This inoculum effect
does not appear to be a universal phenomenon but rather seems to be limited to a subset of strains.
More interestingly, standard susceptibility testing may categorize MBL producing Enterobacteriaceae as susceptible to carbapenems, but an inoculum effect
has been observed, suggesting that the susceptibility testing may falsely predict the susceptibility of particular Enterobacteriaceae to carbapenems in the clinical environment (5,6).
A high inoculum effect has been reported with cefepime for ESBL-producing and AmpC-producing isolates of Enterobacteriaceae (16).
Cefepime, piperacillin-tazobactam, and the inoculum effect in tests with extended-spectrum-lactamase-producing Enterobacteriaceae.
This may be at least in part due to the inoculum effect. It is reported (10,11) that ESBL producers appear susceptible at a standard inoculum of 10 (5), but have highly elevated MICs at higher inocula of 10 (7) or 10 (8).
Cefepime, piperacillin-tazobactem, and the inoculum effect in tests with extended spectrum beta-lactamases producing Enterobacteriaceae.
This may in part be due to the inoculum effect
. In vitro, the MICs of cephalosporins rise as the inoculum of ESBL-producing organisms increases.
Moreover, when the organism was tested at a 100-fold higher-than-standard inoculum, a dramatic inoculum effect
occurred, with large increases in the MICs of these agents, analogous to the inoculum effect
that occurs with ESBL-producing Klebsiella spp.
Two factors justify the use of imipenem, even in the cases of apparent in vitro sensibility to piperacilin-tazobactam: the risk of therapeutic failure caused by the increase of the minimum inhibitory concentration (MIC) of the antibiotic in the presence of high inoculum concentration (inoculum effect
)  and the development of bacterial resistance during the therapy .
The study showed ESBL producers were highly resistant to cefepime (97.3%) at standard inoculum, which is in contrast to the study of Thomson et al (14) who showed inoculum effect
was more for cefepime among the ESBL producing Enterobacteriaceae.
Moland, "Cefepime, piperacillin-tazobactam, and the inoculum effect
in tests with extended-spectrum beta-lactamase-producing Enterobacteriaceae," Antimicrobial Agents and Chemotherapy, vol.
Generally, substrate effects tended to be greater than inoculum effects
regarding fermentation kinetics and end products.