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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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Parameter range for which HA-MRSA and CA-MRSA coexist.The blue area indicates the parameter-combinations for which HA-MRSA and CA-MRSA coexist. The dark grey region indicates the parameter-combinations in which HA-MRSA cannot be invaded by CA-MRSA. The light-grey region indicates parameter-combinations in which CA-MRSA cannot be invaded by HA-MRSA. The range between the two red lines corresponds to fitness costs for which selection in the hospital and community act in opposite directions (i.e. CA-MRSA is fitter in the community and HA-MRSA is fitter in the hospital). The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the absence of effective therapy. The y-axis corresponds to the average number of secondary infections caused by a single colonized individual admitted to a hospital containing only susceptible individuals (single-admission reproduction number R0HA,H[41], see Table 1).
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ppat-1003134-g003: Parameter range for which HA-MRSA and CA-MRSA coexist.The blue area indicates the parameter-combinations for which HA-MRSA and CA-MRSA coexist. The dark grey region indicates the parameter-combinations in which HA-MRSA cannot be invaded by CA-MRSA. The light-grey region indicates parameter-combinations in which CA-MRSA cannot be invaded by HA-MRSA. The range between the two red lines corresponds to fitness costs for which selection in the hospital and community act in opposite directions (i.e. CA-MRSA is fitter in the community and HA-MRSA is fitter in the hospital). The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the absence of effective therapy. The y-axis corresponds to the average number of secondary infections caused by a single colonized individual admitted to a hospital containing only susceptible individuals (single-admission reproduction number R0HA,H[41], see Table 1).

Mentions: For the basic model, which ignores both age- and treatment-structure, we find that the interaction between the hospital and the community can in principle generate coexistence between HA- and CA-MRSA. However, we observed this outcome only for a relatively narrow band of fitness-costs for HA-MRSA (Figure 3). Moreover, the width of this band decreases with decreasing transmissibility in the hospital, which we quantified as the average number of secondary cases caused by the admission of one patient to the hospital containing only susceptible patients (y-axis in Figure 3). Of note, the parameter range for which coexistence occurs is much narrower than the parameter range for which HA-MRSA is fitter than CA-MRSA in the hospital but less fit than CA-MRSA in the community (see red bars in Figure 3). Thus opposite directions of selection are not a sufficient condition for coexistence. This is due to the significant linkage between the two systems caused by the high-turnover (admission/discharge) in the hospital, which results in the two strains being cycled into and out of the community, making it harder for the two strains to coexist. If the cost of HA-MRSA exceeds the values in the coexistence range, the equilibrium in which only CA-MRSA is present becomes stable; if the cost is smaller, the equilibrium in which HA-MRSA can exclude CA-MRSA becomes stable. Such a narrow range of coexistence is not unexpected for a homogeneous model. However, the epidemiology of MRSA exhibits several heterogeneities which can stabilize coexistence over a broader range of conditions.


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

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

Parameter range for which HA-MRSA and CA-MRSA coexist.The blue area indicates the parameter-combinations for which HA-MRSA and CA-MRSA coexist. The dark grey region indicates the parameter-combinations in which HA-MRSA cannot be invaded by CA-MRSA. The light-grey region indicates parameter-combinations in which CA-MRSA cannot be invaded by HA-MRSA. The range between the two red lines corresponds to fitness costs for which selection in the hospital and community act in opposite directions (i.e. CA-MRSA is fitter in the community and HA-MRSA is fitter in the hospital). The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the absence of effective therapy. The y-axis corresponds to the average number of secondary infections caused by a single colonized individual admitted to a hospital containing only susceptible individuals (single-admission reproduction number R0HA,H[41], see Table 1).
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1003134-g003: Parameter range for which HA-MRSA and CA-MRSA coexist.The blue area indicates the parameter-combinations for which HA-MRSA and CA-MRSA coexist. The dark grey region indicates the parameter-combinations in which HA-MRSA cannot be invaded by CA-MRSA. The light-grey region indicates parameter-combinations in which CA-MRSA cannot be invaded by HA-MRSA. The range between the two red lines corresponds to fitness costs for which selection in the hospital and community act in opposite directions (i.e. CA-MRSA is fitter in the community and HA-MRSA is fitter in the hospital). The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the absence of effective therapy. The y-axis corresponds to the average number of secondary infections caused by a single colonized individual admitted to a hospital containing only susceptible individuals (single-admission reproduction number R0HA,H[41], see Table 1).
Mentions: For the basic model, which ignores both age- and treatment-structure, we find that the interaction between the hospital and the community can in principle generate coexistence between HA- and CA-MRSA. However, we observed this outcome only for a relatively narrow band of fitness-costs for HA-MRSA (Figure 3). Moreover, the width of this band decreases with decreasing transmissibility in the hospital, which we quantified as the average number of secondary cases caused by the admission of one patient to the hospital containing only susceptible patients (y-axis in Figure 3). Of note, the parameter range for which coexistence occurs is much narrower than the parameter range for which HA-MRSA is fitter than CA-MRSA in the hospital but less fit than CA-MRSA in the community (see red bars in Figure 3). Thus opposite directions of selection are not a sufficient condition for coexistence. This is due to the significant linkage between the two systems caused by the high-turnover (admission/discharge) in the hospital, which results in the two strains being cycled into and out of the community, making it harder for the two strains to coexist. If the cost of HA-MRSA exceeds the values in the coexistence range, the equilibrium in which only CA-MRSA is present becomes stable; if the cost is smaller, the equilibrium in which HA-MRSA can exclude CA-MRSA becomes stable. Such a narrow range of coexistence is not unexpected for a homogeneous model. However, the epidemiology of MRSA exhibits several heterogeneities which can stabilize coexistence over a broader range of conditions.

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