By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: The duration of parenteral antimicrobial therapy for bacteremic urinary tract infection in young infants varies between practitioners and centers. A retrospective review suggests that extending parenteral treatment beyond seven days does not alter outcomes.

SOURCE: Desai S, Aronson PL, Shabanova V, et al; Febrile Young Infant Research Collaborative. Parenteral antibiotic therapy duration in young infants with bacteremic urinary tract infections. Pediatrics 2019;144:e20183844.

The urinary tract is one of the most common sites of bacterial infection in babies younger than 2 months of age, and approximately 10% of these young infants with urinary tract infection have concurrent bacteremia. Despite the relative frequency and importance of these infections, there is not a widely accepted standard duration of initial parenteral therapy. Although longer courses are known to be effective in reducing mortality and morbidity due to the initial infection, prolonged antibiotic therapy can be expensive and carries a risk of secondary infection and blood clots associated with the use of intravenous lines. Thus, Desai and colleagues sought to compare outcomes in children who were treated with shorter courses of parenteral therapy with those who received longer courses.

The study included infants ages 0 to 60 days who were evaluated for possible invasive bacterial infection at 11 geographically diverse children’s hospital emergency departments from July 2011 through June 2016 and who were found to have bacteremia and a urinary tract infection (with the same bacteria identified in both the blood and urine). Children who also had concurrent focal infection (meningitis or septic arthritis, for instance) were excluded from the study. The median duration of parenteral antibiotic treatment was seven days, so researchers compared those who received seven or fewer days of parenteral treatment (short course) and those who received more than seven days of parenteral treatment (long course).

The study included 115 patients. Half were younger than 1 month of age, and 60% were male. Overall, 9% of the included study subjects had been born prematurely, and 17% had a complex chronic medical condition. Fever was a presenting finding in 89% of the infected babies. Escherichia coli was the most common etiologic agent identified, accounting for 81% of infections. None of the causative bacteria was an extended spectrum beta-lactamase producing organism. There was in vitro evidence that each infecting bacteria could have been susceptible to an oral antibiotic.

Half of the included patients received seven or fewer days of parenteral therapy, and half of the patients received seven, 10, or 14 days of therapy (presumably corresponding to established protocols). Great variation in the duration of treatment occurred among the 11 centers participating in the study. Centers varied from 11% to 81% receiving “short” courses of parenteral antibiotics. Children who appeared to be ill on presentation and children with non-E. coli infections tended to be treated with longer courses of parenteral antibiotics.

Six infants had a recurrent urinary tract infection 15 to 30 days after the initial hospital discharge. Two of them had received short-course parenteral antibiotics and four had received long-course parenteral antibiotics. In two of the children with recurrent infection who had received long-course parenteral antibiotics, a different germ caused the second infection. Overall, 13% of the babies required medical care within the month after the initial urinary tract infection; this rate was similar between short- and long-course treatment groups.

Interestingly, prescribing providers opted for short-course treatment in 60% of the 67 babies who appeared well and had no underlying chronic medical condition. Longer-course treatment outcomes were no better than shorter-course treatment outcomes in this “healthy” subset of patients.

The authors noted that shorter-course treatment was associated with shorter hospital stays (4.5 vs. 10.8 days) but not with any other different outcome (recurrent infection or subsequent use of healthcare resources). They acknowledged that their study did not include a review of oral antibiotic treatment after the initial parenteral course.

COMMENTARY

Over recent decades, there has been widespread recognition of the importance of appropriately diagnosing and managing young infants with fever. Despite a variety of diagnostic schemes (with newer biomarkers emerging) and despite lots of outcome data, there still is not a clear consensus about how best to handle young infants with fever. Part of the challenge comes from trying to avoid the small risk of death from missed diagnoses and inadequate treatments with the seemingly less onerous risks of prolonged hospital stays, increased costs, and nonfatal complications of treatment. Desai and colleagues used the natural experiment of varying practice patterns to show clearly that longer-course treatment was associated with increased lengths of stay (and, presumably, cost) without adding any measurable reduction in the risk of poor outcomes. One could speculate that the two babies who had subsequent urinary tract infections from different bacteria after their initial longer course of parenteral treatment might have been predisposed to the development of new or resistant infection by that longer course of treatment.

Of course, skeptics could claim that the researchers only included 115 children. Pediatricians frequently subject febrile newborns to parenteral antibiotics for 24-48 hours while awaiting negative cultures to confirm the lack of bacterial infection and realizing that no more than a small percent of those febrile babies has a serious bacterial infection. Proponents of longer-course parenteral antibiotic therapy still could believe that they are preventing bad outcomes in the half percent or so of babies who would have been missed by this small study. Non-skeptics will point out that no children were helped by longer-course parenteral antibiotics over the five years of the study in 11 different pediatric centers — making the benefit hidden by the size of the study to be very, very small.

How should clinicians respond to these data? Certainly, those working at institutions that mandate or encourage longer intravenous courses of antibiotics for bacteremic urinary tract infection in young infants should reconsider their policies. All practitioners should feel free to consider limiting parenteral therapy to no more than seven days, especially when managing a baby who appears otherwise well without underlying medical conditions. Also, further research should be done; it is possible that even seven days is longer than needed to treat infected newborns adequately.