PMID: 9526190Apr 4, 1998Paper

Population dynamics of tuberculosis treatment: mathematical models of the roles of non-compliance and bacterial heterogeneity in the evolution of drug resistance

The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease
M Lipsitch, B R Levin

Abstract

Patient non-compliance and/or spatial heterogeneity in drug concentration or effectiveness may contribute to the emergence of drug resistance during multiple-drug chemotherapy of tuberculosis. Using mathematical models of mycobacterial population dynamics under antimicrobial treatment, to assess the effects of non-compliance, heterogeneity and other factors on the success of treatment. A mathematical model is used to generate predictions about the ascent of drug resistance in treated hosts with non-compliance and/or a 'protected compartment' of bacteria where only one drug is active; simulations of a more realistic version of this model take into account random mutation, and different assumptions about the size of, and growth rate of bacteria in, the protected compartment. The existence of a protected compartment can increase the likelihood of resistance to the single drug active in that compartment, but only if bacteria resistant to that drug can grow in the protected compartment or if the host is non-adherent to the treatment regimen. However, the protected compartment may also slow the ascent of bacteria resistant to drugs not active in it (e.g. isoniazid) by providing a reservoir of non-selected mycobacteria. The model pred...Continue Reading

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