Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in ESBL UTIs

• Status: Not yet recruiting
• Trial end date: 2027-09-01
• Target enrollment: 0
• Participant gender: All

Summary

To evaluate if the combination of pivmecillinam and clavulanic acid (PAC) is non-inferior to ciprofloxacin or trimethoprim-sulfamethoxazole as step down oral therapy in patients with febrile UTI caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales (EPE).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Lund University
• Treatments: Amdinocillin Pivoxil; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acid; Clavulanic Acids

Criteria

Inclusion Criteria:

1. Age ≥ 18 years

2. Urine and/or blood culture positive for EPE.

3. In-patient who has received 1-5 days of empiric intravenous antibiotics

4. Fever (≥ 38.3 C) or shaking chills at least once at home or in hospital

5. Clinical suspicion of UTI based on at least one of the following symptoms:

1. Dysuria, urinary urgency, difficulty urinating or increased urinary frequency

2. Positive dipstick analysis including positive nitrite or leucocytes ≥ 1

3. Percussion/palpation tenderness over kidneys or bladder tenderness

6. Discontinuing parenteral treatment and starting treatment with per oral antibiotics is considered safe according to treating physician.

Exclusion Criteria:

1. Known or suspected allergy towards beta-lactams, fluoroquinolones or trimetoprim-sulfamethoxazole

2. Clinical isolate of EPE is pivmecillinam-resistant, or resistant to both ciprofloxacin and trimethoprim-sulfamethoxazole, or resistant to ciprofloxacin and the patient has eGFR below 20 mL/min (i.e. when trimethoprim-sulfamethoxazole is not recommended).

3. Known or suspected pregnancy

4. Aortic aneurysm, myasthenia gravis, long QT-syndrome, severe liver damage, genetic metabolic diseases associated with severe carnitine deficiency, creatinine clearance < 15 ml/min and/or megaloblastic haematopoiesis.

5. Treatment with Tizanidine (interacts with ciprofloxacin) or dofetilide (interacts with trimethoprim-sulfamethoxazole).

6. Other reason to which patient is unfit to be included in the study according to treating physician, e.g. cognitive impairment making the patient unable to leave informed consent or missing personal identification number complicating follow-up.