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Bacteremia in Children: Etiologic Agents, Focal Sites, and

Risk Factors
by L. F. Nimri,a M. Rawashdeh,b and M. M. Meqdama
aDepartment of Applied Biology, and bDepartment of Pediatrics, Jordan University of Science and Technology, Irbid, Jordan

Summary
A prospective study was carried out on 210 cases of children under 10 years of age with fever. Cases
of gastroenteritis, respiratory tract infections, and suspected sepsis in children seen or admitted to
the pediatric hospital were studied. Clinical and microbiological data were recorded in a questionnaire or obtained from patient medical records. Most of the children with septicemia (71.3 per cent)
were less than 1 year old. Focal source of bacteremia was gastroenteritis (40.4 per cent), pneumonia
or bronchopneumonia (20 per cent), meningitis (7.4 per cent), and urinary tract infections (7.4 per
cent). The predominant pathogens isolated from blood or stool specimens were Gram-positive
bacteria (53.3 per cent), mainly Streptococcus pneumoniae and coagulase-negative Staphylococcus
spp. The Gram-negative bacteria (45.6 per cent) were mainly Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Yersinia spp. One case of Candida
albicans (1.1 per cent) was reported. Pasteurella pneumotropica was reported in two cases for the
first time. The mortality rate was 4 per cent, mostly from septicemia cases. Long duration of hospitalization (> 10 days) and parenteral feeding were identified as risk factors. Resistance of the
isolated pathogens to several commonly used antibiotics was observed. Empirical treatment with
antibiotics is recommended only in life-threatening cases.

Introduction
Bacteremia has been increasingly reported in
children under 5 years of age. There are no reliable
data on the incidence or prevalence of invasive
bacterial infections involving children in Jordan.
Bacteremia in certain infections is considered the best
practical way to identify the causative organism. The
isolation of bacteria from blood cultures is usually
indicative of a serious invasive infection that requires
immediate antibiotic treatments.1 Septicemia is a
pathological condition with a high mortality rate that
varies between 30 and 70 per cent and depends on
several factors including virulence of the pathogen
and host factors.21,22 The majority of the bacteremia
cases are caused by a number of pathogens including
Staphylococcus spp., Streptococcus spp., Enterobacter
spp., Escherichia coli, Klebsiella pneumoniae, and
Pseudomonas spp.20
In such a potentially life-threatening condition,
isolation of the causative pathogen in blood culture is
crucial for proper antimicrobial treatment. Different
organisms have different antimicrobial susceptibili-

ties and successful treatment is dependent on the

prompt administration of the correct drug.10,15 This
may improve the prognosis of the patients with
septicemia. The delay, however, may mean unnecessary treatment or the use of ineffective therapy given
to antibiotic resistant organisms.
There is a wide variation in the incidence and
clinical characteristics of invasive infections caused
by different species of bacteria. Identifying the
causative species and characterizing the clinical
significance in a particular age group in a community
is essential for the prevention and treatment of these
infections.
We carried out a prospective study in children
under 10 years old who had a temperature of 39C,
regardless of the presumed clinical source of fever, to
identify the most frequently encountered causative
agents, their susceptibilities to the commonly used
antibiotics, and factors contributing to these infections in this age group.

Acknowledgements

Subjects
A total of 210 children under 10 years old presenting
to a pediatrician with a temperature of 39C during
the 2-year period between 1998 and 1999 were
eligible for this study. These included cases of
gastroenteritis, respiratory tract infection, meningitis,

This study was supported by a grant (no. 25/97) from the Deanship
of Research at Jordan University of Science and Technology.
Correspondence: Dr Laila Nimri, Department of Applied Biology,
JUST, P.O. Box 3030, Irbid 22110, Jordan. Tel 9622 709-5111; Fax
9622 709-5014. E-mail <nimri@just.edu.jo>.

