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Managing the febrile infant: What is the standard of care?

This first article of two parts reviews the current guidelines and rationale for the evaluation and treatment of the febrile infant younger than 90 days.

Joseph V. Dobson, MD; Paul F. Jacques, DHSc, PA-C; Megan Bales; Ramsay Lee

Joseph Dobson is associate professor and medical director, the Children’s Hospital Emergency Department, Medical University of South Carolina (MUSC), Charleston. Paul Jacques is on the faculty of the MUSC physician assistant program. Megan Bales and Ramsay Lee were students in the MUSC PA program at the time this article was written. The authors have indicated no relationships to disclose relating to the content of this article.

Fever is the most common symptom among children and infants seen for outpatient evaluation. In the pediatric emergency setting, fever accounts for up to 20% of all encounters.¹ Determining whether the cause of fever in an infant younger than 90 days is a benign and self-limited febrile illness or a serious bacterial infection (SBI) represents a unique challenge. An extensive clinical and diagnostic evaluation is required. Rapid identification of SBI is difficult, lengthy, and—because most patients, depending on their age, are hospitalized pending laboratory, culture, and sensitivity results—expensive. New tests, such as viral immunoassays, enhanced urinalysis, and several biochemical markers, may aid PAs in screening for SBI in febrile infants. These tests have the potential to identify the etiology of fever in this patient population, reduce unnecessary antimicrobial use, and reduce hospitalization costs. However, these tests have not yet been adopted as the standard of care. Furthermore, despite extensive research, a lack of universal consensus among practitioners regarding the appropriate management of the febrile infant still exists.

SBIs in the febrile infant include meningitis, pneumonia, bacteremia/sepsis, urinary tract infection (UTI), cellulitis, osteomyelitis, and bacterial gastroenteritis. The goal is to identify febrile infants at risk for these life-threatening infections early enough to intervene effectively and prevent morbidity and mortality.

During the initial examination, the three primary clinical considerations that help in the evaluation and treatment are (1) the general appearance of the infant, (2) the infant’s age, and (3) the severity of the fever. The algorithm “Initial examination of the febrile infant” illustrates the approach discussed in this article.

INITIAL EXAMINATION

Traditional recommendations state that all febrile infants younger than 90 days should have a screening laboratory evaluation, known as a septic workup (SWU), for SBI. Febrile infants frequently have no localizing signs or symptoms; often they display only nonspecific irritability, poor feeding, or changes in sleep pattern. This immature developmental response to fever coupled with an underdeveloped immune system puts them at risk for unrecognized life-threatening infections.

Physical assessment alone is a poor and inaccurate predictor of SBI. An SWU identifies an infectious process in a significant percentage of febrile infants.^2,3 While categorizing the infant as well-appearing or ill-appearing does play a critical role in assessment, relying on general appearance may cause even an experienced clinician to miss a life-threatening infection.⁴

For evaluation purposes, the febrile infant is divided into two age categories: a neonate is an infant from birth to age 28 days, and a young infant is aged 29 to 90 days. While these age cutoffs may seem arbitrary, research supports this distinction for determining a final disposition: admission versus outpatient treatment.

The temperature that constitutes a fever in the young infant is a rectal temperature of 38°C (100.4°F) or higher.^4-6 Most studies in the literature have used this temperature cutoff when analyzing the risk of SBI, and so it represents the current best evidence-based value. A parental report of fever should be accepted as accurate for the purposes of evaluation.⁷ Clinicians should also be aware that SBIs can occur in the absence of a fever or in a hypothermic infant.⁴ Therefore, an ill-appearing, nonfebrile infant should also be considered at risk for SBI.

UTIs account for up to one-third of SBIs in young infants.⁵ Neonates are predominantly at risk for perinatally acquired infections, including infections with Listeria monocytogenes, gram-negative enteric organisms (predominantly Escherichia coli), group B streptococci, and herpes simplex virus (HSV). Young infants are also at risk for infection with community-acquired organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Salmonella species. The SWU consists of a battery of laboratory tests to identify these SBIs (see Table 1).

