The efficacy of pivmecillinam in oral step-down treatment in hospitalised patients with E. coli bacteremic urinary tract infection; a single-arm, uncontrolled treatment study.

BACKGROUND: The role of oral beta-lactam antibiotics in treating febrile urinary tract infections (UTI) is not yet definite. Today, fluoroquinolones together with trimethoprim-sulfamethoxazole (TMP-MTX) are considered standard of care and often the only available evidence-based oral treatment for febrile UTI. This study clarifies the efficacy and safety of pivmecillinam (PIV) used as step-down therapy for bacteremic urinary tract infection (UTI).

METHODS: A single-arm, uncontrolled treatment trial was conducted in the period September 2017-March 2020. Candidates for inclusion were men and women suffering from E. coli bacteremia due to UTI and were consecutively included in a Norwegian hospital. Exclusion criteria were among others: other ongoing bacterial infection, septic shock, pyonephrosis/abscess and pregnancy. After 3 days of parenteral antibiotic, the treatment was converted to the study drug; oral PIV 400 mg QID for 1 week. Primary endpoint was a combination of three elements; afebrility, no need for retreatment and improvement in self-reported health status. Test Of Cure (TOC) was 1 week post-treatment. Secondary endpoints included among others microbiological efficacy and CRP value < 30 mg/L.

RESULTS: Of 476 screened subjects, 53 patients were included. Median age was 67 years, 28 (56%) were women. 50 patients were evaluated for per-protocol analysis. 44 of 50 patients (88%) (95% CI [75.7-95.5]) reached the primary endpoint on TOC. 14 of 48 patients (29.2%) had significant growth (> 103  CFU/mL) of E.coli on TOC. CRP-level was strongly associated to treatment outcome, (OR 0.006 [95% CI 0.00-0.11], p < 0.001).

CONCLUSIONS: This trial documents that PIV 400 mg QID given for 1 week following 3 days of parenteral antibiotics, is a suitable treatment option in patients suffering from bacteremic UTI due to E. coli. Randomised clinical trials studying the efficacy of PIV vs standard of care of febrile UTI are warranted. Trial registration The trial was registered at ClinicalTrials.gov under the identifier: NCT03282006 13/09/2017 and approved by The Regional Committees for Medical Research Ethics South East Norway (2015/2384/REK sør-øst) and the Norwegian Medicines Agency (SLV; reference No 16/06018-09; EudraCT No 2016-000984-18) before initiation.