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.

Primary outcomes

• To evaluate the timing of microbiological eradication [Within two weeks from the antibiotic therapy initiation]: To evaluate the timing of microbiological eradication in patients who received cefepime/enmetazobactam (FEP/META) compared to best available therapy (BAT) for targeted treatment of bacteremic complicated urinary tract infections (cUTIs) due to ESBL/OXA48 producers Gram-negatives

Secondary outcomes

• To investigate clinical cure [At day 3-7 after positive blood culture between two groups]: To investigate clinical cure (defined as complete resolution of baseline signs and symptoms present at screening) at day 3-7 after positive blood culture between two groups

Other outcomes

• To evaluate mortality at day 30 and day 90 [At day 30 and at day 90, after initiation of therapy]: All-cause mortality at day 30 and at day 90, after initiation of therapy, between two groups
• Difference in C-reactive protein (CRP) at Day 7 [At day 7 after initiation therapy]: To investigate the difference between the two study groups in C-reactive protein (CRP) levels at Day 7 after initiation of therapy
• Difference in procalcitonin (PCT) at Day 7 [At day 7 after initiation therapy]: To investigate the difference between the two study groups in procalcitonin (PCT) levels at Day 7 after initiation of therapy
• To investigate differences in recurrence rates between the two groups [At day 30 and 90 after initiation therapy]: Relapse (new infection with the same pathogen emerging after treatment) and/or Reinfection (new infection with a different pathogen emerging after treatment) rates at day 30 and 90 between two groups

Sex: All, ages: 18 Years to any

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)

• Cecilia Maria Bonazzetti, MD, Principal investigator, IRCCS Azienda Ospedaliero-Universitaria di Bologna