It is 4 p.m. at the end of a busy clinic day. A new mother calls to report that her 2-week-old infant is running a fever of 100.6° F. The fever has been present for about 2 hours. The temperature was taken rectally, and the infant is not overdressed. The mother reports that the infant is acting normally, eating well, sleeping well and has no other physical symptoms. You could try to add this patient to an already overbooked schedule this afternoon or see the infant in the morning. Which is the best course of action?
Evaluation of any illness in a young infant is a diagnostic challenge. The medical literature can offer assistance. In infants younger than 3 months, it is difficult to assess behavior changes, and the immune system is immature.1 Young infants can easily be misdiagnosed because they often don't produce reliable clinical presentations when serious illness is present. Fever may be the only symptom.2
Fever is defined as a temperature of 100.4° F or greater (38°C). In infants, body temperature should always be measured rectally, if possible. Axillary and tympanic membrane temperatures are not reliable.1,2 All infants younger than 90 days old should be assessed as soon as possible after the onset of a fever, preferably within the first 24 hours.
Approximately 10% of young, febrile infants have a serious bacterial infection (SBI).3 The most common causes of SBI in infants are occult bacteremia, meningitis and urinary tract infection.3 The most common organisms are group B streptococci, Escherichia coli and Listeria monocytogenes.2 Evidence suggests that early evaluation and intervention can significantly reduce morbidity and mortality in infants with fever.3
Patients whose only sign or symptom of illness is fever are considered to have fever without a source.2 Febrile infants younger than 90 days old often present without other symptoms or physical examination findings.4 Based on clinical picture alone, it is challenging, if not impossible, to distinguish a life-threatening illness from one that is not.
Infant Younger Than 28 Days
You decide to work the infant into your schedule. When the mother arrives at the office, the infant is afebrile and well appearing. The comprehensive physical examination reveals no abnormalities. You are wondering how seriously to take the fever since the patient is now afebrile and looking well. Should this infant be sent home or is further evaluation necessary?
While it may seem reassuring that the infant is afebrile, it is well documented in the literature that an infant with a fever recorded by a reliable adult should be treated as a febrile infant.1 Research suggests that clinical judgment and the well appearance of an infant are not dependable measures in determining the presence of SBIs.5 No provider should let a lack of fever in the office or the healthy appearance of the infant influence clinical decision making.
The infant in this case is less than 28 days old. This baby is assumed to be at high risk because infants younger than 28 days old have higher rates of SBIs than older infants.5 Infants younger than 28 days old should be hospitalized for a thorough sepsis evaluation (Table 1).1-3 All infants with a fever should undergo a complete blood count, an absolute neutrophil count and a urinalysis as part of the evaluation. If an absolute neutrophil count is unavailable, a complete blood count with differential would be sufficient. Sepsis evaluation should include cultures of the blood, urine and cerebral spinal fluid to assess for the most common SBIs. If the infant is having diarrhea, a stool culture should be included.
Some additional diagnostic measures should be considered. It would be wise to add a C-reactive protein (CRP) or a procalcitonin (PCT) to the sepsis evaluation. CRP and PCT are more reliable measures for detecting SBIs in well-appearing febrile infants than white blood cell counts or the absolute neutrophil count.6
Procalcitonin has the highest predictive value for detecting invasive infection.6 This is even more evident within the first 8 hours of fever.6 Check with your lab for PCT availability and turnaround time. Include a stool culture if diarrhea is present.2 Diarrhea in young infants can be hard to distinguish from a normal stooling pattern. When in doubt, order the stool culture. Occult pneumonia is typically found in infants with a fever of 104° F (40.0° C) or higher and a white blood cell count greater than 20,000.1 If occult pneumonia is suspected, a chest x-ray should be ordered.1
Empiric antibiotics should be started once the cultures have been collected. To target the typical organisms responsible for SBI in infants, ampicillin and cefotaxime are used.2 Acyclovir should be considered in cases of a maternal history of herpes simplex virus or cerebrospinal fluid pleocytosis.2 If all cultures are negative, antibiotic therapy can be stopped and the infant should be sent home.3
Infants 28 to 90 Days Old
A sense of déjà vu surfaces when another infant presents to your clinic in a similar fashion. A mom reports that her 8-week-old infant is running a fever of 100.6° F. The fever has been present for a couple of hours. The temperature was taken rectally, and the infant is not overdressed. You note that the only difference between this patient and the last is the age of the infant. You decide to see the patient immediately.
