Comparison of Broth Microdilution, Disk Diffusion and Strip Test Methods for Cefiderocol Antimicrobial Susceptibility Testing on KPC-Producing Klebsiella pneumoniae

The aim of this study was to compare the reference broth microdilution (BMD) method with the Disk Diffusion (DD) test and strip test against a collection of 75 well-characterized Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) clinical strains to assess cefiderocol (CFD) antimicrobial activity. Whole-genome sequencing was performed on KPC-Kp strains by Illumina iSeq100 platform. The Categorical Agreement (CA) between the BMD method and DD test was 92% (69/75) with a Major Error (ME) of 16.7% (6/36). Additionally, the CA between the BMD method and test strip was 90.7% (68/75) with a Very Major Error (VME) of 17.9% (7/39) and 82.7% (62/75) between the strip test and DD with a ME of 30.2%. KPC-Kp strains showing resistance to CFD were 27 out of 75 (36%) by three methods. Specifically, 51.9% (14/27) of KPC-Kp resistant to CFD harbored bla(KPC-3), while 48.1% (13/27) harbored mutated bla(KPC-3). Moreover, KPC-Kp strains carrying a mutated bla(KPC-3) gene exhibited high MIC values (p value < 0.001) compared to wild-type bla(KPC-3). In conclusion, the DD test resulted as a valid alternative to the BMD method to determine the in vitro susceptibility to CFD, while the strip test exhibited major limitations.

Automated summary

The aim of this study was to compare the BMD method with the DD test and strip test in assessing the antimicrobial activity of CFD against KPC-Kp strains. The CA between the BMD method and DD test was 92%, while the CA between the BMD method and strip test was 90.7%. KPC-Kp strains showing resistance to CFD were 36% by three methods. The DD test was found to be a valid alternative to the BMD method, while the strip test exhibited major limitations.