Management of Febrile Infants and Children

Brian P. Gilligan, M.D. and Anthony P. Pohlgeers, M.D.

 

Introduction

The evaluation and management of young children with fever is a common problem. It has been estimated that nearly 35% of unscheduled ambulatory visits are for fever in children.1 However up to 22% of these children will lack a definite source for their fever.2 While the majority of these children will have a viral syndrome, differentiating them from children with occult bacteremia, and therefore children at increased risk for serious bacterial infection, is not always clinically possible. The evaluation of these children who have a fever without a source has been a topic of much investigation over the last 25 years. This article will review the literature and discuss the current management strategies.

Definitions

To begin our discussion we need to clarify several definitions. (Table 1) In infants less than 90 days, fever is defined as a temperature greater than 38°C rectally. Axillary and tympanic temperatures are not reliable in this age range. Occasionally low grade fevers are thought to be related to over-bundling. If this is suspected, unbundle the infant for 15 - 30 minutes and recheck the temperature. The otherwise well appearing infant may be considered afebrile if the repeat temperature is normal.3

In children from 3 to 36 months considered at risk for occult bacteremia, fever is defined as 39°C, although some authors would consider 39.5°C the cut off from 2-3 years.4 Children with occult bacteremia appear well except for fever, but they have pathogenic bacteria in their blood stream and are therefore at increased risk for serious bacterial infections. Studies have shown that febrile children, both with and without bacteremia, will respond to antipyretics equally.5 Therefore a decrease in fever following administration of acetaminophen does not decrease the risk of bacteremia.

Toxic appearing infants and children present lethargic, with poor perfusion and abnormal ventilation. They may be breathing too fast, too slow, or be outright apneic with cyanosis. Experienced clinicians generally can differentiate toxic children from those with occult bacteremia.

Background

The phenomenon of occult bacteremia began to appear in the medical literature in the early 1970's. Initial reports by Burke, et al 6 and others 1,7,8 led to the recognition that young febrile children without an obvious source for their fever were at risk for bacteremia and therefore more serious infections. Recommendations were made to obtain blood cultures on all of these children.6 Studies since have quantified the risk of occult bacteremia in children to be 2.8-11%.9 In children with fever greater than 39°C and a WBC greater than 20,000, the risk of bacteremia increases to about 13%.10 Serious bacterial infections occur in approximately 10% of patients with occult bacteremia.11

Throughout the 1980's, several studies focused on developing criteria to select infants at low risk for serious bacterial infections. These low risk criteria, known as the Rochester criteria, reduce the risk of serious bacterial infection from 7-9% in well appearing febrile infants (28-90 days) to less than 1% if all criteria are met.12,13 (Table 2) The Yale Observation Scale, another clinical aid to detect occult bacteremia, has failed to be as clinically useful in febrile children from 3 - 36 months.14,15

In 1993, practice guidelines for the management of infants and children less than 36 months with fever without a source were published.3 These guidelines have remained the gold standard, a conservative approach to managing fever without a source, but they are not universally accepted or practiced.16,17 In general, academic centers and emergency departments have utilized the guidelines, assuming a "risk-minimizing" approach, while community physicians tend to adopt a "test-minimizing" approach with close follow-up care.18 Discussions continue on the optimal management of febrile infants without a source. 19,20,21,22

Since the practice guidelines were published, on-going research has continued. Invasive Haemophilus influenzae type b (Hib) infections have decreased by 95% with the success of the Hib conjugate vaccine.23,24 Where Hib was previously responsible for 13% of occult bacteremia and 42% of serious bacterial infections, Streptococcus pneumoniae is now responsible for more than 90% of occult bacteremia.25,26 S. pneumoniae bacteremia has a low rate of conversion to serious bacterial infections (6%), but is still responsible for the majority of occult bacteremia complications. Several studies have shown that parenteral antibiotics (Ceftriaxone) decrease the risk of meningitis in children with occult bacteremia.11,23,27 Oral antibiotics are not effective in decreasing the risk of meningitis when administered at the time of initial blood cultures. 9

Approach to the Febrile Child

In the evaluation of the febrile child without a source, most authors will differentiate recommendations based on age. This has developed since the ability to determine illness by physical exam, and the risk of serious illness, changes with age. In general, a child's immune system is adequately developed by 36 months of age, at which time the risk of occult bacteremia is reduced, and one can more fully rely on clinical exam. All febrile children who are toxic appearing require hospitalization and evaluation for sepsis. These children should be empirically started on antibiotics as determined by age and presumptive diagnosis.Additional areas of research in febrile children are focussing on occult urinary tract infections, occult pneumonia, and occult pneumococcal bacteremia. These topics and the approach to management of the febrile child less than 36 months will be discussed below.

