Management and evaluation for fever in infant

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OCTOBER 1,2001 / VOLUME64, NUMBER 7 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1219

Special Situations

TOXIC APPEARANCE

Toxic-appearing infants and children arepale or cyanotic,lethargic or inconsolably irri-table. In addition, they may have tachypneaand tachycardiawith poor capillary refil l.

A variety of conditions other than infection

may result in a toxic appearance.In all instances,immediate resuscitation is warranted,appropri-ate diagnostic studies and cultures should beobtained,and empiric antibiotic therapy shouldbe administered unless a condition other thansepsis is immediately identified.2

VIRAL OR BACTERIAL INFECTION

Viral infection is the cause of fever in mostinfants and young children. With stomatit is,varicella or another readily identified exan-them, the cause of the fever may be readilyapparent on physical examination, and further

diagnostic evaluation may not be required.3 If a focal bacterial infection such as pneumonia,meningitis or osteomyeli tis is suspected,effortsshould be made to identify the specific infec-tion and initiate appropriate treatment.

CHRONIC ILLNESSES

Infants and children with fever who haveknown chronic illnesses that affect immune

Acute febrile illness in an infantor a young child is a commonclinical scenario that can be adiagnostic challenge.The eval-uation is guided by the history

and physical examination, along with judi-ciously selected screening tests. The over-whelming majori ty of nontoxic but febrile

infants and young children have a viral infec-tion. The physician’s primary task is to iden-tify the infant or child who is at risk for seri-ous bacterial infection.

A practice guideline on the evaluation andmanagement of infants and young childrenwith fever without source was published in1993.1 Although elements of this guidelineremain controversial, the expert panel’s defin-itions of terms such as “fever without source,”“serious bacterial infection” and “ toxicappearance” are widely accepted (Table 1) .1 Inthis art icle,“infant” describes a child younger

than one year old. “Young infant” refers to achild younger than three months old, and“older infant” describes a child older thanthree months but younger than 12 months.“Young child” refers to a child one to threeyears of age.

A practice guideline for the management of febrile infants and children younger than three

years of age sparked controversy when it was published in 1993. Surveys indicate that many

office-based physicians do not agree with recommendations for venipuncture and bladder

catheterization in nontoxic febrile children, and that many employ watchful waiting rather

than empiric antibiotic therapy. Surveys of parents note a preference for less testing and

treatment. More aggressive management may be appropriate in febrile infants younger than

three months old; however, criteria have been proposed to identify infants older than one

month who are at low risk for serious bacterial infection. Because of widespread vaccination

againstHaemophi lus inf luenzae infection, Strep to coccus pneumoniae has become the cause

of most cases of bacteremia. The risk of serious bacterial infection is greater in younger chil-

dren and in those with higher temperatures and white blood cell counts. Controversy persists

regarding the age, temperature and white blood cell count values that serve as indications

for further evaluation or empiric antibiotic therapy. (Am Fam Physician 2001;64:1219-26.)

Evaluation and Management of Infants

and Young Children with FeverMICHAEL LUSZCZAK,LTC,MC, USA, Darnall Army Community Hospital, Fort Hood,Texas

PROBLEM-ORIENTED DIAGNOSIS

Members of various family practice department s develop articles for “Problem-Oriented Diagnosis.” This art icle is one in a series coor - dinated by the Depart- ment of Family Medi- cine at t he Uniformed Services University o f the Health SciencesF. Edw ard Hébert School of M edicine,Bethesda, Md. Guest editor s of the series are Francis G. O’Connor,LTC, MC, USA, and Jeannet te E. South - Paul, COL, MC, USA.

See edito rial on page 1148.



tors12have argued that microscopic urinalysisfails to detect 10 to 20 percent of urinary tractinfections in infants and young children, andthat culture of urine obtained by bladdercatheterization is the only acceptable option.

PNEUMONIA, OTITIS MEDIA AND ENTERITIS

A recent study13 found that 26 percent of children with fever and leukocytosis (a whiteblood cell count greater than 20,000 per mm3

[20 109per L] ) had pneumonia,even in theabsence of respiratory symptoms.

