Evaluation of wild-type MIC distributions as a tool for determination of clinical breakpoints for Mycobacterium tuberculosis
(2009) In Journal of Antimicrobial Chemotherapy 64(4). p.786-793- Abstract
- 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%).... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1507321
- author
- Schon, Thomas ; Jureen, Pontus ; Giske, Christian G. ; Chryssanthou, Erja ; Sturegård, Erik LU ; Werngren, Jim ; Kahlmeter, Gunnar ; Hoffner, Sven E. and Angeby, Kristian A.
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- testing, susceptibility, ethambutol, isoniazid, pharmacokinetics, rifampicin
- in
- Journal of Antimicrobial Chemotherapy
- volume
- 64
- issue
- 4
- pages
- 786 - 793
- publisher
- Oxford University Press
- external identifiers
-
- wos:000270592400019
- scopus:70349445065
- ISSN
- 1460-2091
- DOI
- 10.1093/jac/dkp262
- language
- English
- LU publication?
- yes
- id
- 5cf566a8-21ef-4c37-927c-b4548bf4fe7f (old id 1507321)
- date added to LUP
- 2016-04-01 11:56:59
- date last changed
- 2022-05-18 23:02:56
@article{5cf566a8-21ef-4c37-927c-b4548bf4fe7f,
abstract = {{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.}},
author = {{Schon, Thomas and Jureen, Pontus and Giske, Christian G. and Chryssanthou, Erja and Sturegård, Erik and Werngren, Jim and Kahlmeter, Gunnar and Hoffner, Sven E. and Angeby, Kristian A.}},
issn = {{1460-2091}},
keywords = {{testing; susceptibility; ethambutol; isoniazid; pharmacokinetics; rifampicin}},
language = {{eng}},
number = {{4}},
pages = {{786--793}},
publisher = {{Oxford University Press}},
series = {{Journal of Antimicrobial Chemotherapy}},
title = {{Evaluation of wild-type MIC distributions as a tool for determination of clinical breakpoints for Mycobacterium tuberculosis}},
url = {{http://dx.doi.org/10.1093/jac/dkp262}},
doi = {{10.1093/jac/dkp262}},
volume = {{64}},
year = {{2009}},
}