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, isoniazid 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 isoniazid (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.
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, isoniazid 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 isoniazid (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.
Authors: Pawan K Angra; Thomas H Taylor; Michael F Iademarco; Beverly Metchock; J Rex Astles; John C Ridderhof Journal: J Clin Microbiol Date: 2012-02-01 Impact factor: 5.948
Authors: Gustavo E Velásquez; Meredith B Brooks; Julia M Coit; Henry Pertinez; Dante Vargas Vásquez; Epifanio Sánchez Garavito; Roger I Calderón; Judith Jiménez; Karen Tintaya; Charles A Peloquin; Elna Osso; Dylan B Tierney; Kwonjune J Seung; Leonid Lecca; Geraint R Davies; Carole D Mitnick Journal: Am J Respir Crit Care Med Date: 2018-09-01 Impact factor: 21.405
Authors: Kristian Angeby; Christian G Giske; Pontus Juréen; Thomas Schön; Jotam G Pasipanodya; Tawando Gumbo Journal: Antimicrob Agents Chemother Date: 2011-09 Impact factor: 5.191
Authors: L Lalande; L Bourguignon; S Bihari; P Maire; M Neely; R Jelliffe; S Goutelle Journal: Antimicrob Agents Chemother Date: 2015-06-15 Impact factor: 5.191
Authors: L Davies Forsman; C G Giske; J Bruchfeld; T Schön; P Juréen; K Ängeby Journal: Antimicrob Agents Chemother Date: 2015-03-30 Impact factor: 5.191
Authors: Thulasi Warrier; Marielle Tropis; Jim Werngren; Anne Diehl; Martin Gengenbacher; Brigitte Schlegel; Markus Schade; Hartmut Oschkinat; Mamadou Daffe; Sven Hoffner; Ali Nasser Eddine; Stefan H E Kaufmann Journal: Antimicrob Agents Chemother Date: 2012-01-30 Impact factor: 5.191
Authors: Rob C van Wijk; Wanbin Hu; Sharka M Dijkema; Dirk-Jan van den Berg; Jeremy Liu; Rida Bahi; Fons J Verbeek; Ulrika S H Simonsson; Herman P Spaink; Piet H van der Graaf; Elke H J Krekels Journal: Br J Pharmacol Date: 2020-11-03 Impact factor: 8.739