Disclaimer: The guidelines for evaluating febrile infants in this publication are based on current U.S. practices and epidemiology. These may not apply to other regions, particularly low- and middle-income countries, where vaccination rates, healthcare access, and local factors may differ. Local guidelines should be consulted in those settings.
You have new patients!
You are working in an emergency department, and during your shift, you see a number of different patients.
Bed 1
In bed 1, a parent brings a full-term 2-month-old male infant who has been complaining of fever at home for 1 day. The child has been drinking well, has normal urine output, and has no associated symptoms.
Prenatal care was normal, infant was born by normal vaginal delivery with no complications and went home with mom after a couple of days. Of note, the mother had a fever during delivery and received antibiotics—no sick contacts at home.
The male infant is vigorous and appears well during your examination. Currently afebrile with normal vital signs.
Bed 2
In bed 2, you find a well-appearing 2-month-old female infant with complaint of fever at home. This child has had fever for 1 day. She also has a runny nose and a couple of episodes of vomiting after feeding. The family is visiting from out of town and has no way to contact their pediatrician.
Prenatal care was normal, infant was born by normal vaginal delivery with no complications and went home with mom after a couple of days—no sick contacts at home.
The female infant is vigorous and well-appearing during your examination. Currently afebrile with normal vital signs.
Bed 3
In bed 3, you have a 3-year-old fully vaccinated boy who has had fever of up to 38.5°C every day for the last week. Aside from the fever, there were no significant respiratory symptoms, vomiting, or diarrhea. He has been able to drink well, although not eating his usual amount.
Vital signs are remarkable for fever of 39°C, mild tachycardia to 120 bpm, and respiratory rate of 32 rpm. On exam, he has mildly injected conjunctiva, cervical adenopathy, and some peeling of his fingers.
How will you approach each of these patients?
Introduction
Fever is a common childhood complaint frequently encountered in emergency medicine [1]. It is a symptom of an underlying illness or infection and occurs when the body’s temperature rises above its normal range [2]. In children, a fever is generally defined as a temperature of 38°C (100.4°F) or higher in infants under 3 months and 38.5°C (101°F) in older toddlers and children [3].
Many causes of fever in children include viral or bacterial infections, autoimmune disorders, allergies, and reactions to medication. In some cases, the cause of the fever may be difficult to determine [2].
In emergency medicine, the primary concern with fever in children is identifying the underlying cause and treating it appropriately. This may involve a thorough physical examination, blood tests, imaging studies, or other diagnostic tests to help identify the cause of the fever.
In addition to treating the underlying cause of the fever, several measures can be taken to help manage the symptoms of fever in children. These may include administering acetaminophen or ibuprofen to help lower the child’s temperature, ensure adequate hydration, and closely monitor the child’s temperature and other vital signs [4].
It is important to seek medical attention promptly if your child has a fever accompanied by other symptoms such as difficulty breathing, severe headache, rash, or lethargy. With prompt diagnosis and treatment, most cases of fever in children can be successfully evaluated and managed in the emergency department.
Temperature should ideally be measured rectally in infants [5]. In older toddlers and children, oral or axillary measurements are acceptable, understanding there is an approximate 0.5°C difference between the latter and rectal temperatures [6]. Also, rectal or oral measurements might be contraindicated in patients with immunodeficiency or neutropenia.
The pathophysiology of fever is associated with the liberation of cellular mediators such as interleukins, tumor necrosis factor, and interferon and their impact on prostaglandins at the hypothalamic level, raising the endogenous thermostat [7]. Fever is thought to be a benign and useful mechanism to stimulate the immune system, although it does increase metabolic demands, which can affect homeostasis at various levels [8].
This chapter will review the evaluation of febrile children in the emergency department.
What do you need to know?
Fever in infants
The American Academy of Pediatrics (AAP) recently updated its guidelines [9] for evaluating and managing fever in infants, providing evidence-based recommendations for healthcare providers.
According to the new guidelines, any infant younger than 60 days of age with a fever (rectal temperature of 38°C or higher) should be evaluated promptly. Fever in this age group can be a sign of a serious bacterial infection or invasive infection that requires urgent medical attention. The evaluation should include a complete physical examination, blood tests, urine tests, and possibly a lumbar puncture.
The guidelines also emphasize the importance of assessing the infant’s overall clinical appearance, including their hydration status, activity level, and interaction with caregivers. Any infant who appears ill, dehydrated, or has other concerning symptoms should be evaluated and managed as an inpatient.
