Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women.
BACKGROUND
Growing antibiotic resistance warrants studying nonantibiotic prophylaxis for recurrent urinary tract infections (UTIs). Use of lactobacilli appears to be promising.


METHODS
Between January 2005 and August 2007, we randomized 252 postmenopausal women with recurrent UTIs taking part in a double-blind noninferiority trial to receive 12 months of prophylaxis with trimethoprim-sulfamethoxazole, 480 mg, once daily or oral capsules containing 109 colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily. Primary end points were the mean number of symptomatic UTIs, 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 trimethoprim-sulfamethoxazole group and 6.8 in the lactobacilli group. In the intention-to-treat analysis, 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 noninferiority margin. At least 1 symptomatic UTI occurred in 69.3% and 79.1% of the trimethoprim-sulfamethoxazole and lactobacilli participants, respectively; median times to the first UTI were 6 and 3 months, respectively. After 1 month of trimethoprim-sulfamethoxazole prophylaxis, resistance to trimethoprim-sulfamethoxazole, trimethoprim, and amoxicillin had increased from approximately 20% to 40% to approximately 80% to 95% in E coli from the feces and urine of asymptomatic women and among E coli causing a UTI. During the 3 months after trimethoprim-sulfamethoxazole discontinuation, resistance levels gradually decreased. Resistance did not increase during lactobacilli prophylaxis.


CONCLUSIONS
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 trimethoprim-sulfamethoxazole. However, unlike trimethoprim-sulfamethoxazole, lactobacilli do not increase antibiotic resistance. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN50717094.
Division of Infectious Diseases, Tropical Medicine and AIDS, Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Mariëlle A J
MA
Beerepoot
Gerben
G
ter Riet
Sita
S
Nys
Willem M
WM
van der Wal
Corianne A J M
CA
de Borgie
Theo M
TM
de Reijke
Jan M
JM
Prins
Jeanne
J
Koeijers
Annelies
A
Verbon
Ellen
E
Stobberingh
Suzanne E
SE
Geerlings
D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007778:Lactobacillus; D008875:Middle Aged; D017698:Postmenopause; D013413:Sulfadoxine / Q000008:administration & dosage; D016896:Treatment Outcome; D014295:Trimethoprim / Q000008:administration & dosage; D014552:Urinary Tract Infections / Q000517:prevention & control*; D014556:Urine / Q000382:microbiology
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; C000301:trimethoprim, sulfadoxine drug combination; D000658:Amoxicillin; D013413:Sulfadoxine; D014295:Trimethoprim