Definitions and Epidemiology

Fever is defined as any elevation in body temperature equal to or above 38.0° C and typically is the result of infection. The most reliable method to measure temperature is with a rectal thermometer, particularly in high-risk groups, such as infants 0 to 3 months of age, as axillary, oral, and tympanic thermometers are unreliable in this age group. The rectal route should not be used in patients who are potentially immunocompromised (e.g., children with fever who are receiving cytotoxic chemotherapy) because of the risk of mucosal damage, bacteremia, or transmission of infection. The cutoff for a clinically significant fever (i.e., one that triggers a laboratory evaluation) varies with the age and immunologic status of the child. A rectal temperature of 38.0° C is generally considered to be a clinically significant fever in an infant younger than 3 months, necessitating a thorough laboratory workup, whereas a toddler with a temperature of 39.5° C and an upper respiratory infection may not need any workup beyond a thorough history and physical examination. Fever is to be distinguished from hyperthermia, which is an elevation in the body’s temperature “set point.” Causes of hyperthermia include heatstroke, salicylate ingestion, malignant hyperthermia as a complication of inhalational anesthetics, and elevation in temperature secondary to hypothalamic central nervous system (CNS) damage.

The cause of fever varies with the age of the child (Table 167-1). The majority of pediatric fever is due to infections, and most infections are attributable to a viral source. 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 herpes simplex virus (HSV) or respiratory syncytial virus (RSV), particularly in the first month of life, can lead to significant morbidity and mortality.

Bacterial disease is also an important cause of fever in children. Serious bacterial illness (SBI) is typically 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. Studies have found the risk of SBI in febrile infants younger than 3 months with a temperature above 38.0° C to be between 6 and 10%; children younger than 28 days have the highest incidence.² Pathogens change during early infancy, with vertical transmission of organisms such as group B streptococcus, Listeria monocytogenes, and HSV being 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, the urinary tract is the most common site of infection, followed by bacteremia and meningitis. UTIs are more common in white girls compared with other races and are of higher prevalence in patients in whom no source for infection is found and who have higher temperatures (i.e., >39.0° C).³

Children younger than 3 months may present with an apparent viral syndrome and still harbor serious bacterial illness. Levine and colleagues studied 1248 infants younger than 60 days who had temperatures above 38.0° C. Of these children, 22% were positive for RSV. Although, overall, children with documented RSV had a lower incidence of concomitant SBI than did those without RSV (12.5 vs. 7%), there was no significant difference in rates of SBI in children younger than 28 days (14.2% in RSV-negative neonates vs. 10.1% in RSV-positive infants). Most of the bacterial infections were UTIs.⁴ Older children 3 to 36 months of age with recognizable viral syndromes (e.g., croup, bronchiolitis, varicella, stomatitis) have a very low incidence of bacteremia. Greenes and co-workers found that among 1347 patients with temperature above 39.0° C who had a recognizable viral syndrome, the risk of bacteremia was 0.2%.⁵

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.⁶ The term typically refers to children 3 to 36 months of age who are highly febrile (>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%.^7,8 Vaccination has proved remarkably effective, nearly eradicating H. influenzae type b as a significant pathogen and greatly reducing the burden of pneumococcal disease (Fig. 167-1).^9–11 Currently, the rate of occult bacteremia is below 1%, with pathogens such as N. meningitidis becoming proportionally more prevalent. Continued surveillance is ongoing to ensure that there is not a rise in invasive disease caused by nonvaccine serotypes. Urinary pathogens, occurring in 2% of febrile children younger than 5 years, continue to be an important source of bacterial illness in infants and children. Rates are highest in boys younger than 6 months (2.7%) and girls younger than 12 months (6-8%).^12,13

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 (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).¹⁴

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. CNS lesions such as brain tumors also can infrequently be manifested with fever.