This infant is febrile at the time of the visit, but otherwise appears well. No abnormalities are found during the physical examination. You are prepared to hospitalize this infant for sepsis evaluation and treatment. You pause for a moment to consider that the older age of this infant may change the recommended approach. What is the best approach for an infant older than 28 days but still younger than 90 days old?
While patient safety must remain at the forefront of clinical decision making, consider the invasive nature, potential for overtreatment and general risk involved in a full sepsis workup. Given that only a small number of infants actually have an SBI, the risk/benefit ratio is a consideration.3 In an effort to respect those considerations, the approach to a 28- to 90-day-old infant is more involved than that for an infant younger than 28 days. With this age group, the option of outpatient care with less work-up can be appropriate.
The 28- to 90-day-old infant is susceptible to SBIs caused by group B Streptococcus, Listeria monocytogenes, Salmonella enteritis, Escherichia coli, Neisseria meningitidis and Staphylococcus pneumonia, Haemophilus influenzae B and Staphylococcus aureus.2 To ensure that an SBI is not missed in young infants, patients can be categorized into low-risk and high-risk groups.1,2 Over the past 30 years, multiple criteria have been evaluated in research to identify low-risk and high-risk infants.1,2,5 The Rochester criteria (Table 2) are most commonly used, since they do not require an invasive lumbar puncture to differentiate risk.1,2
Infants are considered low risk if they were previously healthy, have no focal bacterial infection on physical exam, have a normal complete blood count, a normal urinalysis and, if diarrhea is present, a negative stool culture.1-3 This criteria have a negative predictive value of greater than 98% for SBIs.2 Infants are considered high risk if they are younger than 28 days old, were born prematurely, have chronic medical conditions, are ill-appearing, have an abnormal complete blood count, or an abnormal urinalysis. The low-risk criteria must all be present to qualify for that distinction, but any one element of the high-risk criteria qualifies the patient to be high risk.1-3
Another lab value to consider adding to the list of high-risk category criteria is an abnormal PCT or CRP. Research has proven these to be a more reliable measure than the complete blood count.6 However, if the patient displays one or more high-risk criteria, he or she should be hospitalized for a sepsis workup and antibiotic therapy.
Managing the Low-Risk Infant
Some controversy exists in the published research, but the majority of experts agree that management of the low-risk infant can be provided on an outpatient basis.1,2,3-5 The most important element of treating the febrile infant on an outpatient basis is close follow-up.4 Before recommending outpatient management, the provider should be confident that the patient has a dependable caregiver, close access to a hospital, and reliable transportation.2,4 If any of these are lacking, the patient should be managed as if he or she were in the high-risk category.
