Inoculum effect of high concentrations of methicillin-susceptible Staphylococcus aureus on the efficacy of cefazolin and other beta-lactams

The existence of a cefazolin inoculum effect (InE) of methicillin-susceptible Staphylococcus aureus (MSSA), which is speculated to be a reason for cefazolin treatment failure in MSSA infections, is controversial. In Japan, although cefazolin is one of the therapeutic choices for patients with MSSA infection, there are few reports of this effect. Additionally, the association between InE and blaZ type in beta-lactams other than cefazolin has not been well documented. In this study, we confirmed an MSSA InE in several beta-lactams, including cefazolin, and its relationship with blaZ, using 52 MSSA isolates from blood cultures. Three isolates (5.8%) that possessed type A blaZ showed a pronounced cefazolin InE. Five isolates (9.6%) showed pronounced InE with sulbactam/ampicillin; four isolates had type C blaZ and one had type A blaZ. However, we confirmed InE in MSSA isolates with blaZ not only type A and C but also B and D. For cefotaxime, ceftriaxone, imipenem, and meropenem, regardless of the presence of blaZ, we did not observe a significant increase in MICs at a high inoculum of MSSA. Hence, our results suggest that the above four beta-lactams are good alternatives to cefazolin if InE leads to treatment failure in a patient.