Cefepime/Enmetazobactam for Bacteremic Complicated Urinary Tract Infections

The study aims to evaluate the time to blood culture negativization in patients treated with cefepime/enmetazobactam (FEP/META), a drug recently introduced into clinical practice, compared with the best available therapy (BAT) for targeted treatment of complicated urinary tract infections with bacteremia caused by microorganisms harboring specific antibiotic resistance mechanisms (extended-spectrum beta-lactamase producers and OXA-48-type carbapenemase producers).

This is an investigator-initiated, observational, pharmacological, prospective multicenter cohort study that will enroll one hundred patients with urinary tract infection and bacteremia treated with cefepime/enmetazobactam, and an equal number treated with the best currently available antibiotic therapy.

Among the secondary objectives, the study aims to investigate clinical cure (defined as complete resolution of the signs and symptoms present at the time of screening) between the two groups, mortality at day 30 and day 90, the safety of cefepime/enmetazobactam, differences between the two groups in the trends of biological biomarkers, and differences in relapse rates between the two groups.

Inclusion criteria

• Patients with bacteremic cUTIs caused by Gram-negative bacteria treated with FEP/META or BAT
• Adult population (age ≥ 18 years)
• Signed informed consent form

Exclusion criteria

• Polymicrobial/mixed infections (Gram-positive bacteria or fungi together with Gram-negative microorganisms), except in cases involving multiple Gram-negative bacteria susceptible to the study drugs
• Patients with negative blood cultures
• Isolation of Gram-negative microorganisms not susceptible to the study drugs (e.g., KPC-producing organisms)
• Patients in palliative care or with a high likelihood of death within 72 hours from the index positive blood culture
• Patients treated with inappropriate therapy for more than 48 hours
• Patients discharged early without follow-up blood cultures
• History of significant hypersensitivity or allergic reactions to cefepime, to any of the excipients in the respective formulations, or to beta-lactamase inhibitors (e.g., tazobactam)