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

Inclusion Criteria12

• Age ≥ 18 years
• Fever (≥ 38.3 C) or shaking chills at least once at home or in hospital
• Clinical suspicion of UTI including at least one of the following symptoms:
• Dysuria, urinary urgency, difficulty urinating, new or worsened urinary incontinence, macroscopic haematuria or increased urinary frequency
• Low abdominal pain or flank pain with percussion or palpation tenderness over kidneys and/or bladder.
• Urine (≥ 103 CFU/mL) and/or blood culture positive for EPE* with susceptibility to pivmecillinam†.
• In-patient who has received 1-5 days of EPE-active‡ intravenous antibiotics
• 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.