Susceptibility Pattern of Streptococcus pneumoniae Among
Pre-school Children in Kota Bharu, Malaysia
by Alam Sher Malik,* Asma Ismail,* Ross A. Pennie** and Jaya V. Naidu*
* School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150, Kelantan, Malaysia
** Faculty of Health Sciences, McMaster University, Ontario, Canada
Summary
Streptococcus pneumoniae (5. pneumoniae) is the most common bacterial cause of pneumonia,
meningitis, and otitis media, with the highest incidence among young children and the elderly.
S. pneumoniae was once routinely susceptible to penicillin, but since the mid-1980s the incidence of
resistance to penicillin and other antimicrobial agents has been increasing all over the world.
To optimize empirical regimens and initial therapy for S. pneumoniae infections, clinical healthcare providers must be informed about the prevalence and pattern of drug resistance among the
isolates in their communities. No such data are available for the Malaysian population. Therefore,
this study was designed to determine the antibiotic susceptibility pattern of S. pneumoniae among
colonized pre-school children in Kota Bharu, Malaysia. Pharyngeal swabs were collected from
children 1 month to 6 years of age. S. pneumoniae isolates were identified according to the standard
and tested for penicillin resistance with a 1-ftg oxadllin disk by the Kirby-Bauer disk diffusion
methods.
Of 355 nasopharyngeal specimens obtained from kindergarten students, in-patients and pedlatric
clinics over a period of 1 year, S. pneumoniae was isolated from 36 (10 per cent). All isolates, except
one, were susceptible to penicillin. The resistant isolates was susceptible to erythromycin,
chloramphenicol and cephalosporins.
Introduction
Streptococcus pneumoniae is the most common bacterial
cause of pneumonia and meningitis in children and
adults.1 It is also the most common bacterial aetiology of
acute otitis media, causing 30-50 per cent of episodes.2
In the United States, every year an estimated 6 million
cases of otitis media 500,000 cases of pneumonia and
over 6000 cases of meningitis are caused by this
organism,3'4 with the highest incidence among young
children and the elderly.5-6
5. pneumoniae normally resides in the pharynx of
healthy people. The rate of colonization is particularly
high in young children living in institutions, ranging
from 25 to 50 per cent. Most children are colonized at
sometime during the first year of life.7'8 S. pneumoniae
was once routinely susceptible to penicillin, but since the
mid-1980s the incidence of resistance to penicillin and
other antimicrobial agents has been increasing.9'10
Resistant strains have been identified in many countries
including South Africa, New Guinea, US, Australia,
Canada, Israel, Poland, Spain, France. Hungary, and
Acknowledgements
We gratefully acknowledge the financial support by Universiti
Sains Malaysia for this study. We are thankful to Siti Rokiah
Wan Talib (Paediatric Wards) and Latifah bt Seman (Paediatric
Clinics) for their help to make this study possible.
10
© Oxford University Press 1998
Romania. Data are scant from most Asian countries.'' In
Pakistan 14 percent of healthy carriers of S. pneumoniae
had penicillin-resistant strains.12
Resistant strains of 5. pneumoniae can spread readily
in communities13'14 and may increase the public health
impact of 5. pneumoniae infections because of reduced
effectiveness of antimicrobial treatment. Of special concern is resistance to extended-spectrum cephalosporins,
which are often used as empirical therapy for meningitis."
To optimize the empirical regimens and initial therapy
for S. pneumoniae infections, clinical health-care providers must be informed about the prevalence and
patterns of drug resistance among the isolates in their
communities. No such data are available for the
Malaysian population. We conducted an investigation
to determine the prevalence of colonisation of drug
resistant 5. pneumoniae among children in our community. The objectives of the present study were: (a)
to determine the rate of nasopharyngeal colonization
of S. pneumoniae among pre-school children in Kota
Bharu; (b) to determine the rate of penicillin resistance
among the S. pneumoniae colonizing those children; and
(c) to determine the antibiotic susceptibility pattern of
any penicillin-resistant strains of 5. pneumoniae.
Methods
After written permission was obtained from school
Journal of Tropical Pediatrics
Vol. 44
February 1998
A. SHER MALIK ET AL
administrators and parent/guardians, nasopharyngeal
swabs were performed on children aged 1-72 months
in the following venues in and around Kota Bharu,
Kelantan, Malaysia: kindergarten schools, pediatric outpatients clinics, and in-patient wards of Hospital
Universiti Sains Malaysia. The study period was March
1 1995 to February 29 1996. Excluded from the study
were children currently taking antibiotics, those who had
done so within the previous 2 weeks, and children who
were seriously ill.
