Lactobacilli versus antibiotics to prevent urinary tract infections: A randomized, double-blind, noninferiority trial in postmenopausal women

OBJECTIVE To compare the effects of lactobacilli and antibiotic agents as prophylaxis against recurrent urinary tract infections (UTIs) in postmenopausal women. DESIGN Randomized double blind non-inferiority multicenter study (trial registration: ISRCTN 50717094). METHOD We randomized 252 postmenopausal women with recurrent UTIs to receive 12 months of prophylaxis with co-trimoxazole (CTX) or oral capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Primary end points were the mean number of symptomatic UTIs, the proportion of participants with at least 1 UTI during 12 months, time to first UTI, and development of antibiotic resistance by Escherichia coli. RESULTS The mean number of symptomatic UTIs in the year preceding randomization was 7.0 in the CTX group and 6.8 in the lactobacilli group. After 12 months of prophylaxis, these numbers were 2.9 and 3.3, respectively. The between-treatment difference of 0.4 UTIs per year (95% CI: -0.4 to 1.5) was outside our non-inferiority margin. At least 1 symptomatic UTI occurred in 69.3% and 79.1% of the CTX and lactobacilli participants, respectively; median times to first UTI were 6 and 3 months respectively. After 1 month of CTX prophylaxis, resistance to CTX, trimethoprim, and amoxicillin had increased from approximately 20 to 40% to 80 to 95% in E. coli from feces and urine. During the 3 months after CTX discontinuation, resistance levels gradually decreased. Resistance did not increase during lactobacilli prophylaxis. CONCLUSION In postmenopausal women with recurrent UTIs, L. rhamnosus GR-1 and L. reuteri RC-14 do not meet the noninferiority criteria in the prevention of UTIs when compared with CTX. However, unlike CTX, lactobacilli do not increase antibiotic resistance.