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Methods

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urinary tract infections (UTI), or suspected sepsis

that were admitted to Prince Rahma Hospital in
Irbid, Jordan. It is the largest community pediatric
hospital affiliated with Jordan University of Science
and Technology that receives patients from the
northern region in the country. Clinical, microbiological data and other information such as temperature,
immunodeficiencies, and antibiotic therapy were
recorded from the patients medical record. A questionnaire concerning demographic data, age, sex,
chief complaint, duration of symptoms, and hospital
stay was completed for each patient.
Microbiology
A blood specimen was collected from each patient
and inoculated in a biphasic blood culture bottle
(BioMerieux, France). Bottles were incubated at
37C and continuously monitored for evidence of
bacterial growth. An aliquot of the positive blood
culture was aseptically taken by a syringe for Gram
stain and subcultured on enriched and selective
media for a wide variety of pathogens. Stool samples
were also collected from the same patients and
cultured on selective media. The organisms grown on
agar plates from both blood and stool specimens
were identified by standard laboratory methods
including biotyping and API 20E (BioMerieux,
France).
Susceptibility tests
The antibiotic sensitivity of the isolates was tested for
11 antibiotics on MullerHinton agar using disc
diffusion assay.14 Susceptibility testing to at least six
out of 10 antibiotics was performed on each isolate.
Antibiotics tested were amoxicillin, ampicillin,
augmentin, doxicillin, gentamicin, novecin, tetracycline, tobramycin, rifampicin, erythromycin and
vancomycin (for the Gram-positive isolates). Nonsusceptible refers to resistant and intermediately
resistant.
Data analysis
Univariate analyses were performed using Epi-Info
version 6.0 (Centers for Disease Control and Prevention, Atlanta, USA). Means and proportions were
compared by standard tests (chi-squared and t-tests)
A p value of 0.05 was considered significant.
Results
Positive cultures
Pathogens were isolated from a total of 94 out of the
210 patients (44.8 per cent). The mean age of the
patients was 16.6 months 14.8 (range: 1120
months), 61.3 per cent of these patients were males
(Table 1). Results of stool cultures and the isolated
species are shown in Table 2.

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TABLE 1
Characteristics of 94 patients with bacteremia
Characteristics
Age group (months)
112
1324
2536
> 36
Sex
Males
Females
Primary infection
Gastroenteritis
Pneumonia or
bronchopneumonia
Meningitis
Sepsis
Urinary tract infections
Septic arthritis
Undetermined

No. of patients (%)

67 (71.3)
10 (10.6)
8 (8.5)
9 (9.6)
57 (60.6)
37 (39.4)
38 (40.4)
19 (20.2)
7 (7.4)
7 (7.4)
7 (7.4)
2 (2.1)
14 (14.9)

TABLE 2
Bacterial species isolated from 94 blood and stool
cultures
Species isolated

No. of isolates (%)

Blood cultures
Coagulase negative Staphylococcus spp.
Staphylococcus aureus
Streptococcus spp.
Enterococcus spp.
Escherichia coli
Enterobacter taylorae
Salmonella typhi
Shigella sonnei
Klebsiella pneumoniae
Neisseria meningitidis
Haemophilus influenzae
Pseudomonas aeruginosa
Pasteurella pneumotropica
Yersinia enterocolitica
Yersinia pseudotuberculosis
Candida albicans
Unidentified

19 (20.1)
5 (5.3)
21 (22.3)
3 (3.2)
9 (9.6)
2 (2.1)
4 (4.3)
1 (1.1)
8 (8.5)
4 (4.3)
6 (6.4)
1 (1.1)
2 (2.1)
2 (2.1)
2 (2.1)
1 (1.1)
4 (4.3)

Stool cultures
Escherichia coli
Candida albicans
Salmonella typhi
Shigella spp.
Yersinia enterocolitica
Yersinia pseudotuberculosis
Aeromonas salmonicida

19 (50.0)
5 (13.2)
4 (10.5)
2 (5.3)
4 (10.5)
2 (5.3)
2 (5.3)

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Focal sites and causative species

