Three versus five days of pivmecillinam for community-acquired uncomplicated lower urinary tract infection: A randomised, double-blind, placebo-controlled superiority trial

Abstract

Background To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract infection (UTI). Methods A randomised, double-blind, placebo-controlled trial conducted at nine primary care centres in Denmark. 368 women (18–70 years) with symptoms compatible with UTI were randomised to blinded therapy of 5 days [5d] or 3 days followed by 2 days of placebo [3d] from May 2015 to November 2017. Clinical data were assessed using a validated questionnaire at inclusion (day-0), daily the following 7 days and once again within the 2nd to 6th week after intervention. Bacteriological data were collected prior to intervention and twice between day 7 and 42. Main clinical endpoints were days to symptom resolution within 7 days after inclusion and proportions with clinical success at the end of intervention. Main bacteriological endpoint was proportion of participants with significant reduction of bacteriuria (≥ 10 2 CFU/mL) in 1st control urine sample. ClinicalTrialsRegister.eu: 2014–001321-32. Findings 180 (5d) and 188 (3d) participants were included in the study (mean age: 35.4 [5d] and 34.9 [3d]). Of these, 125 (70% [5d]) and 122 (66% [3d]) had a positive baseline urine culture. Forty-four participants were lost to follow-up, leaving 161 [5d] and 163 [3d] participants for analysis, respectively. Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P = .894). Clinical success at the end of treatment occurred for 117 of 153 (76%) receiving the 5d-course and for 115 of 157 (73%) receiving the 3d course (difference 3.2% [95% CI -7.1% - 13.5%]; P = .601). Bacteriological success was seen in 92 of 104 (88%) participants given the 5d course and in 86 of 99 (87%) given the 3d course (difference 1.6% [95% CI -8.4%-11.6%]; P = .895). Interpretations A 5-day course of pivmecillinam was not superior to a 3-day course in clinical or bacteriological outcomes for UTI. Primary funding source The Danish Regions [no. 14/217].

Pivmecillinam for Uncomplicated Lower Urinary Tract Infections Caused by Staphylococcus saprophyticus—Cumulative Observational Data from Four Recent Clinical Studies

“…In Study 4 [24], 13 out of 19 (68%) participants with S. saprophyticus were clinically cured, and 14 out of 16 (88%) achieved bacteriological cure. The failures were evenly distributed among the two treatment arms.…”

“…Among the 12 cases with MIC determined in Study 4 [24], the MIC did not correlate with the outcome. Testing S. saprophyticus under more organ-specific conditions in vitro (e.g., in urine), may reveal other findings for mecillinam that better correlate with the outcome, compared to the standard testing, according to EUCAST.…”

“…The presence of significant bacteriuria was defined as ≥10 3 bacteria/mL for S. saprophyticus [28]. The MIC of mecillinam was determined in thirteen isolates from Study 4 [24], by E-test, according to the manufacturer (Biomerieux). The test was repeated three times for each isolate.…”

“…In this study, we present (to our knowledge) the largest cumulative data from the clinical trials on pivmecillinam´s efficacy for UTIs caused by S. saprophyticus. The data is cumulated from four recent randomized controlled trials on the efficacy of empirical pivmecillinam for UTIs [21,22,23,24].…”

Retrospective study of men with E. coli UTI treated with an oral antibiotic, and risk for a new prescription or hospital admission due to UTI

“…Pivmecillinam and nitrofurantoin have shown excellent efficacy in treating UTI in women and have been recommended as first-line options for UTI in women for a while [8][9][10]. Thus, it has seemed reasonable to also consider these two antibiotics as alternatives for UTI in men, especially as the high resistance for fluoroquinolones and trimethoprim [3,4] and the newly increased risk awareness for the former [11] have limited the oral options.…”