Using pivmecillinam with amoxicillin/clavulanic acid for treating complicated urinary tract infections
Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in Febrile UTIs Caused by ESBL-producing Enterobacterales (PACUTI)
This study is testing if a new combination of two antibiotics, pivmecillinam and amoxicillin/clavulanic acid, can effectively treat complicated urinary tract infections in adults who are switching from intravenous to oral medication.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 330 (estimated) |
| Ages | 18 Years to 130 Years |
| Sex | All |
| Sponsor | Lund University Academic / other |
| Locations | 5 sites (Helsingborg and 4 other locations) |
| Trial ID | NCT05224401 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 and older who have febrile urinary tract infections caused by ESBL-producing bacteria and have received initial intravenous antibiotic treatment.
Not a fit: Patients who do not have febrile urinary tract infections or those whose infections are not caused by ESBL-producing bacteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could provide a safer and effective oral treatment option for patients with complicated urinary tract infections caused by antibiotic-resistant bacteria.
How similar studies have performed: Other studies have suggested that beta-lactams can be effective alternatives to fluoroquinolones for treating similar infections, indicating potential success for this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Helsingborg and 4 other locations
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.