Infants Less than 28 Days

Infants less than 28 days who present with fever greater than 38°C rectally require a full septic work-up including blood, urine, and cerebral spinal fluid (CSF) cultures. It must be remembered that lower than normal temperature can also be associated with serious illness and requires evaluation. Ancillary data that is usually included consists of microscopic analysis of the urine and spinal fluid, serum electrolytes, glucose, spinal fluid protein and glucose and, complete blood count (CBC) including platelet count. These patients are uniformly admitted to the hospital for 48 to 72 hours and receive intravenous antibiotics (Ampicillin and Gentamicin / Cefotaxime) until all cultures are negative. This approach is necessary given the patients immature immune system, the inability to rely on physical findings, and the severity of the organisms that cause illness in this age group. The organisms typically implicated include Group B Streptococcus, E coli, Listeria, Klebsiella, and other enteric organisms usually contracted during the delivery process.

Some investigators have suggested that the low risk criteria may be applied to infants less than 28 days and therefore reserve mandatory hospital admission for infants less than 7 days.2,20,28 In one study, Jaskiewicz, et al assigned low risk criteria to 227 infants less than 28 days and found only one with a serious bacterial infection.28 However, Ferrera, et al reported 6.3% of 48 low risk infants less than 28 days had serious bacterial infections.29 In two additional studies, 5 of 109 infants and 6 out of 225 infants meeting the low risk criteria were found to have serious bacterial infections.30,31 Thus at present, screening tools to identify febrile infants at low risk for serious bacterial infections are not fully effective.32

Infants 28 to 90 Days

Infants from 28 to 90 days who present with a fever greater than 38°C rectally without a source require evaluation for serious bacterial infections. Patients not meeting low risk criteria and appearing toxic should receive a full sepsis work-up with blood, urine and CSF cultures, parenteral antibiotics, and hospital admission. Children who meet the low risk criteria may be evaluated and treated as outpatients. This recommendation is based on a meta-analysis performed by Klassen and Rowe which demonstrated a reduction in the risk of serious bacterial infection from 7% in this age group to 0.2% when patients meet the low risk criteria.13 (Table 2)

The evaluation of the low risk patient from 28-90 days may be approached in two acceptable ways. The typical approach is to obtain a CBC, blood culture, urinalysis and urine culture, and other tests as clinically indicated (chemistry, chest x-ray, lumbar puncture for CSF, and stool WBC's / culture if diarrhea is present). The patient may be discharged home with 18 - 24 hour follow-ups if the entire initial evaluation is negative. The alternative approach is to only obtain a urine culture and insure close follow-up. In either case, the initiation of empiric antibiotic therapy with ceftriaxone without prior blood culture and lumbar puncture can result in diagnostic confusion if the child subsequently deteriorates. Completion of the sepsis work-up prior to empiric antibiotic therapy may prevent the difficulty of differentiating viral meningitis from partially treated bacterial meningitis should the child deteriorate.3

Outpatient management of these young patients is acceptable only when parents are experienced, reliable, have adequate transportation, and will return for re-assessment. Afebrile and clinically well patients at follow-up may be discharged home without further antibiotics assuming all cultures are negative. The patient with otitis media may be started on oral antibiotics at this time. If at any time the blood or CSF culture grows a pathogenic bacteria, the patient should return and requires a septic work-up with parenteral antibiotics and hospital admission. An afebrile infant with a positive urine culture may be started on appropriate oral antibiotics and discharged home assuming close outpatient follow-up with radiographic evaluation can be arranged.3

Children 3 to 36 Months

Evaluation of the child from 3 to 36 months for fever without a source takes place when the fever is greater than 39°C. Some authors narrow this into two groups, 3-24 months and 24-36 months. In children from 3-24 months, the overall incidence of occult bacteremia is thought to be 2.6% with a fever of 39°C. In children from 24-36 months the risk of bacteremia decreases to 1% at 39°C. However the risk of bacteremia returns to 2.6% in 24-36months by using 39.°5.33,34 Screening tests are often used to determine who to obtain blood cultures on and treat empirically with antibiotics (IM Ceftriaxone) if no source can be found. In general, a WBC is obtained on all patients with fever without a source, and if it is greater than 15,000/mm3, or has an absolute neutrophil count (ANC) of 10,000, a blood culture is sent and Cetriaxone given. Likewise, urinalysis and urine cultures are sent on all boys less than 6 months and girls less than 2 years. Twenty-four hour follow-up is required on all patients receiving Ceftriaxone for the above indications.

