Temperature Greater Than or Equal to 40 C in Children Less Than 24 Months of Age: A Prospective Study

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Temperature

Greater

Than

or Equal

to 40 C in Children

Less Than

24 Months

of Age: A Prospective

Study

Paul L. McCarthy, M.D., James F. Jekel, M.D., and Thomas F. Dolan, Jr., M.D.

From the Departments ofPediatrics and Epidemiology and Public Health, Yale University School of Medicine and Yale-New Haven Hospital, New Haven, Connecticut

ABSTRACT. In a prospective study, .330 consecutive

chil-dren less than 24 months old coming to the emergency room

of Yale-New Haven Hospital with a temperature 40 C

were evaluated. Nearly all patients had a white blood cell

(WBC) count, erythrocyte sedimentation rate (ESR)

(Win-trobe), blood culture, and chest roentgenogram. Eighty-eight

percent were evaluated 24 to 48 hours later. The mean WBC

count and ESR were significantly elevated in children with

positive blood cultures or pneumonia. The risk of bacteremia

was increased threefold and the risk of pneumonia was

increased twofold in children with a WBC count 15,000/

cii mm or an ESR 30 mm/hr compared to children

without leukocytosis or elevated ESR. Sixty-one percent of

children with bacteremia or pneumonia, 63% of children in

whom these diagnoses were not apparent on physical

exam-ination, and 86% of children with otitis media complicated

by pneumonia or bacteremia had either a WBC count 15,000/cu mm or an ESR 30 mm/hr. A WBC count 15,000/cu mm and an ESR 30 mm/hr were more

effective than a polymorphonuclear leukocyte count

10,000/cu mm and/or a band count 500/cu mm in

screening young children with high fever for bacteremia, pneunlonia, or complicated otitis media. Pediatrics,

59:663-668, 1977, BACTEREMIA, PNEUMONIA, FEVER, WHITE BLOOD

CELL COUNT, ERYTHROCYTE SEDIMENTATION RATE.

than 24 months of age may appear as seemingly trivial illnesses. Samson4 reported that children

less than 16 months of age with bacterial

menin-gitis may have none of the classic physical

findings associated with this disease.

Consequently, there has been a continuing effort to develop criteria which are indicators of

serious illnesses in febrile children. McCarthy and

Dolan5 reported the association between a temperature 41.1 C and bacterial meningitis. Age less than 24 months, temperature 40 C,

and leukocytosis (white blood cell {WBC] count 15,000/cu mm) were correlated with bacter-emia in several reports.’’ Todd’ found that a polymorphonuclear leukocyte (PM N) count

10,000/cu mm and/or neutrophil band count

500/cu mm were excellent indicators of

bacte-rial infections.

We studied consecutive children less than 24 months old who came to the Yale-New Haven Hospital pediatric emergency room with a temperature 40 C to evaluate the use of WBC count and erythrocyte sedimentation rate (ESR)

as indicators of bacteremia, pneumonia, or other

culture-proven bacterial illnesses.

Recent investigators have emphasized the diag-nostic challenge of the young child with fever. McCarthy et al.,’ McGowan et al.,2 and Teele et al.’ have noted that bacteremia in children less

(Received July 13; revision accepted for publication October

13, 1976.)

ADDRESS FOR REPRINTS: (P.L.M.) Department of

Pedi-atrics, Yale-New Haven Hospital, 789 Howard Avenue, New

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INITIAL

HISTORY AND PHYSICAL

SUGGESTED STUDIES INITIAL

PNEUMONIA CBC, ESR, BC, CXR

FOLLOW UP

CLINIC OR ADMI SSION INITIAL IMPRESSION

RECOGN I ZA BLE

VIRAL INFECTION

IViral ezonthem -snonthem,

ICroup, Gostrosntsritis, Post L immunization tivir, Other

OTITIS MEDIA

RECOGNIZABLE BACTERIAL INFECTION

ICeIIuIitis, Epiglottitis,

I Meningitis, Sepsis, Other

AT DISCRETION OF

HOUSE OFFICER

CBC1, ESR1, BC, CXR4

CBC, ESR, BC

[OtMrs ot discretion

L of touss officer’

NON-SPECIFIC ILLNESS

1RhInoMo, Ned throot,

I

Non-sp.clfic rash, Mild

I

vomIting end /sr dlerrheo,

I Irritobllity, Other

CBC, ESR, BC, CXN

C Soo test ]

Repeat #{163}zominotion,

Review of FINAL studIes: DIAGNOSIS LP, CXR,

Cultures

1Complets blood count

tErythrocyte ssdimentotion rote 3BIood culture

4Chist roentgsnogrom ‘See test

FIG. 1. Protocol used to evaluate febrile children.

