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Genomic determinants of penicillin G susceptibility and cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus bloodstream isolates.

Created on 06 Oct 2026

Authors

Samantha Poloni, Adeline Gagnon, Benoit Valot, Alexandre Meunier, Didier Hocquet, Xavier Bertrand, Adrien Biguenet, Kevin Bouiller

Published in

The Journal of antimicrobial chemotherapy. Volume 81. Issue 11. Oct 06, 2026.

Abstract

This study aimed to describe penicillin G susceptibility, blaZ diversity, and genetic determinants of the cefazolin inoculum effect (CfzIE) among MSSA bloodstream isolates.
The first three non-duplicate MSSA isolates recovered each month from blood cultures at our French university hospital between January 2010 and December 2023 were selected. Whole-genome sequencing was performed using the Illumina NextSeq platform to characterize blaZ and its genetic context. Susceptibility to penicillin G and the CfzIE were assessed using phenotypic methods.
Among 488 MSSA isolates, 373 (76.5%) carried blaZ, of which 119 (31.9%) exhibited CfzIE. Thirty BlaZ allotypes were identified overall; 26 were included in the genetic determinant analysis after exclusion of isolates with multiple or truncated blaZ. In multivariable analysis, BlaZA3 was strongly associated with CfzIE (aOR, 15.72; 95% CI, 3.33-74.24; P < 0.001), as was CC7 (aOR, 5.48; 95% CI, 1.45-20.69; P = 0.011). Among BlaZA3 isolates, CfzIE was mainly observed with complete blaR1. Among 122 isolates with a penicillin G inhibition zone ≥26 mm, seven carried blaZ, including six with sharp zone edges and truncated blaZ sequences.
CfzIE was mainly associated with a BlaZA3-related genetic background, particularly in the presence of complete blaR1, rather than with blaZ type alone. Approximately one-quarter of MSSA bloodstream isolates were susceptible to penicillin G, and rare phenotype-genotype discrepancies were associated with truncated blaZ sequences.

PMID:
42836776
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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