The incidence of bacteremia does not differsignificantly in febrile infants and young chil-dren with or without otitis media.14,15 There-fore, most authorities advise that otitis medianot be considered a cause of fever and recom-mend that febrile infants and children with oti-tis media be evaluated for an occult infection.

Stool culture is recommended only in febrileinfants and children who have diarrhea.1

Parental and Physician Preferences

Because of current uncertainty about theevaluation and treatment of infants and

young children with fever, some authors haverecommended that increased considerationbe given to parental input.

In one study,1671 percent of parents of chil-dren with fever preferred options with lesstesting and treatment, accepting the very smallbut real risk associated with failure to identifyand treat hidden infection. These parentsreported a variety of reasons for their prefer-ence, including a desire for fewer painful tests,less waiting time, smaller chance of unneces-sary antibiotic therapy and a belief that theycould return to the emergency department if

their child’s condition deteriorated. In con-trast, the 29 percent who preferred the moreaggressive option universally cited desire forlower risk as the reason for their selection.

In general, parents tend to emphasize theshort-term pain, discomfort and inconven-ience of tests. Physicians are more likely todiscount these considerations and focus onminimizing the risk of adverse outcomes.17

Among physicians, widespread differencesregarding the management of febrile childrenhave been repeatedly documented. Not sur-prisingly, physicians in private office settingstend to adopt strategies involving less diag-nostic testing or empiric treatment, whereashospital-based physicians are most likely totest and treat.11,18

It is important to recognize that parentsoften do not adhere to recommendations forre-evaluation of a febrile child. Factors mostoften associated with a failure to follow up

include parental age younger than 21 years,lack of ownership of a car and parental per-ception of a lesser degree of illness in theirchild.19

Fever and Riskof Serious Bacterial Infection

YOUNG INFANTS

Approximately 10 percent of well-appear-ing young infants with a temperature higherthan 38°C (100.4°F) harbor a serious bacterialinfection or meningitis.20-22 In contrast, fewerthan 2 percent of well-appearing older infants

and young children with a temperature higherthan 39°C (102.2°F) manifest bacteremia.14,23

Because of the greater probability of seriousbacterial infection, a more aggressive approachto the evaluation and management of fever iswarranted in young infants. Specific criteria,commonly termed the “Rochester criteria,”have been proposed to identify febrile younginfants at low risk for serious bacterial infec-tion (Table 2) .21

Some authors have suggested that theRochester criteria be used to identify infantsolder than one week who are at low risk for

serious bacterial infection.12 However, tworecent studies24,25 examining the use of riskstratification criteria in infants younger thanone month with a temperature of 38°C orhigher found that 3 to 5 percent of the infantsidentified as “low risk” developed a seriousbacterial infection. Furthermore, the reliabil-ity of risk stratification criteria is affected byless than complete adherence to stated guide-

Fever




lines within the studies used to validate thecriteria. Management out of accordance withprotocol was reported in 7 percent of younginfants with fever who were enrolled in onerecent study.26

OLDER INFANTS AND YOUNG CHILDREN

With widespread immunization againstHaemophilus influenzae infection, Streptococ- cus pneumoniae has become the predominantcause of serious bacterial infection in infantsand young children. Streptococcal bacteremiaaffects fewer than 2 percent of well-appearingolder infants and young children with a tem-perature above 39°C.14,23Most children in thisage group clear streptococcal bacteremiawithout antibiotic therapy.

Approximately 10 percent of infants and

young children with fever and S. pneumoniae

bacteremia progress to a serious bacterial

infection, and from 3 to 6 percent progress tomeningitis (i.e., approximately one case per1,000 to 2,500 of these febrile children).27,28

The risk of pneumococcal bacteremia variesbased on the patient’s age, temperature andwhite blood cell count.Age. The spectrum of likely pathogens in

bacteremia has changed since the introduc-tion of H. influenzae type b conjugate vaccine.The distribution of bacteremia as a functionof age also has changed.

