Prophylactic Antibiotics Earn Poor Grades for Kids' UTIs

PHILADELPHIA, July 10 -- Not only did prophylactic antibiotic therapy fail to reduce recurrence of urinary tract infections (UTIs) in young children, it was linked to an increase in resistant infections.

Prophylactic antibiotics led to a 7.5 times increased risk of a resistant infection in recurrent UTIs, Patrick H. Conway, M.D., of the University of Pennsylvania, and colleagues reported in the July 11 issue of the Journal of the American Medical Association.

Estimates of the cumulative incidence of infections in children younger than six (3% to 7% in girls; 1% to 2% in boys) suggest that 70,000 to 180,000 of the babies born in the U.S. each year will have had a UTI by age six.

After the first of these infections, Dr. Conway said, American Academy of Pediatrics practice guidelines recommend an imaging study to evaluate vesicoureteral reflux. If the child has this condition, daily antibiotic treatment is recommended in an attempt to prevent recurrent infections.

However, he added, evidence is limited regarding risk factors for recurrent infection and the risks and benefits of antibiotic treatment.

So, in the first large-scale study of its kind, the researchers studied 74,974 children from a network of 27 general pediatric practices in urban, suburban, and semi-rural areas in Delaware, New Jersey, and Pennsylvania.

The cohort included children six or younger who were diagnosed with a first UTI from July 1, 2001 through May 31, 2006.

Time-to-event analysis was used to determine the risk factors for recurrent infections and the association between antimicrobial prophylaxis and recurrent infection.

In addition, a nested case-control study of children with a recurrent UTI was used to identify the risk of resistant infections.

Among children in the network, 611 (0.007 per person-year) had a first UTI and 83 (0.12 per person-year after first UTI) had a recurrent infection. In multivariable Cox time-to-event models, factors associated with an increased risk of recurrent infection included:

• White race, nearly twice the risk (0.17 per person-year; hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.22-3.16),
• Age 3 to 4 (0.22 per person-year; HR, 2.75; CI, 1.37-5.51),
• Age 4 to 5 (0.19 per person-year; HR, 2.47; CI, 1.19-5.12),
• Grade 4 to 5 vesicoureteral reflux (0.60 per person-year; HR, 4.38; CI, 1.26-15.29),
• Sex and grade 1 to 3 vesicoureteral reflux were not linked to risk of recurrence.

Antimicrobial prophylaxis was not associated with a decreased risk of a recurrent UTI (HR, 1.01; CI, 0.50-2.02), the researchers found, even after adjusting for propensity to receive prophylaxis.

In addition, exposure to prophylactic antibiotics significantly increased the risk of antimicrobial resistance among 83 children (13.6%) with a recurrent UTI (HR, 7.50; CI, 1.60-35.17), the researchers said.

Resistance was defined as a pathogen resistant to any antimicrobial. Pathogens included Escheria coli (78%), other gram-negative rods (16%), Enterococcus (4%), and other organisms (2%).

Prophylactic antimicrobials included cotrimoxazole (61%), amoxicillin (Augmentin) (29%), nitrofurantoin (7%), and other antimicrobials including first- through third-generation cephalosporins (3%).

Study limitations included its observational design and the fact that 65% of the children did not have a voiding cystourethrogram, thereby preventing a full study of the effect of vesicoureteral reflux on recurrent infections and the effectiveness of prophylactic treatment by reflux grade.

Also, the researchers said, the lack of circumcision data in 47% of male children limited the ability to assess risk on the basis of this important factor.

Further investigation in a randomized trial is needed to better understand of the efficacy of prophylactic antibiotic therapy, especially in subgroups including nonwhites and older children.

Considering the unfavorable risk/benefit ratio in this study, the researchers concluded, "we think it is prudent for clinicians to discuss the risks and unclear benefits of prophylaxis with families" before starting antimicrobials after a first UTI."