MATERIALS AND METHODS

Froni Ju1 15, 1974, to July 1, 1975, children

less than 24 months old with a rectal temperature

40 C who were seen in the pediatric

emer-genc room at Yale-New Haven Hospital were

evaluated according to a fever protocol (Fig. 1).

Each child was seen by the pediatric resident

on call. After an initial history and physical

examination, and prior to obtaining laboratory

data, the house officer recorded an initial

ilnpres-sion. Prior to obtaining a chest roentgenogram or performing a lumbar puncture, the resident recorded findings suggestive of pneumonia or

meningitis.

If a child had a recognizable viral infection,

further laboratory studies were done only at the

discretion of the house officer, e.g., a chest

roentgenogram for a child with rubeola. If a

diagnosis of a recognizable bacterial infection was

made, studies which were appropriate for the

illness were Ol)tained in addition to those

suggested by the protocol, e.g., a wound culture

for a child with cellulitis. No mvringotomies or

l)t111ionarY taps were performed on children with

otitis niedia or pneumonia, respectively. Lumbar

puncture was suggested for children with

nonspe-cific signs and symptoms who were less than 6 months of age and/or had a WBC count

20,O()O/cu 111111. Otherwise, a lumbar puncture

was left to the discretion of the house officer. A

urine culture was done if a child had a nonspecific

illness without upper respiratory tract symptoms.

All children entered on the fever protocol with first febrile seizures had a lumbar puncture

performed.’ Children with a temperature 41.1

C and those less than 3 months old with a

temperature 40 C were admitted for

observa-tion and/or therapy after a WBC count, ESR

determination, lumbar puncture, chest

roentgen-ogram, and cultures of blood and urine were done. ‘#{149}

The resident listed an initial diagnosis after

WBC count, ESR, lumbar puncture, and chest

roentgenogram results were known. An attending pediatrician (P.L.M. or T.F.D.) was then consulted about the patient. Children were then admitted or sent home with a referral to a fever follow-up clinic staffed by the authors (P.L.M. and T.F.D.) and the house officer who saw the child initially. At the fever follow-up visit, which took place 24 to 48 hours after the initial exami-nation, a repeat examination and a review of bacteriology cultures were done.

Results of blood cultures were interpreted by the bacteriology laboratory and nonpathogenic contaminant organisms were excluded: Staph

ijlo-coccus epidermidis (two) and Serratia species

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TABLE I

SELECTED DIAGNOSTIC METHODS AND RESULTS

RESULTS

#{176}Seetext.

with positive blood cultures were admitted for

evaluation (including lumbar puncture, chest

roentgenogram, and repeat blood culture) of soft

tissue complications, especially meningitis,

pneu-monia, septic arthritis, or cellulitis. Children with an initially positive urine culture

(

10,000

organisms per cubic millimeter) obtained by

clean-catch bag method had a repeat urine

culture done by suprapubic aspiration. The ESR

was measured by the Wintrobe method.

In the 12-month study period, 334 children less than 24 months old with a temperature 40 C were seen and 330 were studied according to the fever protocol. Table I shows the laboratory and

other diagnostic studies performed on children

with high fever. Ninety instances of bacteremia, pneumonia, or other culture-proven bacterial

illnesses occurred in 82 patients. Of 329 blood

cultures, 7.3% yielded a pathogen: Diplococcus

pnellnloniae (15), Heniophilus influenzae type b

(

5), Salmonella species (2), and Neisseria

meningi-tidis (2). All children with septic meningitis had

positive blood cultures (H. influenzae {3}, N.

nieningitidis [1]). Two children with Salmonella

bacteremia yielded the same organism in the

stool. One child had shigellosis. One child with an

Lschericlua coli urinary tract infection had

pneu-mococcal bacteremia. Of 52 children with

pneu-monia, one had bacteremia (H. influenzae type

b).

Five patients in the study were less than 3

months old, and one had a positive blood culture.

Twenty-one of 24 positive blood cultures

occurred in the 266 children between 3 and 18

months of age. Seventeen children had a

temper-ature 41.1 C; of these, four had bacteremia and

two had bacterial meningitis. No other

associa-tions were noted between age, temperature, and

diagnosis.

