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Fever Without Source in Infants and Young Children

Michael A. Davis, MD

Two-thirds of children visit their physician with an acute febrile illness before the age of three. The most common causes of fever in children are respiratory, urinary tract, gastrointestinal, and central nervous system infections. Bacteremia may occur with any of these infections. Fever without a source that is related to a viral illness is often difficult to differentiate from occult bacteremia.

Clinical Evaluation of the Febrile Child

The child's health status, course of the current illness, birth and past medical history, and immunization status are evaluated.

Infants can be considered at low risk for serious bacterial infection if they had been healthy with no previous hospitalizations, were delivered at term and discharged home with their mother without complications, and had no previous antimicrobial therapy.

Physical Examination

Assessment of cardiopulmonary status includes a determination of vital signs. Children who are toxic require immediate cardiovascular stabilization and a complete sepsis evaluation, with empiric antimicrobial therapy.

Fever is usually defined as a rectal temperature of at least 38.0EC (100.4EF). Axillary and tympanic measurements are unreliable. Serious infections can also occur in afebrile or hypothermic infants. Fever may also be related to vaccine reactions.

Over bundling of small infants can cause temperature elevations. When this is suspected, the temperature should be rechecked with the child unbundled for 15 minutes.

If no focal bacterial infection (eg, skin, soft tissue infection, otitis media) is apparent, the child is at low risk for serious bacterial infection.

Children with clinical signs of a serious illness or sepsis (lethargy, signs of poor perfusion, marked hypoventilation or hyperventilation, or cyanosis) are considered to be toxic.

The quality of cry, reaction to parents, color, state of hydration, response to social overtures, affect, respiratory status and effort, and peripheral perfusion should be assessed.

Neonates with acute bacterial meningitis often lack meningismus. Meningitis in neonates may manifest as temperature instability (hyperthermia or hypothermia), poor feeding, listlessness, lethargy, irritability, vomiting, or respiratory distress. A bulging fontanelle may be seen in up to one-third of cases, although it usually appears later in the course of illness. The most common CNS signs in the newborn are lethargy and irritability.

In older infants and children, initial symptoms of bacterial meningitis consist of fever, signs of increased intracranial pressure, and cerebral cortical dysfunction. The fever in children who have bacterial meningitis usually is greater than 38.3 degrees C. Increased intracranial pressure initially is manifested as vomiting and lethargy. Older children and adolescents frequently present with headache, fever, altered sensorium, and meningismus. Kernig's or Brudzinski's signs may be absent in up to 50% of adolescents and adults with bacterial meningitis.

Laboratory Studies

Reassuring laboratory screening values include a white blood cell count of 5,000 to 15,000/mm³ (5.0 to 15.0 x 10/L), an absolute band cell count of <1,500/mm³, and fewer than 5 white blood cells per high-power field in stool specimens in infants with diarrhea.

A gram-stained smear of urine sediment is a sensitive screening test, and a urine culture can confirm urinary tract infection.

Blood cultures are valuable in confirming bacteremia.

Lumbar puncture is mandatory when the diagnosis of meningitis is suspected in a febrile child because it is the only test that can exclude this diagnosis.

Management

Toxic-appearing Infants and Children

All toxic-appearing febrile infants and children less than 36 months of age should be hospitalized for evaluation and treatment of meningitis or possible sepsis.

Occult bacteremia can lead to osteomyelitis, septic arthritis, meningitis, urinary tract infections, pneumonia, enteritis, and meningitis.

Febrile Infants Less than 28 Days of Age

Fever in infants less than 28 days of age always mandates a sepsis evaluation and hospitalization for parenteral antibiotic therapy until culture results are known.

Laboratory evaluation includes an examination of cerebrospinal fluid for cells, glucose, protein and culture; a urinalysis and urine culture; and a blood culture.

Febrile Infants 28 to 90 Days of Age

Infants who do not meet low-risk criteria should be hospitalized for a sepsis evaluation and empiric antimicrobial therapy, until culture results are known.

Febrile infants less than three months of age who meet low-risk criteria, can be observed after a urine culture has been obtained.

Empiric parenteral antimicrobial therapy may be used in the outpatient management of low-risk infants. Ceftriaxone ( Rocephin), a third-generation parenteral cephalosporin with a half-life of 5-6 hours, is often used; 50 mg/kg once daily. Empiric antimicrobial therapy is initiated after blood and urine cultures and a lumbar puncture have been completed.

Children who have met low-risk criteria with reliable parents can be treated as outpatients if close follow-up within 18-24 hours can be ensured. Caregivers are instructed to check the child every 4 hours for activity, rectal temperature, and skin color. The caregiver should call the physician if any changes occur, including skin rash, skin mottling, cyanosis, poor feeding, bulging fontanelle, difficulty arousing or consoling, or jerking movements.

If the clinical condition worsens, the child is admitted for parenteral antimicrobial therapy and a sepsis evaluation.

Febrile Children 3 Months to 36 Months of Age

Occult bacteremia in febrile children 3 to 36 months of age without a source of infection has an incidence of 3-11%, with a mean probability of 4.3% in children with a temperature of at least 39.0EC (102.2EF). The risk of bacteremia correlates with the height of the fever in this age group.

Nontoxic-appearing children with a fever of less than 39.0EC (102.2EF), who have been previously healthy, may be managed expectantly if there is no apparent focus of infection. Acetaminophen, 15 mg/kg/dose q4h, is given for fever, and the child is reevaluated if the fever persists for more than 48 hours or if the child's clinical condition worsens.

Children with a fever greater than 39.0EC (102.2EF) warrant further evaluation or intervention, which may include a lumbar puncture, white blood cell count, and empiric antimicrobial therapy.

Children with a white blood cell count of 15,000/mm³ (15.0 x 10⁹/L) or more require a blood culture and treatment with empiric antimicrobial therapy.

Children with a white blood cell count of less than 15,000/mm³ (15.0 x 10/L) and a benign clinical appearance can be managed expectantly with antipyretics and return of the child if fever persists for more than 48 hours, or if the child's clinical condition worsens.

Febrile children who are managed as outpatients should be assessed every four hours and the physician should be informed of any changes, including skin rash, mottling or cyanosis, poor feeding or vomiting, inconsolability, or a bulging fontanelle. §