Using pivmecillinam with amoxicillin/clavulanic acid for treating complicated urinary tract infections

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial evaluates the effectiveness of a combination of pivmecillinam and amoxicillin/clavulanic acid (PAC) as a step-down oral therapy for patients with febrile urinary tract infections (UTIs) caused by extended spectrum beta-lactamase (ESBL) producing bacteria. The study compares the PAC combination to standard treatments such as ciprofloxacin, trimethoprim-sulfamethoxazole, or ertapenem. Participants must be adults who have received initial intravenous antibiotics and are transitioning to oral therapy. The goal is to determine if PAC is as effective as the standard treatments in managing these infections.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Age ≥ 18 years
2. Fever (≥ 38.3 C) or shaking chills at least once at home or in hospital
3. Clinical suspicion of UTI including at least one of the following symptoms:

   1. Dysuria, urinary urgency, difficulty urinating, new or worsened urinary incontinence, macroscopic haematuria or increased urinary frequency
   2. Low abdominal pain or flank pain with percussion or palpation tenderness over kidneys and/or bladder.
4. Urine (≥ 103 CFU/mL) and/or blood culture positive for EPE\* with susceptibility to pivmecillinam†.
5. In-patient who has received 1-5 days of EPE-active‡ intravenous antibiotics
6. Discontinuing parenteral treatment and starting treatment with oral antibiotics is considered safe according to the treating physician.

   * EPE refers to ESBL-producing Enterobacterales. This includes Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, and Citrobacter koseri.

     * Susceptibility for pivmecillinam in the study is based on zone diameter breakpoints for pyelonephritis (≥ 20 mm) which was received by personal communication with professor Christian Giske, the chairman of the European Committee of Antimicrobial Susceptibility Testing (EUCAST) (26).

       * EPE-active intravenous antibiotics refers to EUCAST susceptibility testing and will most often be piperacillin-tazobactam, meropenem or imipenem-cilastatin in the Swedish setting, and less often aminoglycosides or newer beta-lactamase-inhibitor-containing beta-lactam antibiotics (27). Participants who have only received one dose of EPE-active intravenous antibiotics are also eligible and are considered within the "1-5 days" of antibiotics.

Patients may only be recruited and randomised once in this trial.

Exclusion criteria (any of the following)

1. Known or suspected pregnancy.
2. Known or suspected life-threatening allergy towards beta-lactam antibiotics.
3. Clinical isolate of EPE is resistant to ciprofloxacin, TMX and ertapenem.
4. Severe renal insufficiency with estimated glomerular filtration rate (eGFR) \<10mL/min or requiring any form of dialysis.
5. Severe decompensated liver failure (i.e., child Pugh class B or C).
6. Genetic metabolic diseases associated with severe carnitine deficiency.
7. Megaloblastic haematopoiesis.
8. Co-treatment with valproate or valproic acid (due to interaction with pivmecillinam and ertapenem respectively)
9. Other reason to which patient is unfit to be included in the study according to treating physician, e.g., cognitive impairment preventing informed consent and follow-up, inability to speak and/or read Swedish, missing national personal identification number or missing telephone number preventing follow-up or planned duration of antibiotics \> 10 days due to complicating factors.

Where it's running

• Helsingborg hospital
  Helsingborg, Sweden Recruiting
• Kristianstad hospital
  Kristianstad, Sweden Recruiting
• Skåne University Hospital, Lund
  Lund, Sweden Recruiting
• Skåne University Hospital, Malmö
  Malmö, Sweden Recruiting
• Västmanland hospital Västerås
  Västerås, Sweden Recruiting

Study contacts

• Principal investigator: Oskar Ljungquist, MD, PhD. — Lunds universitet
• Study coordinator: Oskar Ljungquist, M.D, PhD
• Email: oskar.ljungquist@med.lu.se
• Phone: +46424063182

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.