Clinically, focal source of bacteremia was determined
in 80 out of the 94 positive cases (85.1 per cent) (Table
2). A focal site of infection could not be identified in
14 (14.9 per cent) of the patients. Most of the
bacteremia cases (71.3 per cent) were documented in
patients less than 1 year old, of whom 51.1 per cent
were less than 6 months old. Only 9.5 per cent of the
cases were documented in children aged between 3
and 10 years. From the diagnosis made by the pediatrician, the focal infections of bacteremia in these
patients were gastroenteritis (40.4 per cent), pneumonia or bronchopneumonia (20 per cent), meningitis (7.4 per cent), sepsis (7.4 per cent), UTI (7.4 per
cent), and septic arthritis (2.1 per cent). None of the
patients were documented to have immunodeficiency. Gram-positive bacteria were predominant
(53.3 per cent), while Gram-negative accounted for
45.6 per cent, and Candida albicans accounted for 1.1
per cent. The most common cause of bacteremia in
these patients was coagulase negative Staphylococcus
spp. (CoNS) (20.1 per cent), mainly Staphylococcus
epidermidis, Streptococcus spp. (22.3 per cent),
mainly group A beta-hemolytic streptococci, Neisseria meningitidis (4.3 per cent), Klebsiella pneumoniae
(8.5 per cent), Haemophilus influenzae (6.4 per cent),
Salmonella typhi (4.5 per cent), Yersinia enterocolitica
(2.1 per cent), Yersinia pseudotuberculosis (2.1 per
cent), Pasteurella pneumotropica (2.1 per cent), and
Shigella sonnei (1.1 per cent). (Table 2).
The majority of CoNS spp. (70 per cent) were
isolated from children less than 18 months old; 30 per
cent were isolated from the age group 1836 months.
Ten per cent of the bacteremia in the hospitalized
cases were suspected to be nosocomial in origin and
one case was polymicrobial. Risk factors identified
were: age of 1 year or less (95 per cent CI = 1.162.55,
p < 0.001); length of stay in hospital (10 12.2 days,
p = 0.008); and parenteral feeding (p < 0.001).
Symptoms recorded beside fever depending on the
primary site of infection were vomiting (90.9 per
cent), diarrhea in 85.5 per cent of the gastroenteritis
cases, cough (95 per cent) in respiratory tract infections, and febrile convulsions were reported in eight
patients (8.5 per cent).
Mortality rate
The overall mortality rate in these cases was 4 per
cent due to infections with Neisseria meningitides
(two cases), Streptococcus pneumoniae (one case),
and Candida albicans (one case).
Treatment
Oral treatment was given to the majority of these
cases, i.e. 92 (97.8 per cent) on the date of the initial
blood culture. Of these treated patients, 35 (38 per
cent) received parenteral antibiotics either as single
or as combination antibiotics. The combination of
claforan/ampicillin was the most prescribed.
358

Electrolytes and intravenous fluids were given to

cases with diarrhea and dehydration. Patients
suspected of having meningitis or sepsis received
empiric parenteral antibiotics and were reported to
have improved conditions at follow-up.
Susceptibility testing
Non-susceptibility of the isolates was observed for at
least two of the antibiotics tested. The highest was
recorded for ampicillin (72.2 per cent), augmentin
(50 per cent), amoxicillin (46.2 per cent), and
erythromycin (45.4 per cent of the Gram-positive
isolates).
Other laboratory tests
Additional laboratory tests were performed on all
patients, such as the white blood cell counts which
were 20000 cells/mm3. Other tests were performed
depending on the primary diagnosis of the pediatrician. These tests included serological tests (e.g.
latex test for Brucella and Widal test for Salmonella),
tests and cultures of CSF obtained from eight
patients suspected to have meningitis, detection of
parasites in stool for patients with gastroenteritis,
and urine analysis and cultures in the case of patients
with suspected UTI.
Discussion
Bacterial infections are major causes of morbidity
and mortality in children. The detection, identification, and susceptibility testing of a causative
species of bacteremia is essential for the proper treatment, and better prognosis of the patient.
In this study, bacteremia was confirmed in 94 (44.8
per cent) patients out of 210 children with various
diseases. The most common primary infection was
identified in 80 (85.1 per cent): gastroenteritis (40.4
per cent) and pneumonia (20.4 per cent). The
causative species were also identified in 90 (95.7 per
cent) of the cases in blood and stool cultures.
The most common pathogens were Streptococcus
spp. (22.3 per cent) especially S. pneumoniae mainly
isolated from cases with pneumonia. Streptococcus
pneumoniae was also reported as the most common
pathogen in children with bacteremia aged 336
months.8 Pneumonia counted for 7 per cent of these
children while other respiratory tract infections
counted for 24 per cent, gastroenteritis (9 per cent),
and UTI (5 per cent). In another study, the source of
bacteremia cases of pneumococcal infections, were
pneumonia (37 per cent), otitis media (30 per cent),
meningitis (11.5 per cent), and no focal source (33
per cent).19 Group A streptococci (e.g. S. pyogenes)
although an uncommon cause of meningitis, was
reported in few cases as a result of bacteremia or
surgery.13
Coagulase negative staphylococci (CoNS)
accounted for 20.1 per cent of the blood culture
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isolates obtained from clinically defined infections.

