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Wild-type distributions of seven oral second-line drugs against Mycobacterium tuberculosis

På svenska

Author

  • T. Schon
  • P. Jureen
  • E. Chryssanthou
  • C. G. Giske
  • Erik Sturegård
  • G. Kahlmeter
  • S. Hoffner
  • K. A. Angeby

Summary, in English

OBJECTIVES: To determine wild-type minimum inhibitory concentration (MIC) distributions for Mycobacterium tuberculosis, as the background data for defining susceptibility breakpoints are limited. METHODS: We determined wild-type MIC distributions of M. tuberculosis using a 96-stick replicator in Middlebrook 7H10 (7H10) medium for ethionamide (ETH), prothionamide, thiacetazone, cycloserine, rifabutin (RFB), clofazimine and linezolid in consecutive susceptible clinical isolates (n = 78). RESULTS: Tentative epidemiological wild-type cut-offs (ECOFF) were determined for all investigated drugs where World Health Organization recommended critical concentrations for 7H10 are lacking, except for ETH. As the ECOFF was closely related to the non-wild-type strains for ETH and thiacetazone, the use of an intermediary (1) category in drug susceptibility testing could increase reproducibility. The cross-resistance between ETH and isoniazid was 21%. Applying 0.5 mg/l as a breakpoint for RFB classified two non-wild type and rpoB mutated isolates as susceptible for RFB and resistant against rifampicin. CONCLUSIONS: We propose that wild-type MIC distributions should be used as a tool to define clinical breakpoints against second-line drugs. This is increasingly important considering the rapid emergence of drug resistance.

Publishing year

2011

Language

English

Pages

502-509

Publication/Series

The International Journal of Tuberculosis and Lung Disease

Volume

15

Issue

4

Document type

Journal article

Publisher

International Union against Tuberculosis and Lung Disease

Topic

  • Respiratory Medicine and Allergy

Keywords

  • MIC susceptibility testing
  • pharmacokinetics
  • linezolid
  • ethionamide
  • second-line drugs

Status

Published

Research group

  • Clinical Microbiology, Malmö

ISBN/ISSN/Other

  • ISSN: 1815-7920