Article Type : Research Article
Authors : Belykh NA, Anikeeva NA, Goryachev VV, Kuznetsova AN, Faletrov MV, Fokicheva NN, Shilina SA, Fedoseeva NY and ??lashnikova ON
Keywords : Bacterial meningitis; Children; H Influenzae; S pneumoniae; Antibacterial therapy
A retrospective analysis of 23 cases of bacterial meningitis
(BM) in children in 2016-2019 was carried out. The examined patients were not
vaccinated against H. Influenzae type
B and S. pneumoniae. The dominant
pathogens of BM were H. Influenzae
(52.2%), S. pneumoniae (8.7%), N.
meningitidis (4.3%). BM caused by H. Influenza was characterized by a wave-like
course with complications, which required correction of antibiotic therapy
(ABT). This indicates the feasibility of vaccinating of the children against
hemophilic infection.
Acute bacterial meningitis (BM) remains a serious global health
threat with high mortality and morbidity, despite advances in antibiotic
therapy and modern vaccination strategies. Children are particularly vulnerable
to ABM because of their relatively immature immune systems, particularly their
impaired immunity to the polysaccharide capsule of bacteria commonly associated
with ABM. It has been estimated that over 75% of all cases of ABM occur in
children under 5 years of age, and it is one of the most common
life-threatening infections in children worldwide. The WHO estimates that about
170 000 deaths occur annually from the disease worldwide; the case fatality
rate can be as high as 50% if not treated [1]. The estimated median risk of at
least one major or minor sequel from ABM after hospital discharge is 19.9%.
Adverse outcome varies with age group, geographic location and the infecting
organism. In middle- and low-income countries, ABM remains the fourth leading
cause of disability [2]. Even with early diagnosis and adequate treatment 15%
of patients die, as a rule, within 24 and 48 hours after the onset of the first
symptoms [3]. Annually more than 4000
cases of BM in children and 500 deaths were registered in USA in 2003-2007
years [4]. Annually incidence
of BM in Russia is 8.22 cases per 100 thousand population [4]. Most cases of BM
are associated with opportunistic flora (S.
agalactiae B, E. col, and
L monocytogenes) in newborns and S. Pneumoniae,
N. meningitides and H. influenzae in children and
adolescent. [5,6]. Vaccination of the children against N. meningitides and
H. influenza are not mandatory. Becose prevalence of BM by these
pathogenes in children is higher. But during 2004-2007 yars among pathogens of
BM in children were identyfed only in 38% cases. N. meningitides was a main pathogens (24%) and in isolated
cases it was H. influenza and S. aureus.
To study of the clinical and
etiological features of cases of the bacterial meningitis in children of the
Ryazan region in 2016-2019 years.
A retrospective analysis of
medical documentations of 23 patients (17 boys and 23 girls) with BM was made.
The children treated in Ryazan City Hospital (average age – 2.3 year old).
All patient with BM were admitted to
infectious hospital for emergency indications. More than half of patients were delivered
from regional hospitals (52.1%) and 30.1% from home by ambulance. The
gender-age structure of patients presents in table (Table 1).
The majority of sick children admitted to the hospital on 2nd day of the disease (8/34.7%); 5 (21.7%) patients – on the 3rd and 6 (26.1%) – on 4th days of disease and only one patient admitted in 1st day of sick. In 30.4 % the pathogens failed to isolate. The most prevalent pathogens caused bacterial meningitis was H. influenzae (12 cases, 52.2 %). Two patients was isolated N. meningitides (8.7%), S. pneumonia in 1 case (4.3 %) and S. agalactiae in 1 child (4.3%). All patient have typical complaints and clinic of bacterial meningitis. It was febril fiver in 1st day of the deases. The fiver was poorly controlled by antipyretics. Most children had repeated woming with not food intake (82.6%), headache (86.9%), and hyperesthesia (82.6%) (Figure 1).
Figure 1: Rate of pathogens that caused bacterial meningitis in children in Ryazan region (2016-2019 years).
Table 1: The gender-age structure of patients with BM.