A recent large, prospective study14 of

approximately 9,000 well-appearing olderinfants and young children with fever con-vincingly demonstrated S. pneumoniaeas thepathogen in 92 percent of occult bacteremiacases. In this study, the incidence of pneumo-coccal bacteremia did not differ significantlyfrom six months to three years of age. How-ever, the risk of pneumococcal bacteremia wasfound to be significantly lower in the infantswho were three to six months old. Neverthe-less, the authors of the study advocated cau-tion, citing this cohort as the peak age for thedevelopment of pneumococcal meningitis.

Temperature. The risk of bacteremiaincreases as temperature rises, but the lowoverall prevalence of bacteremia limits theusefulness of degree of fever as a clinical toolfor risk stratification (Figure 1) .14 Althoughan infant or a young child with a temperaturehigher than 40.9°C (105.6°F) is more thanthree times more likely to harbor bacteremiathan an infant or a young child with a tem-perature of 39°C, most well-appearing chil-dren will not have bacteremia.14

Infants and young children with fever areoften given antipyretics at the time they pre-

sent for care. Febri le children treated withantipyretics are more likely to display in-creased activity level and alertness, but thedegree of temperature reduction in responseto antipyretic therapy is not predictive of thepresence or absence of bacteremia.29

Whi te Blood Cell Count. The prevalence of bacteremia in well-appearing older infantsand young children increases with elevation

1222 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME64, NUMBER 7 / OCTOBER 1,2001

TABLE 2

Rochester Criteria for Identifying Febrile Infantsat Low Risk for Serious Bacterial Infection

Infant appears generally well

Infant has been previously healthy:

Born at term (!37 weeks of gestation)

No perinatal antimicrobial therapyNo treatment for unexplained hyperbilirubinemia

No previous antimicrobial therapy

No previous hospitalization

No chronic or underlying illness

Not hospitalized longer than mother

Infant has no evidence of skin, soft tissue, bone, joint or ear infection

Infant has these laboratory values:

White blood cell count of 5,000 to 15,000 per mm 3 (5 to 15 109 per L)

A bsolute band cell count of "1,500 per mm3 ("1.5 109 per L)

Ten or fewer white blood cells per high-power field on microscopic

examination of urine

Five or fewer white blood cells per high-power field on microscopic

examination of stool in infant with diarrhea

Adapted with permission from Jaskiewicz JA, McCarthy CA, Richardson AC,Wh ite KC, Fisher DJ, Dagan R, et al. Febrile inf ants at low risk for serious bacterial infection—an appraisal of t he Rochester criteria and implications for management . Febrile Infant Collaborat ive Study Group. Pediatrics 1994;94 :390 -6.

Because of the greater probability of serious bacterial infec-

tion, a more aggressive approach to the evaluation and

management of fever is warranted in young infants.



of the white blood cell count (Figure 2) .14

Investigators in the most recent and largeststudy conducted to date14 found that the riskof bacteremia increases from 0.5 percent forwhite blood cell counts less than 15,000 permm3 (15 109 per L) to greater than 18 per-cent for white blood cell counts over 30,000per mm3(30 109 per L).

The 1993 practice guideline for the man-agement of fever recommends a white bloodcell count of 15,000 per mm3 as the thresh-old, or cutoff value, for deciding to obtain

blood for culture and initiate empiric antibi-otic therapy.1 Much of the controversy relat-ing to the practice guideline involves theselection of this cutoff value. One set of investigators14 has advocated 18,000 whiteblood cells per mm3 (18 109 per L) as thecutoff value, arguing that use of this highercount is justified by the post-vaccination dis-appearance of H. influenzae infection and alower overall prevalence of bacteremia thanpreviously reported.

Controversies and Comments

The evaluation of infants and young chil-dren with fever will probably remain contro-versial. Much of the dispute involves the likeli-hood of bacteremia progressing to meningitisand the efficacy of empir ic antibiotic therapyin preventing this outcome.

