Commercially available tests for determining cefiderocol susceptibility display variable performance in the Achromobacter genus.

Cefiderocol is a siderophore-conjugated cephalosporin increasingly used in the management of Achromobacter infections. Testing for cefiderocol susceptibility is challenging with distinct recommendations depending on the pathogens. We evaluated the performance of commercial tests for testing cefiderocol susceptibility in the Achromobacter genus and reviewed the literature. Diffusion (disks, MIC gradient test strips [MTS], Liofilchem) and broth microdilution (BMD) methods (ComASP™, Liofilchem; UMIC®, Bruker) were compared with the BMD reference method according to the EUCAST guidelines on 143 Achromobacter strains from 14 species with MIC50/90 of ≤ 0.015/0.5 mg/L. A literature search was conducted regardless of method or species. None of the methods tested fulfilled an acceptable essential agreement (EA). MTS displayed the lowest EA (30.8%) after UMIC® (49%) and ComASP™ (76.9%). All methods achieved an acceptable bias, with MICs either underestimated using MTS (-1.3%) and ComASP™ (-14.2%) or overestimated with UMIC® (+ 9.1%). Inhibition zone diameters ranged from 6 to 38 mm (IZD50/90=33/30 mm). UMIC® and ComASP™ failed to categorize one or the two cefiderocol-resistant strains of this study as resistant unlike the diffusion-based methods. The literature review highlighted distinct performance of the available methods according to pathogens and testing conditions. The use of MTS is discouraged for Achromobacter spp. Disk diffusion can be used to screen for susceptible strains by setting a threshold diameter of 30 mm. UMIC® and ComASP™ should not be used as the sole method but have to be systematically associated with disk diffusion to detect the yet rarely described cefiderocol-resistant Achromobacter sp. strains.

Jean-Pierre V ，Sorlin P ，Jeannot K ，Chiron R ，Lavigne JP ，Pantel A ，Marchandin H ... -  《Annals of Clinical Microbiology and Antimicrobials》

Performance of the Disc Diffusion Method, MTS Gradient Tests and Two Commercially Available Microdilution Tests for the Determination of Cefiderocol Susceptibility in Acinetobacter spp.

Jeannot K ，Gaillot S ，Triponney P ，Portets S ，Pourchet V ，Fournier D ，Potron A ... -  《Microorganisms》

Performance of discs, sensititre EUMDROXF microplates and MTS gradient strips for the determination of the susceptibility of multidrug-resistant Pseudomonas aeruginosa to cefiderocol.

To evaluate the performance of commercially available tests to determine the susceptibility of multidrug-resistant (MDR) clinical Pseudomonas aeruginosa strains to cefiderocol. A collection of 150 clinical strains of P. aeruginosa resistant to ceftazidime, (MIC, Minimal Inhibitory Concentration, MIC > 8 mg/L) imipenem (MIC> 4 mg/L) and ceftolozane/tazobactam (MIC> 4/4 mg/L), isolated from 2015 to 2022 was selected. Cefiderocol susceptibility was determined in parallel (a) by disc diffusion using Mast, Oxoid and Liofilchem discs deposited on Mueller-Hinton agar batches from Bio-Rad, BioMérieux, Mast, Becton Dickinson, I2A and Oxoid; (b) by MIC gradient test strips (MTS) (Liofilchem); and (c) by EUMDROXF Sensititre microplates. MICs and inhibition zones were compared with the broth microdilution reference method (BMD) MICs. The MIC50 and MIC90 of cefiderocol were 1 mg/L and 8 mg/L by BMD, respectively, including 21.3% (32/150) resistant strains. None of the methods tested fulfilled acceptable criteria (essential agreement [EA] ≥ 90%; bias = ± 30%). Although the Sensititre EUMDROXF microplates overestimated MIC values (categorical agreement [CA] = 86.7% [130/150, 95% CI 80.3-91.2]; EA = 69.3% [104/150, 95% CI 61.6-76.2]; bias = 68.2%), MTS strips underestimated the MIC values for many strains (CA = 86.7%, 130/150, 95% CI 80.3-91.2; EA = 69.3%, 104/150, 95% CI 61.6-76.2; bias = -30.4%), classifying properly only 50% (16/32) of resistant strains. Finally, many cefiderocol-resistant strains were not identified by the disc method, although the CA ranged from 78.0% (117/150, 95% CI 70.7-83.0) to 89.3% (134/150, 95% IC 83.4-93.3) according to Mueller-Hinton agar batches. Determination of cefiderocol susceptibility in MDR P. aeruginosa clinical strains by Sensititre EUMDROXF microplates is an alternative to the reference BMD method. However, MIC values ± 1 dilution apart from the breakpoint (2 mg/L) should be controlled by BMD whereas the use of MTS gradient strips is discouraged. Disc diffusion might be useful for screening, unfortunately many cefiderocol-resistant strains are not detected.

Devoos L ，Biguenet A ，Rousselot J ，Bour M ，Plésiat P ，Fournier D ，Jeannot K ... -  《-》

Cefiderocol susceptibility of Achromobacter spp.: study of an accurately identified collection of 230 strains.

Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat pathogens due to both intrinsic resistance and the possibility of acquired antimicrobial resistance. Species identification remains challenging leading to imprecise descriptions of resistance in each taxon. Cefiderocol is a broad-spectrum siderophore cephalosporin increasingly used in the management of Achromobacter infections for which susceptibility data remain scarce. We aimed to describe the susceptibility to cefiderocol of a collection of Achromobacter strains encompassing different species and isolation sources from CF or non-CF (NCF) patients. We studied 230 Achromobacter strains (67 from CF, 163 from NCF patients) identified by nrdA gene-based analysis, with available susceptibility data for piperacillin-tazobactam, meropenem and trimethoprim-sulfamethoxazole. Minimal inhibitory concentrations (MICs) of cefiderocol were determined using the broth microdilution reference method according to EUCAST guidelines. Strains belonged to 15 species. A. xylosoxidans represented the main species (71.3%). MICs ranged from ≤ 0.015 to 16 mg/L with MIC50/90 of ≤ 0.015/0.5 mg/L overall and 0.125/2 mg/L against 27 (11.7%) meropenem-non-susceptible strains. Cefiderocol MICs were not related to CF/NCF origin or species although A. xylosoxidans MICs were statistically lower than those of other species considered as a whole. Considering the EUCAST non-species related breakpoint (2 mg/L), 228 strains (99.1%) were susceptible to cefiderocol. The two cefiderocol-resistant strains (A. xylosoxidans from CF patients) represented 3.7% of meropenem-non-susceptible strains and 12.5% of MDR strains. Cefiderocol exhibited excellent in vitro activity against a large collection of accurately identified Achromobacter strains, irrespective of species and origin.

Jean-Pierre V ，Sorlin P ，Pantel A ，Chiron R ，Lavigne JP ，Jeannot K ，Marchandin H ，Collaborative study group on antimicrobial resistance of Achromobacter spp. ... -  《Annals of Clinical Microbiology and Antimicrobials》

Performance evaluation of Bruker UMIC(®) microdilution panel and disc diffusion to determine cefiderocol susceptibility in Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter xylosoxidans and Burk

Bianco G ，Boattini M ，Comini S ，Gaibani P ，Cavallo R ，Costa C ... -  《-》