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PLoS Pathogens: On Being the Right Size: The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community
PLoS Pathogens: On Being the Right Size: The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community
[Source: PLoS Pathogens, full text: (LINK). Abstract, edited.]
[Source: PLoS Pathogens, full text: (LINK). Abstract, edited.]
On Being the Right Size: The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community
Roger D. Kouyos (1,2), Pia Abel zur Wiesch (2), Sebastian Bonhoeffer (2)
<SUP></SUP>1 Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland, 2 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America
Abstract
The evolution of drug resistant bacteria is a severe public health problem, both in hospitals and in the community. Currently, some countries aim at concentrating highly specialized services in large hospitals in order to improve patient outcomes. Emergent resistant strains often originate in health care facilities, but it is unknown to what extent hospital size affects resistance evolution and the resulting spillover of hospital-associated pathogens to the community. We used two published datasets from the US and Ireland to investigate the effects of hospital size and controlled for several confounders such as antimicrobial usage, sampling frequency, mortality, disinfection and length of stay. The proportion of patients acquiring both sensitive and resistant infections in a hospital strongly correlated with hospital size. Moreover, we observe the same pattern for both the percentage of resistant infections and the increase of hospital-acquired infections over time. One interpretation of this pattern is that chance effects in small hospitals impede the spread of drug-resistance. To investigate to what extent the size distribution of hospitals can directly affect the prevalence of antibiotic resistance, we use a stochastic epidemiological model describing the spread of drug resistance in a hospital setting as well as the interaction between one or several hospitals and the community. We show that the level of drug resistance typically increases with population size: In small hospitals chance effects cause large fluctuations in pathogen population size or even extinctions, both of which impede the acquisition and spread of drug resistance. Finally, we show that indirect transmission via environmental reservoirs can reduce the effect of hospital size because the slow turnover in the environment can prevent extinction of resistant strains. This implies that reducing environmental transmission is especially important in small hospitals, because such a reduction not only reduces overall transmission but might also facilitate the extinction of resistant strains. Overall, our study shows that the distribution of hospital sizes is a crucial factor for the spread of drug resistance.
Author Summary
The increasing spread of bacteria, which are resistant to antibiotics, is a serious threat to clinical care. Currently, several countries aim at concentrating highly specialized services in large hospitals in order to improve patient outcomes. However, empirical studies have shown that resistance levels correlate with hospital size. To illustrate this correlation, we analyze two published datasets from the US and Ireland and controlled for antimicrobial usage, disinfection and length of stay. The proportion of patients acquiring both sensitive and resistant infections in hospitals strongly correlated with hospital size. Moreover, we observe the same pattern for both the percentage of resistant infections and the temporal increase of hospital-acquired infections. To investigate to what extent hospital size can directly affect the prevalence of antibiotic resistance, we use mathematical models describing the epidemic spread of resistance in hospitals and the community. We find that small hospitals typically lead to considerably lower resistance levels than large hospitals. However, this beneficial effect of small hospital size may be reduced if bacteria are transmitted indirectly via the environment. Therefore, reducing environmental transmission might be particularly important in small hospitals. Overall, our findings suggest that the short-term benefits of larger hospitals may come at the price of increasing resistance in the long term.
Citation: Kouyos RD, Abel zur Wiesch P, Bonhoeffer S (2011) On Being the Right Size: The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community. PLoS Pathog 7(4): e1001334. doi:10.1371/journal.ppat.1001334
Editor: Bruce R. Levin, Emory University, United States of America
Received: September 9, 2010; Accepted: March 15, 2011; Published: April 14, 2011
Copyright: ? 2011 Kouyos et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: We acknowledge financial support from the Swiss National Science Foundation (www.snf.ch). Sebastian Bonhoeffer acknowledges support from the European Research Council (268540 PBDR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: rkouyos@princeton.edu
# These authors contributed equally to this work.
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Roger D. Kouyos (1,2), Pia Abel zur Wiesch (2), Sebastian Bonhoeffer (2)
<SUP></SUP>1 Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland, 2 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America
Abstract
The evolution of drug resistant bacteria is a severe public health problem, both in hospitals and in the community. Currently, some countries aim at concentrating highly specialized services in large hospitals in order to improve patient outcomes. Emergent resistant strains often originate in health care facilities, but it is unknown to what extent hospital size affects resistance evolution and the resulting spillover of hospital-associated pathogens to the community. We used two published datasets from the US and Ireland to investigate the effects of hospital size and controlled for several confounders such as antimicrobial usage, sampling frequency, mortality, disinfection and length of stay. The proportion of patients acquiring both sensitive and resistant infections in a hospital strongly correlated with hospital size. Moreover, we observe the same pattern for both the percentage of resistant infections and the increase of hospital-acquired infections over time. One interpretation of this pattern is that chance effects in small hospitals impede the spread of drug-resistance. To investigate to what extent the size distribution of hospitals can directly affect the prevalence of antibiotic resistance, we use a stochastic epidemiological model describing the spread of drug resistance in a hospital setting as well as the interaction between one or several hospitals and the community. We show that the level of drug resistance typically increases with population size: In small hospitals chance effects cause large fluctuations in pathogen population size or even extinctions, both of which impede the acquisition and spread of drug resistance. Finally, we show that indirect transmission via environmental reservoirs can reduce the effect of hospital size because the slow turnover in the environment can prevent extinction of resistant strains. This implies that reducing environmental transmission is especially important in small hospitals, because such a reduction not only reduces overall transmission but might also facilitate the extinction of resistant strains. Overall, our study shows that the distribution of hospital sizes is a crucial factor for the spread of drug resistance.
Author Summary
The increasing spread of bacteria, which are resistant to antibiotics, is a serious threat to clinical care. Currently, several countries aim at concentrating highly specialized services in large hospitals in order to improve patient outcomes. However, empirical studies have shown that resistance levels correlate with hospital size. To illustrate this correlation, we analyze two published datasets from the US and Ireland and controlled for antimicrobial usage, disinfection and length of stay. The proportion of patients acquiring both sensitive and resistant infections in hospitals strongly correlated with hospital size. Moreover, we observe the same pattern for both the percentage of resistant infections and the temporal increase of hospital-acquired infections. To investigate to what extent hospital size can directly affect the prevalence of antibiotic resistance, we use mathematical models describing the epidemic spread of resistance in hospitals and the community. We find that small hospitals typically lead to considerably lower resistance levels than large hospitals. However, this beneficial effect of small hospital size may be reduced if bacteria are transmitted indirectly via the environment. Therefore, reducing environmental transmission might be particularly important in small hospitals. Overall, our findings suggest that the short-term benefits of larger hospitals may come at the price of increasing resistance in the long term.
Citation: Kouyos RD, Abel zur Wiesch P, Bonhoeffer S (2011) On Being the Right Size: The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community. PLoS Pathog 7(4): e1001334. doi:10.1371/journal.ppat.1001334
Editor: Bruce R. Levin, Emory University, United States of America
Received: September 9, 2010; Accepted: March 15, 2011; Published: April 14, 2011
Copyright: ? 2011 Kouyos et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: We acknowledge financial support from the Swiss National Science Foundation (www.snf.ch). Sebastian Bonhoeffer acknowledges support from the European Research Council (268540 PBDR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: rkouyos@princeton.edu
# These authors contributed equally to this work.
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