Two approaches to evaluation and treatment are available for the low-risk, 28- to 90-day-old febrile infant. The first is management with outpatient empiric antibiotic therapy. Before administering empiric antibiotics, cultures of the blood, urine and cerebral spinal fluid must be obtained.1,2 After the antibiotics are given, the reliability of the cultures is compromised, which results in gaps in data - particularly for an infant whose condition is declining instead of improving.7
Once the cultures have been obtained, ceftriaxone can be given intramuscularly and the patient should return to the clinic within 18 to 24 hours.1,2 A second shot of ceftriaxone can be administered at that time.1 If the cultures of blood or cerebral spinal fluid are positive, the infant should be hospitalized for parenteral antibiotic therapy.1,2
The second approach is even less invasive. Because patients who fall into the low-risk category face less than a 2% chance of having an SBI, another accepted approach exists. The provider may limit further workup to a urine culture and perform close observation.2 To determine whether the infant is at low risk, a urinalysis and complete blood count are required; a PCT or CRP would be an informative addition, if possible.2,6 The urine culture is a key component because 20% of young infants with a urinary tract infection present with a normal urinalysis.1 Urinary tract infection is the most common occult infection in the febrile young infant and should remain at the top of the provider's differential diagnosis for these patients.1,2,5 Close observation should include daily follow-up clinic visits until the patient is afebrile. If at any point the patient's condition declines or the urine culture is positive, the infant is considered at high risk and should be hospitalized for culturing of blood and cerebral spinal fluid and parenteral antibiotic therapy.1,2 Close observation in imperative to the safety of this approach.3 If the clinic is not open for daily follow-up (i.e., holiday or weekend) or the patient does not have a reliable parent, hospitalization with a full sepsis workup is the safest option.3
An additional consideration when treating all infants younger than 90 days old is the use of viral testing. As with most patients, the etiology of the majority of febrile illnesses in young infants is viral. Viral testing can be used in combination with the high-risk category criteria as an additional modality to limit the need for antibiotics and length of hospitalization.8 The available viral tests that are helpful with young infants are respiratory syncytial virus, influenza A and B, adenovirus, enterovirus, parainfluenza virus, herpes simplex virus and rotavirus.
Viral testing should be guided by the seasonal trends of illness.2,8 If a high-risk infant has a positive viral diagnostic test combined with a negative blood culture, the provider can be confident enough to consider discontinuing antibiotics and discharging the infant from the hospital.3,8 It is important that clinical judgment be combined with the additional information of positive virus testing before discontinuing antibiotics or discharging the infant.8
Rely on Guidelines
Research has not identified a method that can determine with complete certainty which infants with fever need evaluation and treatment and which do not.5 Risk to these infants can be managed by using practice guidelines to tailor the evaluation and treatment of the young febrile infant (Table 3).
It is well documented in the literature that infants younger than 28 days old are at high risk and require hospitalization for a thorough sepsis evaluation and treatment. Infants 28 to 90 days old should be evaluated and categorized as low risk or high risk to guide further evaluation and treatment. High-risk 28- to 90-day-old infants also should be hospitalized for sepsis evaluation and treatment. Low-risk 28- to 90-day-old infants allow for outpatient management as long as the ability for follow-up visits every 24 hours and access to critical care outside office hours are available.
Using these guidelines, NPs and PAs can provide evidence-based care to febrile infants 0 to 90 days old while minimizing risk, invasive testing and overtreatment.
1. Baraff LJ. Management of infants and young children with fever without source. Pediatr Ann. 2008;37(10):673-679.
2. Nield LS, et al. Fever Without a Focus. In: Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier/Saunders; 2011: 896-902.
3. Byington CL, et al. Costs and infant outcomes after implementation of a care process model for febrile infants. Pediatrics. 2012;130(1):e16-e24.
4. Pantell RH, et al. Management and outcomes of care of fever in early infancy. JAMA. 2004;291(10):1203-1212.
5. Roberts KB. Young, febrile infants: a 30-year odyssey ends where it started. JAMA. 2004;291(10):1261-1262.
6. Luaces-Cubells C, et al. Procalcitonin to detect invasive bacterial infection in non-toxic-appearing infants with fever without apparent source in the emergency department. Pediatr Infect Dis J. 2012;31(6):645-657.
7. Paquette K, et al. Is a lumbar puncture necessary when evaluating febrile infants (30 to 90 days of age) with an abnormal urinalysis? Pediatr Emerg Care. 2011;27(11):1057-10561.
8. Byington CL, et al. Serious bacterial infections in febrile infants 1 to 90 days old with and without viral infections. Pediatrics. 2004;113(6):1662-1666.
Erin Hoffman is the immediate past president of the Society of Physician Assistants in Pediatrics. She is the academic director for the physician assistant program at the University of Nebraska Medical Center, where she is also an assistant professor. Hoffman has completed a disclosure statement and reports no relationships related to this article.