Pediatric Fever - Clinical Tree

Key Concepts

Fever is the most common complaint among pediatric patients presenting to the emergency department (ED). Although rates of bacterial illness are lower since the advent of universal vaccination for Haemophilus influenzae type b and Streptococcus pneumoniae , serious bacterial infection (SBI) should be considered in the under-vaccinated or unvaccinated child.
Viruses cause the vast majority of childhood febrile illnesses and are generally self-limited and benign.
SBI is the growth of pathogenic bacteria in a previously sterile site, such as urinary tract infection (UTI), bacteremia, meningitis, osteomyelitis, bacterial gastroenteritis, bacterial pneumonia, cellulitis, or septic arthritis.
The rate of SBI in infants younger than 3 months old with fever is between 6% and 10%.
Infants 28 days old and younger are at much higher risk for bacterial illness with fever because of their immature immune systems and incomplete vaccination status.
Empirical treatment of a febrile neonate is indicated, and appropriate antibiotic regimens include ampicillin plus either gentamicin or cefotaxime, which cover the bacterial organisms likely in this age group.
Empiric treatment for herpes simplex virus (HSV) in neonates with a maternal history of genital herpes, ill appearance, fever and seizure, cutaneous vesicles on physical examination, transaminitis, or evidence of coagulopathy is recommended.
The most common cause of SBI in children continues to be UTI. In infants who are not toilet-trained, bladder catheterization is the best method for collecting uncontaminated urine. However, for select patients, bagged urine may be obtained, and if results do not indicate infection, no further studies are needed. Suprapubic aspiration may be considered when a urine sample cannot otherwise be obtained.
Bacterial meningitis can occur at any age, but most commonly presents in a relatively small proportion of febrile infants younger than 3 months old (3/1000).
Respiratory syncytial virus (RSV) and influenza are common viral causes of fever and respiratory distress in infants, but the presence of viral infection does not lower the risk of concomitant SBI in children younger than 28 days old.
In older infants and children, the documented presence of RSV or influenza significantly reduces the incidence of SBI and can be used to modify the evaluation. Because UTI is still common in this population, a urinalysis should be obtained.
There are numerous risk-stratification strategies (e.g., Boston, Rochester, and Philadelphia criteria) reported in the literature that have similar performance characteristics. All involve a laboratory evaluation designed to identify a subset of febrile infants younger than 3 months old that can safely be managed as outpatients with or without antibiotics.
Standardization and adoption of a clinical practice guideline for the evaluation of the febrile infant have been shown to reduce variation and cost.
Due to universal vaccination against pneumococcus, the evaluation of highly febrile children 3 to 36 months old has evolved from one of universal screening for occult bacteremia to one where clinical assessment determines the need for bloodwork.
Inflammatory markers, such as C-reactive protein (CRP) and procalcitonin, have been shown to predict bacterial illness in febrile children more accurately than the white blood cell (WBC) count but does not solely rule out SBI.
Traumatic lumbar punctures occur relatively commonly in young infants and can make interpretation of cell counts difficult. The use of various formulas to account for the protein and WBCs in the cerebrospinal fluid (CSF) after a traumatic tap should be used with caution.
As the risk of meningitis is exceedingly low, we do not recommend lumbar puncture in well-appearing children with a simple febrile seizure.
Children presenting with fever and petechiae are at risk for infection with meningococcus; blood should include a complete blood count (CBC) and culture and, if available, CRP and procalcitonin (>0.5 ng/mL). Children with an abnormal CRP, WBC count (<5000/mm ³ or >15,000/mm ³ ), or bandemia should be treated with parenteral antibiotics and admitted. Lower risk, well-appearing children with normal laboratory parameters can be considered for close outpatient follow-up.
Children with fever who also are receiving cytotoxic chemotherapy for cancer are at high risk for bacteremia and sepsis and should receive prompt broad-spectrum antibiotic therapy after appropriate diagnostic evaluation (at minimum, a CBC and blood culture).
Patients with fever and a history of sickle cell disease are at risk for bacteremia from encapsulated organisms due to functional asplenia and should be considered high risk, admitted, and treated.