The highest incidence of sepsis caused by Staphylococcus epidermidis was observed in children less than
12 months old. Our results are in agreement with
other studies that reported CoNS as the most
common bacteria isolated from infants with sepsis.17
The frequent finding of CoNS and S. pneumoniae
were also reported by a study that used molecular
diagnosis by PCR.1
Staphylococcus epidermidis and other CoNS was
reported to have emerged as a major cause of nosocomial infections.6 They are part of the normal skin
and mucosal micro flora, and their presence in blood
cultures might indicate catheter and medical devicerelated sepsis or a contaminant of blood cultures.9
The interpretation of their presence is a major
concern for clinicians and clinical microbiology
laboratories. The decision for therapy relies mostly
on the observation of sepsis symptoms and the
number of positive blood cultures. However, the
criteria of multiple blood cultures could not be
applied in pediatric patients who cannot undergo
multiple venous puncture. Escherichia coli was
isolated from 9.6 per cent of the cases; it was reported
to be the most frequent Gram-negative bacterial
species recovered from blood cultures.1
Bacteremia caused by Klebsiella pneumoniae
accounted for 7.4 per cent of the cases. In a study of
neonatal sepsis in Ethiopia, Klebsiella was reported
as the leading etiologic agent (38 per cent).7 Yersinia
enterocolitica (two cases) and Yersinia pseudotuberculosis (two cases) were isolated from blood and
stool cultures of gastroenteritis cases; these isolates
were non-susceptible to ampicillin. Pasteurella pneumotropica was isolated from blood cultures of two
patients and were identified by the API system but,
the source of infection, which is usually from animals,
was not established. Shigella sonnei was isolated
from blood and stool cultures of a 10-month-old
child who had severe diarrhea. Isolation of Shigella
spp. from blood is considered as an unusual medical
event and is not frequently reported.3
Candida albicans was isolated from the blood
culture of a 10-month-old male. This was a fatal case
because antifungal treatment was not given. The
Canadian Infectious Disease Society reported 11.6
per cent infection rate in children and an overall
mortality rate of 27 per cent that varies with the
species of Candida.23
Enterococcus taylorae was isolated from blood
cultures of three children (3.2 per cent) who had been
hospitalized for 10 days. Intravascular device was
used during their stay, which might be a risk factor for
a nosocomial infection with these species. They were
reported as a nosocomial infection due to use of
intravascular device in 44 per cent of the bacteremia
cases in 66 per cent of children 1 year old or less.5
Haemophilus influenzae was isolated from six (6.4
per cent) blood cultures mostly from children <5
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December 2001

years old. A study on the epidemiology of systemic

Haemophilus influenzae disease in Korean children
reported infections in 92 per cent of children <5 years
old.11
Pseudomonas aeruginosa was isolated from one
blood culture of a 12-month-old male in our study. It
was reported with the predominant pathogens in a
study of cases of children undergoing transplantation.20
Polymicrobial bacteremia was reported in a 6month-old male diagnosed with sepsis; the species
isolated from the blood culture were Pasteurella
pneumotropica and Enterococcus taylorae. He was
discharged with no complications after a parenteral
antibiotics treatment, a combination of claforan and
ampicillin.
There was no attempt to isolate anaerobic bacteria
in this study although it might have been the cause of
bacteremia in some of the cases where no aerobic
bacteria were detected in blood cultures. Anaerobic
bacteria were reported to constitute 18 per cent of
the total number of isolates from blood.2 Of particular concern is the increased number of nonsusceptible isolates to more than one antimicrobial
agent commonly used for treatment. Multiple drug
non-susceptibility was observed in 62 per cent of the
isolates especially in species isolated from patients
who had a long duration of stay (> 10 days).
Multiple-drug resistance of isolates from
bacteremic children is also reported by others.18,19
This is of particular concern to clinicians since they
have to treat patients with invasive disease more
cautiously.
The use of parenteral antibiotics at the initial visit
resulted in improved conditions at follow-up than
those cases who were treated with oral antibiotics.
This was reported in cases of pneumococcal infections.4 Early treatment also prevented complications, such as rheumatic fever, that might result
from infections with group A -hemolytic streptococci.16 Empirical treatment with antibiotics for
febrile infants until the blood culture results were
available was used and was recommended in another
study.12 This kind of treatment for febrile infants who
do not appear toxic, may promote further development of drug-resistant bacteria and is not recommended for those children who look well and are
without any obvious focus of infection.
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