The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Evaluation of wild-type MIC distributions as a tool for determination of clinical breakpoints for Mycobacterium tuberculosis

På svenska

Author

  • Thomas Schon
  • Pontus Jureen
  • Christian G. Giske
  • Erja Chryssanthou
  • Erik Sturegård
  • Jim Werngren
  • Gunnar Kahlmeter
  • Sven E. Hoffner
  • Kristian A. Angeby

Summary, in English

Objectives: The aim of this study was to establish wild-type MIC distributions of first-line drugs for Mycobacterium tuberculosis, as well as to explore the usefulness of such distributions when setting clinical breakpoints. Methods: We determined the MICs of rifampicin, isonlazid and ethambutol for M. tuberculosis using a Middlebrook 7H10 dilution method for 90 consecutive clinical isolates, 8 resistant strains and 16 isolates from the WHO proficiency test panel. M. tuberculosis H37Rv was used for quality control and susceptibility results using 7H10 were compared with the results obtained with BACTEC460. Results: The agreement with BACTEC460 was very high for isonlazid (99.1%) and rifampicin (99.1%) but lower for ethambutol (94.7%). Intra- and inter-assay variation was below one MIC dilution. The MIC distributions for isoniazid and rifampicin provided a clear separation between susceptible and resistant strains. Regarding ethambutol, the current breakpoint for 7H10 (5 mg/L) is close to the wild-type and all strains (n=6) showing a disagreement between BACTEC460 and 7H10 were distributed very close to the breakpoint (MIC 4-8 mg/L). This problematic relation was confirmed by investigating isolates from the WHO panel with an agreement <95% (64%-88% among 26 laboratories, n=4) for which the MICs were 4-8 mg/L . Conclusions: Utilizing the wild-type MIC distribution was found to be as useful in M. tuberculosis as in other bacteria when setting clinical breakpoints. We suggest that the present clinical breakpoints should be re-evaluated, taking into account wild-type MIC distributions and available pharmacokinetic data.

Publishing year

2009

Language

English

Pages

786-793

Publication/Series

Journal of Antimicrobial Chemotherapy

Volume

64

Issue

4

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Pharmacology and Toxicology

Keywords

  • testing
  • susceptibility
  • ethambutol
  • isoniazid
  • pharmacokinetics
  • rifampicin

Status

Published

Research group

  • Clinical Microbiology, Malmö

ISBN/ISSN/Other

  • ISSN: 1460-2091