💬In plain words
What the trial is, and whether it could suit you
The goal of this clinical trial is to learn if oral treatment with pivmecillinam is effective to treat febrile urinary tract infections in adult patients. Hospitalized patients who have received 2-4 days of intravenous antibiotic therapy for febrile urinary tract infections, and have responded to treatment, will be randomized to either pivmecillinam or standard treatment (other oral or intravenous antibiotics).
The main question the study aims to answer is if oral follow-up with pivmecillinam is as effective as standard treatment. Patients will be evaluated for clinical response (resolution of fever and urinary tract symptoms) and microbiological response (no growth of bacteria in urine) 7 and 28 days after the end of treatment. Patients will also be asked about side effects. Some of the participants will also be examined for changes in the gut microbiome and drug exposures in blood and
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
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.
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