EUCAST has evaluated (August 2022) commercially available tests and all have problems with accuracy, reproducibility, bias and/or for some, with skipped wells. For this reason, it is difficult to resolve the susceptibility interpretation of isolates in the ATU (area of technical uncertainty) in routine testing. Considering the current limitations and the need for testing in multiresistant bacteria, these are the recommendations of EUCAST until the issue of confirmatory MIC determination is solved.
- Disk diffusion. Laboratories are recommended to start testing cefiderocol with disk diffusion. Resistance to beta-lactam agents is increasing and therapeutic alternatives are few. Disk diffusion, when correctly performed and calibrated using quality material and recommended quality control guidelines, is predictive of susceptibility and resistance outside the ATU.
Template zone diameter distributions for relevant species against which to calibrate in-house results, are available. - Inside the ATU, and as long as there is no alternative method to resolve interpretative uncertainties (eg MIC-testing in the routine laboratory or assistance from a reference laboratory), EUCAST recommends colleagues to ignore the ATU and interpret using the zone diameter breakpoints in the breakpoint table.
- However, as with all AST methods and for all antimicrobial agents, results depend on the quality of materials used. EUCAST does not have the resources to systematically investigate all products from all manufacturers. Below a few commonly used manufacturers of disks and MH agars are mentioned but others are not. Assume that those that are not mentioned may have undisclosed problems.
For cefiderocol, using a cross-over protocol, disks from three manufacturers and Mueller-Hinton media from five manufacturers were evaluated.
If care is taken to ensure that the EUCAST QC criteria for the two strains, E. coli ATCC 25922 and P. aeruginosa ATCC 27853, are met, i.e. with the mean of at least 5 repeated tests is within +/-1 mm of the target values, disk diffusion using EUCAST breakpoints performed well. When the mean value was more than +/-1 mm from the target, an increasing proportion of results were erroneous. This was particularly problematic for Pseudomonas aeruginosa.
Among the evaluated cefiderocol 30 µg disks (Liofilchem, Mast and Oxoid) and Muller-Hinton agars (BBL, bioMérieux, Bio-Rad, Liofilchem and Oxoid), disks from Oxoid and MH agar from Bio-Rad produced larger than acceptable zone diameters for both QC strains and clinical isolates. Combining Oxoid disks with Bio-Rad MH agar increased the problem further.
Further work to elucidate the problems surrounding cefiderocol susceptibility testing is ongoing. Two commercial products currently under investigation, are UMIC (Bruker) and ComASP (Liofilchem).
The issue has been discussed by the EUCAST Steering Committe, January 2023, and it was decided that issues have not yet been resolved and that the warning should remain.
A EUCAST evaluation is ongoing and results will be made available as soon as testing is completed and an analysis by the committee performed.