An inoculum effect on other cephalosporin and carbapenem MICs has also been previously documented; several studies have shown that MICs for piperacillintazobactam, and to a lesser extent meropenem, are increased with higher inocula of [beta]-lactamase producing and nonproducing isolates [6, 7, 11-13].
Extended-spectrum cephalosporins and the inoculum effect in tests with CTX-M-type extended-spectrum [beta]-lactamase-producing Escherichia coli: potential clinical implications of the revised CLSI interpretive criteria," International Journal of Antimicrobial Agents, vol.
Moland, "Cefepime, piperacillin-tazobactam, and the inoculum effect in tests with extended-spectrum beta-lactamase-producing Enterobacteriaceae," Antimicrobial Agents and Chemotherapy, vol.
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.
Some, but not all, animal studies have demonstrated that the inoculum effect
may be clinically relevant.
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.
The inoculum effect is typically seen with the third generation cephalosporins, cefotaxime, ceftriaxone and ceftazidime.
Cefepime, piperacillin-tazobactem, and the inoculum effect in tests with extended spectrum beta-lactamases producing Enterobacteriaceae.
A high inoculum effect
has been reported with cefepime for ESBL-producing and AmpC-producing isolates of Enterobacteriaceae (16).
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).
Generally, substrate effects tended to be greater than inoculum effects
regarding fermentation kinetics and end products.
In conclusion, outer membrane defects and the inoculum effects
(13) that may adversely elevate MIC values must still be considered if cefepime is chosen as an alternative therapy against ESBL-KP strains.