Foundations

Background

Fever is the most common chief complaint of pediatric patients presenting to the emergency department (ED). Most cases of fever are viral in origin, benign in course, and resolve spontaneously. Management of children with fever varies by the age of the child, with the following common divisions: 0 to 28 days old, 1 to 2 months old, 2 to 3 months old, 3 to 6 months old, 6 to 36 months old, and 3 years old to adulthood. Understanding that risk is a continuum, these divisions reflect differing immunologic and vaccination milestones, as well as a spectrum of age-specific pathogens.

Anatomy, Physiology, and Pathophysiology

Fever is defined as any elevation in body temperature of 100.4°F (38.0°C) or above. The most reliable method to measure temperature is with a rectal thermometer and is the preferred method of measurement in high-risk groups, such as infants 0 to 3 months old. However, the rectal route should not be used in patients who are potentially immunocompromised (e.g., children receiving cytotoxic chemotherapy) because of the risk of mucosal damage leading to bacteremia. The cutoff for a clinically significant fever (i.e., one that may trigger a laboratory evaluation) varies with the age and immunologic status of the child. A rectal temperature of 100.4°F (38.0°C) is considered a clinically significant fever in an infant younger than 3 months, often warranting laboratory evaluation; however, a toddler with a temperature of 103.1°F (39.5°C) and an upper respiratory infection may not need any evaluation beyond a thorough history and physical examination.

Causes of fever vary with the age of the child ( Table 161.1 ). The majority of pediatric fever is due to infections, and most infections are attributable to a viral source. (See Chapter 120 for a discussion of COVID-19 in children) Upper respiratory infections, viral gastroenteritis, croup, bronchiolitis, stomatitis, roseola, infectious mononucleosis, and varicella are all known causes of fever. Most viral illnesses are benign and self-limited, but infection with measles, herpes simplex virus (HSV), or respiratory syncytial virus (RSV) can lead to significant morbidity and mortality, particularly in the first month of life.

TABLE 161.1

Etiology of Fever in Children

Age	Bacterial Causes	Viral Causes	Other
0–8 days old	Group B streptococcus	HSV	Bundling (skin temperature only) ^a
	Listeria monocytogenes	Varicella	Environmental
	Escherichia coli	Enteroviruses
	Chlamydia trachomatis	RSV
	Neisseria gonorrhoeae	Influenza
1–3 months old	Haemophilus influenzae	Varicella
	Streptococcus pneumoniae	Enteroviruses	Environmental
	Neisseria meningitidis	RSV
	E. coli	Influenza
3–36 months old	S. pneumoniae	Varicella	Leukemia
	N. meningitidis	Enteroviruses	Lymphoma
	E. coli	RSV	Neuroblastoma
		Influenza	Wilms’ tumor
		Mononucleosis
		Roseola
		Adenovirus
		Norwalk virus
		Coxsackievirus
3 years old to adulthood	S. pneumoniae	Varicella	Leukemia
	N. meningitidis	Enteroviruses	Lymphoma
	E. coli	RSV	Neuroblastoma
	Group A streptococcus	Influenza	Wilms’ tumor
		Mononucleosis	Juvenile rheumatoid arthritis
		Roseola
		Adenovirus
		Norwalk virus

HSV, Herpes simplex virus; RSV, respiratory syncytial virus.

a Bundling may raise skin temperature but does not change rectal temperature. Irrespective of how measured, a fever in this high-risk population should not be attributed to bundling alone.

Bacterial disease is also an important cause of fever in children. Serious bacterial infection (SBI) is defined as the presence of pathogenic bacteria in a previously sterile site and includes urinary tract infection (UTI), bacteremia, meningitis, osteomyelitis, bacterial gastroenteritis, bacterial pneumonia, cellulitis, and septic arthritis. The risk of SBI in febrile infants younger than 3 months old with a temperature of at least 100.4°F (38.0°C) is between 6% and 10%; children younger than 28 days old have the highest incidence. Hyperpyrexia (rectal temperature ≥40.0°C) is associated with a higher risk of SBI. Pathogens change during early infancy, with vertical transmission of organisms such as group B streptococcus, Listeria monocytogenes, and HSV more common in neonates. By 1 to 2 months of age, organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and urinary pathogens (Escherichia coli or Enterococcus) become more common. In all children younger than 3 months old, the urinary tract is the most common site of infection, followed by bacteremia and meningitis.

