1. Towards clinical breakpoints for non-tuberculous mycobacteria-Determination of epidemiological cut off values for the Mycobacterium avium complex and Mycobacterium abscessus using broth microdilution
- Author
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Froberg, Gabrielle, Maurer, Florian P., Chryssanthou, Erja, Fernstrom, Louise, Benmansour, Hanaa, Boarbi, Samira, Mengshoel, Anne Torunn, Keller, Peter Michael, Viveiros, Miguel, Machado, Diana, Fitzgibbon, Margaret M., Mok, Simone, Werngren, Jim, Cirillo, Daniela Maria, Alcaide, Fernando, Hyyrylainen, Hanne-Leena, Aubry, Alexandra, Andres, Sonke, Nadarajan, Darshaalini, Svensson, Erik, Turnidge, John, Giske, Christian G., Kahlmeter, Gunnar, Cambau, Emmanuelle, van Ingen, Jakko, Schön, Thomas, Froberg, Gabrielle, Maurer, Florian P., Chryssanthou, Erja, Fernstrom, Louise, Benmansour, Hanaa, Boarbi, Samira, Mengshoel, Anne Torunn, Keller, Peter Michael, Viveiros, Miguel, Machado, Diana, Fitzgibbon, Margaret M., Mok, Simone, Werngren, Jim, Cirillo, Daniela Maria, Alcaide, Fernando, Hyyrylainen, Hanne-Leena, Aubry, Alexandra, Andres, Sonke, Nadarajan, Darshaalini, Svensson, Erik, Turnidge, John, Giske, Christian G., Kahlmeter, Gunnar, Cambau, Emmanuelle, van Ingen, Jakko, and Schön, Thomas
- Abstract
Objective: For non-tuberculous mycobacteria (NTM), minimum inhibitory concentration (MIC) distri-butions of wild-type isolates have not been systematically evaluated despite their importance for establishing antimicrobial susceptibility testing (AST) breakpoints.Methods: We gathered MIC distributions for drugs used against the Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) obtained by commercial broth microdilution (SLOMYCOI and RAPMYCOI) from 12 laboratories. Epidemiological cut-off values (ECOFFs) and tentative ECOFFs (TEC-OFFs) were determined by EUCAST methodology including quality control (QC) strains.Results: The clarithromycin ECOFF was 16 mg/L for M. avium (n = 1271) whereas TECOFFs were 8 mg/L for M. intracellulare (n = 415) and 1 mg/L for MAB (n = 1014) confirmed by analysing MAB subspecies without inducible macrolide resistance (n = 235). For amikacin, the ECOFFs were 64 mg/L for MAC and MAB. For moxifloxacin, the WT spanned >8 mg/L for both MAC and MAB. For linezolid, the ECOFF and TECOFF were 64 mg/L for M. avium and M. intracellulare, respectively. Current CLSI breakpoints for amikacin (16 mg/L), moxifloxacin (1 mg/L) and linezolid (8 mg/L) divided the corresponding WT dis-tributions. For QC M. avium and M. peregrinum, >= 95% of MIC values were well within recommended QC ranges.Conclusion: As a first step towards clinical breakpoints for NTM, (T)ECOFFs were defined for several antimicrobials against MAC and MAB. Broad wild-type MIC distributions indicate a need for further method refinement which is now under development within the EUCAST subcommittee for anti-mycobacterial drug susceptibility testing. In addition, we showed that several CLSI NTM breakpoints are not consistent in relation to the (T)ECOFFs. Gabrielle Froeuroberg, Clin Microbiol Infect 2023;29:758 (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access artic, Funding Agencies|Stockholm Region; Karolinska Institute clinical research grant; Mukoviszidose Institut gGmbH, Bonn; German Cystic Fibrosis Association Mukoviszidose e.V; Swedish Heart and Lung Foundation; Swedish research council; Swiss Innovation Agency Innosuisse
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- 2023
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