Limiting Testing in Febrile Young Infants with Abnormal Urinalyses

By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN; Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates

SYNOPSIS: According to a 26-site study, febrile infants younger than 2 months of age who have abnormal urinalyses are at very low risk of having meningitis and might not necessarily need to be subjected to lumbar puncture.

SOURCE: Mahajan P, VanBuren JM, Tzimenatos L, et al. Serious bacterial infections in young febrile infants with positive urinalysis results. Pediatrics 2022;150:e2021055633.

Urinary tract infection accounts for about three-fourths of serious bacterial infections in febrile infants during the first two months of life, with invasive bacterial infection (bacteremia and meningitis) being less common. It has not been clear just how much a febrile young infant with a urinary tract infection is at risk of having concurrent bacteremia or meningitis, and clinicians vary in the practice of doing cerebrospinal fluid analysis for febrile babies with known urinary tract infection.

Investigators at a consortium of 26 emergency departments in the United States conducted a secondary analysis using data from a large, prospective study of infants aged 60 days or less who presented with fever between March 2011 and April 2019. A total of 7,407 febrile babies were enrolled, but some were excluded from the study (such as those born prematurely, those with significant comorbidities, those who used antibiotics during the two days prior to admission, and those who were critically ill and required intubation or hemodynamic support with vasoactive medications). There were 1,090 babies (58% male, 64% more than 4 weeks of age) with positive urinalyses (defined as having nitrites or leukocyte esterase or more than five white blood cells per high-powered field in the urine).

Patients with positive/abnormal urinalyses had higher absolute neutrophil counts and higher procalcitonin levels and were more likely to be admitted to the hospital than those with normal urinalyses. Approximately 50% of babies with abnormal urinalyses (and less than 1% of those with normal urinalyses) had urinary tract infections based on culture results.

Of patients with abnormal urinalyses, 5.8% had bacteremia and 0.4% had bacterial meningitis (as compared to 1.1% and 0.6% of those with normal urinalyses). Of 697 babies 28-60 days of age with an abnormal urinalysis, none had meningitis.

Of patients with abnormal urinalysis results and less than 4,000 neutrophils/mm³ of blood and a procalcitonin level of less than 0.5 ng/mL, there were none with bacteremia or meningitis. In fact, of 283 patients with abnormal urinalyses and a procalcitonin level of less than 0.5 ng/mL, none had bacterial meningitis.

The authors summarized their findings saying that, among febrile infants younger than 2 months of age who were not critically ill, having an abnormal urinalysis result was associated with a greater risk of bacteremia and a lesser risk of meningitis than was seen in similar children with normal urinalyses. Among febrile young infants during the second month of life, having a positive urinalysis, especially with a low procalcitonin level, rendered meningitis an extremely unlikely diagnosis and could be used as evidence to consider not performing a lumbar puncture.

COMMENTARY

Approximately 90% of infants who develop fever during the first two months of life do not have serious bacterial infection, and, on initial presentation, it is difficult to identify which babies might benefit from antimicrobial therapy. Thus, many babies with mere viral infections receive antibiotics while waiting for culture results. Better understanding of factors noted at presentation potentially could help focus additional testing and antimicrobial therapy on those children who really need it.

In general, guidelines from the American Academy of Pediatrics are very helpful in managing febrile young infants.^1,2 Published in 2021, those guidelines suggest full evaluation (including sampling of blood, urine, and spinal fluid) and presumptive antibiotic treatment for healthy-appearing febrile babies aged 8 to 21 days.¹ For children aged 22-28 days, blood and urine would be sampled (with cultures included in the testing), but lumbar puncture and antibiotic therapy would depend on initial findings and clinician judgment.¹ For infants aged 29-60 days, urinalysis and blood culture should be done, but urine culture, lumbar puncture, and antibiotic treatment would depend on initial findings and clinician judgment.¹ These new data help guide clinician judgment when the initial urinalysis is suggestive of infection, specifically suggesting that lumbar puncture is unlikely to be necessary.

Beyond diagnostic stewardship, young infants with febrile urinary tract infections also should benefit from judicious antimicrobial stewardship. Several studies in recent years point toward the adequacy of shorter-than-standard initial courses of intravenous antibiotics to treat young infants with urinary tract infections.

A multicentered study reported in 2016 included 251 young infants with bacteremic urinary tract infections.³ Intravenous antibiotics were given for 7.8 ± 4 days, with institutions varying the duration of intravenous antibiotic therapy from 5.5 to 12 days.³ There were no relapses of bacteremia.³ Relapses of urinary infection were rare and unrelated to the duration of intravenous antibiotic therapy.³ The authors suggested that shorter treatment courses with parenteral antibiotics might be appropriate.³ A similar 2019 multicentered study of 115 young infants with bacteremic urinary tract infections found that children who were sicker at presentation were more likely to get longer courses of antibiotics, but that outcomes were the same between those who received less than seven days of parenteral therapy and those who received longer intravenous courses.⁴

A similar study reported in 2017 considered non-bacteremic urinary tract infections in young infants at 46 children’s hospitals who did not have any comorbidities.⁴ The use of intravenous antibiotics for more than four days decreased from 50% of children in 2005 to 19% of children in 2015, with no change in readmission rates.⁴ These authors also advocated consideration of shorter courses of intravenous antibiotics for young infants with urinary tract infections.⁵

A 2018 survey of 279 physicians revealed that the duration of intravenous antibiotic treatment for a 2-week-old with a febrile urinary tract infection varied by specialty — two days for general pediatricians and pediatric hospitalists, five days for infectious disease specialists, and seven days for neonatologists.⁶

Finally, a systematic review this year suggests that otherwise healthy young infants with bacteremic urinary tract infections do as well with initial intravenous antibiotics of seven days or less duration as those treated with longer initial intravenous courses.⁷ For young infants with non-bacteremic urinary tract infections, three days of initial intravenous antibiotic therapy seems equal to longer courses.7 The authors of the systematic review suggested that studies of oral treatment alone are needed.⁷

REFERENCES

1. Pantell RH, Roberts KB, Adams WG, et al. Evaluation and management of well-appearing febrile infants 8 to 60 days old. Pediatrics 2021;148:e2021052228.
2. Al Masri NI, Abbas MI, Fischer PR. Evaluation and management of febrile infants. Infectious Disease Alert 2021;41:6-8.
3. Schroeder AR, Shen MW, Biondi EA, et al. Bacteraemic urinary tract infection: Management and outcomes in young infants. Arch Dis Child 2016;101:125-130.
4. Desai S, Aronson PL, Shabanova V, et al. Parenteral antibiotic therapy duration in young infants with bacteremic urinary tract infections. Pediatrics 2019;144:e20183844.
5. Lewis-de Los Angeles WW, Thurm C, Hersh AL, et al. Trends in intravenous antibiotic duration for urinary tract infections in young infants. Pediatrics 2017;140:e20171021.
6. Joshi NS, Lucas BP, Schroeder AR. Physician preferences surrounding urinary tract infection management in neonates. Hosp Pediatr 2018;8:21-27.
7. Hikmat S, Lawrence J, Gwee A. Short intravenous antibiotic courses for urinary infections in young infants: A systematic review. Pediatrics 2022;149:e2021052466.