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Tuberculosis: drug resistance, fitness, and strategies for global control


Böttger, E C; Springer, B (2008). Tuberculosis: drug resistance, fitness, and strategies for global control. European Journal of Pediatrics, 167(2):141-148.

Abstract

Directly observed standardized short-course chemotherapy (DOTS) regimes are an effective treatment for drug susceptible tuberculosis disease. Surprisingly, DOTS has been reported to reduce the transmission of multi-drug resistant tuberculosis, and standardized short-course chemotherapy regimens with first-line agents have been found to be adequate treatments for some patients with drug resistant tuberculosis, including multi-drug resistance. These paradoxical observations and the apparent heterogeneity in treatment outcome of multi-drug resistant tuberculosis when using standard regimens may be due in part to limitations of in vitro drug susceptibility testing based on unique but mistakenly used techniques in diagnostic mycobacteriology. Experimental data and mathematical models indicate that the fitness cost conferred by a resistance determinant is the single most important parameter which determines the spread of drug resistance. Chromosomal alterations that result in resistance to first-line antituberculosis agents, e.g. isoniazid, rifampicin, streptomycin, may or may not be associated with a fitness cost. Based on work in experimental models and from observations in clinical drug resistant isolates a picture emerges in which, among the various resistance mutations that appear with similar rates, those associated with the least fitness cost are selected in the population.

Abstract

Directly observed standardized short-course chemotherapy (DOTS) regimes are an effective treatment for drug susceptible tuberculosis disease. Surprisingly, DOTS has been reported to reduce the transmission of multi-drug resistant tuberculosis, and standardized short-course chemotherapy regimens with first-line agents have been found to be adequate treatments for some patients with drug resistant tuberculosis, including multi-drug resistance. These paradoxical observations and the apparent heterogeneity in treatment outcome of multi-drug resistant tuberculosis when using standard regimens may be due in part to limitations of in vitro drug susceptibility testing based on unique but mistakenly used techniques in diagnostic mycobacteriology. Experimental data and mathematical models indicate that the fitness cost conferred by a resistance determinant is the single most important parameter which determines the spread of drug resistance. Chromosomal alterations that result in resistance to first-line antituberculosis agents, e.g. isoniazid, rifampicin, streptomycin, may or may not be associated with a fitness cost. Based on work in experimental models and from observations in clinical drug resistant isolates a picture emerges in which, among the various resistance mutations that appear with similar rates, those associated with the least fitness cost are selected in the population.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:February 2008
Deposited On:07 Oct 2008 15:18
Last Modified:21 Sep 2018 16:51
Publisher:Springer
ISSN:0340-6199
OA Status:Green
Publisher DOI:https://doi.org/10.1007/s00431-007-0606-9
PubMed ID:17987316

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