Overall, the AAP guidelines aim to provide a systematic approach to evaluating and managing fever in infants, focusing on early recognition and treatment of serious bacterial infections while minimizing unnecessary diagnostic testing and hospitalization. It is important for healthcare providers and parents to be aware of these guidelines and to seek prompt medical attention if an infant develops a fever.
Prenatal risk factors should be assessed and include prematurity, prenatal care, maternal infections such as Group B Streptococcus and herpes, prolonged rupture of membranes, birth by C-section of normal vaginal delivery, maternal fever, and need for peripartum antimicrobial administration. Postnatal factors may include admission to the neonatal intensive care unit, the presence of respiratory support, central or peripheral lines, exposure to sick contacts, or the use of antibiotics as a newborn. Social determinants of health, such as access to healthcare, education, adequate environment, economic stability, and social and community support, play a key role in the decision-making process considering the disposition of the febrile infant once assessed in the emergency department.
Clinical prediction rules have been developed and validated, and guidelines have been adapted to include their use. Currently, the Step-by-step and the PECARN prediction rules offer a high sensitivity (96.7% and 92%, respectively) for the detection of SBI/IBI in infants and, more importantly, a very high negative predictive value (>99%) by which if all the high-risk lab criteria, including inflammatory markers, are negative, the presence of IBI/SBI is extremely unlikely [10] [11].
Infants < 21 days of age
The risk of serious bacterial infection (SBI), which includes bacteremia, urinary tract infection, and meningitis in infants younger than 21 days of age, is very high, and clinical examination parameters are not sensitive or specific enough to determine which infants are not at risk of sepsis. Patients at this age with a fever > 38°C, hypothermia, bradycardia, or apnea have a high risk of sepsis and septic shock. Infants under 21 days of age require thorough evaluation, including complete blood cell counts (CBC), blood culture, catheterized urine sample for microscopic urinalysis and urine culture, and a spinal puncture (LP) for evaluation and culture of cerebrospinal fluid. In addition, these patients should receive parenteral antibiotics such as Ampicillin, Gentamycin, and/or Cefotaxime as per local guidelines. For patients of this age, it is important always to consider the possibility of herpes simplex virus (HSV) infection, and parenteral acyclovir should be considered pending results of HSV nucleic amplification tests (HSV DNA PCR) or viral culture studies [12]. These patients should be admitted to an inpatient level of care for close monitoring and pending results of blood, urine, and CSF cultures.
Infants 22-28 days
It is important to understand that any current guidelines for evaluating febrile infants apply to well-appearing children. Suppose there is any concern or clinical finding regarding an ill-appearing infant. In that case, a thorough examination and laboratory testing, including blood, urine, CSF cultures, broad-spectrum antibiotics, and admission to a hospital service, are indicated [13].
Infants in this age range are still considered at high risk for serious invasive infections, especially if there are any risk factors, as described above. Current guidelines still strongly recommend considering full evaluation of the patients 22 to 28 days old, strongly consider antibiotic management pending culture results, and possible admission to a hospital.
However, in select infants of this age range, a more conservative approach has been suggested: obtaining catheterized urine samples, a complete blood count, urine and blood cultures, and introducing inflammatory markers. Currently studied and available inflammatory markers include c-reactive protein (CRP), Procalcitonin, and absolute neutrophil count (ANC). These tests’ recommended cut-offs are CRP > 20 mg/L, Procalcitonin > 0.5 ng/ml, and ANC > 4000/µL or <1000/µL, respectively.
If a well-appearing infant has normal urinalysis, normal WBC, and negative inflammatory markers, one possibility would be admission to a hospital service with or without obtaining a lumbar puncture. However, this opens the opportunity to admit without giving antimicrobial agents and observing pending culture results [14]. However, if any of the screening labs or inflammatory markers are elevated, antibiotics and admission are necessary. Still, the possibility of HSV infection should be considered at this age.
Infants 29-60 days
For this age group, for well-appearing infants with a temperature >38°C, the recommendation is to obtain urine and blood, including cultures and inflammatory markers [15]. At this age, obtaining a lumbar puncture is no longer mandatory for a well-appearing child with otherwise normal laboratory evaluation and negative inflammatory markers. If inflammatory markers are elevated in the absence of a positive urinalysis, a lumbar puncture is indicated to rule out meningitis. If the urinalysis is positive and inflammatory markers are below the threshold, there is no clear indication to perform a spinal tap, and the infant can be treated for a urinary tract infection potentially with oral antimicrobials and can be considered a candidate to be discharged home with close follow up within 24 hours. Suppose all the screening labs and inflammatory markers are within normal limits. In that case, there is no indication for antibiotic treatment, and the patient can be observed at home with close follow-up in 24 hours [16]. Recent literature suggests that well-appearing infants with an uncomplicated urinary tract infection (UTI) have a very low risk of bacteremia and an even lower risk of meningitis.