In males < 6 months with fever without a source, urinary tract infections (UTI) occur in approximately 7%, and in females < 1 year with fever without a source UTI occurs in approximately 8%. The rate of UTI in uncircumcised males is 5-20 times that of circumcised males.37 Therefore, urinalysis and urine culture should be performed in all males < 6 months and all females < 2 year when there is no other source for infection. Girls older than 2 years can generally give a history of UTI symptoms, obviating the need for routine evaluation. Up to 20% of young children with a culture proven UTI will have a normal urinalysis, therefore urinalysis alone is not adequate. A urine culture must also be sent. Also, the contamination rates of "bag urine" specimens are unacceptably high, therefore they should not be used.

The white blood cell count can be used to define the risk of bacteremia. The relative risk of bacteremia is five fold higher if the white blood count is 15,000/mm3 or more (13% vs. 2.6%). 3 Therefore when the white blood cell count is greater than 15,000/mm3 a blood culture should be obtained. The recommendation of using white blood count greater than 15,000/mm3 as a determinate to treat empirically with antibiotics is based on two additional points: 1. A WBC is easy to obtain and, 2. The number of cases of bacteremia with WBC counts less than 15,000/mm3 is decreasing with the disappearance of serious H. influenza type-b infections.

Elevated absolute neutrophil count (ANC), age less than 2 years, and high fevers were predictive of occult pneumococcal bacteremia in one study.4 An ANC greater than 10,000 cells/mm3 correlated with an 8.1% risk of occult pneumococcal bacteremia versus a 0.8% risk if the ANC was less than 10,000 cells/mm3 . The risk of pneumococcal bacteremia also correlated statistically with height of fever, and age less than 2 years old.4

Children having fevers associated with an obvious viral infection (varicella, croup, herpes gingivostomatitis, bronchiolitis) do not need to have blood work done if they are otherwise stable. Their risk of bacteremia is less than 1%.35 However, nonspecific viral symptoms like diarrhea, and congestion are commonly reported in children with occult bacteremia.7,36 If children present with high fever and mild upper respiratory infection symptoms, the clinician should consider evaluating them for bacteremia.

A chest radiograph should be considered if physical exam findings include tachypnea, cough, rales, and rhonchi; if the temperature is > 40°C and white blood count is > 15000/mm3; or if on follow-up the patient is still febrile and without a source. A recent study by Bachur, et al38 looked at empiric chest radiographs in the setting of highly febrile children with a leukocytosis and no clinical evidence of pneumonia or other major source. They found radiographic evidence of pneumonia in 38 of 146 patients (26%) and concluded that empiric chest radiographs should be obtained in children less than 5 years old with fever greater than 39°C, leukocytosis greater than 20,000/mm3 and without a major source of infection.38 Children with focal findings on chest radiographs are known to be at risk for bacteremia, as are those with otitis media.39,40 Their risk of bacteremia is the same as in children with fever without a source.

A lumbar puncture is indicated in any child in whom the clinician considers the diagnosis of meningitis. Assuming that a lumbar puncture was performed because a child had meningeal signs, but has a normal spinal fluid analysis, one must assume the patient is at increased risk for bacteremia and therefore a blood culture should be obtained and ceftriaxone considered.

Conclusion

The optimal management of infants and children with fever without a source still remains in question. Clinical judgement should not be replaced by automatic laboratory evaluation and widespread antibiotic use. However, physicians need to be aware of the risk for serious bacterial infections in our young patients, prudently evaluate them and treat with empiric antibiotics when needed. With the development and approaching distribution of the pneumococcal vaccine, invasive pneumococcal infection will hopefully go the way of H. influenza type b and disappear from fully immunized children.35,41 Until then, a cautious approach, which minimizes risk for development of serious bacterial infections is recommended.

REFERENCES

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Jacksonville Medicine / October, 2000

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