Cefepime for Ceftriaxone-Resistant Enterobacterales With Chromosomal AmpC beta-Lactamases

To the Editor—The current Infectious Diseases Society of America (IDSA) guidance on the treatment of antimicrobial-resistant gram-negative infections by Tamma et al [1] suggests that cefepime should be avoided when treating AmpC-producing organisms with a minimum inhibitory concentration (MIC) of ≥ 4 μg/mL. The rationale behind this recommendation is that there is a higher likelihood that these isolates may contain an extended spectrum β-lactamase (ESBL), for which cefepime may result in suboptimal treatment [1]. The Clinical and Laboratory Standards Institute (CLSI) currently designates Enterobacterales isolates with a cefepime MIC of 4–8 μg/mL as susceptible dose-dependent (SDD) [2]. The IDSA guidance cites a retrospective study by Lee et al [3], performed in Taiwan, which noted that 89% of Enterobacter cloacae isolates with SDD MICs were ESBL producers. Of the identified E. cloacae isolates that were ESBL producing, cefepime MICs were elevated (median, 4 μg/mL; interquartile range, 1 to >16 μg/mL) compared with isolates that were non–EBSL producing (0.5 μg/mL; <0.25 to 2 μg/mL). Although ESBL-producing isolates more commonly had MICs in the SDD range, ESBL production was identified in cefepime-susceptible isolates (MIC ≤ 2 μg/mL) as well. In fact, 44% of cefepime-susceptible isolates were ESBL producing [3].