In order to discharge an infant home, the clinician must ensure that the parents understand the degree of risk, the importance of prompt follow-up within 24 hours, the capacity and ability to return to medical care, and the understanding to return immediately if there is any deterioration in the infant’s status. If not all of these criteria can be fulfilled, and there are social, language, or intellectual barriers to healthcare, the patient should be admitted to the hospital for observation.
In infants older than 30 days of age, antimicrobial regimens can include ceftriaxone for the treatment of bacteremia and/or urinary tract infections, with the consideration of ceftazidime or vancomycin for the treatment of bacterial meningitis. Oral regimens of first or second-generation cephalosporins can be considered for uncomplicated urinary tract infections. Always consider the local flora, antibiograms, and susceptibility to antibiotics before prescribing antimicrobial courses.
Also, it’s important to remember that if there is any concern, a full septic workup should be obtained, and broad-spectrum antibiotics should be used pending the culture results.
Infants older than 2 months of age
Vaccination has significantly reduced the incidence of bacterial infections in children, including serial bacterial infections. For example, the Haemophilus influenzae type b (Hib) vaccine has been highly effective in reducing the incidence of invasive Hib disease, which can cause meningitis, pneumonia, and other serious infections in young children. The introduction of the pneumococcal conjugate vaccine (PCV) has also led to a significant reduction in the incidence of invasive pneumococcal disease, including pneumonia and meningitis. E. coli has become the most common pathogen responsible for IBI in infants, bacteremia, and meningitis.
Furthermore, vaccination can indirectly reduce the incidence of serial bacterial infections by reducing the overall burden of bacterial infections in the community. When fewer people are infected with a particular bacterium, there is less opportunity for that bacteria to be transmitted from person to person, known as herd immunity, reducing the risk of serial infections for the general population.
Vaccination has significantly reduced the incidence of bacterial infections in children, including serial infections. Vaccination is a safe and effective way to protect children from serious bacterial infections and is an important part of routine healthcare for children.
For the evaluation of well-appearing, febrile infants older than 2 months of age, the main recommendation is always to consider the possibility of a urinary tract infection (UTI). The incidence of bacteremia and meningitis in areas with adequate vaccination coverage has decreased to approximately 1% risk of bacteremia and <0.5% risk of bacterial meningitis. However, the risk of UTI remains at 10-20% risk.
In general, the risk of UTI is similar in females and males up to 6 months of age. However, it drops for circumcised males after 6 months. The prevalence of UTI remains high in females up to 24 months of age.
As discussed above, if there is any concern about a high fever or a child who is not well-appearing, a more aggressive evaluation should be undertaken, and appropriate antimicrobial therapy should be considered.
The need to obtain a lumbar puncture (LP) in a well-appearing infant in this age group is of less debate currently as the incidence of bacterial meningitis is so rare, especially with a reassuring examination and low-risk screening labs.
After 2 months of age, it is important to consider the prevalence of viral infections. Common viral infections such as Respiratory Syncytial Virus (RSV), Influenza Virus, Rhinovirus, Enterovirus, Metapneumovirus, and Coronavirus, including SARS-COVID-2 virus, are prevalent in infants, and studies reveal that the presence of these viral infections is related to less possibility of serious invasive bacterial etiology perhaps with the exception of UTI’s. The incidence of UTIs in children with associated RSV infection is still high and warrants evaluation. However, it is important always to be vigilant of the possibility of HSV disease, a thorough maternal history, exposure, and physical examination is important, as well as considering obtaining blood, skin, mucosal, and CSF samples to send for culture or nucleic acid amplification and consider starting antiviral therapy presumptively due to the severity of these infections in infants, specially central nervous system or disseminated disease, which carry high morbidity and mortality.
Recent antimicrobial use also needs to be considered in infants within this age group. If any oral antimicrobials have been administered within 72 hours, the clinician should consider the possibility of partially treated infection or masking of signs and symptoms of bacterial infection. In this scenario, obtaining urine and blood cultures should be strongly considered.
There is poor evidence regarding the extent of evaluation in recently immunized infants. Recent immunizations are generally considered vaccinations administered in the previous 24 to 48 hours. In general, for a well-appearing infant older than 2 months, with a normal physical examination after a recent immunization less than 24 hours prior to the evaluation, the general consensus is not necessarily to obtain any testing but to direct the patient for a follow-up evaluation in the next 24 hours to ensure fever is not further present within 48 hours after vaccinations. However, the clinician should consider the possibility of catheterized urine evaluation within 48 hours of immunization due to the prevalence of UTI.
