Shorter Antibiotic Course Not as Effective for Children With UTIs

Abbreviated antibiotic treatment didn't measure up for children with urinary tract infection (UTI), the SCOUT trial found.

Stopping antibiotics when symptoms improved after an initial 5-day course yielded a 4.1% rate of persistent symptomatic UTI by follow-up at day 11-14 compared with 0.6% when kids had the full 10-day course, Nader Shaikh, MD, MPH, of the Children's Hospital of Pittsburgh, and colleagues reported.

The upper limit of the confidence interval for the absolute difference exceeded the prespecified 5% margin required for noninferiority.

However, the failure rate of short-course therapy was still low enough to suggest it could be considered as a reasonable option for kids exhibiting clinical improvement after 5 days of antimicrobial treatment, the researchers wrote in JAMA Pediatrics.

They pointed to a post hoc analysis showing a similar rate of UTI within 9 days of study treatment discontinuation (P=0.32) and the "large number of children needed to be treated with standard-course therapy to prevent 1 child from developing kidney scarring" -- an estimated 469.

"The treatment failure rates were lower than we expected in both treatment groups," Shaikh told MedPage Today.

While short, 3- to 7-day courses of antimicrobial therapy have long been standard for adults, he noted that there was little data to guide duration of treatment in children. "Although some pediatric data suggest that shorter durations of antimicrobials are effective in children, these data are limited and contradictory," his group explained.

"The SCOUT trial is an important addition to the scientific literature to guide shared decision-making between healthcare professionals and primary caretakers," Aaron Milstone, MD, MHS, and Pranita Tamma, MD, MHS, both of Johns Hopkins University School of Medicine in Baltimore, wrote in an editorial accompanying the study.

"The slightly increased risk of treatment failure with the added benefit of convenience and potentially less adverse events should be discussed with parents; in this way, they can contribute to conversations surrounding the ultimate duration of therapy prescribed," they added. "These conversations should acknowledge signs of clinical failure that would warrant a return to medical care and monitoring of antibiotic-associated adverse events."

The SCOUT (Short Course Therapy for Urinary Tract Infections) noninferiority trial was conducted at outpatient clinics and emergency departments at two children's hospitals from May 2012 through August 2019. Participants included children ages 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobial therapy. The trial randomized 664 children (96% girls, median age 4 years) to an additional 5 days of antibiotics or placebo.

Treatment failure was not related to age, presence of fever, prescribed antimicrobial therapy, or study site. One (0.3%) child assigned to standard-course therapy and six (1.8%) kids assigned to short-course therapy had a febrile UTI between day 6 and a day 11-14 visit. In the per-protocol analysis, differences in the proportion of kids with treatment failure between treatment groups were smaller.

Additional findings included that children receiving short-course therapy were more likely to have asymptomatic bacteriuria (absolute risk difference [ARD] 5.3%, 95% CI 1.7-8.9) or a positive urine culture (ARD 10.4%, 95% CI 6.6-14.2) at or before the day 11-14 visit. A total of nine children (2.7%) assigned to standard-course therapy and 14 kids (4.2%) assigned to short-course therapy had a UTI within 9 days of study treatment discontinuation.

There were no differences between groups in rates of UTI after the first follow-up visit, incidence of adverse events, or incidence of gastrointestinal colonization with resistant organisms.

Limitations of the study included a slight imbalance between treatment groups in number of children excluded from the primary analysis, the researchers noted. Also, emergence of antimicrobial resistance was assessed only for Escherichia coli and Klebsiella pneumoniae strains, and there was a lack of detailed data on societal costs and benefits of each treatment strategy.

Other limitations included an absence of data on adherence to originally prescribed antimicrobials on days 1 to 5, lack of strain-level data on recovered uropathogens, and lack of data on outcomes, such as kidney scarring, they added.

"Future research is needed to address an effective duration of therapy for children with complicated UTIs and those with UTIs warranting hospitalization," Milstone and Tamma added.

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