Paediatrica Indonesiana

VOLUME 52

November

NUMBER 6

Original
Article

Fever and laboratory profiles as

predictors of serious bacterial
infection in children
1

Ni Putu Veny Kartika Yantie , BNP Arhana , Purnomo

Suryantoro

Abstract

Background There is a debate on the use of high

fever with other morbidities to predict serious

bacterial infection (SBI). Bacterial
LQIHFWLRQ RFFXUV LQ RI FKLOGUHQ ZLWK IHYHU RI
&

Various laboratory parameters including increased

C-reactive protein (CRP) levels, leukocyte counts,
and absolute neutrophil counts (ANC) have been
studied for their usefulness in predicting the
occurrence of SBI, but with varied results. The
ability to discriminate whether a patient has a SBI
can lead to improved patient management.

Objective 7R HYDOXDWH IHYHU RI

&
OHXNRF\WH FRXQWV RI PP $1&RI

PPDQG&53RI

PJ/DV
SUHGLFWRUVRI6%,LQFKLOGUHQDJHG PRQWK \HD
UV
Methods A case-controlled study was conducted by
collecting data from medical records at Sanglah
Hospital, Denpasar. Subjects in the case group were
diagnosed with SBIs (bacterial meningitis, bacterial
pneumonia, bacteremia or sepsis, urinary tract
infections, or bacterial gastroenteritis), and subjects
in the control group non serious bacterial infections
(non-SBI). Data was analyzed using
ELYDULDWHDQGPXOWLYDULDWHPHWKRGVZLWKFRQILGHQFHLQWHUYDOV
DQGDVWDWLVWLFDOVLJQLILFDQFHYDOXHRI3

Results Sixty subjects were VWXGLHG ZLWKVXEMHFWVLQWKHFDVH

JURXS

DQG

LQ

WKH FRQWURO

JURXS. Baseline

characteristics

of

VXEMHFWVZHUHVLPLODUEHWZHHQWKHWZRJURXSV)HYHUDQG&53ZHUH
SUHGLFWRUVRI6%,>25
&, WR


&, WR

-DQG

25

 3 UHVSHFWLYHO\@

Conclusion

)HYHU&DQG&53
PJ/ZHUHVLJQLILFDQW predictors of serious
bacterial
infections
in
children.
[Paediatr
Indones. 2012;52:313-6].
Keywords: serious bacterial
infection, fever, leukocytes,
neutrophil, C-reactive protein,
children

evercommon
in children
is one of
most
complaints
in the
pediatric
emergency rooms. Although the
majority of these children have a
benign cause for their fever,
distinguishing the
child with a serious bacterial infection
(SBI), such as bacteremia, urinary tract
infection
(UTI),
meningitis,
bacterial
gastroenteritis,
and
pneumonia
is

important and may be difficult to perform.

Bacterial infection
RFFXUVLQ

RIFKLOGUHQZLWKIHYHURI&

,IDSDWLHQWVIHYHUKDVODVWHGIRUPRUHWKDQ

KRXUV
ZLWKDWHPSHUDWXUHRI&

 WKHIROORZLQJ

bacterial markers have been reported to

be predictive
RI6%,OHXNRF\WHFXWRIIYDOXHRI PP,
ANC
FXWRIIYDOXHRI PP, and C-reactive
protein
&53

FXWRII

OHYHO

RI

PJ/

Similar

study

of

(PDLO kartika.veny@yahoo.co.id

SUHGLFWRUVIRU6%,LQFKLOGUHQDJHGPRQWKVZLWK
IHYHUVKRZHGWKDWSDWLHQWVZLWKOHXNRF\WHVRI

mm had a five times greater risk of SBI. In

contrast, other studies reported that age and
high fever were not significant predictors of
SBI, while leukocyte counts and CRP were
2,4
associated with increased SBI.
However,
QRQH RI WKHVH VWXGLHV ZHUH GRQH LQ FKLOGUHQ DJHG

)URP WKH 'HSDUWPHQW RI &KLOG +HDOWK 8GD\DQD 8QLYHUVLW\

0HGLFDO

School, Sanglah Hospital, Bali , and Gadjah Mada

University, Sardjito
2

Hospital, Yogyakarta , Indonesia.