Pathophysiology

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. The immature neonatal immune system as well as exposure to certain pathogens during the birthing process (e.g., group B streptococcus, Chlamydia trachomatis, Neisseria gonorrhoeae) places the newborn at particular risk for SBI. Young infants are also at risk for disseminated infection as they are unable to mount the immune response needed to prevent a localized infection from spreading. Thus a simple cellulitis, mastitis, omphalitis, or, rarely, gonococcal eye disease can lead to sepsis or focal seeding of the CNS, making aggressive evaluation and treatment of such infections crucial. Immune function improves during the first 2 to 3 months of life, but the risk of SBI does not diminish appreciably until the primary series of vaccinations against H. influenzae type b and pneumococcus is completed (6 months of age).

History

In dealing with a febrile child, history taking should focus on the length of illness, presence of localizing symptoms, and any pertinent past medical history. In infants younger than 28 days, birth history, particularly the presence of potentially transmittable maternal infection (HSV or group B streptococcus), is critically important. Immunization status, sick contacts, use of antipyretics before evaluation, and prior use of antibiotics are also important historical items. Defervescence after acetaminophen administration has not been shown to reliably exclude bacteremia in children of any age.¹⁵ 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 frequently a complaint in gastroenteritis, but it may also be seen in patients with stomatitis as the painful aphthous ulcerations in the mouth make fluid intake difficult. Any history of lethargy, irritability, or altered mental status can be elicited with severe dehydration but raises the specter of meningitis or encephalitis. A rash occurs in many viral illnesses, such as roseola, but it also may be seen in life-threatening conditions, such as meningococcemia, Rocky Mountain spotted fever, and toxic shock syndrome. Complaints of headache and neck pain (meningitis or encephalitis) or ear pain (otitis media) are also important historical points.

Physical Examination

The physical examination of the febrile child should begin with a complete set of vital signs, including pulse oximetry. Hypoxia or significant respiratory distress manifested by tachypnea, grunting respirations, nasal flaring, or retractions may accompany sepsis or pulmonary infection. Stridor can be seen with croup but also 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 is often seen in other conditions, such as early shock, myopericarditis, and dehydration. Greenes and colleagues found that in infants younger than 12 months, heart rate increases linearly by 9.6 beats/minute with each 1° C increase in body temperature; however, caution must be exercised in attributing tachycardia to fever alone.¹⁶ 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, and in children who lack immunocompetence, fever may be the only presenting sign of serious illness, including meningitis. The physical examination in this age group is sufficiently insensitive to exclude SBI, and clinicians should not be falsely reassured by a normal physical examination in small children.

Ancillary Testing

Numerous laboratory and radiographic studies can be used to evaluate the febrile child. In general, testing should be directed at identification of the source of infection or evaluation for complications. Several guidelines exist for the evaluation of febrile children, although there is marked variation in adherence to these guidelines. Pantell and associates found that office-based practitioners followed published guidelines only 42% of the time in the evaluation of febrile children.¹⁷ 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.

General Approach to the Febrile Infant and Child

The initial approach to any child with a febrile illness is a rapid assessment for evidence of cardiopulmonary compromise or shock. Significant respiratory distress, hypoxemia unresponsive to supplemental oxygen, or altered mental status may necessitate intubation by rapid sequence induction and mechanical ventilation. Evidence of shock (poor perfusion, hypotension, altered mentation) should be aggressively treated with fluid resuscitation. An intravenous or intraosseous line should be placed, and the initial resuscitative fluid should be 20 mL/kg of isotonic crystalloid. This should be repeated to a total of 60 mL/kg if signs of hypovolemia persist, after which vasopressor therapy (dopamine 1-20 µg/kg/min or norepinephrine 0.1-3 µg/kg/min titrated to blood pressure) should be considered.

Every effort should be made to obtain appropriate specimens for culture (blood and urine), even in the critically ill child, before antibiotic administration. Lumbar puncture may be deferred in the critically ill child until stabilization occurs. Empirical antibiotic therapy should be directed at the most likely causative organisms based on age. Sterilization of the CSF occurs quickly once antibiotic administration has been initiated: within 15 minutes to 2 hours in patients with meningococcal meningitis and within 4 to 10 hours in patients with pneumococcal meningitis.²⁹

Serious Bacterial Illness