Invasive Bacterial Infections (IBI)
IBI is used to discuss the evidence of localized bacterial infections in infants and toddlers. A thorough physical examination should provide a clue of the presence of any of these disease processes. The term usually includes acute otitis media, cutaneous cellulitis or omphalitis around the umbilicus in infants, bacterial arthritis, skin abscess, and mastitis. Occult causes of IBI are less evident by physical examination and require a high index of suspicion, and the likely need for laboratory or imaging evaluation includes bacterial pneumonia, osteomyelitis, epidural abscess, brain abscess, or meningitis. Ill-appearing infants with focal infections do require a thorough evaluation, including cultures of abscess drainage, fluid aspirates, and skin or mucosal discharge [17].
Hyperpyrexia
The literature describes a linear correlation between high fever and serious bacterial infection. Hyperpyrexia is defined as rectal temperature ≥40°C (104°F) and is uncommon among febrile infants but is highly associated with invasive bacterial infection. If an infant presents with hyperpyrexia, blood cultures should be obtained and treated with broad-spectrum antimicrobials pending the blood culture results.
Fever of unknown origin / Fever without a source
Fever of unknown origin (FUO) is generally defined as a temperature >38.3°C (101°F), at least once daily, that lasts for at least 8 days and for which the cause cannot be identified after an initial workup. FUO can be challenging to diagnose, especially in children, as it can be caused by a variety of infectious, inflammatory, and neoplastic diseases, usually in this order of prevalence. Fever without a source (FWS) is generally defined as fever for less than 1 week without adequate explanation after a thorough history and physical examination.
The evaluation of FUO in children typically involves a comprehensive history and physical examination, as well as laboratory tests, imaging studies, and sometimes more invasive procedures [18]. It is important to understand the local distribution of infectious agents and the regional or ethnic presentation of specific inflammatory or rheumatologic conditions. Still, there is a small minority of patients in whom, after thorough evaluations, no cause is identified.
The following is a general approach to the evaluation of FUO in children:
History and physical examination: A thorough history and physical examination are critical in identifying any clues that may help narrow down the potential causes of the fever. Important details to gather include the child’s age, travel history, recent infections, medication use, and exposure to animals or sick contacts. Concerning fever, it is important to verify its height, duration, pattern, if it is documented or subjective, and any other associated symptoms surrounding febrile spikes. Associated complaints or symptoms can be useful in helping establish a correlation. Respiratory symptoms, gastrointestinal complaints, bone and muscle aches, and skin rashes may suggest specific etiologies that may present with prolonged fevers. Travel and exposure are key questions that can help narrow the possibility of etiologic agents. Contact with sick individuals, pets, farms, and other animals can point to specific infectious etiologies. It is easy to find lists of common infectious diseases by geographic location.
Vital signs should be documented, and discrepancies should be analyzed. For example, fever and bradycardia might suggest a few specific conditions (tick-borne or mosquito-related illnesses, legionella, Leptospira). Weight loss might suggest systemic diseases or malignancy.
The physical examination should include a detailed examination of all organ systems. Detailed skin evaluation might suggest dermatologic manifestations, as skin rashes can be associated with specific infectious or rheumatologic diseases. Examination of mucosal surfaces, including conjunctiva, mouth, and genitalia, might provide clues to systemic, rheumatologic, infectious, or inflammatory diseases. Lung and cardiovascular exam might reveal evidence of effusions or endocarditis. Attention to typical and atypical lymphadenopathy, organomegaly, or bone or muscle tenderness that might suggest infiltrative disease, inflammatory or infectious process. The genitourinary examination should be considered to exclude sexually transmitted diseases, pelvic masses, and inflammatory or malignant etiologies. Finally, a detailed neurological assessment might suggest subtle neuro deficits that might point to neuropathies, spinal pathology, medication, or toxic overdoses.
The physical exam should be repeated frequently in children, as it often evolves and changes according to disease progression.
Often, the initial assessment will be performed by a primary care clinician in an outpatient setting unless the child has become ill, has rapidly progressing symptoms or deterioration, or initial common studies have been performed and need for more complex testing needs to be performed.
Laboratory tests: A complete blood count with differential cell count, blood cultures, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), liver and renal function tests, and urinalysis should be obtained as part of the initial workup. Depending on the clinical presentation and suspected etiology, additional tests such as serologic studies, viral cultures, and molecular diagnostic tests may be indicated. Leukocytosis, cytopenia, anemia, thrombocytosis or thrombocytopenia, and atypical cell lines such as atypical leukocytes, bandemia, eosinophilia, can all point to various infectious etiologies, and might suggest viral, fungal, parasitic, rickettsial, and chronic disease or malignancy. Inflammatory markers are non-specific but can help the clinician trend the progression of a disease process.
