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REGULAR ARTICLE
Keywords
Bacterial meningitis, Disease severity, Paediatric,
Prognostic factors, Sequelae
ABSTRACT
Aim: This retrospective chart review aimed to identify factors in childhood bacterial
Correspondence
Dr Liang Yi Justin Wee, Department of Paediatrics,
KK Womens and Childrens Hospital, 100 Bukit
Timah Road, Singapore 229899, Singapore.
Tel: (+65) 6225 5554 |
Fax: (+65) 6394 2488|
Email: weeliangyi@gmail.com
Received
7 May 2015; revised 6 August 2015;
accepted 23 September 2015.
DOI:10.1111/apa.13228
INTRODUCTION
Bacterial meningitis can have potentially devastating consequences, especially in infancy and childhood. Compared
to viral or aseptic meningitis, it carries a higher risk of
mortality and morbidity if left untreated (1). Globally, the
risk of long-term disabling sequelae from bacterial meningitis has been estimated at around 20% (2,3). The negative
health impact from childhood bacterial meningitis persists
even into adulthood, as it is associated with lower educational achievement and less economic self-sufficiency in
adult life (4).
During the last two decades, vaccines against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis have been introduced.
Abbreviations
CSF, Cerebrospinal fluid; CI, Confidence interval; GBS, Group B
Streptococcus; GCS, Glasgow Coma Scale; Hib, Haemophilus
influenzae type b; ICU, Intensive care unit; IQR, Interquartile
range; OR, Odds ratio; PCR, Polymerase chain reaction.
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Key Notes
2015 Foundation Acta Pdiatrica. Published by John Wiley & Sons Ltd 2016 105, pp. e22e29
Wee et al.
RESULTS
Initially, 121 cases of childhood bacterial meningitis were
identified from data provided by the microbiology laboratory. After review, two cases were excluded as they had
prior neurosurgical intervention and seven cases were
excluded as their medical records were incomplete or
unavailable. A final total of 112 meningitis cases were
included in the study, as shown in Figure 1.
Demographics
A total of 109 patients whose ages ranged from three days
to 15 years were included. However, a total of 112
episodes of meningitis were analysed as three patients
had recurrent meningitis. The median age was 0.33 years,
with an interquartile range (IQR) of 0.081.92 years. We
noted that 59 cases (53%) were male, 63 (56%) were of
Chinese ethnicity, 29 (26%) were of Malay ethnicity, 13
(12%) were of Indian ethnicity, and the remaining seven
cases (6%) were from other ethnic groups. This matched
the proportion of each ethnic group under the age of 15
in Singapores population in 2014 (15). With regard to
age, 32 cases (29%) were neonates up to one month of
2015 Foundation Acta Pdiatrica. Published by John Wiley & Sons Ltd 2016 105, pp. e22e29
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Wee et al.
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Outcomes
We found that seven (6%) of the 112 cases succumbed to
meningitis and one other case died of an unrelated cause,
which was an idiosyncratic drug reaction. Of these seven,
the causative organisms were two cases of Streptococcus
pneumoniae, two cases of GBS and one case each of
Escherichia coli, Streptococcus pyogenes and Klebsiella
pneumoniae.
Table 2 shows the number of cases who were still being
followed up, as well as the number of cases suffering from
specific complications at each time point. Five years after
meningitis, 23 (32%) of the 73 cases still had residual
sequelae. All three patients with recurrent meningitis were
readmitted after completing the full course of antibiotic
therapy for the first episode of meningitis and had not been
discharged against medical advice. Two of these patients did
not complete five years of follow-up after meningitis, while
the third had no residual sequelae five years after meningitis.
Prognostic factors
As previously mentioned, due to the small number of cases
who succumbed to meningitis, the requirement for ICU
admission was used instead of mortality as an indicator of
disease severity. In the first half of the study period (1998
Number (%)
23
22
16
15
12
9
9
6
(21)
(20)
(14)
(13)
(11)
(8)
(8)
(5)
1
Other Gram-positive bacteria included Streptococcus bovis (three
cases), Streptococcus milleri (two cases), Listeria monocytogenes
(two cases), Enterococcus faecalis (one case) and Streptococcus pyogenes
(one case).
2
Other Gram-negative bacteria included Klebsiella pneumoniae (two cases),
Pseudomonas aeruginosa (one case), Morganella morganii (one case),
Proteus mirabilis (one case) and Edwardsiella tarda (one case).
