Real-world experience with cefepime/zidebactam under compassionate use

Cefepime/zidebactam is a β-lactam/β-lactam enhancer combination with activity against carbapenem-resistant (CR) Gram-negative pathogens, including metallo-β-lactamase (MBL)-producing organisms. Before regulatory approval, cefepime/zidebactam was available through a compassionate-use programme for patients with CR Gram-negative infections who had limited available treatment options.

We conducted a retrospective, multi-country analysis of patients who received cefepime/zidebactam through compassionate use between 2022 and 2025. Data included demographics, comorbidities, acute complications, prior antibiotic exposure, infection characteristics, microbiology, treatment details, and investigator-assessed outcomes.

Eighty-five patients were included (median age 48 years; 57.6% in an intensive care unit at initiation). Primary infections included pneumonia/respiratory infection (30.6%), bone and joint infection (24.7%), and complicated urinary tract infection/pyelonephritis (14.1%). Pseudomonas aeruginosa was the predominant pathogen (77.6%), followed by Klebsiella pneumoniae (14.1%) and Acinetobacter baumannii (11.8%); infections involving at least two Gram-negative pathogens occurred in 10.6%. Among isolates with available genotypic data, MBLs were common and predominantly NDM. The cefepime/zidebactam minimum inhibitory concentration (MIC)50 and MIC90 were 8 and 32 mg/L, respectively. Investigator-assessed clinical success at the end of therapy was achieved in 88.2% of patients (95% CI, 79.7-93.5), and microbiological eradication in 89.4% (95% CI, 81.1-94.3); on-therapy mortality was 10.6% (95% CI, 5.7-18.9). Treatment-emergent adverse events occurred in five patients (5.9%, 95% CI, 2.5-13.0), with one discontinuation.

In this uncontrolled compassionate-use case series, cefepime/zidebactam treatment was accompanied by high investigator-assessed clinical success and microbiological eradication in patients with severe infections caused by CR Gram-negative pathogens. These observations require confirmation in prospective controlled studies.