Cefepime failure for the treatment of cefepime-susceptible, KPC-producing Escherichia coli emphysematous cystitis

Background The growing incidence of carbapenem-resistant Enterobacterales (CRE) poses a challenge to clinical practice. Despite some Klebsiella pneumoniae carbapenemase (KPC)-positive Enterobacterales testing as susceptible to cefepime, in vivo data show that cefepime is not a reliable treatment option for infections caused by carbapenemase-producing CRE (CP-CRE). Contemporary guidance recommends against cefepime use for the treatment of KPC-positive infections; however, the clinical implications of this practice are unknown. Case Summary Here, we present a case of clinical failure after cefepime treatment for a KPC-producing Escherichia coli urinary tract infection that tested as cefepime-susceptible in vitro that was successfully treated with ceftazidime/avibactam. This case is concordant with the in vivo PKPD findings that the presence of KPC blunted the microbiologic activity of human-simulated cefepime exposures despite MICs that would suggest susceptible or susceptible dose-dependent (SDD) interpretation. Conclusion This case adds to the growing literature supporting the use of carbapenemase testing for Enterobacterales isolates that demonstrate resistance to one or more carbapenems to guide therapy. Until confirmatory clinical data are available, clinicians and laboratorians must consider selective reporting or other strategies in the setting of contradictory phenotypic susceptibility data and genotypic resistance markers.