Reprint requests to1L3XWX9HQ\.DUWLND<DQWLH
'HSDUWPHQWRI&KLOG+HDOWK 8GD\DQD8QLYHUVLW\0HGLFDO6FKRRO
6DQJODK+RVSLWDO -OPulau Nias, Denpasar,

%DOL7HO)D[

Paediatr Indones, Vol. 52, No. 6, November

2012 313

Ni Putu Veny Kartika Yantie et al: Predictors of serious bacterial

infection in children
PRQWK \HDUV7KHUHIRUH ZHHYDOXDWHGIHYHU
RI & OHXNRF\WHFRXQWRI PP $1&RI PP

DQG&53RI

PJ/DVSUHGLFWRUVIRU
6%,LQFKLOGUHQDJHG PRQWK \HDUV

was analyzed for each factor separately

with bivariate analysis (Chi square test).
Multivariate analysis was performed
using logistic regression with backward
stepwise
elimination.
Results
were
presented in OR,
FRQILGHQFHLQWHUYDOV DQGDVWDWLVWLFDOVLJQLILFDQFH
YDOXHRI3

Methods
A case-control study was conducted in
children aged
PRQWK \HDUV DGPLWWHG WR WKH 'HSDUWPHQW
RI

Child Health, Udayana University Medical

School
6DQJODK +RVSLWDO 'HQSDVDU IURP
-DQXDU\ WR -DQXDU\
Subjects in the case group were
children with SBI, including bacteriemia or
sepsis, bacterial meningitis, bacterial
pneumonia, urinary tract infections, or
bacterial gastroenteritis, according to the
standard diagnostic tests at Sanglah
Hospital. As the control group, we included
all children without SBI, which included any
diagnosis beyond the diagnosis of SBI.
Patients
with
malignancies,
trauma,
immune disorders or incomplete data were
excluded. Data was collected
IURPPHGLFDOUHFRUGV:HILUVWLGHQWLILHG6%,DQGQRQ

SBI
subjects,
then
retrospectively
collected the data of fever, leukocyte
counts, ANCs, and CRP levels at the time
of hospital admission. This study was
approved by the Research Ethics
Committee
of
Udayana
Medical
School/Sanglah Hospital.
Required sample size was calculated
using the unpaired case control method,
with an assumed odds ratio (OR) for each
variable (fever, leukocytes, ANC,
DQG &53

:H FDOFXODWHG WKH ODUJHVW 25 IRU IHYHU

ZLWKDW\SH,HUURURIDQGSRZHURI

UHVXOWLQJ

Table 1. Baseline characteristics of subjects

LQVXEMHFWVLQHDFKJURXSZLWKRXWPDWFKLQJ'DWD

Characteristics

SBI
n=30

Age, n
1 <3 months
3 36 months
OQPVJU
Male gender, n
Duration of fever, n
<72 hours
JQWTU
Nutritional status
Undernourished
Well-nourished
Overweight
Obese
Hydration status
No dehydration
Mild-moderate dehydration
Medication history
Antibiotics, n
Antipyretics, n
Diagnoses, n
Pneumonia
Bacterial meningitis
Sepsis
UTI
Bronchiolitis
Rhinotonsilopharingitis
Febrile seizure
Others

non-SBI
n=30

4
17
9
19

4
22
4
24

17
13

22
8

16
14
0
0

9
19
1
1

30
0

29
1

11
23

10
26

15
7
6
2
-

14
7
4
5*

*Others: encephalitis (1), acute otitis media (1), acute diarrhea

(1), hydrocephalus (1), epilepsy (1)

Table 2. Bivariate analysis of prediction of SBI

Variables

SBI

non-SBI

OR

95%CI

P value

Fever, n
u%
- u%
Leukocytes count, n

14
16

2
28

12.25

2.46 to 60.9

0.001

19
11

8
22

4.75

1.58 to 14.24

0.004

17
13

4
26

8.51

2.37 to 30.46

0.001

18
12

6
24

6.00

1.89 to 19.04

0.002

OO

<15,000/mm
CRP level, n
OI.
<10 mg/L
ANC, n

OO
3
<10,000/ mm

314Paediatr Indones, Vol. 52, No. 6,

November 2012

Ni Putu Veny Kartika Yantie et al: Predictors of serious bacterial

infection in children

Results
7KHUHZHUHVXEMHFWVLQWKHFDVHJURXS
6%,

DQG
QRQ6%,

VXEMHFWVLQWKHFRQWUROJURXS

6XEMHFWV

DJHVUDQJHGIURP

PRQWKWR

\HDUV1RVXEMHFWV had severe dehydration. Baseline

characteristics of subjects are shown in Table 1.

Predictive factors for SBI in children

are shown in Table 2. Bivariate analysis
revealed that fever of
!& OHXNRF\WHFRXQWRI! PP, CRP of
! PJP/ DQG$1&RI PP, were all
significant predictive factors for SBI.
Multivariate
DQDO\VLV UHYHDOHG WKDW IHYHU RI& DQG &53
RI

PJ/ZHUHVLJQLILFDQWSUHGLFWLYHIDFWRUVIRU6%,
>25
&, WR


&, WR

DQG25

 3 UHVSHFWLYHO\@

(Table 3).

