Fever

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Objectives

Upon finishing this module, the student will be able to:

Identify the components of the Pediatric Assessment Triangle (PAT).
Understand an approach to evaluating well-appearing neonates and young infants with a fever.
Discuss the disposition for neonates and young infants with a fever.
List risk factors that place neonates or young infants at increased risk for herpes simplex virus infection.

Contributors

Update Authors: Elio Morales, MD; and Michael D. Parsa, MD.

Original Authors: Ann Nadon, DO; Mark Crosby, DO; and Michael D. Parsa, MD.

Update Editor: Navdeep Sekhon, MD.

Original Editor: S. Margaret Paik, MD.

Last Updated: May 2024

Introduction

Pediatric fever is a common presenting complaint to emergency departments (EDs). In one US study, fever represented 19% of pediatric ED visits. Fever has a broad differential diagnosis which includes infectious and non-infectious etiologies. Infectious etiologies can range from an uncomplicated viral infection to a potentially life-threatening etiology such as pneumococcal meningitis. Regarding invasive pneumococcal infections, one study showed decreased rates of these infections in neonates and young infants, even in those too young to be vaccinated, after the introduction of pneumococcal vaccination in the US.

This curriculum will focus on fever in neonates and young infants given the increased risk for serious bacterial infection in this patient population. A healthy neonate with a fever has up to a 10% rate for serious bacterial infection. For information regarding children from two months to 36 months, please see #10 in the references section below.

Case Study

A 27-day-old boy that was born at full term is brought to the emergency department (ED) due for one day of fever. The patient is noted to have a rectal temperature of 38.5 degrees Celsius. The patient is well-appearing. A head-to-toe exam reveals no obvious source for the fever. The patient has voided six wet diapers in the past 24 hours and has not had any feeding difficulties. The patient’s mother reports no complications during the recent pregnancy or delivery and the patient did not have a stay in the neonatal intensive care unit.

Initial Actions and Primary Survey

It is important to consider a patient’s vital signs during the initial assessment of a patient. Abnormal vital signs such as hypotension or hypoxemia should be addressed promptly. One evaluation method you may find useful when assessing your pediatric patients is the Pediatric Assessment Triangle (PAT). Using the PAT can help rapidly identify a pediatric patient in need of prompt resuscitation. The three components of the PAT are:

Appearance: Tone, interactiveness, gaze, cry, consolability (is the patient moving and have good muscle tone, is the patient consolable, does the patient have a blank/glassy-eyed stare, does the patient have a strong or weak cry).
Work of Breathing: (Breath sounds, positioning, retractions, nasal flaring (do you hear striding/grunting/wheezing, is there nasal flaring or retractions, is there head-bobbing in the neonate).
Circulation to Skin: Pallor, mottling, cyanosis.

Lastly, a complete head-to-toe assessment is invaluable to evaluate a neonate or young infant for potential sources of fever.

Presentation and Diagnostic Testing

The American Academy of Pediatrics (AAP) published clinical practice guidelines in 2021.⁵ This curriculum will discuss key elements from this guideline. Very importantly, this guideline is intended to be applied only to well-appearing febrile young infants. In the 2021 AAP guidelines, children are categorized into three groups based on age. The inclusion criteria for this guideline include febrile infants who:

Are well appearing.
Have documented rectal temperatures of > 38°C or 100.4°F at home in the past 24 hours or determined in a clinical setting.
Had a gestation between >37 and <42 weeks.
Are eight to 60 days of age and at home after discharge from a newborn nursery or born at home.

There are several exclusion criteria listed in this guideline. One notable exclusion criterion is having an obvious bacterial source for fever, such as cellulitis.

For well-appearing eight to 21-day-old patients with a fever, the indicated diagnostics include urinalysis, blood culture, lumbar puncture, and obtaining serum inflammatory markers (e.g. CRP, ANC, procalcitonin). CBC is optional in this group.

For well-appearing 22 to 28-day-old patients with a fever, the indicated diagnostics include urinalysis, CBC, blood culture, and serum inflammatory markers. If inflammatory markers are elevated, then a lumbar puncture should be performed. If the inflammatory markers are normal, then a lumbar puncture may be performed. If a lumbar puncture is not performed, then the child should be observed in a hospital. However, if a lumbar puncture is performed, then a child may potentially be discharged and observed at home if cerebrospinal fluid (CSF) pleocytosis is not present, with the caveat that the child should receive parenteral antimicrobials and be reassessed in 24 hours.

For well-appearing 29 to 60-day-old patients with a fever, the indicated diagnostics include urinalysis, CBC, blood culture, and serum inflammatory markers. If inflammatory markers are elevated, a lumbar puncture may be performed. If inflammatory markers are normal, then a lumbar puncture does not need to be performed.

For the well-appearing patient between the age of two months and three years, the predominant cause of fever is viral, and routine laboratory studies of the blood are not indicated. However, there is an increased risk of UTI in the following patient populations (especially if temperature is above 39°C):

Females under the age of two years.
Uncircumcised males under the age of one year.
Circumcised males under the age of six months.