2015 Foundation Acta Pdiatrica. Published by John Wiley & Sons Ltd 2016 105, pp. e22e29
Wee et al.
Time point
Total number still on follow up
Residual sequelae present
Complications
Developmental delay or learning difficulties
Epilepsy on antiepileptic drugs
Cerebral palsy or other neuromotor deficits
Sensorineural hearing loss
Hydrocephalus/shunt placement
Requirement for assisted feeding
Cortical blindness
Six months
One year
Two years
Five years
93
44% (41)
86
36% (31)
81
36% (29)
73
32% (23)
30%
22%
17%
11%
10%
8%
4%
27%
15%
17%
8%
8%
5%
5%
27%
15%
17%
8%
9%
5%
5%
26%
16%
19%
5%
10%
4%
6%
(28)
(20)
(16)
(12)
(9)
(7)
(4)
(23)
(13)
(15)
(9)
(7)
(4)
(4)
(22)
(12)
(14)
(9)
(7)
(4)
(4)
(19)
(12)
(14)
(6)
(7)
(3)
(4)
DISCUSSION
The rates of mortality and development of long-term
sequelae in our study population, which were 6% and
32% respectively, were comparable to similar statistics
from other developed countries (2,3,1012). The microbiological profile of the study cases was similar to that
observed in other developed countries. In South Korea,
an analysis of 402 cases of childhood bacterial meningitis,
of which 29.9% were neonates, showed GBS to be the
most common causative organism (24.6%), followed by
Streptococcus pneumoniae (22.6%) and Haemophilus
influenzae (16.7%) (10). Organisms associated with the
genitourinary tract such as GBS and Escherichia coli
were implicated by other studies in the majority of
neonatal meningitis cases (16).
In our study, pneumococcus as the causative organism,
leukopenia on initial blood count and a CSF:serum glucose
ratio <0.25 were found to be factors predictive of increased
disease severity, as indicated by the need for ICU admission,
whereas a high CSF white blood cell count (>1000/mm3)
was found to be associated with a lower likelihood of
requiring ICU admission. A similar study from Taiwan
concluded that pneumococcal meningitis had the highest
mortality rate, whereas Hib meningitis was associated with
the highest rate of sequelae (17). Leukopenia is reflective of
severe sepsis, and lower peripheral blood and CSF white
blood cell counts may indicate inadequacy of the immune
response. Chao et al. (18) found an association between
low CSF white blood cell counts and higher mortality in
pneumococcal meningitis. Nigrovic et al. (19) found that
pretreatment with parenteral antibiotics prior to lumbar
puncture did not change CSF white blood cell counts, but
was associated with higher CSF glucose and lower CSF
protein levels. Hence, a lower CSF white blood cell count
may be a useful predictor of disease severity in established
bacterial meningitis regardless of whether parenteral antibiotics were administered before the lumbar puncture. Lower
glucose levels in the CSF have been associated with
increased inflammation and cytokine levels (20) and have
been shown to return to normal sooner in patients receiving
2015 Foundation Acta Pdiatrica. Published by John Wiley & Sons Ltd 2016 105, pp. e22e29
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Wee et al.
Prevalence in study
population (%)
p-value
p-value
53
0.44 (0.210.95)
0.038
0.41
29
42
29
1.0 (0.452.3)
0.70 (0.331.5)
1.5 (0.653.3)
1
0.44
0.41
Not done
Not done
Not done
20
14
21
2.8 (1.07.2)
1.3 (0.473.9)
0.64 (0.251.7)
0.054
0.6
0.48
5.2 (1.518.2)
Not done
Not done
54
1.45 (0.683.2)
0.34
Not done
28
24
16
44
74
38
66
78
53
1.3
3.7
1.1
1.7
4.3
0.40
3.6
4.9
1.6
0.67
0.007
1
0.18
0.003
0.044
0.009
0.005
0.25
Not done
5.6 (1.717.9)
Not done
0.26 (0.0860.76)
4.5 (1.414.4)
Not done
(0.552.9)
(1.59.2)
(0.382.9)
(0.823.7)
(1.611.6)
(0.180.92)
(1.49.5)
(1.515.5)
(0.783.5)
0.009
0.004
0.79
0.20
0.014
0.01
0.08
The odds ratio (OR) for significant risk factors after multivariate analysis was indicated as the multivariate OR.