Children younger than 3 months old may present with an apparent viral syndrome and still harbor SBI. Levine and colleagues studied 1248 infants younger than 60 days old who had temperatures above 100.4°F (38.0°C). Of these children, 22% were positive for RSV. Overall, children with documented RSV had a lower incidence of concomitant SBI than those without RSV (12.5% vs. 7%), but there was no significant difference in rates of SBI in those younger than 28 days old (14.2% in RSV-negative vs. 10.1% in RSV-positive). Most of the bacterial infections were UTIs. Older children 3 to 36 months old with recognizable viral syndromes (e.g., croup, bronchiolitis, varicella, stomatitis) have a very low incidence of bacteremia; in over 1300 patients with a temperature above 102.2°F (39.0°C) who had a recognizable viral syndrome, the risk of bacteremia was 0.2%.

Occult bacteremia describes the presence of pathogenic bacteria in the bloodstream of a well-appearing febrile child in the absence of a focus of infection; it was first described as a clinical entity in the 1970s. The term typically refers to children 3 to 36 months old who are highly febrile (>102.2°F [39.0°C]) but appear well. Before the adoption of the conjugate vaccines against Haemophilus influenzae type b and S. pneumoniae, the incidence of bacteremia in this population was approximately 5%. Vaccination has proved remarkably effective, nearly eradicating H. influenzae type b as a significant pathogen and greatly reducing the burden of pneumococcal disease ( Fig. 161.1 ). ^, Currently, the rate of occult bacteremia is less than 1%, with pathogens such as N. meningitidis becoming proportionally more prevalent. Urinary pathogens, occurring in 5% of febrile children younger than 2 years old, continue to be a common source of bacterial illness in infants and children. Risk factors include female sex, absence of another apparent source of infection, fever higher than 102.2°F (39.0°C), white race, and for boys, uncircumcised status.

Fig. 161.1, Decline in incidence of occult bacteremia after the introduction of the conjugate vaccine against Haemophilus influenzae (A) and Streptococcus pneumoniae (B).

Bacterial illness in school-age children and adolescents includes focal infections, such as streptococcal pharyngitis, cellulitis, and pneumonia, as well as bacteremia and meningitis. N. meningitidis has a bimodal distribution, with the highest incidence in children younger than 12 months old (9.2/100,000 population). A second peak occurs during adolescence, when the rate of illness is 1.2/100,000 population, with a significant proportion of cases occurring in college students who reside in a dormitory setting (3.2/100,000 population).

Although it is much less common than in viral or bacterial infection, fever can also be a presenting sign of autoimmune diseases, such as juvenile rheumatoid arthritis or Kawasaki disease. Central nervous system (CNS) lesions such as brain tumors also can infrequently manifest with fever.

The body’s ability to fight infection varies with age. Maternal antibodies confer some protection after birth, but the infant’s immune system is initially inadequate, particularly T-cell function and the ability to mount an immunoglobulin G response to infection. Their immature immune system and exposure to certain pathogens during the birthing process (e.g., group B streptococcus, Chlamydia trachomatis, Neisseria gonorrhoeae ) places the newborn at particularly high risk for SBI. Young infants are also at risk for disseminated infection because they are unable to mount the immune response needed to prevent bacterial spread. Thus, a simple cellulitis, mastitis, omphalitis, or, rarely, gonococcal eye disease, can lead to sepsis or seeding of the CNS. Immune function improves during the first 2 to 3 months of life, as does the ability to assess a child clinically. Infants begin the primary series of vaccinations against acquired infections, such as S. pneumoniae and H. influenzae, at 2 months of age, providing further protection against common bacterial pathogens. As a result, empirical testing and treatment give way to more selective evaluations above 2 to 3 months old.