Six of 24 children with initially positive blood

cultures had persistent bacteremia with D.

pneu-moniae (four), Salmonella species (one), and N.

;neningitidis (one). Only one child with persisting

bacteremia, in this instance caused by Salmonella

species, had been treated with antibiotics (oral

ampicillin for otitis media) prior to knowing the

results of the first blood culture. Of 18 children

without persisting bacteremia, 12 had received

either oral or intravenous antibiotics prior to knowing the results of the first blood culture because of the presence of meningitis, pneumo-nia, septic shock, or otitis media. The six children

Diagnostic method No. No. (%)

Positive

Complete 1)lOOd cell count 327 ..

Erythrocte sedimentation rate 273 ...

Blood culture 329 24#{176}( 7.3)

Chest roentgenogram 289 52#{176}( 18.0)

Lumbar puncture 137 4’ ( 2.9)

Urine culture 95 3* ( 3.2)

Rectal culture 52 3#{176}( 5.8)

Throat culture 31 1 ( 3.2)

Wound culture :3 3 (100.0)

with nonpersisting bacteremia who received no

antibiotics prior to knowing the results of the first blood culture all had pneumococcal bloodstream

invasion. No soft tissue complications, other than

those noted during the initial evaluation, were

identified in children with either persisting or

nonpersisting bacteremia. After bacterial

blood-stream invasion was documented, antibiotics were used as described previously.’

Two hundred ninety-one children had

follow-up evaluation: 57 were admitted to the hospital

from the emergency room, 151 had fever

follow-U visits, 19 were followed up by private

physi-cians, and 64 were followed up by phone or an

outreach worker.

The mean WBC count and ESR were

signifi-cantly elevated (P .05) in children with

positive blood cultures (16,086 ± 8,350, 29.3 ±

15.3) and positive chest roentgenograms

(16,012 ± 7,356, 29.8 ± 15.4) compared to those

with negative blood cultures (12,384 ± 5,669,

22.6 ± 12.9) and negative chest roentgenograms

(11,980 ± 5,440, 21.9 ± 12.3). In seven children

with nonbacteremic but proven bacterial

infec-tions, the mean WBC count and ESR were

11,200/cu mm and 21 mm/hr, respectively.

Table II demonstrates that children had a threefold greater risk of bacteremia and a twofold greater risk of pneumonia if their WBC count was

15,000/cu mm than if < 15,000/cu mm.

Simi-larly, children had a threefold greater risk of

bacteremia and a twofold greater risk of pneu-monia if the ESR was 30 mm/hr than if it was

< 30 mm/hr.

Otitis media, diagnosed in 148 patients, was often complicated by pneumonia (12 patients) or bacteremia (10 patients, one of whom had septic

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TABLE II

PREnIcrIvE VALUE OF WBC COUNT AND ESR FOR BACTEREMIA, PNEUMONIA, OTHER CULTURE-PROVEN BACTERIAL ILLNESSES, COMPLICATED OTITIS MEDIA

Patients WBC Count ESR (mm/hr) WBC Count Neither

(per CII A

nun) ‘- -‘

.30 < 30

15,000/cu ;iiiii

and/or ESR

WBC Count

15,O()()/cu mm

,-15,000 < 15,000 30 mm/hr nor ESR

.30iiin/hr

% with positive blood culture 14.5 4.9 15.7 3.9 14.6 2.9

% withpositive chest x-ray film 25.3 12.7 27.0 14.4 25.2 12.9

% with other culture-proven 1.2 2.5 1.4 2.0 1.6 2.5

bacterial illnesses

% with positive blood culture or 38.5 17.6 40.0 16.3 37.4 14.2

positive chest x-ray film

% with otitis and bacteremia or 28.6 9.4 32.4 7. 1 28.8 3.7

pneumonia

children with complicated otitis media was

18,100/cu mm and 33.7 mm/hr, respectively, compared to a mean WBC count of 12,400/cu

mm and a mean ESR of 22.5 mm/hr in children

with uncomplicated otitis media. If otitis media

was present, complications were three times as frequent if the WBC count was 15,000/cu mm

and four times as frequent if the ESH was 30

mm/hr than if it was < 15,000/cu mm and 30

nim/hr, respectively (Table II).

Only 2.9% of children with neither a WBC

count 15,000/cu mm or an ESR 30 mm/hr

had bacteremia (Table II).