Age |
Sex |
|
Boys |
Girls |
|
0-12 months |
5 |
1 |
1-3 year |
8 |
3 |
3-5 year |
2 |
0 |
5-10 year |
0 |
0 |
10-17 year |
2 |
2 |
Together: |
17 (73.9 %) |
6 (26.1 %) |
Symptoms |
Number |
|
n=23 |
% |
|
General
cerebral symptoms |
||
Woming with not food
intake |
19 |
82,6 |
Convulsions |
7 |
30,5 |
Headache |
19 |
82,6 |
psikhomotor agitation |
8 |
34,7 |
Lethargy, deafening |
8 |
34,7 |
Stupor, coma |
12 |
52,2 |
Meningeal
symptoms |
||
Kernings symptom |
13 |
56.5 |
Stiff neck |
18 |
78.2 |
Brudzinskys symptom |
9 |
39.1 |
Meningeal pose |
3 |
4.3 |
Intoxication
symptoms |
||
Fever |
23 |
100 |
Refusal to eat and
drink |
16 |
69.6 |
Pale skin |
20 |
87.0 |
Hemorrhagic rush |
5 |
22.0 |
Hemodynamic
instability |
13 |
56.5 |
Respiratory
failure |
6 |
26.0 |
Intestinal
paresis |
7 |
30.5 |
DIC
syndrome |
2 |
8.7 |
Different neurological
symptoms were in exanimated patients: 7 children had convulsions (30.3%),
monotonous cry – in 5 (21.7%), psikhomotor agitation – in 8 (34.7%),
photophobia – in 1 (4,3%). Cerebral, meningeal and intoxication symptoms
prevaleted in the clinic of disease (Table 2).
The disease progressed with
toxicosis deferent severity. Fifteen patients have febrile fever (65.2%), in 5
children it was hectic (21.7%), in 3-subfebrile one. Cataral inflammation of
appear respiratory tract had 3 patients (13.0%), respiratory disorders
(tachypnea or bradipnea, shallow breathing, decrees of saturation) had 6
children (26.0%). Most of patients have changes in blood analysis: 14 patients
(60.7%) had leukocytosis, 5 patients (21.7%) had leukopenia. The disease was
accompanied by infectious toxicities of varying severity in all patients. Fifteen
patients (65.2%) had febrile fever, 5 (21.7%) – hectic fever and 3 (13.0%)
patient had sub febrile fever. Catarrhal inflammation of ??? upper respiratory
tract had 3 (13.04%) patients. Hemodynamic disorders (tendency to tachycardia
or bradycardia, hypertension, hypotension, microcirculation disorder, decreased
CVP) were recorded in 13 (56.5%) children. Changes the blood analysis: 14
(60.7%) patients had leukocytosis, in 5 (21.7%) cases was leukopenia. There was
a shift in the leukocyte formula to the left in most cases: to stab neutrophils
– in 14 (60.7%) patients, to young forms of neutrophils - in 2 (8.7%) ones.
Only 1 (4.3%) patient had not changes in the leukocyte formula. An increase in
ESR had all patients. All the patients had of changes of cerebrospinal fluid
(CSF), it was colorless, cloudy. CSF was flowing out in frequent drops in 13
(56.5%) patients; leaked out under high pressure (jet) in 7 (30.4%). Most of
the examined (82.6%) had neutrophil pleocytosis. The protein content varied
within wide limits – from 0.2 to 1.056 g/l. Globulin reactions (Pandey,
Nonne-Apelt’s) were sharply positive in all cases (++++). Third-generation
cephalosporin, such as ceftriaxone or cefotaxime, was as first-line, empiric
therapy for BM. The median of ABT was 17 days (min=8; max=15). Antibiotics were
used for the longest time in the treatment of BM caused by H. Influenza
(21.3±1.2 days). In cases of BM of pneumococcal and meningococcal etiology, the
average of course of therapy was 15.3±1.2 and 12.0±1.2 days, respectively.
Against the background of the treatment, the timing of fever relief varied from
1 to 15 (min=3.5; max=12) days. General cerebral symptoms leveled off on days
2-16 (Me=4 [2.5; 8]), meningeal symptoms – on days 2-13 of therapy (Me=6 [3;
8]). The condition was assessed as moderate in 18 people (78.3%) on the 7th day
of therapy. Sanitation of CSF was occurred on the 5-15th day (Me=11 [9; 15.5]),
but it was prolonged to 15-20 days in 3 (13.0%) patients. BM caused by S.
pneumonia was verified in 2 children (aged 3 months and 1 year old). These
children were not vaccinated against this infection due to parental refusal.
