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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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Coexistence between HA-MRSA and CA-MRSA in the transient phase after the introduction of CA-MRSA into the HA-MRSA-infected host population in the treatment- and age-structured model (corresponding to the red area in Figure 5).Colors indicate which strains have frequencies >5% among the colonized patients in the hospital (HA-MRSA) and the community (CA-MRSA): Blue indicates coexistence (i.e. both strains >5%), dark grey indicates HA-MRSA only, and light grey CA-MRSA only. The dashed orange line delimits the parameter region in which HA-MRSA can invade MSSA (criterion for invasion: frequency of MRSA >5%, 50 years after its introduction; see Figure S2).
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ppat-1003134-g007: Coexistence between HA-MRSA and CA-MRSA in the transient phase after the introduction of CA-MRSA into the HA-MRSA-infected host population in the treatment- and age-structured model (corresponding to the red area in Figure 5).Colors indicate which strains have frequencies >5% among the colonized patients in the hospital (HA-MRSA) and the community (CA-MRSA): Blue indicates coexistence (i.e. both strains >5%), dark grey indicates HA-MRSA only, and light grey CA-MRSA only. The dashed orange line delimits the parameter region in which HA-MRSA can invade MSSA (criterion for invasion: frequency of MRSA >5%, 50 years after its introduction; see Figure S2).

Mentions: We first considered the interaction between CA-MRSA and HA-MRSA (in analogy to the above analyses). We find that the two strains can coexist during a long transient phase (10–50 years) for a broad range of conditions, which do not support coexistence at equilibrium (see Figure 7). Moreover, we can substantially reduce the range of realistic parameters by considering the interaction between HA-MRSA and MSSA: as we know that HA-MRSA has attained substantial frequencies (in the USA at least) after <50 years of methicillin use, the model is only consistent with reality for those parameter-combinations for which this is the case. Figure S2 shows that an invasion of HA-MRSA into the MSSA equilibrium is only possible if the fitness cost of HA-MRSA is below a threshold that is dependent upon the average number of secondary cases caused by the admission of one patient to the hospital containing only susceptible patients (R0HA,H). This threshold is indicated in Figure 7 by the dashed orange line. As it is also a fact that CA-MRSA was able to invade HA-MRSA, the realistic parameter range in Figure 7 is delimited by the dark grey area (corresponding to parameter values where the CA-MRSA invasion is impossible) to the left and the orange line to the right. Thus, Figure 7 indicates that we would expect a long-term coexistence between HA-MRSA and CA-MRSA for most realistic parameter combinations.


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

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

Coexistence between HA-MRSA and CA-MRSA in the transient phase after the introduction of CA-MRSA into the HA-MRSA-infected host population in the treatment- and age-structured model (corresponding to the red area in Figure 5).Colors indicate which strains have frequencies >5% among the colonized patients in the hospital (HA-MRSA) and the community (CA-MRSA): Blue indicates coexistence (i.e. both strains >5%), dark grey indicates HA-MRSA only, and light grey CA-MRSA only. The dashed orange line delimits the parameter region in which HA-MRSA can invade MSSA (criterion for invasion: frequency of MRSA >5%, 50 years after its introduction; see Figure S2).
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1003134-g007: Coexistence between HA-MRSA and CA-MRSA in the transient phase after the introduction of CA-MRSA into the HA-MRSA-infected host population in the treatment- and age-structured model (corresponding to the red area in Figure 5).Colors indicate which strains have frequencies >5% among the colonized patients in the hospital (HA-MRSA) and the community (CA-MRSA): Blue indicates coexistence (i.e. both strains >5%), dark grey indicates HA-MRSA only, and light grey CA-MRSA only. The dashed orange line delimits the parameter region in which HA-MRSA can invade MSSA (criterion for invasion: frequency of MRSA >5%, 50 years after its introduction; see Figure S2).
Mentions: We first considered the interaction between CA-MRSA and HA-MRSA (in analogy to the above analyses). We find that the two strains can coexist during a long transient phase (10–50 years) for a broad range of conditions, which do not support coexistence at equilibrium (see Figure 7). Moreover, we can substantially reduce the range of realistic parameters by considering the interaction between HA-MRSA and MSSA: as we know that HA-MRSA has attained substantial frequencies (in the USA at least) after <50 years of methicillin use, the model is only consistent with reality for those parameter-combinations for which this is the case. Figure S2 shows that an invasion of HA-MRSA into the MSSA equilibrium is only possible if the fitness cost of HA-MRSA is below a threshold that is dependent upon the average number of secondary cases caused by the admission of one patient to the hospital containing only susceptible patients (R0HA,H). This threshold is indicated in Figure 7 by the dashed orange line. As it is also a fact that CA-MRSA was able to invade HA-MRSA, the realistic parameter range in Figure 7 is delimited by the dark grey area (corresponding to parameter values where the CA-MRSA invasion is impossible) to the left and the orange line to the right. Thus, Figure 7 indicates that we would expect a long-term coexistence between HA-MRSA and CA-MRSA for most realistic parameter combinations.

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