coexistence changes only weakly, because reducing the cost of resistance in the hospital does not affect relative fitness in the community (Figure 6). Thus, context specific fitness costs further facilitate coexistence between HA- and CA-MRSA. It is remarkable that decreasing the cost of HA-MRSA in the hospital has a much stronger effect in the presence of age structure than in its absence (which indicates that age structure helps separate the hospital from the community). Thus there is a synergistic effect between age-structure and hospital specific reduction of fitness costs.


Hospital-community interactions foster coexistence between methicillin-resistant strains of Staphylococcus aureus.

Kouyos R, Klein E, Grenfell B - PLoS Pathog. (2013)

A) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the basic model.The red area indicates coexistence in the age-structured model. B) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the treatment-structured model. The red area indicates co-existence in the treatment- and age-structured model. The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the community in the absence of effective therapy. The y-axis corresponds to ratio between the fitness costs of HA-MRSA in hospital and community.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585153&req=5

ppat-1003134-g006: A) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the basic model.The red area indicates coexistence in the age-structured model. B) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the treatment-structured model. The red area indicates co-existence in the treatment- and age-structured model. The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the community in the absence of effective therapy. The y-axis corresponds to ratio between the fitness costs of HA-MRSA in hospital and community.
Mentions: HA-MRSA is most likely adapted to the hospital environment in other ways than by its broad antibiotic resistance spectrum (e.g. tolerance to disinfectants, smaller requirements of invasibility, etc.) [2], [22]. Accordingly, it is likely better able to compete against CA-MRSA (in the absence of therapy) in the hospital as opposed to the community. Taking this effect into account, we find that as the fitness-cost of HA-MRSA in the hospital decreases relative to CA-MRSA, the maximal fitness cost of HA-MRSA for which coexistence occurs is strongly increased. By contrast the minimal cost for coexistence changes only weakly, because reducing the cost of resistance in the hospital does not affect relative fitness in the community (Figure 6). Thus, context specific fitness costs further facilitate coexistence between HA- and CA-MRSA. It is remarkable that decreasing the cost of HA-MRSA in the hospital has a much stronger effect in the presence of age structure than in its absence (which indicates that age structure helps separate the hospital from the community). Thus there is a synergistic effect between age-structure and hospital specific reduction of fitness costs.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America. roger.kouyos@uzh.ch

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus