ABSTRACT Cefepime is generally recommended for treatment of clinically significant AmpC producers, including Citrobacter freundii complex ( Cfre ), Enterobacter cloacae complex ( Eclo ), and Klebsiella aerogenes ( Kaer ). Clinicians increasingly use the results of multiplex PCR panels to make early treatment decisions, with cefepime often chosen when an AmpC producer is detected without a bla CTX-M extended-spectrum beta-lactamase (ESBL) or carbapenemase. To understand the safety of this approach, we evaluated the prevalence of cefepime resistance among 4,687 Cfre ; 9,878 Eclo ; and 4,800 Kaer clinical isolates collected in our hospital network in New England, USA, from 2015 to 2024. We additionally reviewed Blood Culture Identification 2 (BCID2) (bioMérieux) results for 136 blood cultures and the sequenced genomes of 184 isolates (14 cefepime-susceptible dose-dependent SDD, 34 cefepime-resistant). Cefepime-SDD and cefepime-resistant isolates made up 0.4% (18/4,687) and 1.3% (59/4,687) of Cfre , 2.0% (194/9,879) and 3.0% (299/9,879) of Eclo , and 0.3% (16/4,800) and 0.6% (28/4,800) of Kaer . Of 117 Eclo and Kaer identified in blood cultures on the BCID2, 4.3% (5/117) were cefepime-SDD or cefepime-resistant and negative for an ESBL or carbapenemase target. Among sequenced cefepime-SDD isolates, 21% (3/14) carried an ESBL. Cefepime-resistant isolates carried diverse beta-lactamase genes, including ESBL genes, carbapenemase genes, and plasmid-borne ampC . While reduced cefepime susceptibility was generally associated with carriage of more beta-lactamase genes, 57% of cefepime-SDD and 35% of cefepime-resistant isolates encoded only chromosomal ampC . Our results highlight variable cefepime susceptibility rates for AmpC producers across clinical settings and demonstrate diverse mechanisms underlying reduced cefepime susceptibility.
Schrader et al. (Fri,) studied this question.