A meta-analysis30 of studies involving theuse of empiric antibiotics in older infants andchildren with fever concluded that treatmentfor possible occult bacteremia does notdemonstrate a significant outcome advantagefor antibiotic therapy. The authors advisedthat clinical judgment should not be replaced

by widespread antibiotic use in infants andyoung children with fever.

The authors of a commentary on the 1993practice guideline argued that young childrenwith fever should be carefully assessed forfocal bacterial infection.11If no focus is foundand a child appears well, no tests other thanurinalysis are routinely indicated, and antibi-otics should not be given.

In another report,31 investigators ques-tioned the efficacy of the empir ic administra-tion of antibiotics. They pointed out thatorally administered antibiotics have not beenshown to prevent meningitis.These investiga-tors argued that their meta-analysis demon-strated no difference between older infantsand children treated with orally or parenter-ally administered antibiotics, and they con-


FIGURE 1.

Bacteremia and Fever

FIGURE 2.

Bacteremia and White Blood Cell Count

The rightsholder did not

grant rights to reproducethis item in electronicmedia. For the missingitem, see the original printversion of this publication.

The rightsholder did notgrant rights to reproducethis item in electronicmedia. For the missingitem, see the original printversion of this publication.



cluded that physicians should reconsider thecriteria used to identify patients who willreceive empiric antibiotic therapy.

Physician adherence to the 1993 practiceguideline varies. In a recent survey18 on themanagement of children with fever withoutsource, family physicians, pediatricians andemergency department physicians were askedhow they would manage hypothetic casesinvolving nontoxic febrile infants and chil-dren of various ages. The survey findingsshowed general agreement concerning man-

agement of the youngest infants, but consid-erable variation in management approacheswith increasing patient age.Family physicianswere found to be the least aggressive, andemergency department physicians the mostaggressive.

The panel of experts who developed the1993 practice guideline never intended theirrecommendations to be a substitute for phy-

sician judgment. Even though physician prac-tice varies significantly, the practice guidelinecontinues to provide a useful framework forevaluating infants and young children withfever (Figures 3 1 and 4 1,10,13,14 ) .Although it hasbeen suggested that the guideline be modifiedto expand use of “ low risk” criteria in febrileinfants older than one week, recent studieshave demonstrated the unpredictability of serious bacterial illness in febrile infantsyounger than one month.24,25 Other authorshave presented viable arguments for using

observation instead of empiric antibiotic ther-apy in well-appearing infants and young chil-dren who have fever without source.11,27,30

S. pneumoniae is the pathogen in approxi-mately 90 percent of cases of occult bac-teremia in febrile older infants and youngchildren.14 The recently introduced pneumo-coccal conjugate vaccine may soon end thedebate surrounding the evaluation and treat-


Nontoxic Young Infant with Fever

Previously healthy, nontoxic young infant ("3 months of age)

with a temperature of 38°C (100.4°F) without source

O ption 1: blood and urine cultures, lumbar

puncture, parenterally administered antibiotics

O ption 2: urine culture and

careful observation

Admit infant to hospital for blood and

urine cultures, lumbar puncture and

parenterally administered antibiotics.

A lternatively, if the risk of bacteremia

is low (see Table 2), consider

admission and observation without

antibiotic therapy pending culture

results.

Infant does not meet

low-risk criteria.

A dmit infant to hospital for

blood and urine cultures,

lumbar puncture and

parenterally administered

antibiotics.

Consider low-risk criteria (see Table 2):

G enerally well appearance

No focal infection

WBC count of 5,000 to 15,000 per mm3 (5 to 15 109 per L)

Absolute band cell count of less than 1, 500 per mm3 (1.5 109 per L)

Normal urinalysis

If diarrhea, < 5 WBC s per high-power field on microscopic

examination of stool

>1month of age "1 month of age

Infant meets low-risk criteria.

Re-evaluate infant within 24 hours.