Treatment

Neonates are at higher risk of invasive bacterial infections. For this reason, neonates under 21 days old who are well-appearing but are febrile should receive parenteral antimicrobials and be observed in the hospital regardless of initial diagnostic testing results.

For the well-appearing patient between 22 to 28-days-old, the disposition is based on laboratory studies. If the CSF shows pleocytosis or the urinalysis is suggestive of a urinary tract infection (UTI), the patient should be admitted for IV antibiotics. If the CSF and UA are normal and the inflammatory markers are abnormal, the patient should be admitted and IV antibiotics should be considered. Parenteral antibiotics can be given if the CSF, inflammatory markers, and UA are all normal. If discharged, the patient should receive a dose of IV antibiotics and the following discharge criteria should be met:

Verbal teaching and return precautions given to parents.
Follow-up plans within 24 hours are established.
Plans developed for medical care if condition worsens.

When choosing antimicrobial treatment, it is important to keep in mind the most common organisms implicated in bacteremia in febrile infants less than 60 days old - escherichia coli, group B streptococcus, and staphylococcus aureus.

There are scenarios when you may order antimicrobials empirically for a patient while awaiting more definitive diagnostic testing such as blood and CSF cultures. To make this decision, it is advised that one consults the 2021 AAP guidelines. For example, well-appearing 22 to 28-day-old infants who are hospitalized with a fever and abnormally elevated inflammatory markers may receive parenteral antimicrobials while awaiting cultures, even if their lumbar puncture has no CSF pleocytosis.

Treatment will be based on your clinical suspicion of what the etiology of the fever is, and diagnostics may guide your treatment plan. A patient with pneumonia will be managed differently than a child with osteomyelitis.

Pearls and Pitfalls

Herpes Simplex Virus (HSV) should be kept on the differential diagnosis for febrile young infants who have risk factors for HSV infection or whose clinical presentation suggests an HSV infection. In one North American study, HSV was identified in 0.42% of patients 60 days old or younger who presented to an ED and had CSF studies performed within 24 hours. According to the AAP 2021 guidelines, a clinician should consider HSV "when there is a maternal history of genital HSV lesions and in infants with vesicles, seizures, hypothermia, mucous membrane ulcers, CSF pleocytosis in the absence of a positive Gram stain result, leukopenia, thromboctyopenia, or elevated alanine aminotransferase levels."
The 2021 AAP guidelines contain figures with algorithms that can be easily referenced by a clinician taking care of a well-appearing febrile young infant.
When antibiotic administration is indicated, antibiotic selection should be guided by local sensitivity and resistance patterns. However, it is advised to avoid using ceftriaxone in patients less than one month of age due to the risk of hyperbilirubinemia.
Rare, non-infectious causes of fever in neonates include but are not limited to: Kawasaki disease, Behçet's disease, hemophagocytic lymphohistiocytosis (HLH), and autoinflammatory syndromes.

Case Study Resolution

The 27-day-old well-appearing boy in the case study underwent urinalysis and serum diagnostic testing. The patient had a urinalysis that was not consistent with a urinary tract infection. Serum inflammatory markers in the patient were normal. A lumbar puncture was not performed after a shared decision-making conversation with parents regarding CSF evaluation. The patient was given empiric antibiotics in the ED, observed in the hospital and was discharged after an uneventful stay and negative diagnostic testing, including negative blood cultures at 36 hours.

References

Cruz AT, Freedman SB, et al. Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation. Pediatrics. 2018.
De Rose DU, Coppola M, et al. Overview of the Rarest Causes of Fever in Newborns: Handy Hints for the Neonatologist. J Perinatol. 2021.
Dieckmann RA, Brownstein D, Gausche-Hill M. The Pediatric Assessment Triangle: A Novel Approach for the Rapid Evaluation of Children. Pediatr Emerg Care. 2010.
Ishimine P. Fever in the Young Infant, Chapter 9, Pediatric Emergencies: A Practical, Clinical Guide. Oxford University Press. 2021.
Pantell RH, Roberts KB, et al. Clinical Practice Guideline: Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics. 2021.
Poehling KA, Talbot TR, et al. Invasive Pneumococcal Disease Among Infants Before and After Introduction of Pneumococcal Conjugate Vaccine. JAMA. 2006.
Powell EC, Mahajan PV, et al. Epidemiology of Bacteremia in Febrile Infants Aged 60 Days and Younger. Ann Emerg Med. 2018.
Rodriguez DM, et al. Fever and Serious Bacterial Illness in Infants and Children, Chapter 119, Tintinalli's Emergency Medicine: A Comprehensive Study Guide. McGraw Hill Education. 2020.
Shapiro DJ, Fine AM. Patient Ethnicity and Pediatric Visits to the Emergency Department for Fever. Pediatric Emergency Care. 2019.
Fever Without Localizing Signs (2-36 Months) Evidence-Based Guideline. Texas Children's Hospital Evidence-Based Outcomes Center. 2021 Apr.