Neutrophil band counts 500/cu mm were seen in 91% of the patients who had a complete blood cell count. There was no significant differ-ence in mean band count between children with

and without bacteremia or pneumonia.

Table III shows that one half of the children

with bacteremia and 40% of those with pneu-monia had a WBC count 15,000/cu mm, which was similar to the sensitivity of the ESR

30 mm/hr for these diagnoses. Combining leukocytosis and/or elevated ESR identified three fourths of children with bacteremia, 60% of children with pneumonia, and nearly all children with complicated otitis media.

There were 46 children with pneumonia (27) or bacteremia (19) whose signs and symptoms on initial physical examination did not indicate the

diagnosis, that is, the initial impression was other

than pneumonia or bacteremia. Forty-six percent of these 46 children had a WBC count 15,000/

cu mm, 39% had an ESR 30 mm/hr, and 63%

had one or the other elevation.

A PMN count 10,000/cu mm identified 37%

of children with bacteremia, 25% with pneumo-nia, and 41% with complicated otitis media.

DISCUSSION

Our data demonstrate a clinically useful

asso-ciation between a WBC count 15,000/cu mm

and an ESR 30 mm/hr and pneumonia or bacteremia in children less than 24 months of age with a temperature 40 C. If these selected elevations of WBC count and ESR are docu-mented in a young child with a high fever, the work-up should include a blood culture and a chest roentgenogram. Our data in no way minimize the importance of evaluating this group of patients for other serious illnesses, such as meningitis, cellulitis, or urinary tract infections.

An ESR 30 mm/hr was equally predictive and sensitive for pneumonia or bacteremia as a

WBC count 15,000/cu mm. Combining an

ESR 30 mm/hr and/or a WBC count

15,000/cu mm, while not decreasing the

predictive value (Table II), increased the

sensi-tivity (Table III) of these selected elevations to

61% for children with pneumonia or bacteremia,

63% for children in whom these diseases were not

apparent on physical examination, and 86% for patients with complicated otitis media.

Todd6 showed that a segmented neutrophil

count 10,000/cu mm and/or a neutrophil band count 500/cu mm had 80% specificity and 75%

sensitivity for bacterial infections. In our study,

only one third of the children with bacteremia

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TABLE III

SEN5ITIvrn OF WBC COUNT AND ESR FOR BACTEREMIA, PNEUMONIA, COMPLICATED OTITIS,

OTHER CULTURE-PROVEN BACTERIAL ILLNESSES

Patients Positive Blood Culture Positive Chest X-ray Film Other Bacterial Illnesses Positive Blood Culture and/or Chest X-ray Film Goniplicated Otitis Media

% with WBC count 15,000/ 50 40 14 43 55

cu mm

% with ESR 30 mm/hr 58 40 20 44 72

% with WBC count 15,000/

cu mm and/or ESR 30

mm/hr

75 58 29 61 86

-% with neither WBC count

15,000/cu mm nor ESR

30 mm/hr

25 42 71 39 14

PMN count 10,000/cu mm. A.neutrophil band

count 500/cu mm was extremely nonspecific

because nearly all patients had this number of

bands. We recommend a WBC count 15,000/

cu mm as a more effective means of screening young children with high fever for bacteremia or pneumonia.

Portnoy et a!.” studied 246 nonconsecutive, hospitalized children of all ages with pneumonia, bronchiolitis, or laryngotracheobronchitis. No fever data were given. The mean WBC count was

16,725/cu mm in 92 children with radiologic pulmonary infiltrates; in children with bronchio-litis or laryngotracheobronchitis it was 13,550/cu mm and 13,000/cu mm, respectively. Fifty-two percent of children with pneumonia had serologic and/or culture evidence of viral infection.

Our data also demonstrate an association between pneumonia and leukocytosis and delin-eate the predictive value and sensitivity of a WBC count 15,000/cu mm for pulmonary infiltrates in the group of young children with high fever that we evaluated. Only one child (with H. influenzae type b bacteremia) had an

etiology established for the pneumonia.

Clarifica-tion of the etiology of pneumonia in young children with high fever would have required more extensive evaluation, including pulmonary taps9” and viral studies.’#{176}’2 Such evaluation is certainly not indicated routinely because children with pulmonary infiltrates, fever (temperature

40 C), and/or a WBC count 15,000/cu mm

have a rapid symptomatic response to antibiotic therapy.

