Real-world outcomes of cefepime/enmetazobactam for Enterobacterales infections: a retrospective descriptive study

ABSTRACT Cefepime/enmetazobactam (FEP/META) is a novel β-lactam/β-lactamase inhibitor combination with activity against Enterobacterales, including extended-spectrum β-lactamase-producing isolates, but real-world clinical data outside randomized trials remain limited. We conducted a retrospective multicenter descriptive study across 13 Italian hospitals. Eligible patients had infections caused by Enterobacterales and received ≥72 h of cefepime/enmetazobactam therapy (alone or in combination with other antimicrobials) under a compassionate-use program. Thirty-two patients were included. The most frequently isolated pathogens were Escherichia coli (16/32, 50.0%) and Klebsiella pneumoniae (13/32, 40.6%). Extended-spectrum β-lactamase production was documented in 29/32 isolates (90.6%), while β-lactam/β-lactamase inhibitor resistance and fluoroquinolone resistance were each observed in 18/32 isolates (56.2%). Four isolates were ertapenem-resistant but remained susceptible to imipenem and meropenem; no carbapenemase production was confirmed. FEP/META was safely administered as targeted therapy in most cases and was used both as monotherapy and in combination regimens, according to clinical severity and source of infection. Clinical cure was achieved in all patients, and microbiological eradication was documented in 25/32 cases (78.1%). No in-hospital deaths were recorded. Despite the inherent limitations of retrospective real-world studies, our findings suggest that cefepime/enmetazobactam may be a well-tolerated component of carbapenem-sparing treatment strategies for selected documented Enterobacterales infections. In 32 real-world documented Enterobacterales infections, cefepime/enmetazobactam achieved 100% clinical cure and 78.1% microbiological eradication, with favorable tolerability. IMPORTANCE Antibiotic-resistant infections are an increasing challenge, and clinicians need effective treatments that can reduce reliance on carbapenems, which are often considered last-line antibiotics. Cefepime/enmetazobactam is a new antibiotic combination with activity against resistant Enterobacterales, particularly ESBL-producing bacteria, but real-world clinical data remain limited. This multicenter Italian study describes its use in 32 patients with Enterobacterales infections, including urinary tract, bloodstream, and respiratory infections. Clinical cure was achieved in all patients, microbiological eradication was documented in most cases, and no in-hospital deaths occurred. These findings suggest that cefepime/enmetazobactam may be a useful and well-tolerated carbapenem-sparing option for selected resistant gram-negative infections, while emphasizing the need for larger studies to confirm its role in routine clinical practice.