Parents were interviewed by a research nurse and the
following demographic information was collected: age,
race, number of siblings, place of residence, use of
antibiotics, and use of other medications. Participating
children were examined by a pediatrician in order to
document the presence of illness and the nutritional
status, based on a modified Wellcome classification of
protein-energy malnutrition. Children with body weights
of greater than or less than 80 per cent expected for age
were denned as having 'good' or 'poor' nutritional
status, respectively.
Culture specimens were collected from the nasopharynx using a cotton-tipped flexible metal applicator.
One swab was inserted into each subject's posterior
nasopharynx, rotated slowly for approximately 30 s,
removed, and inoculated immediately onto a blood agar
plate, and incubated at 37°C for 24-48 h in a 3-12 per
cent CO2-enriched atmosphere. Organisms were identified and confirmed as S. pneumoniae by using standard
diagnostic microbiological techniques.16 Penicillin susceptibility was performed by the disk diffusion method17
using Mueller-Hinton agar containing 5 per cent lysed
human blood and 1 per cent vitox (Oxid). A l-/ig
oxacillin disk (breakpoint, 20 mm) was used18"20 for this
purpose.
During the course of study, oropharyngeal cultures
were obtained from 147 children. The culture was taken
with a cotton-tipped wooden applicator from the posterior wall and tonsillar areas of the oropharynx. Each
applicator was then immediately placed into the Stuart's
transport medium and sent to the bacteriology laboratory
for inoculation on blood agar plates within 4-6 h after
collection. These specimens were further processed
similarly to the nasopharyngeal swabs.
The 5. pneumoniae colonization rate was defined as
the percentage of children found to have a nasopharyngeal culture positive for 5. pneumoniae. Statistical
analyses were performed using Chi-square and Fisher
exact tests.
Results
Nasopharyngeal cultures were obtained from 355
children between the ages of 1 and 72 months (mean
35 months, median 36 months). The majority, 301, were
healthy on the day of culture, while 27 had respiratory
infection, 18 had diarrhoea, and 9 had developmental
delay. The demographic characteristics and bacteriological culture results are illustrated in Table 1.
Journal of Tropical Pediatrics
Vol.44
February 1998
S. pneumoniae was isolated from 36 (10 per cent) of 355
children. When the following features of the study
participants were analysed, no statistically significant
differences were noted in the rates of S. pneumoniae
nasopharyngeal colonization: race (Malay, Chinese,
Indians), gender, venue of enrolment, location of
family home, and number of siblings. There was a
trend (P = 0.07 by Chi square) for the 111 children with
poor nutritional status to have a rate of 5. pneumoniae
colonization (14 per cent) that was greater than the
colonization rate (8 per cent) of well nourished children.
Only one of the 36 S. pneumoniae isolates was
resistant to penicillin by the oxacillin disk diffusion
method. Its penicillin minimum inhibitory concentration
was not determined. The isolate was found to be
susceptible to erythromycin, chloramphenicol and
cephalosporins by disk diffusion methodology.
The rate of S. pneumoniae isolation from oropharyngeal swabs was very low. Only one isolate was recovered
from the oropharyngeal swabs of 147 children. This
isolate was susceptible to penicillin by the oxacillin disk
diffusion method.
Discussion
Most infections caused by 5. pneumoniae are treated
empirically because sensitive and rapid diagnostic tests
are not immediately available. Until recently, penicillin
and related drugs have been the treatments of choice for
all S. pneumoniae infections. The emergence of drug
resistance among S. pneumoniae has increased
the complexity of decisions concerning management of
infections caused by this pathogen.'8 Upper respiratory
tract colonization studies are important in monitoring the
patterns of resistance to antimicrobial agents within
communities.12 Surveillance for drug-resistant S. pneumoniae in respiratory secretions obtained by nasopharyngeal swabs may provide useful information on
the prevalence of drug-resistant strains causing invasive
disease.21
The overall colonization rate of 10 per cent in the
present study is comparable to the colonization rate of
11 per cent among Chinese children in Hong Kong, but
significantly less than 56 per cent among Vietnamese
children reported in the same study.8 The high
colonization rate in Vietnamese children in Hong Kong
was attributed to extreme overcrowding in that community. In the present study the colonization rate detected
with nasopharyngeal swabs (10 per cent) was significantly higher than that detected with oropharyngeal
swabs (0.7 per cent) (P < 0.001). Similar findings were
reported in other studies. Maria el al. reported that in all
age groups 5. pneumoniae was isolated significantly
more often from the nasal than from the oropharyngeal
site.22 In our study, the possibility of sampling or
laboratory error needs to be considered as a cause of
very low colonization rate in oropharyngeal swabs.
