The Febrile Infant: New AAP Guidance

Sixteen years in the making, the American Academy of Pediatrics just released a new Clinical Practice Guideline (CPG), “Evaluation and Management of Good-Looking Fever Babies 8-60 Days Old.” The recommendations are derived from interpretations of successive studies in young febrile but good-looking infants covering the incidence of invasive bacterial infection (IBI), diagnostic modalities, and treatment during the first 2 months of life, extending the approaches for evaluation and empirical treatment. were further refined.

Pediatricians have long had solid information to assess the risk of IBI in febrile infants 0-3 months, but there has been a continuing desire to further refine the proposed evaluation of these very young infants. A study of infants with fever from the Pediatric Research in Office Settings network, along with subsequent evidence, has identified the first 3 weeks of life as the period at highest risk for IBI, with the risk gradually declining between age 22 and 56 days.

Critical Notes

First some notes. Babies aged 0-7 days are not treated in the CPG and all should be treated as high risk and receive a full IBI evaluation according to the newborn protocols. Second, the recommendations only apply to “good looking” infants. Any sick baby should be treated as high risk and given a full IBI evaluation and started on empirical antimicrobials. Third, although the CPG is concerned with infants aged 8-21 days, the recommendations are to treat all infants in this age group as high-risk, even if they look well, and to have a full IBI evaluation and empirical therapy. complete pending results. Fourth, these guidelines only apply to babies born at least 37 weeks gestational. Finally, the new CPG Action Statements are intended as recommendations rather than a standard of medical care, leaving some latitude for clinicians to interpret individual patient scenarios. Where appropriate, parents’ values ​​and preferences should be included as part of shared decision-making.

The CPG divides young febrile infants into three cohorts based on age:

8-21 days old

22-28 days old

29-60 days old

Age 8-21 days

For good-looking, febrile infants aged 8-21 days, the CPG recommends a complete IBI evaluation that includes urine, blood, and cerebrospinal fluid (CSF) for culture, with all infants in this cohort considered high-risk. Inflammatory markers can be obtained, but the evidence is not extensive enough to evaluate their role in decision-making for this age group. A two-step urinalysis method (urine analysis followed by culture if the urinalysis looks alarming) is not recommended for infants aged 8-21 days. Urine samples for culture from these young infants should be obtained by catheterization or suprapubic aspiration.

The CPG recommends that blood cultures and CSF be collected by lumbar puncture from this cohort. These infants should be hospitalized, treated empirically with antimicrobials, and actively monitored. However, if the cultures are negative after 24-36 hours, the doctor should discontinue antimicrobials and discharge the baby if there is no other reason for continued hospitalization.

Age 22-28 days

Good looking febrile babies aged 22-28 days are in a medium risk zone. The recommendation for infants in this cohort is to obtain a urine sample by catheterization or suprapubic aspiration for both urinalysis and culture. Physicians may consider taking urine samples for non-invasive analysis (eg urine bag) in this cohort, but this is not the preferred method.

Blood cultures should be taken from all infants in this group. Inflammatory markers can help clinicians identify infants at greater risk for IBI, including meningitis. Previous data suggested that inflammatory markers such as serum white blood cell counts > 11,000/µL, serum absolute neutrophil counts > 4,000/µL, and elevated levels of C-reactive protein and procalcitonin could help healthcare providers identify febrile patients. infants with true IBI. A 2008 study showed that procalcitonin had the best receiver operational characteristic curve in predicting IBI in young infants with fever. Other research supported that finding and identified cut-offs for procalcitonin levels > 1.0 ng/ml. The CPG recommends that a procalcitonin level of 0.5 ng/mL or higher be considered positive, indicating that the child is at greater risk for IBI and possibly an extensive IBI workout. Therefore, inflammatory markers in 22-28 days old infants may play a role in the decision to perform a lumbar puncture.

Much more nuanced recommendations on whether or not to treat empirically with antimicrobials in this cohort can be found in the CPG, including whether it should be treated in hospital or at home. Treatment recommendations vary widely for this cohort based on the tests obtained and whether the tests were positive or negative at the initial evaluation.

Age 29-60 days

The CPG will be most helpful when clinicians are faced with good-looking, feverish infants in the 29 to 60-day age group. As with the other groups, a urinalysis is recommended; however, the CPG suggests that the two-step approach — obtaining a urinalysis using a non-invasive method and obtaining culture only if the urinalysis is positive — is reasonable. This means that a bag or free-flowing urine sample would be suitable for urinalysis, followed by catheterization/suprapubic aspiration if culture is required. This would save about 90% of infants from invasive urine collection. However, only catheter or suprapubic samples are suitable for urine culture.

The CPG also recommends that clinicians obtain a blood culture from all of these infants. Inflammatory markers should be assessed in this cohort, as avoiding lumbar puncture for CSF culture in this cohort would be appropriate if the inflammatory markers are negative. If CSF is obtained in this age cohort, enterovirus testing should be added to the testing regimen. Again, for any infant considered to be at higher risk for IBI based on screening tests, the CPG recommends a 24- to 36-hour exclusion period with empirical antimicrobial treatment and active in-hospital monitoring.


The recommended approach for febrile infants aged 8-21 days is relatively aggressive, with evaluation of urine, blood, and CSF for IBI. Physicians are given some leeway for babies aged 22-28 days, but the guidelines recommend a more flexible approach to evaluating good-looking, feverish babies aged 29-60 days, when a two-step urine evaluation and assessment of inflammation markers clinicians and parents can help better discuss the risks and benefits of more aggressive testing and empirical treatment.

The author wishes Dr. Ken Roberts for his review and helpful comments on this summary of the CPG highlights. Summary points of the CPG were presented by the writing group at the Pediatric Academic Societies (PAS) 2021 meeting (virtual).

William T. Basco, Jr, MD, MS, is a professor of pediatrics at South Carolina Medical University and director of the division of general pediatrics. He is an active health researcher and has published more than 60 manuscripts in the peer-reviewed literature.

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