Development of a EUCAST disk diffusion method for the susceptibility testing of rapidly growing anaerobic bacteria using Fastidious Anaerobe Agar (FAA) - Development study using Bacteroides species

Herjan Bavelaar, Ulrik Stenz Justesen, Trefor E Morris, Bethan Anderson, Sarah Copsey-Mawer, Tore Taksdal Stubhaug, Gunnar Kahlmeter, Erika Matuschek. Accepted for publication in CMI, April 2021.

Comment on: Efficacy of temocillin against MDR Enterobacterales: a retrospective cohort study

Christian G Giske, Gunnar Kahlmeter, Alasdair MacGowan, John Turnidge on behalf of the EUCAST Steering Committee.

Comments on a recently published paper by Alexandre et al. (J Antimicrob Chemother 2021; 76:784-8) which demonstrated good clinical efficacy of temocillin in the treatment of infections originating from the urinary tract. EUCAST agrees with the overall conclusion that temocillin has proven clinical efficacy in infections originating from the urinary tract. However, there are several conclusions in the paper that need further discussion.

After a long review process and public consultation, EUCAST concluded that 2 g × 3 will ensure successful outcomes in all patients with infections originating in the urinary tract. The breakpoints susceptible ≤0.001 mg/L and resistant >16 mg/L avoid dividing the WT of relevant organisms and increase the chance of reproducible susceptibility results. These conclusions are in line with official recommendations both in France and other EU countries where the drug is available.

Daptomycin in the treatment of enterococcal bloodstream infections and endocarditis: a EUCAST position paper. CMI 26, P1039-1043, 2020 (https://doi.org/10.1016/j.cmi.2020.04.027). 

J. Turnidge, G. Kahlmeter, R. Cantón, A. MacGowan, C.G. Giske, on behalf of theEuropean Committee on Antimicrobial Susceptibility Testing

Scope: This position paper describes the view adopted by EUCAST on the role of daptomycin in the treatment of serious infections caused by Enterococcus species.

Background: High-dose daptomycin is considered effective in the treatment of enterococcal bloodstream infection (BSI) and endocarditis, although published clinical experience with the latter condition is limited.

Methods: EUCAST reviewed the available published data on pharmacokinetics-pharmacodynamics (PK-PD), resistance selection, clinical efficacy and safety for the use of 10-12 mg/kg/day of daptomycin for these conditions, noting that the doses licensed by the European Medicines Agency are only 4-6 mg/kg/day, and only for infections caused by Staphylococcus aureus.

Findings and recommendations: The PK-PD evidence shows that, even with doses of 10-12 mg/kg/day, it is not possible to treat infections caused by isolates at the upper end of the wild-type distributions of Enterococcus faecalis (with MICs of 4 mg/L) and E. faecium (with MICs of 4 or 8 mg/L). For this reason, and because there are ongoing issues with the reliability of laboratory testing, EUCAST lists daptomycin breakpoints for Enterococcus species as "IE"-insufficient evidence. EUCAST advises increased vigilance in the use of high-dose of daptomycin to treat enterococcal BSI and endocarditis. Additional PK-PD studies and prospective efficacy and safety studies of serious Enterococcal infections treated with high-dose daptomycin may permit the setting of breakpoints in the future.

Publications from the Subcommittee on Antimycobacterial susceptibility testing

1. Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives.  

2. Antimicrobial susceptibility testing of Mycobacterium tuberculosis complex isolates - the EUCAST broth microdilution reference method for MIC determination

3. Multicentre testing of the EUCAST broth microdilution reference method for MIC determination on Mycobacterium tuberculosis

4. What is the role of the EUCAST reference method for MIC testing of the Mycobacterium tuberculosis complex?

Papers on MIC distributions and ECOFFs of Mycobacterium tuberculosis.

Rapid AST directly from positive blood culture bottles

The EUCAST rapid disc diffusion method for antimicrobial susceptibility testing
directly from positive blood culture bottles. Emma Jonsson et al. JAC 2019

EUCAST rapid antimicrobial susceptibility testing (RAST) in blood cultures:
validation in 55 European laboratories. Anna Åkerlund et al. JAC 2020. 

Susceptibility testing of difficult organisms.

Burkholderia pseudomallei multi-centre study to establish EUCAST MIC and zone
diameter distributions and epidemiological cut-off values. Onur Karatuna et al. CMI 2020

The quality of AST material

The quality of antimicrobial discs from nine manufacturers - EUCAST evaluations in 2014 and 2017. Jenny Åhman et al. CMI, 2019

EUCAST evaluation of 21 brands of Mueller-Hinton dehydrated media for disk diffusion testing and 

Supplementary material. Jenny Åhman, CMI, 2020.

The relationship between phenotypic and genotypic AST

1st report in CMI from the EUCAST Subcommittee on the role of whole genome sequencing in antimicrobial susceptibility testing. M. J. Ellington et al., CMI 2015. 

EUCAST - the 2014 Garrod lecture.

EUCAST – are we heading towards international agreement?

Journal of Antimicrobial Chemotherapy Advance Access published June 18, 2015.
Gunnar Kahlmeter.
 

EUCAST in 2014 - Eurosurveillance

Widespread implementation of EUCAST breakpoints for antibacterial susceptibility testing in Europe.

Eurosurveillance, Volume 20, Issue 2, 15 January 2015.
D Brown, R Cantón, L Dubreuil, S Gatermann, C Giske, A MacGowan, L Martínez-Martínez, J Mouton, R Skov, M Steinbakk, C Walton, O Heuer, M J Struelens, L Diaz Högberg, G Kahlmeter.
 

EUCAST Disk Diffusion

Development of the EUCAST Disk Diffusion Method for antimicrobial susceptibility testing method and its implementation in routine microbiology laboratories.
E. Matuschek, D. F. J. Brown and G. Kahlmeter. Published in CMI 2013

The role of pharmacokinetics/pharmacodynamics in setting clinical
MIC breakpoints - the EUCAST approach (published in CMI 2012)

J. W. Mouton, D. F. J. Brown, P. Apfalter, R. Canton, C. G. Giske, M. Ivanova, A. P. MacGowan, A. Rodloff, C.-J. Soussy, M. Steinbakk and G. Kahlmeter. CMI 2012.

EUCAST Expert rules in antimicrobial susceptibility testing.
R. Leclercq, R. Canton, D. F. J. Brown, C. G. Giske, P. Heisig, A. P. MacGowan, J. W. Mouton, P. Nordmann, A. C. Rodloff, G. M. Rossolini, C.-J. Soussy, M. Steinbakk, T. G. Winstanley and G. Kahlmeter. CMI 2012.

European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). EUCAST Discussion Document E. Dis 5.1: determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution. Clin Microbiol Infec 2003; 9 (insert): 1-7.
Link to full document

This discussion document was not developed into a EUCAST definitive document because EUCAST was aware of the proposed development of an international (ISO) standard for broth microdilution, which was eventually published in 2006.