Febrile Infants Aged ≤60 Days: Evaluation and Management in the Emergency Department (Pharmacology CME and Infectious Disease CME)

Table of Contents

 

About This Issue

Febrile infants aged ≤60 days are commonly encountered in the emergency department. These infants are at high risk for bacterial infections, and if left untreated, invasive bacterial infections can lead to severe outcomes. This issue reviews the most up-to-date evidence to provide recommendations for evaluation and management of febrile young infants aged ≤60 days. In this issue, you will learn:

Infectious sources in the febrile infant

Recommendations for evaluation of well-appearing febrile infants aged ≤60 days

Risk stratification criteria for management of ill-appearing infants and well-appearing infants in different age groups

Testing recommendations, including when to test for enterovirus and parechovirus, testing for respiratory viruses other than SARS-CoV-2, and testing for suspected focal infections

Guidance for applying risk-stratification criteria to decide which infants need a lumbar puncture and which should be treated with empiric antibiotics

Which febrile infants should be hospitalized and which can be discharged with close follow-up

1. About This Issue
2. Abstract
3. Case Presentations
4. Introduction
5. Critical Appraisal of the Literature
6. Etiology and Pathophysiology
7. Differential Diagnosis
8. Prehospital Care
9. Emergency Department Evaluation
   1. History
   2. Physical Examination
10. Diagnostic Studies
    1. Risk Stratification
       1. Ill-Appearing Febrile Infants
       2. Well-Appearing Febrile Infants
          1. Infants Aged 8 to 21 Days
          2. Infants Aged 22 to 28 Days
          3. Infants Aged 29 to 60 Days
       3. Risk-Stratification Algorithms That Serve as the Basis for the AAP Clinical Practice Guideline
       4. Cerebrospinal Fluid Testing
11. Situation-Specific Testing
    1. Resource-Limited Facilities
    2. Testing for Enterovirus and Parechovirus
    3. Testing for Respiratory Viruses Other Than SARS-CoV-2
    4. Other Diagnostic Testing
    5. Testing for Suspected Focal Infections
12. Application of Risk-Stratification Criteria and Treatment
    1. Application of Risk-Stratification Criteria
       1. Ill-Appearing Infants
       2. Well-Appearing Infants
          1. Well-Appearing Febrile Infants Aged ≤21 Days
          2. Well-Appearing Febrile Infants Aged 22 to 28 Days
          3. Well-Appearing Febrile Infants Aged 29 to 60 Days
    2. Empiric Antibiotic Therapy
       1. Febrile Infants Aged ≤21 Days
       2. Febrile Infants Aged 22 To 28 Days
       3. Febrile Infants Aged 29 To 60 Days
       4. Ill-Appearing Febrile Infants
13. Special Circumstances
    1. Patients With Fever at Home but Afebrile in the Emergency Department
    2. Febrile Infants With Abnormal Urinalyses
14. Controversies and Cutting Edge
    1. SARS-CoV-2 Positivity and Prevalence of Urinary Tract Infection and Invasive Bacterial Infection
    2. The Role of Shared Decision-Making
    3. AAP Clinical Practice Guideline Recommendation to Send Urine Culture Only if the Urinalysis is Abnormal
    4. Disparities in Management of Febrile Infants
    5. Neonatal Herpes Simplex Virus Infection
    6. Machine Learning–Derived Risk-Stratification Algorithms
    7. RNA Biosignatures
15. Disposition
16. Risk Management Pitfalls for Febrile Young Infants
17. 5 Things That Will Change Your Practice
18. Summary
19. Time- and Cost-Effective Strategies
20. Case Conclusions
21. Clinical Pathways
    1. Clinical Pathway for Management of Febrile Infants Aged ≤21 Days in the Emergency Department
    2. Clinical Pathway for Management of Febrile Infants Aged 22-28 Days in the Emergency Department
    3. Clinical Pathway for Management of Febrile Infants Aged 29-60 Days in the Emergency Department
22. Tables
23. References

Abstract

Emergency clinicians frequently provide care to febrile infants aged ≤60 days in the emergency department. In these very young infants, fever may be the only presenting sign of invasive bacterial infection and, if untreated, invasive bacterial infection can lead to severe outcomes. This issue reviews newer risk-stratification tools and the 2021 American Academy of Pediatrics clinical practice guideline to provide recommendations for the evaluation and management of febrile young infants. The most recent literature assessing the risk of concomitant invasive bacterial infection with urinary tract infections or positive viral testing is also reviewed.

Case Presentations

A full-term, well-appearing 25-day-old boy presents to the ED for evaluation of fever...

• The patient felt warm to the parents today but has otherwise been asymptomatic.
• The physical examination is normal, except for a fever of 38˚C measured rectally in the ED.
• What is the differential diagnosis? How should you approach evaluation and treatment? Can this baby be discharged home?

A 40-day-old girl presents to the ED in January for evaluation of a rectal temperature of 100.4˚F (38˚C) measured at home...