Clinical Features

History taking should focus on the length of illness, localizing symptoms (e.g., headache and neck pain [meningitis or encephalitis] or ear pain [otitis media]), exposure to ill contacts, travel history, and pertinent past medical history. For infants younger than 28 days old, document birth history, including gestational age and the presence of potentially transmittable maternal infections (HSV or group B streptococcus). Document immunization status, sick contacts, use of antipyretics before evaluation, and prior use of antibiotics. Defervescence after acetaminophen administration has not been shown to reliably exclude bacteremia in children of any age. Prior antibiotic use may mask the classic findings in diseases, such as meningitis. Cough and congestion may suggest pneumonia or viral upper respiratory infection, whereas a harsh, barking, or seal-like cough is often a predominant complaint in viral laryngotracheitis (croup). Parents may report vomiting and diarrhea as a component of gastroenteritis, or the presence of sore throat and lymphadenopathy with viral or streptococcal pharyngitis. Decreased oral intake or decreased urine output is a frequent complaint in gastroenteritis but may also be seen in patients with stomatitis because painful oral aphthous ulcerations prevent fluid intake. A history of lethargy, irritability, or altered mental status can occur with severe dehydration but should raise concern for meningitis or encephalitis. A rash occurs in many viral illnesses (e.g., roseola) but may be seen in life-threatening conditions, such as meningococcemia, Rocky Mountain spotted fever, and toxic shock syndrome (TSS).

The physical examination of the febrile child should begin with a complete set of vital signs, including pulse oximetry. Hypoxia or significant respiratory distress (e.g., tachypnea, grunting respirations, nasal flaring, or retractions) may accompany sepsis or pulmonary infection. Stridor can be seen with croup but also can occur with retropharyngeal abscess, epiglottitis, or bacterial tracheitis. Signs of shock, such as hypotension and poor peripheral perfusion, should be noted. Children typically mount a tachycardic response to fever, and hypotension is often a late and dire finding. Tachycardia is often due to the fever itself, but tachycardia out of proportion to the degree of fever can be seen with early shock, myopericarditis, and dehydration. Estimations of heart rate increase based on fever in infants younger than 12 months old (i.e., heart rate increases linearly by 9.6 beats/min with each 1°C increase in body temperature) should be used with caution and clinical signs of sepsis evaluated before attributing tachycardia to fever alone. Once oxygenation, ventilation, and perfusion have been assessed and deemed adequate, the physical examination should focus on a thorough search for focal infection. In young infants, particularly those younger than 3 months old, and in children who lack immunocompetence, fever may be the only presenting sign of SBI, including meningitis. The physical examination in this age group is insufficiently sensitive to exclude SBI, and emergency clinicians should not be falsely reassured by a normal physical examination in young children. Those who do appear toxic may have decreased tone, poor skin turgor, poor tracking, increased or decreased respiratory effort, a weak cry or suck, or delayed capillary refill times. The neonate who refuses to feed should have a full SBI evaluation, irrespective of temperature. See Chapter 155 .

Diagnostic Testing

Numerous laboratory and radiographic studies can be used to evaluate the febrile child. In general, testing should be directed at the identification of the source and complications of infection. Several guidelines exist for the evaluation of febrile children, although there is marked variation in adherence to these guidelines. Office-based practitioners have been found to follow published guidelines only 42% of the time in the evaluation of febrile children. Clinicians with less experience and those based in the hospital tend to order more tests compared with more experienced clinicians and those practicing in an office setting, respectively. The use of institutional clinical decision rules and guidelines can help streamline appropriate testing. ^,

White Blood Cell Count

An elevated white blood cell (WBC) count (>15,000/mm ³ ) can be an indicator of bacteremia but is also present in many viral illnesses. Leukopenia (<5000/mm ³ ) can also be a sign of SBI or early sepsis. Pneumococcal infection is classically associated with leukocytosis, whereas infection with N. meningitidis and H. influenzae may be present even with normal WBC counts. In children with fever greater than 102.2°F (39.0°C), Lee and colleagues found that the rate of pneumococcal bacteremia increased from 0.5% with a WBC count between 10,000 and 15,000/mm ³ to 3.5% if the WBC count was 15,000 to 20,000/mm ³ and up to 18% with a WBC count above 30,000/mm ³ . More extreme leukocytosis is associated with an increased risk of bacterial infection, particularly lobar pneumonia, and a WBC count of above 25,000/mm ³ should prompt consideration of a chest radiograph unless another definitive source is apparent.

