No evidence to support 5-day pivmecillinam for uncomplicated UTI
A 3-day course of pivmecillinam to treat uncomplicated lower urinary tract infection (UTI) yielded similar outcomes as a 5-day course, suggesting that 3-day treatment may be sufficient, according to a study from Denmark.
“[A] 5-day course of pivmecillinam was not superior to a 3-day course of pivmecillinam for uncomplicated lower UTI,” said the researchers. “Given the risk of adverse events (AEs), development of antimicrobial resistance, and collateral damage associated with the length of antibiotic use, this study did not find evidence supporting that a 5-day course should be preferred over a 3-day course,” they said.
Participants in this multicentre (nine primary care clinics in Denmark), double-blind study were 368 women with symptoms of community-acquired uncomplicated lower UTI who were randomized to receive pivmecillinam (400 mg TID) for 3 or 5 days (n=188 [mean age 34.9 years] and 180 [mean age 35.4 years], respectively). Women who received the 3-day dose received subsequent placebo for 2 days. A total of 163 and 161 patients randomized to the 3- and 5-day arms, respectively, were included in the analysis. Patients completed a symptom diary on days 0–7, a long-term follow-up questionnaire between days 8 and 42, and provided two urine samples.
Escherichia coli (E. coli) was the most frequently detected cause of UTI in urine cultures (86 and 76 percent in the 3- and 5-day groups, respectively) followed by Staphylococcus saprophyticus (4.9 and 12.8 percent, respectively).
Time to symptom resolution did not significantly differ between individuals who received the 3- and 5-day course of pivmecillinam (mean, 2.94 vs 2.91 days, difference, -0.02, 95 percent confidence interval [CI], -0.4 to 0.3; p=0.894). [EClinicalMedicine 2019;doi:10.1016/j.eclinm.2019.06.009]
Bacteriological success, defined as no growth or a significant reduction (of ≥102 colony-forming units [CFU]/mL) in bacteriuria was also achieved by a similar proportion of individuals assigned to the 3- and 5-day course of pivmecillinam in the first (87 percent vs 88 percent, difference, 1.6 percent, 95 percent CI, -8.4 to 11.6 percent; p=0.895), and second urine sample (between days 15 and 42; 84 percent vs 91 percent, difference, 6.8 percent, 95 percent CI, -3.9 to 17.5 percent; p=0.244). Early bacteriological success did not differ when analysis was limited to patients with E. coli-related UTI (86 percent vs 88 percent, adjusted odds ratio [OR], 0.86; p=0.74)
Likewise, clinical success at treatment end (symptom score <2) was achieved by 73 and 76 percent of individuals who received the 3- and 5-day course of pivmecillinam, respectively (difference, 3.2 percent, 95 percent CI, -7.1 to 13.5 percent; p=0.601), and remained similar between groups when the analysis was limited to those with E. coli only (76 percent vs 80 percent, adjusted OR, 1.36; p=0.41) and at long-term follow-up (day 28; 84 percent vs 74 percent; p=0.060). Ten patients in each group experienced a relapse following clinical success at treatment end.
AEs occurred at a comparable rate between the 3- and 5-day course recipients (42 percent vs 34 percent; p=0.168), and were predominantly gastrointestinal (24 percent). There were no incidents of serious AEs or Clostridium difficile-related diarrhoea.
Guidelines recommend a 3–7-day course of pivmecillinam for uncomplicated cystitis, with the suggestion that a 5- or 7-day course is superior to a 3-day one. [Clin Infect Dis 2011;52:e103-e120] Nonetheless, evidence to support this suggestion is scarce, said the researchers.
“The findings supporting a 3-day course are in line with the recent antibiotic mantra that “shorter is better” and the utility of narrow-spectrum antimicrobial chemotherapies, both important in the context of fighting antimicrobial resistance,” said the researchers, explaining the potential implications of the results.
Thrice-daily dosing may also play a role, they added, with the results showing that the 400 mg TID dose for 3 days as used in this study yielded better outcomes than that of previous studies which used a 400 mg BID dose for 3 days. [Scand J Prim Health Care 2007;25:49-57; Scand J Infect Dis 2002;34:487-492]