Although the same staff performed both swabs, the
oropharyngeal samples were first put into transport
11
A. SHER MAUK ET AL
TABLE 1
Demographical features and rates ofS. pneumoniae isolation among 355 preschool children undergoing
nasopharyngeal culture in Kota Bharu, Malaysia*
Number of
nasopharyngeal
cultures
Number colonized
with S. pneumoniae
(%)
1 to £ 24
>24to £48
> 48 to £72
140
54
161
13 (9.3)
4 (7.4)
19(11.8)
Male
Female
201
154
23(11.4)
13 (8.4)
Malay
Chinese
Indian
Other
213
111
23
8
22 (10.3)
10 (9.0)
3 (13.0)
1 (12.5)
School
Clinic
Hospital ward
175
101
79
19 (10.9)
12(11.9)
5 (6.3)
Urban
Rural
318
37
31 (9.7)
5 (13.5)
28
159
106
62
2(7.1)
14 (8.8)
16(15.1)
4 (6.3)
244
111
20 (8.2)*
16 (14.4)*
Age [months]
Gender
Race
Venue of enrolment
Location of home
Number of siblings
0
1-2
3-4
>4
Nutritional status'
Good
Poor
* No-features showed a statistically significant difference between colonized and non-colonized children.
As determined by modified Wellcome criteria, children were defined to have good nutritional status if they had > 80 per cent body
weight-for-age.
* Almost reached statistical significance by Chi square, P = 0.07.
f
medium, whereas the nasopharyngeal swabs were plated
directly onto blood agar before transportation to the
laboratory.
There was a trend for the colonization rate to be higher
in poorly nourished compared to well nourished
children. The secretary IgA in nasopharyngeal secretions
which prevents the adherence of micro-organisms to the
upper respiratory tract could be different both in quantity
and quality in poorly nourished children and may
increase or prolong the rate of colonization. The age of
acquisition of S. pneumoniae in infants has been reported
to range from 4 days to 18 months.23 The present study
confirmed the early acquisition of nasopharyngeal
S. pneumoniae: 9 per cent of children aged 24 months or
less were culture positive.
Only one of the 36 isolates was found to be resistant to
penicillin. This organism was susceptible to other antibiotics including erythromycin and cephalosporins. This
particular child had recently returned to Malaysia after
visiting his relatives in Thailand. His siblings were not
similarly colonized, and his repeat culture after 2 weeks
was negative for S. pneumoniae.
12
Although the prevalence of penicillin-resistant 5.
pneumoniae was lower (3 per cent) in the current study
population than in some previous reports, the important
fact is that this study has documented the presence of
penicillin-resistant 5. pneumoniae in a sample of Malaysian children. A poor clinical response to penicillin must
now alert physicians to the possibility of an antibioticresistant strain. The majority of previous reports were
conducted among children suffering from upper or lower
respiratory tract infection or otitis media. The incidence
of penicillin-resistant S. pneumoniae is higher in children
who have repeatedly received antibiotics.21"24"27 Both
these risk factors were missing in our study population.
The prevalence of penicillin-resistant S. pneumoniae
varies from nation to nation and within the same nation
in different locations and at different times of the year.
The information collected in one community cannot be
applied to another or to the same community all the time.
There is a need to have constant surveillance, and also
careful evaluation of the antibiotic susceptibilities of
5. pneumoniae isolates from patients with invasive
disease such as bacteremia and meningitis.
Journal of Tropical Pediatrics
Vol.44
February 1998
A. SHER MAUK ET AL
At least four strategies may play a role in preventing
morbidity and mortality associated with infection with
drug resistant S. pneumoniae (DRSP).
(1) Comprehensive surveillance for DRSP can play an
important role for this purpose. This includes the
screening of invasive S. pneumoniae isolates for
resistance to penicillin and other drugs that are likely
to be used in treating these cases.20
(2) Optimal management strategies must be determined
for infections with DRSP. In areas with high rates of
resistance to extended spectrum cephalosporins,
empirical therapy with vancomycin in addition to
an extended spectrum cephalosporin should be
considered for cases of meningitis potentially
caused by 5. pneumoniae until the results of culture
and susceptibility testing are available.
(3) Because infection with DRSP is probably facilitated
by increasing exposure to antimicrobial agents18
strategies for their rational use should be promoted.
(4) Persons aged 2 years or older who are at increased
risk for serious infection and all persons aged more
than 65 years should receive 23-valent S. pneumoniae
capsular polysaccharide vaccine.29
5. pneumoniae protein-conjugate vaccines are being
evaluated for use in young children because the existing
polysaccharide vaccine is not immunogenic in this age
group.
The emergence of DRPS indicates the need to reassess
the efficacy of prophylactic antimicrobial drug regimens
for otitis media and to develop new antimicrobial drugs
for treatment of drug-resistant infection.
10.
11.
12.
13.
14.
15.
16.
17.
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