Secondary-tier testing may involve ANAs, cryoglobulins, immunoglobulins, ferritin, and targeted rheumatologic and immunologic tests to help identify a more specific etiology. Additionally, tumor markers and specialized viral and infectious testing—such as DNA and RNA viral profiles, serologies for viral, bacterial, or rickettsial infections, and RPR or VDRL for presumed syphilis—can be utilized. Stool studies can reveal infectious etiologies, and calprotectin or occult blood can suggest inflammatory pathology.
Imaging studies: Chest X-ray, abdominal ultrasound, and/or computed tomography (CT) scans may be necessary to evaluate for pulmonary, abdominal, or pelvic pathology. Plain films can help evaluate bony malignancy or infections, soft tissue calcifications, and bone density. Magnetic resonance imaging (MRI) or positron emission tomography (PET) scans may be helpful in identifying occult infections or tumors. A conscious balance between radiation, costs, risks and benefits should guide imaging studies. A discussion with radiology experts might help direct the imaging study of choice and the need for contrast material.
Invasive procedures: Depending on the clinical presentation and initial workup, invasive procedures such as bone marrow biopsy, lymph node biopsy, or liver biopsy may be necessary to establish a diagnosis.
It is important to note that the evaluation of FUO in children should be individualized based on the patient’s clinical presentation and suspected etiology. A multidisciplinary approach involving infectious disease specialists, hematologists/oncologists, and rheumatologists may be necessary to establish a diagnosis and guide management.
Revisiting Your Patient
In bed 1, the 2-month male infant with fever at home for 1 day with history of maternal fever during delivery underwent a full septic workup due to the risk factors, received a dose of ceftriaxone and was admitted to the hospital for observation for 24 hours, until urine, blood, and CSF cultures were negative.
In bed 2, your 2-month-old female infant with fever at home only underwent a catheterized urine sample that was unremarkable. Because the mom had no good follow-up with a primary care provider, the infant was admitted to the hospital for 24 hours with no antibiotics until the urine culture was negative for 24 hours.
In bed 3, you have a 3-year-old fully vaccinated child who has had fever of up to 38.5◦C every day for the last week—examination with fever, conjunctivitis, and skin peeling.
This child underwent laboratory workups, including inflammatory markers, blood counts, chemistry, and liver function tests. He was admitted to the hospital for consultation with Cardiology and infectious Diseases to consider further evaluation for Kawasaki disease.
Author
Camilo E. Gutierrez
Dr. Gutiérrez is an Associate Professor of Pediatrics and Emergency Medicine at George Washington University School of Medicine and Health Sciences, practicing Pediatric Emergency Medicine at Children’s National Hospital in Washington, DC. He is a renowned Pediatric Emergency Physician with extensive experience in clinical care, education, and global health. He leads international initiatives to improve pediatric emergency systems, having served in leadership roles for various global organizations. With over 90 international lectures, 30 publications, and a focus on pediatric trauma, critical care, and ultrasound, he is a key advisor in developing acute care systems worldwide.
Listen to the chapter
References
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Reviewed and Edited By
Jonathan Liow
Jonathan conducts healthcare research in the Emergency Department at Tan Tock Seng Hospital. A graduate of the University at Buffalo with a BA in Psychology and Communication, he initially worked on breast cancer research studies at GIS A*STAR. His research interests focus on integrating AI into healthcare and adopting a multifaceted approach to patient care. In his free time, Jonathan enjoys photography, astronomy, and exploring nature as he seeks to understand our place in the universe. He is also passionate about sports, particularly badminton and football.
James Kwan
James Kwan is the Vice Chair of the Finance Committee for IFEM and a Senior Consultant in the Department of Emergency Medicine at Tan Tock Seng Hospital in Singapore. He holds academic appointments at the Lee Kong Chian School of Medicine, Nanyang Technological University, and the Yong Loo Lin School of Medicine, National University of Singapore. Before relocating to Singapore in 2016, James served as the Academic Head of Emergency Medicine and Lead in Assessment at Western Sydney University's School of Medicine in Australia. Passionate about medical education, he has spearheaded curriculum development for undergraduate and postgraduate programs at both national and international levels. His educational interests focus on assessment and entrustable professional activities, while his clinical expertise includes disaster medicine and trauma management.
Arif Alper Cevik, MD, FEMAT, FIFEM
Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.
