AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

This article addresses the often-challenging task of diagnosing and treating febrile illnesses in infants younger than 60 days and discusses appropriate testing, treatment, and disposition of these patients. The parent or caregiver's history, the infant's medical history, the infant's age, and the physical and laboratory findings all significantly influence the manner in which these young patients are managed.

In making decisions about the optimal manner of evaluating these patients, consider a number of factors such as the potential morbidity associated with testing and treatment against the result of failing to recognize and treat a potentially fatal infection. Decisions are complicated by pressures to maximize the value of health care dollars spent to screen patients for serious illness. Despite numerous published studies with specific recommendations for testing, treatment, and follow-up care, the best way to evaluate these patients remains controversial; ongoing research continues to modify treatment.

Within the age group addressed in this article (ie, birth to 60 d), diagnosis and treatment of febrile neonates (ie, age <1 mo) are the least controversial. A thorough physical examination is just the beginning of a complete evaluation of a febrile infant. Febrile neonates warrant thorough evaluation, complete diagnostic testing, and aggressive inpatient treatment with parenteral antibiotics. The source of fever in a very young infant may be a serious bacterial infection (SBI). Patients without a clear source of infection have a small but significant risk of SBI. Sepsis and meningitis—the most feared causes of fever in the very young infant—are associated with potential morbidity and mortality, even with prompt recognition and appropriate management.

Pathophysiology

Neonates have a greater risk of systemic infection than older infants, children, and adults. Hematogenous spread of infection is most common in this age group or in patients who are immunocompromised for some other reason. Likewise, patients with a focal bacterial infection have a greater risk of developing sepsis.

The following are the most common etiologies of SBI in infants younger than 60 days:

• Group B streptococci
• Neisseria meningitidis
• Streptococcus pneumoniae
• Haemophilus influenzae
• Listeria monocytogenes
• Escherichia coli

The presence and severity of fever directly relate to the likelihood of bacteremia; the higher the temperature, the greater the likelihood of bacteremia. However, absence of fever cannot be used to exclude SBI, particularly in newborns who were premature.

Frequency

United States

Fever accounts for as many as 20% of pediatric visits to doctors.

Mortality/Morbidity

Patients with no easily identified source of infection have a small but significant risk of a SBI. If unrecognized or if appropriate treatment is delayed, meningitis is associated with potential morbidity (eg, permanent neurologic deficits) and can be fatal.

Age

Treatment of a febrile infant has changed significantly over the past 10 years. Previously, all infants younger than 90 days who had a fever without focus were completely evaluated for SBI, including having a lumbar puncture (LP) performed; patients were then treated with parenteral antibiotics and were hospitalized for 2-3 days while awaiting culture results.

Today, febrile patients younger than 1 month should still be completely evaluated and admitted to a hospital for conservative treatment, including antibiotic treatment, pending the results of cultures; however, infants aged 1-2 months may not require admission if they (1) appear otherwise healthy on examination, (2) have benign laboratory findings, and (3) lack certain significant risk factors (see Febrile infants aged 1-2 months). This somewhat less conservative approach varies from region to region and depends somewhat upon the populations served and local practices.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Solicit the following patient information from the parent or caregiver:
• • Level of activity or lethargy
  • Feeding patterns and number of wet diapers
  • Vomiting or diarrhea
  • Contact with ill individuals
  • Temperature at home
  • Medical history
  • Immunization history
• Remember that fever alone sometimes makes a child appear rather toxic.
• Ask about the infant's behavior when not febrile.
• • Was behavior normal before becoming febrile?
  • Was the infant lethargic?
  • What were the infant's eating and drinking patterns?

Physical

Perform a complete physical examination, paying particular attention to assessing the infant's hydration status and to identifying a possible source of infection.

• For every febrile infant, record and address vital signs, including at least temperature (Rectal temperature is standard.), pulse, blood pressure, and respiratory rate.
• Pulse oximetry is a more sensitive predictor of pulmonary infection than respiratory rate in patients of all ages, especially infants and young children. Pulse oximetry is mandatory for any child with respiratory symptoms, abnormal lung examination findings, or abnormal respiratory rate. (Remember that respiratory rate increases when an infant is febrile.)
• Record an accurate weight on every chart. All pharmacologic and procedural treatments are based on weight in kilograms. In urgent situations, an estimate (eg, by Broselow tape) can be used.
• Pay particular attention to any of the following physical findings:
• • A toxic appearance denotes a clinical picture involving signs of lethargy, poor perfusion, hypoventilation or hyperventilation, or cyanosis (ie, shock).
  • Note any focus of infection that may be the cause of the fever.
    • Minor foci include otitis media, pharyngitis, sinusitis, and skin or soft tissue infection.
    • Identifiable viral infections may include bronchiolitis, croup, gingivostomatitis, viral gastroenteritis, varicella-zoster virus, or hand-foot-and-mouth disease.
• Petechial or purpuric rashes often are associated with invasive bacteremia. Purpura are associated with meningococcemia more often than petechiae alone.

Causes

• The following organisms are common bacterial causes of fever:
• • S pneumoniae
  • N meningitidis
  • H influenzae
  • L monocytogenes
• Of these, S pneumoniae is the leading cause of nearly all common bacterial upper respiratory tract infections (eg, pneumonia, sinusitis, otitis media) and the most common cause of meningitis and occult bacteremia in the United States.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• A full evaluation for serious bacterial infection includes the following:
• • CBC count with manual differential
  • Blood culture
  • Urinalysis (UA) and urine culture (using a transurethral catheter or suprapubic tap)
  • LP for cerebrospinal fluid (CSF) analysis and culture
  • Stool culture and fecal white blood cell (WBC) count for diarrhea

Imaging Studies

• In the appropriate context, thorough evaluation includes a chest radiograph.
• Although most pediatric pneumonias (like other respiratory infections) are considered secondary manifestations of viral infections, 51% of pediatric patients with pneumonia have serologic evidence of bacterial infection.