Because only seven children with

culture-proven bacterial illnesses (other than bacteremia)

were seen in this study, we hesitate to comment on the sensitivity of a WBC count 15,000/cu

mm and/or an ESR 30 mm/hr for this group of patients.

Antimicrobial therapy for pneumonia or other culture-proven bacterial illnesses was not evalu-ated critically in this study. Rather, the duration and route of treatment and the antibiotic selected for children with bacteremia or other culture-proven bacterial illnesses depended on the organism isolated and the extent, if any, of soft tissue involvement.1 Patients with leukocytosis and/or an elevated ESR but without pneumonia or identifiable bacterial illness at the initial visit were not treated with antibiotics but were followed up as inpatients or outpatients as described here.

CONCLUSIONS

1. In children less than 24 months of age with a temperature 40 C, the mean WBC count and

ESR were significantly elevated in those with positive blood cultures or chest roentgenograms compared with those with negative blood cultures or chest roentgenograms.

2. The risk of bacteremia was threefold and the

risk of pneumonia was twofold in children with a

WBC count 15,000/cu mm or an ESR 30

mm/hr compared with children without

leukocy-tosis or elevated ESR.

3. Combining a WBC count 15,000/cu mm

and/or an ESR 30 mm/hr, while not changing the predictive value, increased the sensitivity of

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examina-tion, and 86% for children with complicated otitis media.

4. A WBC count 15,000/cu mm or an ESR 30 mm/hr was more sensitive for pneumonia

or bacteremia than a PMN count 10,000/cu

mm. A band count 500/cu mm was seen in

91% of children and, therefore, was nonspecific.

We recommend WBC counts and ESRs as a

useful means of screening young children with

high fever for bacteremia or pneumonia.

REFERENCES

I. McCarthy PL, Crundy CL, Spiesel SZ, Dolan TF:

Bacteremia in children: An outpatient review.

Pedi-atnes 57:861, 1976.

2 McGowan JE, Bratton L, Klein JO, Finland NI:

Bactere-mia in febrile children seen in a “walk in” pediatric

clinic. N EngI J Med 288:1309, 1973.

3. Teele DW, Pelton SI, Mvles JAG, et al: Bacteremia in febrile children under 2 years of age: Results of cultures of 1)100(1 of 6(X) consecutive febrile children

seen in a “walk in” clinic. J Pediatr 87:227, 1975. 4. Samson Jil: Febrile seizures and purulent nieningitis.

JAM.. 210:1918, 1969.

5. McCarthy PL, Dolan TF: Hperpyrexia in children:

Eight ‘ear emergencY room experience. Am J Dis

Child 130:849, 1976.

6. Todd JK: Childhood infections: Diagnostic value of peripheral white blood count and differential cell

counts. Am J Dis Child 127:810, 1974.

7. McCarthy PL, Dolan TF: Temperature 40#{176}C. in children less than three months. Clin Pediatr

15:700, 1976.

8. Portnoy B, Hanes B, Salvatore M, Eckert H: The

peripheral white blood count in respiro virus

infec-tion.J Pediatr 68:181, 1966.

9. Escobar JA, Dover AS, Duenas EL, et al: Etiology of respiratory tract infections in children in Cali, Colombia. Pediatrics 57:123, 1976.

10. Mimica I, Donoso E, Howard J,et al: Lung puncture in the etiologic diagnosis of pneumonia. Am J Dis

Child 122:278, 1971.

11. Glezen WP, Denny F’sV: Epidemiology of acute lower

respiratory disease in children. N EngI J Med 288:498, 1973.

12. McCarthy PL, Frank A, Masters S, et al: Prospective

study of children with pneunionia. Read before

the Ambulatory Pediatric Association, St. Louis, 1976.

1:3. Shuttleworth DB, Charney E: Leukocvte count in

childhood pneumonia. Am J Dis Child 122:393, 1971.

ACKNOWLEDGMENT

\Ve thank Dr. Howard Pearson for review of the

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1977;59;663

Pediatrics

Paul L. McCarthy, James F. Jekel and Thomas F. Dolan, Jr.

Age: A Prospective Study

Temperature Greater Than or Equal to 40 C in Children Less Than 24 Months of

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1977;59;663

Pediatrics

Paul L. McCarthy, James F. Jekel and Thomas F. Dolan, Jr.

Age: A Prospective Study

Temperature Greater Than or Equal to 40 C in Children Less Than 24 Months of

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