Studies of antibiotic resistance within the patient, hospitals and the community using simple mathematical models

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Abstract
The emergence of antibiotic resistance in a wide variety of important pathogens of humans presents a worldwide threat to public health. This paper describes recent work on the use of mathematical models of the emergence and spread of resistance bacteria, on scales ranging from within the patient, in hospitals and within communities of people. Model development starts within the treated patient, and pharmacokinetic and pharmacodynamic principles are melded within a framework that mirrors the interaction between bacterial population growth, drug treatment and the immunological responses targeted at the pathogen. The model helps identify areas in which more precise information is needed, particularly in the context of how drugs influence pathogen birth and death rates (pharmacodynamics). The next area addressed is the spread of multiply drug-resistant bacteria in hospital settings. Models of the transmission dynamics of the pathogen provide a framework for assessing the relative merits of different forms of intervention, and provide criteria for control or eradication. The model is applied to the spread of vancomycin-resistant enterococci in an intensive care setting. This model framework is generalized to consider the spread of resistant organisms between hospitals. The model framework allows for heterogeneity in hospital size and highlights the importance of large hospitals in the maintenance of resistant organisms within a defined country. The spread of methicillin resistant Staphylococcus aureus (MRSA) in England and Wales provides a template for model construction and analysis. The final section addresses the emergence and spread of resistant organisms in communities of people and the dependence on the intensity of selection as measured by the volume or rate of drug use. Model output is fitted to data for Finland and Iceland and conclusions drawn concerning the key factors determining the rate of spread and decay once drug pressure is relaxed.