Towards clinical breakpoints for non-tuberculous mycobacteria - Determination of epidemiological cut off values for the Mycobacterium avium complex and Mycobacterium abscessus using broth microdilution.

Fröberg, Gabrielle; Maurer, Florian P; Chryssanthou, Erja; Fernström, 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; Hyyryläinen, Hanne-Leena; Aubry, Alexandra; Andres, Sönke; Nadarajan, Darshaalini; Svensson, Erik; ... (2023). Towards clinical breakpoints for non-tuberculous mycobacteria - Determination of epidemiological cut off values for the Mycobacterium avium complex and Mycobacterium abscessus using broth microdilution. Clinical microbiology and infection, 29(6), pp. 758-764. Elsevier 10.1016/j.cmi.2023.02.007

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OBJECTIVE

For non-tuberculous mycobacteria (NTM), minimum inhibitory concentration (MIC) distributions 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 (TECOFFs) 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 distributions. 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Keller, Peter Michael

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1469-0691

Publisher:

Elsevier

Language:

English

Submitter:

Pubmed Import

Date Deposited:

23 Feb 2023 13:04

Last Modified:

03 Jun 2023 00:13

Publisher DOI:

10.1016/j.cmi.2023.02.007

PubMed ID:

36813087

BORIS DOI:

10.48350/179077

URI:

https://boris.unibe.ch/id/eprint/179077

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