Consequences of the inoculum effect against β-Lactams in methicillin-susceptible staphylococcus aureus (MSSA) strains

Abstract

Objective: Some staphylococcal 13-lactamases could destroy 13-lactams other than penicillin, including cefazolin (Cz) and ampicillin-sulbactam (SAM), especially in the presence of higher inoculum, which is called the inoculum effect (InE). We investigated the incidence and clinical implications of InE against different 13-lactams including in S.aureus (MSSA) strains isolated from bacteremic patients. Material and Methods: Patients with MSSA bacteraemia were included. MSSA strains were tested with the disk diffusion and broth microdilution method at standard and high inoculum. The presence and type of 13-lactamases were confirmed by PCR plus DNA sequencing. InE was defined as a 4-fold or greater increase in minimal inhibitor concentration (MIC) values at high inoculum. Patient data were obtained retrospectively. Results: 85% of the 52 MSSA strains were Type A 13-lactamase positive. 25%, 38.5%, and 3.8% of the strains showed InE against Cz, SAM, and ceftriaxone, respectively. The mortality rate in patients infected with MSSA strains showing SAMInE and treated with SAM was significantly higher than in those not treated with SAM (p=0.044, OR 7.8, 95). Conclusion: SAM was the most affected 13-lactam by type A 13-lactamase of MSSA strains, followed by Cz, and this effect became more prominent with higher inoculum. SAM treatment of the patients infected with the MSSA strains showing SAMInE may increasemortality.