The WBC differential diagnosis has also been used to risk-stratify febrile children in various models; an increase in polymorphonuclear leukocytes increases the risk of bacterial disease. A rise in polymorphonuclear leukocytes is also seen early in some viral infections. An absolute neutrophil count (ANC) above 10,000/mm ³ suggests an increased risk of pneumococcal bacteremia in febrile children (0.8% for children with an ANC below 10,000/mm ³ vs. 8% for children with an ANC above 10,000/mm ³ ). Routine screening of all febrile children greater than 3 months of age with bloodwork has not been shown to be cost-effective in the post-vaccination era. The vast majority of acute febrile illness is due to self-limited viral infection. If the decision is made on clinical grounds to obtain a WBC and if it is abnormal (<5000/mm ³ or >15,000/mm ³ ) or the ANC is greater than 10,000/mm ³ , then we recommend screening for occult bacteremia with a blood culture, understanding that leukocytosis is neither perfectly sensitive nor specific for bacterial illness. We also recommend treatment with ceftriaxone for incompletely immunized children who have a WBC of more than 15,000/mm ³ .

Inflammatory Markers

Both C-reactive protein (CRP) and procalcitonin have been studied as markers of bacterial infection. The utility of the measurement of inflammatory markers is dependent on the cutoff level assigned for clinical significance with lower values having higher sensitivity but lower specificities. Procalcitonin greater than 0.5 ng/mL is highly specific for SBI, though some clinicians use a lower cutoff (>0.2 ng/mL) to increase sensitivity. Both CRP and procalcitonin appear to be more sensitive and specific than the WBC alone, although the lack of widespread availability limits the usefulness of procalcitonin clinically at this time. ^,

Blood Culture

Many centers obtain blood for culture during intravenous (IV) catheter placement after sterile preparation of the skin has been performed. Although this eliminates a second venipuncture solely to obtain blood for culture, in children, the rates of contamination with this technique are higher than a sterile straight stick (9.1% vs. 2.8%). The risks of contamination should be weighed against the ability to obtain blood through a separate venipuncture. The yield of a single blood culture in infants and small children is actually good. The routine sending of more than one sample is generally not needed, and bacteremia is often accurately detected even if only 0.5 to 1 mL of blood is obtained. The advent of automated blood culture systems has led to the identification of true pathogens more quickly than by traditional methods, often within 24 hours. Pathogens isolated in the first 24 hours are more likely to be true pathogens than are bacteria isolated after 24 hours.

Urinalysis and Urine Culture

UTIs are common causes of bacterial illness in febrile children, occurring in 5% of infants 2 to 24 months old with fever 100.4°F (38.0°C) or higher. Accurate documentation of UTI is imperative both to diagnose the cause of a fever and to identify those infants who need follow-up radiographic imaging to exclude anatomic abnormalities that will predispose them to further infection. It is currently recommended that febrile infants with documented UTIs undergo renal ultrasonography to evaluate for urinary tract anomalies. For infants with signs of urosepsis or not improving within 24 hours of antibiotic administration, an ultrasound should be performed to evaluate for obstructive uropathy or rare complications, such as renal or perirenal abscesses. Voiding cystourethrography is not indicated after the first febrile UTI in children unless renal ultrasonography reveals evidence of high-grade vesicoureteral reflux or scarring.

The only reliable method to obtain urine in a non-toilet-trained child is bladder catheterization or suprapubic aspiration. Bladder catheterization is the preferred method in almost all cases. Bag collection of urine is notoriously unreliable; up to 85% of cultures from bag specimens will be falsely positive (defined as a culture growing a single organism with >10 ⁵ colony-forming units [CFUs]/mL or a mix of two or more organisms), which then places these children at risk for unneeded, potentially painful, and expensive follow-up diagnostic testing and antibiotics. However, for select patients, bagged urine may be obtained, and if results do not indicate infection, no further studies are needed. A clean catch urine specimen is appropriate for toilet-trained children.