WKDQFKLOGUHQZLWKRXWEDFWHUHPLD>25
&, WR

:
HIRXQGWKDWIHYHURI&ZDVVLJQLILFDQWO\
associated with increased of SBI occurrence.
Similarly,
WHPSHUDWXUHRI&KDGSUHYLRXVO\EHHQDVVRFLDW
HG ZLWKEDFWHUHPLDZLWK55
3

FRPSDUHG WROHXNRF\WHFRXQWVRI X/ZLWK55

3

Listen Also, Bonadio et al. reported that

WHPSHUDWXUHRI&KDGDJUHDWHUSURSRUWLRQR
I
6%,RFFXUUHQFHFRPSDUHGWRWHPSHUDWXUHRI&
YV UHVSHFWLYHO\

The best cutoff point to assess the occurrence of SBI

was reported to be &

Despite this data, the validity

alIRXQGWKDWLQIDQWVDJHG

days divided into

subject with SBI and without SBI

of higher temperature as a predictor of serious

disease

remains

unclear.

Hsiao

et

JURXSV KDG VLPLODU PHDQ WHPSHUDWXUHV RI

6'

Table 3. Multivariate analysis with backward stepwise elimination of predictive factors of SBI
Step
1

Variable
(GXGTQH u%
.GWMQE[VGUQHOO
%42QHOI.

#0%QHOO
(GXGTQH u%
.GWMQE[VGUQHOO
%42QHOI.
(GXGTQH u%
%42QHOI.

Discussion
Body temperature measurements in
children may flucuate depending on the
thermometer type and the use of
antipyretics. In our study, the use of
antipyretics was similar between groups.
Logistic regression analysis showed that
high fever and CRP levels were
significant markers of SBI occurrence.
During
acute
fever,
higher
temperatures are related to the degree
of bacterial invasion and systemic host
5
response against bacterial infection. A
previous study showed that the risk of
SBI
increased
with
higher
body
temperature with a cutoff point of
6

& $QDYHUDJHWHPSHUDWXUHRI
6'

OR
8.25
2.27

95%CI
1.40 to 48.54
0.40 to 121.73

P value
0.02
0.349

4.63
1.03

1.02 to 20.85
0.15 to 6.91

0.046
0.972

8.31
2.32

1.49 to 46.19
0.63 to 8.55

0.015
0.20

4.66
8.71
6.20

1.11 to 19.67
1.61 to 46.98
1.58 to 24.24

0.036
0.009
0.012

& LQFKLOGUHQZLWKEDFWHUHPLDDQG
6'

&LQ

children without bacteremia was also

reported.
A prior study in Sanglah Hospital
showed that children with bacteremia
had higher temperatures

&YV
6'

& UHVSHFWLYHO\ Our results may

differ because our subjects were in a
different age range. Since infants have
immature
immune
systems,
lower
temperatures do not eliminate the
probability of SBI.
The results of our study were
comparable to
D SUHYLRXV VWXG\ ZKHUH &53 RI PJ/
ZDV found to significantly increase the
probability of SBI. CRP levels have been
shown to have high sensitivity and

specificity in detecting SBI. Hsiao et al.

reported that the mean CRP was
significantly higher in the SBI group than
in the non-SBI group
>

6'

PJG/
6'

YV

PJG/ 3 @ Past studies have also found

that the bacterial markers studied were
more predictive of

6%,LIWKHGXUDWLRQRIIHYHUZDV!

KRXUV&53 performed better than leukocytes

count and ANC for predicting SBI.

Paediatr Indones, Vol. 52, No. 6, November

2012 315

Ni Putu Veny Kartika Yantie et al: Predictors of serious bacterial

infection in children

.RIWHULGLVet
al.
reported
a
correlation between CRP and body
temperature,
where
higher
body
temperature correlates with higher CRP

level. CRP is the best marker for SBI

detection
because
it
has
higher
sensitivity and the tests are relatively

affordable.
Quantitative
CRP
concentration is a valuable laboratory
test in the evaluation of febrile young
children who are at risk for occult
bacteremia and SBI, with a better
predictive value than leukocyte count or

ANC.
CRP is an acute phase reactant
synthesized by the liver due to increased
levels of cytokines, especially IL-6,
released during infection or inflammation.
IL-6 binds to polysaccharides of pathogens
and activates the classical complement
pathway. It is produced 4-6 hours after the
onset of tissue damage or inflammation,
LQFUHDVHV WZRIROG HYHU\ KRXUV DQG SHDNV DW

hours. IL-6 is also a sensitive marker of

bacterial infections.
A limitation in this study was not
analyzing the type and duration of
antibiotic and antipyretic used. Also,
retrieving data retrospectively may give
biased information, especially for the
previous number of febrile days. In
addition,
the
use
of
different
thermometers and complete blood count
equipment may have lead to data errors.
:HFRQFOXGHWKDWIHYHURI&DQG&53RI