FIGURE 3. Algorithm fo r the ma na gem ent o f no nto xic youn g infa nts w ith a t empera ture of 38.0°C (100.4° F) w ithout

source. (WBC = w hite b lood cell; IM = intramuscular; IV = intraveno us)

Adapt ed w ith permission from Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH, Powell KR, et al. Practice guideline f or t he management of inf ants and children 0 to 36 mont hs of age with fever w ithout source. Pediatrics 1993;92:1-12.



ment of infants and young children with fever.Preliminary reports indicate that the vaccineis almost 95 percent effective against the inva-sive pneumococcal serotypes included in thevaccine.32,33

Some authorities have postulated thatwidespread use of the pneumococcal conju-gate vaccine will make white blood cellcounts, blood cultures and empiric antibiotictherapy obsolete in the evaluation and man-agement of febrile older infants and chil-

dren.34 Pending clear demonstration of theeradication of occult pneumococcal bac-teremia by the new vaccine, it remains thetask of each physician to select his or her ownapproach to infants and children at risk,based on parental desire and the physician’spractice environment, perceptions and toler-ance of risk, and the likelihood of opportu-nity for subsequent intervention.

The opinions and assertions contained herein are the private views of the autho r and are not to be con- strued as official or as reflecting the views of the Army Medical Department or the Army Service at large.

The author indicates that he does not have any con- flicts of int erest. Sources of funding: none reported.

The autho r thanks Francis G. O’Connor, LTC, MC,USA, f or assistance in developing t he article concept and for reviewing th e manuscript.

REFERENCES

1. Baraff LJ, BassJW, Fleisher G R, K lein JO , M cCracken

G H, Powell KR, et al. Practice guideline for the man-

agement of infants and children 0 to 36 monthsof

age with fever without source. Pediatrics 1993;

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2. The septic appearing infant. In: Strange G R, C ooper

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Nontoxic Infant or Young Child with Fever

FIGURE 4. Algorithm fo r the ma na gem ent o f no nto xic infa nts or young children wh o ha ve fever witho ut source. (WBC =

w hite bloo d cell; IM = intramuscular; IV = intraveno us)

Adapt ed w ith permission from Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH, Powell KR, et al. Practice guideline for the management of inf ants and children 0 to 36 mont hs of age with f ever w ithout source. Pediatrics 1993;92:1-12 , w ith additional inform ation from references 10, 13 and 14.

Previously healthy, nontoxic infant or child (3 months

to 3 years of age) with fever without source

Temperature !39°C (102.2°F) Temperature < 39°C

1993 practice guideline1:

• Urine culture in males < 6 months old and

females < 2 years old

• Chest radiograph if there is dyspnea, tachypnea,

rales or decreased breath sounds

• Stool culture if blood and mucus are in the

stool, or there are > 5 WBC s per high-power

field on microscopic examination of stool

• Blood culture:

O ption 1: all children with a temperature > 39°C


and a WBC count > 15,000 (15 109 per L)

• Empi ric antibiotic therapy (e.g. , ceftriaxone

[Rocephin], 50 mg per kg IM or IV):


O ption 2: all children with a temperature >39°C

and a WBC count > 15,000 per mm3

• Follow-up: within 24 to 48 hours

Recent recommendations:

• Urine culture in all infantsand children < 2 years

of age who are prescribed empiric antibiotics10

• Chest radiograph for clinical findings (see 1993

practice guideline1); consider radiograph if

infant or child is asymptomatic and has a WBC

count > 20,000 per mm3 (20 109 per L)13

• Stool culture: no new recommendations

• Blood culture: consider selection of

temperature and WBC count thresholds based

on risk (see Figures 1 and 2)14

• Empiric antibiotic therapy (e.g., ceftriaxone,

50 mg per kg); consider selection of

temperature and white blood cell count

thresholds based on risk (see Figures1 and 2)14

• Follow-up: clinical course remains the most

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• Careful physical

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media, osteomyelitis,

impetigo, lymphadenitis,

scarlet fever, streptococcal

pharyngitis)

• No tests or antibiotics if

infant or young child

looks well and no possible

bacterial source is identif ied

• Antipyretic as needed

• Follow-up: re-evaluation if

fever persists more than

48 hours or condition

deteriorates.



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