UTI is defined as the combination of bacteriuria and pyuria. Bacteriuria in the absence of WBCs on microscopic examination represents asymptomatic bacteriuria. Urine is typically analyzed with a dipstick, followed by microscopic analysis of a centrifuged specimen of urine. An “enhanced” urinalysis, which is an examination with a hemocytometer of an unspun specimen of urine for pyuria (defined as >10 WBCs per high-power field) or the presence of any bacteria per high-power field in Gram stain of unspun urine has a negative predictive value of 99.8%, perhaps making urine culture unneeded if pyuria and bacteriuria are absent by use of the enhanced urinalysis method. However, many centers are not using this enhanced method. Because dipstick and microscopic analysis have lower sensitivities, most experts recommend sending urine for culture in high-risk groups (febrile girls <24 months old, uncircumcised boys <12 months old, and circumcised boys <6 months old).

A positive urine culture is defined as the growth of more than 50,000 CFU/mL of a single uropathogen in urine obtained via catheterization or suprapubic aspirate.

Lumbar Puncture

A sample of cerebrospinal fluid (CSF) should be obtained from any child with signs and symptoms of meningitis. Fluid should be obtained with the smallest spinal needle possible (typically a 22-gauge) and sent for cell counts, manual differential diagnosis, Gram staining, culture, and measurement of CSF protein and glucose concentrations. Meningoencephalitis due to HSV is a potential cause of fever, particularly in neonates; if suspected, CSF should be sent for HSV polymerase chain reaction (PCR) testing. Panel-based nucleic amplification tests that detect a wide array of viral and bacterial pathogens can also be useful but should be coupled with traditional CSF cultures as they do not identify every possible pathogen and do not give information on antibiotic susceptibility. ^, The CSF in bacterial meningitis typically contains more than 1000 WBCs/mL, although there is considerable overlap in the CSF profile of bacterial and viral meningitis, making a determination of viral or aseptic meningitis difficult on the basis of CSF parameters, such as cell count, protein, and glucose; thus, CSF culture of a pathogenic bacterium is the “gold standard.” A prediction rule has been developed and validated to differentiate bacterial from aseptic meningitis in children 29 days to 19 years old who have CSF pleocytosis. Children without any of the following criteria have a low risk (0.1%) of bacterial meningitis: positive CSF Gram stain, CSF ANC of 1000 cells/mL or more, CSF protein concentration of at least 80 mg/dL, peripheral blood ANC of 10,000 cells/mL or more, and history of seizure before or at the time of presentation. This may obviate the need for empirical antibiotic therapy and hospital admission in some children who are at low risk for bacterial meningitis.

Contraindications to lumbar puncture include cellulitis over the proposed site of puncture, cardiopulmonary instability, bleeding diathesis, or platelet count below 50,000/μL, focal neurologic deficits, and signs of increased intracranial pressure, including papilledema. In these patients, lumbar puncture should be deferred until the child is stable, and blood should be obtained for culture while the child is treated empirically, recognizing that up to 50% of children with meningitis will not have bacteremia.

CSF contaminated by blood (i.e., a traumatic lumbar puncture) can make interpretation of cell counts and differential diagnoses difficult. In these cases, fluid should be obtained for Gram stain and culture and the child hospitalized and treated presumptively for meningitis until culture data are available.

Stool Studies

Stool studies are indicated in patients in whom bacterial gastroenteritis may be a cause of fever. A stool guaiac test for blood, as well as Gram stain for WBCs, should be performed. The presence of more than five WBCs per high-power field in the stool of a febrile child should trigger a culture of stool for Salmonella, Shigella, Campylobacter, enterotoxigenic E. coli, and Yersinia species. Patients with sickle cell disease are at particular risk for focal complications, such as osteomyelitis from Salmonella infection (see Chapter 167 ).

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here