• The history and physical examination are reassuring, except that she has nasal discharge and a cough.
• Which risk-stratification algorithm should you use for this infant? Would the workup change if a respiratory swab was positive for SARS-CoV-2?

A 50-day-old girl presents to the ED for evaluation of fever...

• The history and physical examination are unremarkable except for the presence of fever of 38˚C measured rectally in the ED. You send blood and urine tests, and the urinalysis results are positive for leukocyte esterase, with >20 white blood cells/high-power field.
• Does this infant require a lumbar puncture? Should the infant be admitted on IV antibiotics or can she receive oral antibiotics and be discharged home?

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Clinical Pathway for Management of Children With Urinary Tract Infection in the Emergency Department

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Tables

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Key References

Following are the most informative references cited in this paper, as determined by the authors.

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(2):e2021052228. (Clinical practice guideline) DOI: 10.1542/peds.2021-052228

10. * Gomez B, Mintegi S, Bressan S, et al. Validation of the “Step-by-Step” approach in the management of young febrile infants. Pediatrics. 2016;138(2):e20154381. (Prospective; 2185 patients) DOI: 10.1542/peds.2015-4381

11. * Kuppermann N, Dayan PS, Levine DA, et al. A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA Pediatr. 2019;173(4):342-351. (Prospective; 1821 patients) DOI: 10.1001/jamapediatrics.2018.5501

41. * Aronson PL, Shabanova V, Shapiro ED, et al. A prediction model to identify febrile infants ≤60 days at low risk of invasive bacterial infection. Pediatrics. 2019;144(1):e20183604. (Case-control; 543 patients) DOI: 10.1542/peds.2018-3604

43. * Milcent K, Faesch S, Gras-Le Guen C, et al. Use of procalcitonin assays to predict serious bacterial infection in young febrile infants. JAMA Pediatr. 2016;170(1):62-69. (Prospective; 2047 patients) DOI: 10.1001/jamapediatrics.2015.3210

44. * Kimberlin DW, Lin CY, Jacobs RF, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics. 2001;108(2):223-229. (Prospective; 186 patients) DOI: 10.1542/peds.108.2.223

48. * Burstein B, Alathari N, Papenburg J. Guideline-based risk stratification for febrile young infants without procalcitonin measurement. Pediatrics. 2022;149(6):e2021056028. (Prospective; 957 patients) DOI: 10.1542/peds.2021-056028

64. * Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics. 2004;113(6):1728-1734. (Prospective; 1248 patients) DOI: 10.1542/peds.113.6.1728

91. * Tzimenatos L, Mahajan P, Dayan PS, et al. Accuracy of the urinalysis for urinary tract infections in febrile infants 60 days and younger. Pediatrics. 2018;141(2). (Prospective; 4147 patients) DOI: 10.1542/peds.2017-3068

96. * Burstein B, Sabhaney V, Bone JN, et al. Prevalence of bacterial meningitis among febrile infants aged 29-60 days with positive urinalysis results: a systematic review and meta-analysis. JAMA Netw Open. 2021;4(5):e214544. (Systematic review and meta-analysis) DOI: 10.1001/jamanetworkopen.2021.4544

98. * Mahajan P, VanBuren JM, Tzimenatos L, et al. Serious bacterial infections in young febrile infants with positive urinalysis results. Pediatrics. 2022;150(4):e2021055633. (Prospective; 7180 patients) DOI: 10.1542/peds.2021-055633

103. *Aronson PL, Louie JP, Kerns E, et al. Prevalence of urinary tract infection, bacteremia, and meningitis among febrile infants aged 8 to 60 days with SARS-CoV-2. JAMA Netw Open. 2023;6(5):e2313354. (Cross-sectional; 14,402 patients) DOI: 10.1001/jamanetworkopen.2023.13354

111. Gutman CK, Aronson PL, Singh NV, et al. Race, ethnicity, language, and the treatment of low-risk febrile infants. JAMA Pediatr. 2023. DOI: 10.1001/jamapediatrics.2023.4890 (Retrospective; 4042 patients)

121. *Brower LH, Wilson PM, Murtagh Kurowski E, et al. Using quality improvement to implement a standardized approach to neonatal herpes simplex virus. Pediatrics. 2019;144(2):e20180262. (Quality improvement) DOI: 10.1542/peds.2018-0262

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Keywords: fever, febrile young infant, febrile infant, fever in infants, pediatric fever, neonatal fever, serious bacterial infection, SBI, invasive bacterial infection, IBI, urinary tract infection, UTI, neonatal herpes simplex virus, herpes simplex virus, Febrile Young Infant Research Collaborative, infant younger than 60 days, bacteremia, bacterial meningitis, Escherichia coli, E coli, Staphylococcus aureus, Listeria monocytogenes, enterovirus, parechovirus, SARS-CoV-2, urinalysis, urine culture, blood culture, CSF culture, CSF pleocytosis, risk stratification, biomarkers, procalcitonin, PCT, temperature, absolute neutrophil count, ANC, C-reactive protein, CRP, antibiotic therapy