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2015 Foundation Acta Pdiatrica. Published by John Wiley & Sons Ltd 2016 105, pp. e22e29
Wee et al.
Table 4 Prognostic factors for residual sequelae five years after meningitis
Factor
Male gender
Age
Up to one month
Between one month and one year
One year and above
Causative organism
Streptococcus pneumoniae
Hib
GBS
History
Fever 48 hours prior to presentation
Drowsiness, lethargy or irritability
Initial physical examination
Altered mental state
Tachycardia or hypotension
Respiratory distress
Initial laboratory tests
Anaemia
Leukopenia
Thrombocytopenia
CRP > 100 mg/mL
Bacteraemia
CSF white blood cell count > 1000/mm3
CSF:serum glucose ratio <0.25
CSF protein > 1 g/L
CSF Gram stain positive
Complications during inpatient stay
Subdural empyema
Seizures requiring antiepileptic drugs
Septic shock
SIADH1
Prevalence in study
population (%)
p-value
p-value
53
0.37 (0.131.1)
0.079
0.41
29
42
29
0.42 (0.131.3)
1.5 (0.564.1)
1.6 (0.505.2)
0.185
0.456
0.535
Not done
Not done
0.051
20
14
21
2.1 (0.647.4)
6.9 (1.529.7)
0.41 (0.121.39)
0.323
0.009
0.174
Not done
29.5 (2.0429)
54
57
1.9 (0.675.4)
0.87 (0.322.4)
0.304
0.803
Not done
Not done
51
45
26
1.5 (0.564.13)
0.84 (0.312.3)
3.8 (1.311.0)
0.457
0.804
0.016
Not done
Not done
28
24
16
44
74
38
66
78
53
2.0
2.0
1.7
2.1
4.5
0.64
4.2
0.38
0.90
(0.686.1)
(0.685.7)
(0.486.1)
(0.785.8)
(0.9321.7)
(0.212.0)
(1.116.9)
(0.101.5)
(0.332.4)
0.25
0.27
0.5
0.20
0.072
0.59
0.042
0.23
1
Not
Not
Not
Not
Not
25
39
19
14
1.5
9.3
7.4
3.2
(0.524.4)
(2.929.7)
(2.027.7)
(0.7713.3)
0.58
<0.001
0.002
0.13
0.013
0.25
0.074
done
done
done
0.28
0.45
done
0.33
0.55
done
Not done
10.6 (1.960.2)
8.4 (1.162.1)
0.008
0.036
0.70
2015 Foundation Acta Pdiatrica. Published by John Wiley & Sons Ltd 2016 105, pp. e22e29
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Wee et al.
5.
6.
CONCLUSIONS
This study represents the experience of a single large medical
centre in a developed, multi-ethnic Asian country over a long
time period of 15 years, with a study population of patients
who all had microbiologically confirmed bacterial meningitis.
Furthermore, 70% of the initial cases had completed an
extended follow-up period of five years. In view of the small
number of cases who succumbed to meningitis, we used the
requirement for ICU admission as a marker of disease
severity, which becomes more relevant than raw mortality
in settings with a low overall incidence of bacterial meningitis.
We found that predictive factors for increased severity of
childhood acute bacterial meningitis, necessitating ICU
admission, included pneumococcus as the causative organism, leukopenia on initial blood count and a CSF:serum
glucose ratio <0.25. Patients with a CSF white blood cell
count >1000/mm3 were less likely to require ICU admission.
Recognition of these common clinical and laboratory parameters, possibly as part of a severity score, can allow for better
allocation of resources by identifying patients who may need
closer monitoring or warrant more aggressive treatment.
Prognostic factors for residual sequelae five years after
meningitis include Hib as the causative organism, seizures
during the childs inpatient stay and septic shock. Knowledge
of these factors would help to identify those patients who may
need more intensive outpatient rehabilitation. It is also
important to note that both pneumococcal and Hib meningitis are vaccine-preventable diseases, further underscoring
the importance of vaccination against these organisms.
7.
8.
9.
10.
11.
12.
13.
14.
CONFLICTS OF INTEREST
The authors have no competing interests to declare.
15.
FUNDING
No funding was received for this study from any organisation.
16.
17.
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Wee et al.
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