PJ/ZHUHVLJQLILFDQWSUHGLFWLYHIDFWRUVIRU6%,
V

*RK3/ /HH6: :RQJ(+3UHGLFWRUVRIVHULRXVEDFWHULDO

LQIHFWLRQLQFKLOGUHQDJHGWRPRQWKVZLWKIHYHUZLWKRXW
VRXUFH6LQJDSRUH0HG--

4. Hsiao AL, Chen L, Baker MD. Incidence and

predictors of
VHULRXVEDFWHULDOLQIHFWLRQVDPRQJWR GD\ROGLQIDQWV
3HGLDWULFV -

*URHQHYHOG $% %RVVLQN $: YDQ 0LHUOR *-

+DFN &(

Circulating inflammatory mediators in patients

with fever: predicting bloodstream infection. Clin
Diagn Lab Immunol.

-
6. Crum M, Murphy E. Acute management of
infants and
FKLOGUHQZLWKIHYHU>FLWHG 0DUFK @$YDLODEOH
IURP http://www.health.nsw.gov.au
$OSUHQ (5 +HQUHWLJ )0 )HYHU ,Q )OHLVKHU *5 /XGZLJ
6

6LOYHUPDQ%.

HGLWRUV6\QRSVLVRISHGLDWULFHPHUJHQF\ medicine. 4

th

HG 3KLODGHOSKLD /LSSLQFRWW :LOOLDPV :LONLQV- S

8. Setyorini A, Arhana BNP, Utama DL. Prevalensi

faktor
prediktif bakteremia pada anak dengan
demam di RSUP
6DQJODK'HQSDVDU0(',&,1$%HUH]LQ(1

(YDOXDWLRQRILQFLGHQFHRIRFFXOW

,D]]HWWL0$
bacteremia

among

children with fever of unknown origin.

%UD]-,QIHFW'LV -

%RQDGLR:$

0F(OUR\.

-DFRE\3/
6PLWK'5HODWLRQVKLS of fever magnitude to
rate of serious bacterial infections in

LQIDQWDJHGZHHNV&OLQ3HGLDWU- ,VDDFPDQ '- 6KXOWV - *URVV 7. 'DYLV 3+ +DUSHU 0

3UHGLFWRUVRIEDFWHUHPLDLQIHEULOHFKLOGUHQWRPRQWKV
RIDJH3HGLDWULFV -

in children.

$YQHU-5$FXWHIHYHU3HGLDWU5HY -

Acknowledgment
:HH[WHQGRXU
JUDWLWXGHWR,*GH5DND:LGLDQD
0' IRUKLVKHOS in constructing the methodology
and statistical analyses in this study.

0DKHVZDUL1(85(&$,QGLDQ3HGLDWU -
.RIWHULGLV'3 6DPRQLV* .DUDW]DQLV'$ )UDJLDGD
NLV*0
Bourolias CA, Maraki, et al. C-reactive protein and
serum procalcitonin levels as markers of bacterial
upper respiratory

WUDFWLQIHFWLRQV$P-,QIHFW'LV -
$QGUHROD%%UHVVDQ6 &DOOHJDUR6 /LYHUDQL$
3OHEDQL0

References

Da Dalt L. Procalcitonin and C-reactive protein as

diagnostic markers of severe bacterial infections
in febrile infants and
FKLOGUHQLQWKHHPHUJHQF\GHSDUWPHQW3HGLDWU,QIHFW'LV
-

3UDWW$$WWLD0:'XUDWLRQRIIHYHUDQGPDUNHUVRIVHULRXV

3XOOLDP31

$WWLD0:

bacterial infection in young febrile children. Pediatrics.

&URQDQ.0&UHDFWLYHSURWHLQLQIHEULOH FKLOGUHQ WR

PRQWKV

%OHHNHU 6( 0RRQV .*0 'HUNHVHQ/XEVHQ *

*UREEHH

RI

DJH

ZLWK

FOLQLFDOO\

XQGHWHFWDEOH

VHULRXVEDFWHULDOLQIHFWLRQ3HGLDWULFV -

source. Acta Pediatrica.

6LPRQ/ *DXYLQ) $PUH'. 6DLQW/RXLV3

/DFURL[-6HUXP procalcitonin and C-reactive
protein levels as markers of bacterial infection:
a systematic review and meta-analysis.

&OLQ,QIHFW'LV -

DE, Moll HA. Predicting serious bacterial infection

in young children with fever without apparent

316Paediatr Indones, Vol. 52, No. 6,

November 2012