Pivmecillinam as Oral Step-Down Treatment for Escherichia Coli Febrile Urinary Tract Infection Versus Standard of Care

Inclusion Criteria: 1. ≥18 years of age. 2. Diagnosis of fUTI, defined as i) fever ≥ 38°C and ii) at least one of the following: flank pain or pelvic pain, nausea or vomiting, dysuria, urinary frequency or urgency, and costovertebral angle tenderness on physical examination. 3. Growth of E. coli in urine with antimicrobial susceptibility to mecillinam. 4. Adequate intravenous antibiotic treatment for fUTI (defined below) for 2 days to which the isolated E. coli is determined susceptible. 5. Defervescence and hemodynamic stability for at least 24 hours, according to the responsible physician. 6. Planned treatment with one of the following antibiotics, should the patient be randomized to the standard-of-care arm. Intravenous antibiotics: 1) Penicillins; ampicillin, piperacillin/tazobactam, ≥2) cephalosporins; cefotaxime, cefuroxime, ceftriaxone, 3) carbapenems; ertapenem, imipenem, meropenem, 4) monobactams; aztreonam, 5) aminoglycosides; amikacin, gentamicin, tobramycin, 6) other; fosfomycin. Oral antibiotics: 1) ciprofloxacin, 2) trimethoprim-sulfamethoxazole, 3) amoxicillin or amoxicillin/clavulanic acid provided that the isolated E. coli is determined susceptible according to the EUCAST-breakpoint for systemic infections, i.e., MIC ≤ 8 mg/l, and high dosing is used (≥750 mg amoxicillin x 3 and ≥750 mg amoxicillin/125 mg clavulanic acid x 3, respectively) and 4) tebipenem (if approved by the EMA). 7. Signed informed consent. Exclusion Criteria: 1. Adequate intravenous antibiotic treatment for \> 4 days prior to randomization or other adequate (microbiologically active) oral antibiotic treatment for the same fUTI episode prior to recruitment. 2. Growth of other bacterial species than E. coli, or fungi, in urine. 3. Contraindication for pivmecillinam (e.g. allergy). 4. Clinical suspicion of bacterial prostatitis. 5. Renal abscess. 6. Kidney transplant. 7. Myelosuppressive disorder with neutrophil count \< 0.5 x 10(9)/L at randomization. 8. Planned antibiotic treatment for fUTI \> 14 days. 9. Likely to be prescribed antibiotic prophylaxis after treatment. 10. Other intravenous or oral antibiotic treatment; ongoing or planned during the follow-up period (i.e. until 28 days after EOT for fUTI). 11. Severe renal impairment (eGFR \< 20 mL/min) at randomization. 12. Morbid obesity (BMI \> 40 kg/m2). 13. Pregnancy or breastfeeding. 14. Unlikely to follow instructions or the study protocol. 15. Previous participation in the study. 16. If consenting to microbiome analysis: i) contraindication for ciprofloxacin (e.g. allergy), ii) unlikely to be able to provide fecal samples per protocol, iii) treatment with antibiotics in the past 3 months before the current fUTI episode, iv) chronic intestinal disease or previous surgery in the gastrointestinal tract. 17. If consenting to pharmacokinetic analysis: expected difficulties in providing blood and urine samples per protocol.