Decoding the cefazolin inoculum effect: phenotypic and genotypic insights beyond the MIC.

Cefazolin inoculum effect occurs in 16.16% of 198 methicillin-susceptible Staphylococcus aureus isolates, with blaZ Type A (71.9%) and Type C (28.1%) predominating among CzIE-positive strains.

• Why it matters: CzIE can undermine cefazolin efficacy in high-inoculum MSSA infections, yet it is not captured by routine MIC testing, leaving mechanisms and clinical risk insufficiently defined.
• What they did: The study compared standard versus high inoculum MICs using an inoculum effect index, then applied whole-genome sequencing for blaZ allotypes, agr genotypes (I–IV), and clonal lineages, plus 24-hour cefazolin time-kill with sulbactam and population analysis profiles.
• The result: CzIE-positive isolates showed initial killing followed by regrowth with cefazolin plus sulbactam, expansion of cefazolin-non-susceptible subpopulations at high inoculum, and agr III predominance with agr dysfunction significantly associated with the CzIE-positive phenotype.

AI summary of the abstract · may contain errors · not medical advice · read the paper.