Diagnosis and Management of UTI in Febrile Infants Age 0–2 Months: Applicability of the AAP Guideline

“Action Statement 4a: When initiating treatment, the clinician should base the choice of route of administration on practical considerations. Initiating treatment orally or parenterally is equally efficacious. The clinician should base the choice of agent on local antimicrobial sensitivity patterns (if available) and should adjust the choice according to sensitivity testing of the isolated uropathogen.”³

Most infants <2 months old with UTIs are hospitalized initially because of fever. Therefore, the decision point for most clinicians is not whether to hospitalize but for how long to hospitalize and treat with intravenous (IV) antibiotics prior to discharging home on oral antibiotics. Although all-oral antibiotic regimens are used to treat UTIs in older infants and children,^14-18 to our knowledge, there are no randomized controlled trials (RCTs) comparing all-IV vs all-oral antibiotics or a longer vs shorter initial IV course that include infants <1 month old. In the trials that do include infants aged 1-2 months,^14,18 the number of subjects in this age group is too small to draw conclusions, a finding supported by a 2014 Cochrane review.¹⁹ An adequately powered RCT of different IV antibiotic durations in this age group would be challenging. For example, nearly 1,000 subjects would be needed to demonstrate a statistically significant difference between a 5% and 10% relapse risk between groups, a difference that some may find clinically important.

The paucity of evidence in this age group may explain the considerable variability in the approach to IV antibiotic duration in young infants. Concerns about enteral absorption and underdeveloped immune systems may prompt some physicians to treat the youngest patients more aggressively. One study demonstrated that the proportion of patients <2 months old receiving prolonged courses (≥4 days) of IV antibiotics for UTIs in 46 U.S. children’s hospitals ranged from 0% to 67%.²⁰ Similar variability across hospitals has been described in other observational studies^21,22 and across subspecialties in one survey of pediatricians.²³

Several observational studies provide additional evidence supporting shorter IV courses. In two studies that examined administrative databases, there was no difference in treatment failure rates between infants aged <2 months²⁰ and <6 months²¹ receiving longer (≥4 days) vs shorter IV courses. In a study of 172 infants <1 month old with UTIs, the median IV duration was 4 days (range 2-12 days), and no subjects experienced treatment failure or relapse.²⁴ In a multicenter study of 251 infants <3 months old with bacteremic UTIs, mean IV antibiotic durations ranged from 5.5–12 days, and no patient had a relapsed bacteremic UTI. Six infants (2.4%) had a relapsed UTI without bacteremia, with no association between IV antibiotic duration and relapse.²²

Based on the available data and known risks of hospitalization and prolonged IV therapy, a reasonable approach for infants <1 month old would be to hospitalize for two to three days while awaiting blood and cerebral spinal fluid (CSF) culture results. Given the possibility of Enterococcus or Enterobacteriaceae that are resistant to third-generation cephalosporins, standard therapy of ampicillin and gentamicin for febrile neonates is reasonable, assuming there is no concern for meningitis. Antibiotics should be narrowed when susceptibilities are known. Once culture results return and signs and symptoms have resolved, discharge home on oral antibiotics is justifiable based on the available literature. For well-appearing infants aged 1-2 months with a presumptive UTI (based on UA results), if hospitalization is not warranted for other reasons, then we recommend outpatient treatment with oral or intramuscular therapy based on local susceptibilities (typically a cephalosporin) and close follow-up for one to two days while awaiting culture results. Although empiric cephalosporin therapy may not provide 100% coverage for all potential organisms, clinical deterioration is uncommon in infants and children receiving discordant therapy.²⁵

“Action Statement 4b: The clinician should choose 7 to 14 days as the duration of antimicrobial therapy.”³

The AAP’s recommendation to provide antibiotics (by oral or parenteral route) for a minimum of seven days total stems from a 2002 meta-analysis comparing long (7-14 days) vs short (≤3 days) courses, where the pooled relative risk of treatment failure with short-course therapy was 1.94 (95% CI: 1.19-3.15).²⁶ However, in this analysis, the trials that demonstrated inferiority with short courses were all trials that used single doses of antibiotics, and a similar Cochrane review comparing 2-4 days with 7-14 days demonstrated no differences in outcomes.²⁷ Therefore, shorter total courses, but not a single dose, are probably appropriate for most UTIs in children. Although there are no obvious biologic reasons why longer total courses would be needed in young infants, there are unfortunately limited data comparing different total antibiotic durations in this age group. We believe that 7-14 days of total therapy is a reasonable recommendation for infants <2 months old, and that future studies should investigate shorter total courses.