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

In English

Författare

  • 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.

Publiceringsår

2011

Språk

Engelska

Sidor

502-509

Publikation/Tidskrift/Serie

The International Journal of Tuberculosis and Lung Disease

Volym

15

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

International Union against Tuberculosis and Lung Disease

Ämne

  • Respiratory Medicine and Allergy

Nyckelord

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

Status

Published

Forskningsgrupp

  • Clinical Microbiology, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1815-7920