The SWU might also include testing for neonatal HSV infection if the mother is known to have HSV infection or has herpetic lesions at the time of delivery or if the neonate has vesicular lesions on physical examination or a focal seizure. Additional studies that may be indicated include blood viral culture, CSF viral culture and polymerase chain reaction, conjunctival viral culture, skin lesion viral culture, nasopharyngeal viral culture, rectal viral culture, and liver function tests.⁸

HOSPITALIZATION VERSUS OUTPATIENT CARE

In an attempt to limit hospitalization of and empiric antibiotic therapy in febrile infants, some researchers identified a subgroup of febrile infants who are at low risk for an SBI.^9-11 While criteria differ slightly between the authors, Table 2 lists a representative set of SWU results that help identify low-risk infants. To be categorized as low risk, a febrile infant must also be well-appearing, previously healthy, and have no focus of bacterial infection on physical examination.

How well do these screening criteria perform in the evaluation of the febrile infant? The answer depends on the infant’s age. Jaskiewicz and colleagues found that only 2 of 227 (1%) febrile neonates who met low-risk criteria had an SBI, but other authors have had less reassuring results with subjects in this age group.¹²Ferrera and team found that 3 out of 48 (6%) neonates who met low-risk criteria had an SBI (two had UTIs and one had bacterial meningitis/UTI).¹³ Baker and Bell studied 254 febrile neonates and found that 5 of 109 (4.6%) infants identified as low risk had an SBI (two neonates with UTIs, two with bacteremia, and one with bacterial gastroenteritis).² In all the studies, the febrile neonates who failed to meet low-risk criteria had a substantially higher risk for an SBI (18.6% in the Baker and Bell study²); however, the low-risk criteria failed to identify all the neonates at risk.

In a consensus statement written by Baraff and colleagues, the majority of expert panel members felt that it was prudent to hospitalize all febrile neonates for parenteral antimicrobial therapy pending culture results.⁴ This still remains the standard of care in most academic medical institutions. On the other hand, research clearly supports outpatient therapy for low-risk febrile young infants. In two studies, Baker and colleagues assessed a total of 1,169 young infants with the same criteria they used to assess neonates in the study discussed earlier; none of the infants categorized as low-risk had an SBI.^2,14 Based on the literature, the majority of the expert panel members chaired by Baraff agreed that when parents are deemed reliable and close follow-up can be ensured, outpatient management of low-risk febrile infants was an alternative to hospitalization. Such infants should meet all the low-risk clinical and laboratory criteria.⁴

TREATMENT

For febrile infants admitted for parenteral antimicrobial therapy, recommendations are for coverage of the most likely pathogens by age group. Recommended empiric antibiotic therapy for infants younger than 29 days is ampicillin (to cover for L monocytogenes) and either a third-generation cephalosporin (typically cefotaxime) or gentamicin. If HSV is suspected, acyclovir should be added. In infants aged 29 to 90 days, empiric therapy is ampicillin or vancomycin (if resistant S pneumoniae is prevalent in the community) and a third-generation cephalosporin. Young infants managed as outpatients can be observed off antibiotics^9,14 or be given a single IM injection of a third-generation cephalosporin (usually ceftriaxone).^4,10 All infants treated as outpatients should be re-examined 18 to 24 hours later, at which time a second injection of ceftriaxone can be given.

CONCLUSION

The guidelines presented in this article describe a traditional and conservative approach to assessing and treating febrile infants, which is the standard of care accepted by many academic institutions and professional organizations.^4,15 In actual practice, however, this approach suffers from a lack of universal agreement. In a survey of pediatric emergency medicine fellowship directors and emergency medicine residency directors, fewer than half strictly adhered to these guidelines.¹⁶ A survey of primary care pediatricians in Utah showed similar compliance rates with published guidelines.¹⁷

In an editorial written by Green and Rothcock, the terms risk minimizer and test minimizer were coined to describe the different approaches to treatment of the febrile infant.¹⁸ The risk minimizer approach is to use laboratory test values to guide treatment; infants are categorized as low risk or high risk in an attempt to screen for and prevent serious infections. However, some clinicians feel that this approach leads to overly invasive workups and an inappropriate use of antibiotic treatments and that it fosters the emergence of multiple antibiotic-resistant strains of bacteria. The test minimizer approach advocates performing a careful physical examination, taking proper follow-up actions, and avoiding the use of antibiotics unless a bacterial pathogen is present.¹⁸ In part 2 of this review, to appear in the March issue of JAAPA, the authors focus on recent research and literature that refine the standard conservative approach and review alternative treatment regimens.

DRUGS MENTIONED

Acyclovir (Zovirax)
Ampicillin (Principen)
Ceftriaxone (Rocephin)
Cefotaxime (Claforen)
Gentamicin (Garamycin)
Vancomycin (Vancocin)

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