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    Step-by-Step Approach to Febrile Infants

    Identifies febrile infants ≤90 days old at low risk of invasive bacterial infections.
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    INSTRUCTIONS

    Use in previously healthy infants ≤90 days old presenting with fever without a source.

    When to Use
    Pearls/Pitfalls
    Why Use
    • Previously healthy infants ≤90 days old with documented fever (≥38.0° C or ≥100.4°F) at home or in the emergency department.
    • Use caution in infants with a short duration of fever, as it takes time for serum inflammatory markers like procalcitonin to rise. Consider observation in the ED, even if laboratory values are initially normal.
    • Use caution in infants 21-28 days old, as the management of this age group remains controversial, and the Step-by-Step algorithm did not perform optimally in this group. Among patients with IBI who the Step-by-Step approach failed to identify as high-risk, 4/7 (57%) of these infants were between 21-28 days old. Studies suggest that the prevalence of bacteremia may be higher in infants between 21 and 28 days old, compared to infants >28 days old, and therefore recommend a full sepsis workup for any infant <28 days old (Powell 2018).
    • The Step-by-Step approach was developed with the goal of identifying febrile infants ≤90 days old who are at low risk of invasive bacterial infection, defined as bacteremia or meningitis.
    • This score was only studied in previously healthy infants, and does not apply to infants with any prior medical history.
    • In the study, “fever without a source” was defined as an infant with a normal physical exam without signs or symptoms of a self-limiting viral illness such as bronchiolitis or gastroenteritis.
    • Performs best when applied to infants with fever duration >2 hours because it relies on the detection of inflammatory markers (procalcitonin and C-reactive protein) that may take time to rise.
    • Differences in prevalence of IBI versus non-IBI should also be taken into consideration when interpreting and applying the results of this study.
    • One comparison study showed that Step-by-Step outperformed the Rochester Criteria and Lab-score (Step-by-Step was 92.0% sensitive for ruling out IBI, versus 81.6% for the Rochester Criteria and 59.8% for the Lab-score).

    Etiology of fever in infants ≤90 days old may range from self-limiting viral illness like bronchiolitis to life-threatening invasive bacterial infection (IBI) like bacteremia or meningitis. The Step-by-Step Approach can be used to rule out IBI with high negative predictive value (99.3%). If IBI can be safely ruled out, these low-risk infants do not require hospital admission and intravenous antibiotics.

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    Next Steps
    Evidence
    Creator Insights

    Management

    Management of invasive bacterial infections in infants:

    • Prompt initiation of broad spectrum antibiotics according to local guidelines is strongly recommended.
    • Optimize respiratory support and hemodynamics if respiratory distress or signs of dehydration or shock are present.
    • Inpatient hospital admission for a minimum of 36-48 hours is recommended if cultures remain negative.

    Studies indicate that 96% of blood cultures will become positive by 36 hours and 99% will become positive by 48 hours, if invasive bacterial infection is present (Biondi 2014, Biondi 2015).

    Critical Actions

    No decision rule should trump clinical gestalt. High suspicion for IBI in a febrile infant should warrant full sepsis workup.

    Formula

    Stepwise approach as follows:

    *Pediatric Assessment Triangle (Dieckmann 2010):

    Appearance:

    • Tone
    • Interactivity
    • Consolability
    • Look/gaze
    • Speech/cry

    Breathing:

    • Tachypnea
    • Abnormal breath sounds
    • Abnormal positioning
    • Retractions
    • Nasal flaring

    Circulation:

    • Pallor
    • Mottling
    • Cyanosis
    • Bleeding

    If any single aspect is abnormal, then the infant should be considered high-risk by the Pediatric Assessment Triangle.

    Facts & Figures

    Interpretation:

    Risk group

    IBI risk

    Recommendation

    Low

    0.7%

    Full sepsis workup likely not needed. Consider a period of ED observation, especially if the duration of fever is <2 hours, and ensure outpatient pediatrician follow-up.

    Intermediate

    3.4%

    Full sepsis workup, including blood, urine, and CSF cultures, initiation of broad spectrum intravenous antibiotics, and inpatient hospital admission MAY be indicated, especially if the patient is between 21 and 28 days old.

    High

    8.1%

    Full sepsis workup, including blood, urine, and CSF cultures, initiation of broad spectrum intravenous antibiotics, chest x-ray, and inpatient hospital admission are recommended.