Procedures

• Lumbar puncture
• Bladder catheterization

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Provide fluid resuscitation to any febrile infant who appears ill and administer IV (or IM) antibiotics after obtaining urine and blood samples. Antibiotics may be administered before the LP if any delay in performing the LP is anticipated. Continue antibiotic administration after admitting the infant to the hospital. Once culture results are obtained, adjust diagnostic procedures and treatment as follows:

• Neonates whose temperatures exceed 38°C (100.4°F)
• • Diagnostic procedures are as follows:
    • Obtain CBC count with differentials.
    • Obtain blood culture.
    • Perform catheter UA.
    • Obtain urine culture.
    • Obtain CSF and culture.
    • Consider obtaining chest radiograph.
    • Consider obtaining stool culture.
  • Treatment is as follows:
    • Administer ampicillin (ie, 50 mg/kg/dose; 100 mg/kg/dose if CSF abnormal) and a third-generation cephalosporin (ie, cefotaxime at 50 mg/kg/dose).
    • Alternative: Administer ampicillin and aminoglycoside (ie, gentamicin at 2.5 mg/kg/dose).
• Febrile infants aged 1-2 months
• • Provide a full evaluation and conservative treatment (including possible hospital admission for close monitoring and parenteral antibiotic administration) for any febrile infant who appears ill.
  • Febrile infants who appear healthy and have no obvious source of infection require further evaluation before disposition is decided.
  • High-risk patients in this age group are patients with a significant medical history (eg, premature infants, infants with prolonged neonatal intensive care unit stays, those who had complicated births, those with congenital heart disease).
  • Low-risk patients in this age group are previously healthy infants who do not appear toxic and who exhibit no focal bacterial infection on physical examination (excluding otitis media). Consider the child's home environment (ie, social situation, presence of a reliable caregiver, availability of transportation and telephone) before placing an infant in the low-risk group. Laboratory test results for a low-risk designation must include the following:
    • Normal UA results (ie, negative nitrite findings and/or <10 WBC/high-power field [hpf])
    • WBC count of 5000-15,000
    • If diarrhea is present, no heme and few to no WBCs in stool
    • CSF with fewer than 8 WBC/mm³ in bloodless specimen
    • Negative CSF Gram stain findings
    • Bands not exceeding 20% of neutrophils
    • No infiltrate on chest radiograph, if performed

Consultations

The need to consult with specialists depends upon the specialty of the physician who conducted the initial patient evaluation and on the ultimate source of fever. General pediatricians can usually easily treat febrile infants on both an inpatient and outpatient follow-up basis.

Diet

Patient tolerance determines diet. Monitor intake and output as an indication of the patient's status because these are among the first areas in which a disturbance indicating illness may be detected.

Activity

Patient tolerance also determines activity level. Monitor patient activity for changes (eg, lethargy, irritability).

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Parenteral antibiotics are the drugs of choice to treat febrile or ill-appearing neonates. Selection of medications depends upon the patient's age. Coverage for Listeria with ampicillin is essential for infants younger than 6 weeks. Typically, cefotaxime or gentamicin is added (ceftriaxone may be avoided because of bilirubin displacement from serum protein-binding sites, but this is not universally recommended nor practiced). Treatment of fever in this age group is somewhat controversial.

Drug Category: Antibiotics

These agents are used to treat occult bacterial infection. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the clinical setting. Whenever feasible, select antibiotics based upon blood culture sensitivity.

Drug Category: Antipyretic agents

Treatment of fever in pediatric patients is somewhat controversial. Antipyretic agents inhibit central synthesis and release of prostaglandins that mediate the effect of endogenous pyrogens in the hypothalamus and, thus, promote the return of the set-point temperature to normal.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients who appear toxic or who fail to improve with outpatient treatment require hospital admission for treatment and further evaluation.

Further Outpatient Care

• All infants (and children) with a febrile illness without an obvious source of bacterial infection require close follow-up care. Instruct parents or caregivers to return if the infant's condition deteriorates.

In/Out Patient Meds

• Tailor medications to the source of infection, if known. Provide empiric treatment based upon the most likely organisms for infection.

Complications

• If occult infection is not suspected and diagnosed in a timely manner, a small but very real possibility exists of the infection progressing to sepsis, meningitis, or another life-threatening illness.

Prognosis

• Prognosis is generally excellent. Most febrile infants (94-96%) lack serious bacterial infection and should fully recover without sequelae.

Patient Education

• For excellent patient education resources, visit eMedicine's Children's Health Center. Also, see eMedicine's patient education article Fever in Children.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The biggest pitfall is not considering the possibility that a febrile infant has a potentially life-threatening illness. If not treated promptly, a small percent of febrile infants who have no obvious source of serious bacterial infection may suffer serious sequelae or death. Physicians who approach their patients as if this is a possibility and who provide appropriate evaluation and treatment are doing their best to avoid a poor outcome.
• Stress to parents and caregivers the importance of follow-up care after patients are discharged. Also stress that an infant whose symptoms worsen should be evaluated prior to the scheduled follow-up appointment or taken to the nearest emergency department for treatment.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Apr 24, 2006