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

Launched by LUND UNIVERSITY · Jan 25, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new combination of antibiotics, pivmecillinam and amoxicillin/clavulanic acid, to see if it works just as well as other standard antibiotics for treating urinary tract infections (UTIs) caused by certain resistant bacteria. These resistant bacteria are known as extended spectrum beta-lactamase (ESBL) producing Enterobacterales. The trial aims to help patients who have had a fever and other symptoms of a UTI and have already received intravenous antibiotics for a few days.

To participate, individuals must be at least 18 years old and have a fever or shaking chills, along with specific symptoms of a UTI. They should also have a positive urine or blood test for the resistant bacteria. Participants will be switching from intravenous antibiotics to oral treatment, which is considered safe by their doctor. The trial is currently recruiting participants of all genders, so if you or a loved one fits these criteria and is interested in joining, this could be an opportunity to contribute to important research in managing antibiotic-resistant infections.

Gender

ALL

Eligibility 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.