According to the epidemiological history, patients had family contact with
adults with symptoms of catarrhal inflammation of upper respiratory tract for
3-5 days before the disease. These cases had a typical acute start of the
disease, which began with febrile fever, vomiting, anorexia, lethargy. Symptoms
of intoxication were prevailed (fever, pallor of the skin with a marble tint
without elements of rash), positive meningeal symptoms (Lessazh, Brudzinsky’s,
bulging of the fontanelle), general cerebral symptoms (impaired consciousness
to stupor) were presented. The patients had grade 2-3 anemia, leukocytosis with
neutrophilia, and ESR acceleration in blood analysis. One of the patients
required ABT correction during treatment. Ceftriaxone in combination with
ampicillin/sulbactam was prescribed as starting drugs, but on 6 day of therapy
ABT was corrected on meropenem, on 13 day – ceftazidime. These patients had of
febrile fever for 13 days, then to sub febrile – up to 14-15 days against the
background of treatment. Consciousness returned to normal on the 1st day in a
one-year-old patient, and on the 6th day of the disease in a child aged 3 months.
Meningeal symptoms were cropped on 3-5 days. Despite a single etiological
factor, the outcome of the disease was different: a one-year-old patient was
discharged on the 22 day with a satisfactory recovery, but a child of 3 months
old on the 23 day he was transferred to the neurological clinic for further
rehabilitation measures in connection with the formation of residual changes in
the central nervous system (he had symptoms of delayed statokinetic development
and focal symptoms). Rate of BM caused by H. influenza was 52.2%. These were
toddlers unvaccinated against Hib-infection due to parental refusal (10 cases,
83.3%) and for health reasons (2 cases, 16.6%). There was family contact with
adults or older children with symptoms of catarrhal inflammation of upper
respiratory tract on 3-7 days before the disease in all cases. All patients had
acute onset of the disease with febrile fiver; 9 (75.0%) patients had severe
intoxication, 4 (33.3%) had sinusitis, 2 (16.6%) children had acute otitis
media. Bright cerebral symptoms were detected in 9 patients (75.0%), Kerning’s
symptom – in 5 (41.6%) children; the rigidity of the occipital muscles – in 8
(66.6%); Brudzinsky's symptom – Iin 4 (33.3%) patients. Classical meningeal
pose was detected in 1 (8.3%) child. All patients had anemia of 2-3 degrees of
severity, leukocytosis with neutrophil, increased ESR.
BM caused by H. Influenza was characterized by an
undulating course of the disease. The duration of the febrile fever period
varied from 2 to 15 days (Me=9 [7.8; 12]), cerebral symptoms were stopped from
3 to 7 days (Me=5 [3.5; 4.5]), meningeal symptoms – from 3 to 13 days (Me=8 [5;
10.25]). The period of treatment in hospital ranged from 20 to 40 days (Me=23
[20.8; 24.8]).
H. Influenza was sensitive to unprotected and protected aminopenicillins,
third-generation cephalosporin in 83.3%. Ceftriaxone used as a starting
antibiotic in 5 (41.6%) patients (immunotherapy – in 3, combination with
vancomycin – in 2 cases), 6 (50%) patients – penicillin with ceftriaxone/sulbactam,
in 2 (16.6%) cases – cefepime. In the prevailing number of patients (92.0%),
ABT was corrected due to the lack of positive dynamics, which may indicate a
different sensitivity of the bacteria in vivo and in vitro. To achieve
sanitation of the cerebrospinal fluid repeated correction of ABT was required
in 11 (91.6%) patients. The time of CSF sanitation varied from 9 to 25 days
(Me=15 [10.8; 17.3]).
The study was demonstrated an
improvement in the quality of bacteriological diagnostics of BM in children and
a change in the etiological structure of BM. BM was more often diagnosed in
toddlers and manifested by the symptoms of meningeal, cerebral and intoxication
syndromes. H. Influenzae was detected
in 52.2% of BM in 2016-2019 years. Patients with BM caused by H. Influenzae had long course of the
disease, repeated correction of ABT, had of complications. It was indicates the
advisability of vaccinating children against hemophilic infection