Study Design and Participants

RECAPTURE 1 and 2 comprised 2 identical phase 3, randomized, multicenter, double-blind, double-dummy, parallel-group trials designed incorporating FDA and EMA guidance [24, 25]. All patients (or their legal representatives) provided written informed consent. The studies were conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Protocols (available at: www.astrazenecaclinicaltrials.com) were approved by study sites' independent ethics committees and/or institutional review boards.

The Supplementary Appendix lists full inclusion/exclusion criteria. In brief, eligible patients were aged 18–90 years, and had cUTI or acute pyelonephritis considered by the investigator to be serious and requiring hospitalization for intravenous (IV) antibiotic therapy. Diagnosis was based on positive urine cultures obtained within 48 hours of enrollment showing 1–2 gram-negative uropathogens at ≥10⁵ colony-forming units (CFU)/mL, and pyuria. Complicated UTI without pyelonephritis was defined as presence of ≥2 symptoms, including ≥1 UTI-specific symptom (dysuria, urgency, frequency, and suprapubic pain with onset/worsening within the previous 7 days) as well as ≥1 complicating factor. Acute pyelonephritis was indicated by flank pain with onset/worsening within the previous 7 days, and/or costovertebral angle tenderness, with fever and/or nausea/vomiting. Patients could be enrolled before cultures were available, providing that positive results were expected, the study drugs were considered appropriate empiric therapy, and a urine Gram stain showed gram-negative bacilli and no gram-positive bacteria. Indwelling bladder catheters in place for >24 hours had to be removed or replaced (unless considered unsafe or contraindicated) before the baseline urine collection. Standardized catheter management guidelines (Supplementary Appendix) were followed.

Key exclusion criteria included complete obstruction of any portion of the urinary tract, perinephric or intrarenal abscess, or prostatitis; UTI symptoms potentially attributable to another process; urinary diversion or vesicoureteral reflux; creatinine clearance (CrCl) ≤30 mL/minute (including patients on dialysis).