    Evidence Appraisal

    Gomez et al conducted a prospective validation study of previously derived criteria, which they applied to 2,185 infants ≤90 days old presenting to the pediatric emergency department at 11 European hospitals. Among this group, 3.9% were diagnosed with an invasive bacterial infection and 19.1% were diagnosed with a non-invasive bacterial infection such as urinary tract infection.

    In a post-hoc analysis (Shaughnessy 2016), the Step-by-Step approach demonstrated superior sensitivity and negative predictive value compared to other risk assessment tools such as the Rochester Criteria or Lab-Score. Sensitivity and negative predictive value for ruling out an IBI were 92.0% and 99.3% for the Step-by-Step, 81.6% and 98.3% for the Rochester criteria, and 59.8% and 98.1% for the Lab-score.

    Literature

    Dr. Santiago Mintegi

    From the Creator

    Why did you develop the Step by Step Approach to Febrile Infants? Was there a particular clinical experience or patient encounter that inspired you to create this tool for clinicians?

    We decided to design this tool because we commonly used different biomarkers that were not adequately included in existing protocols, and we wanted to get a good tool to identify young febrile infants suitable for outpatient management.

    What pearls, pitfalls and/or tips do you have for users of the Step by Step Approach to Febrile Infants? Do you know of cases when it has been applied, interpreted, or used inappropriately?

    We have to clarify better the following:

    1. What to to do with the intermediate group after observation in the ED.

    2. The role of the ED observation in the low risk group. To identify infants that do not need to be observed in the ED.

    3. We have the feedback form other hospitals using the "Step by Step" (abstracts in national meetings) without incidences.

    What recommendations do you have for doctors once they have applied the Step by Step Approach to Febrile Infants? Are there any adjustments or updates you would make to the score based on new data or practice changes?

    I have to remind them of the importance of the infant’s appearance - the first "box" of the algorithm.

    How do you use the Step by Step Approach to Febrile Infants in your own clinical practice? Can you give an example of a scenario in which you use it?
    We use it in all young febrile infants. It is better explained with a clinical scenario, such as this: Steinberg J. Young Febrile Infants: Step-by-Step Evaluation. Am Fam Physician. 2018 Jan 1;97(1):45-46.

    Why did your research team decide to use the age cut-off of 21 days (versus 28 days) for high-risk patients in this study?

    We decided to use it following the results of these two studies:

    Garcia S, Mintegi S, Gomez B, Barron J, Pinedo M, Barcena N, Martinez E, Benito J. Is 15 Days an Appropriate Cut-Off Age for Considering Serious Bacterial Infection in the Management of Febrile Infants? Pediatr Infect Dis J. 2012 May;31(5):455-8

    Martinez E, Mintegi S, Vilar B, Martinez MJ, Lopez A, Catediano E, Gomez B. Prevalence and Predictors of Bacterial Meningitis in Young Infants with Fever without a Source. Pediatr Infect Dis J. 2015 May;34(5):494-8

    How could a risk-calculator like the Step-by-Step approach impact the management of febrile infants, if broadly applied by providers?

    To better identify infants suitable for outpatient management and decrease errors.

    Any thoughts on the Step-by-Step approach in comparison to similar risk-stratification tools like the Rochester Criteria, Philadelphia Criteria, Lab-score, etc?

    We have commented this in some of our papers. The Step-by-Step is more adequate for identifying young febrile infants suitable for outpatient management. Using other risk-stratification tools, you will misclassify more patients.

    Any other research in the pipeline that you’re particularly excited about?

    We are trying to identify children with pleocytosis suitable for outpatient management. The following is the first step:

    Garcia S, Echevarri J, Arana-Arri E, Sota M, Benito J, Mintegi S; Meningitis group of RISEUP-SPERG. Outpatient management of children at low risk for bacterial meningitis. Emerg Med J. 2018 Mar 21. pii: emermed-2017-206834. doi: 10.1136/emermed-2017-206834. [Epub ahead of print]

    About the Creator

    Santiago Mintegi, MD, PhD, is a pediatric emergency physician and quality manager at Cruces University Hospital in Bilbao, Spain. He also serves as a member of the Research in European Pediatric Emergency Medicine (REPEM) network. Dr. Mintegi's research interests include pediatric bacterial infections, febrile infants, and decision tools.

    To view Dr. Santiago Mintegi's publications, visit PubMed

    Content Contributors
    • Emily Heikamp, MD, PhD
    About the Creator
    Dr. Santiago Mintegi
    Content Contributors
    • Emily Heikamp, MD, PhD