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Jurnal Meningitis Anak
Jurnal Meningitis Anak
of
medicine
original article
In June 2002, the Food and Drug Administration received reports of bacterial meningitis in patients with cochlear implants for treatment of hearing loss. Implants that included a positioner (a wedge inserted next to the implanted electrode to facilitate transmission of the electrical signal by pushing the electrode against the medial wall of the
cochlea) were voluntarily recalled in the United States in July 2002.
methods
We identified patients with meningitis and conducted a cohort study and a nested case
control investigation involving 4264 children who had received cochlear implants in the
United States between January 1, 1997, and August 6, 2002, and who were less than six
years of age when they received the implants. We calculated the incidence of meningitis
in the cohort and assessed risk factors for meningitis among patients and among 199
controls, using data from interviews with parents and abstracted from medical records.
From the National Center on Birth Defects and Developmental Disabilities (J.R.,
M.A.H., K.R.B., M.V., P.C., O.D., C.B.), the
Epidemiology Program Office (J.R., S.C.,
K.B., S.M., S.A.), the National Center for Infectious Diseases (C.G.W., S.C.), and the
National Immunization Program (K.B.),
Centers for Disease Control and Prevention,
Atlanta; the Food and Drug Administration,
Rockville, Md. (E.A.M., A.G.); the New York
City Department of Health and Mental Hygiene, New York (S.M.); and the Texas Department of Health, Austin (S.A.). Address
reprint requests to Dr. Reefhuis at the National Center on Birth Defects and Developmental Disabilities, Centers for Disease
Control and Prevention, 1600 Clifton Rd. NE,
MS E-86, Atlanta, GA 30333.
results
conclusions
Parents and health care providers should ensure that all children who receive cochlear
implants are appropriately vaccinated and are then monitored and treated promptly for
any bacterial infections after receiving the implant.
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The
early 10,000 children in the united States with severe-to-profound hearing loss currently have a cochlear implant,
a surgically implanted device that includes an electrode array that is inserted into the cochlea.1 With
the use of cochlear implants, people who have severe-to-profound hearing loss may perceive sounds
and learn to speak.2
In June 2002, one manufacturer of cochlear implants notified the Food and Drug Administration
(FDA) of 15 reports of postimplantation bacterial
meningitis in patients of any age who had received
its implants. Early speculation implicated a positioner, a component used by one manufacturer in
some types of implants.3 This small Silastic wedge
is inserted next to the implanted electrode to facilitate transmission of the electrical signal by pushing
the electrode against the medial wall of the cochlea.
The implants that included a positioner were voluntarily recalled by the manufacturer in July 2002.4
Since the initial reports were issued, however, the
other two manufacturers of cochlear implants in the
United States have notified the FDA of additional
cases of meningitis, principally in young children.
Because the magnitude of the problem was unknown, as were the factors, aside from the use of a
positioner, that might increase the risk of meningitis among implant recipients, the Centers for Disease Control and Prevention (CDC), the FDA, and
the health departments of 36 states, Chicago, New
York City, and Washington, D.C., undertook an investigation. The purpose was to establish the incidence of bacterial meningitis among children with
cochlear implants and to identify specific types of
devices, surgical factors, and patient characteristics
that might be associated with an increased risk of
bacterial meningitis among recipients of cochlear
implants. The focus of the investigation was young
children, because they account for the majority of
known cases and represent the population that will
receive most cochlear implants in the future.
of
medicine
and August 6, 2002, and who were less than six years
old at the time of implantation. All three companies that market cochlear implants in the United
States provided warranty lists (estimated to be 95
percent complete) of children who met these criteria. We combined these lists to define a study population of 4264 children.
Nineteen cases of bacterial meningitis were identified from reports to the companies, the Adverse
Event Reporting System of the FDA, and the surveillance systems of the CDC and state and local
health departments. Seven additional cases were
identified by means of a brief questionnaire that was
mailed to the families of all children in the study
population. The rate of response to the questionnaire was 57.3 percent and did not vary according
to the year of implantation. The use of different
methods of ascertainment and the attention paid to
this issue by the media lead us to believe that our
ascertainment of cases was relatively complete.
definition and confirmation of cases
methods
casecontrol study
study design and population
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july 31 , 2003
Isolation of bacteria from cerebrospinal fluid or isolation of bacteria from blood with abnormal cerebrospinal fluid and symptoms consistent with the presence of bacterial meningitis
Probable
Abnormal cerebrospinal fluid, symptoms consistent with bacterial meningitis, and evidence of bacteria in cerebrospinal
fluid (on antigen testing, Grams staining, or polymerase
chain reaction), or histopathological evidence of bacterial
meningitis on autopsy
Possible
Abnormal cerebrospinal fluid, symptoms consistent with bacterial meningitis, and no evidence suggesting a nonbacterial
cause, or death after an unexplained illness with compatible
symptoms
statistical analysis
Criteria
results
identification of cases
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438
29 days
1.5 mo
1.5 mo
1.5 mo
9 mo
2 mo
2 mo
3 mo
15 mo
9 mo
10
11
12 Episode 1
Episode 2
13
14
15 Episode 1
Episode 2
16
14 days
20 days
13 days
10 days
4 days
4 days
2 mo
4 days
4 Episode 1
Episode 2
1 day
Time from
Implantation
to Diagnosis
Patient
No.
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july 31 , 2003
2 yr 2 mo
3 yr 3 mo
4 yr
4 yr 3 mo
3 yr 8 mo
4 yr 3 mo
M
M
M
M
H. influenzae,
nontypeable
S. pneumoniae
Unknown
S. pneumoniae
S. pneumoniae
S. pneumoniae
H. influenzae,
nontypeable
S. pneumoniae
S. pneumoniae
Haemophilus
influenzae type b
S. pneumoniae
S. pneumoniae
S. pneumoniae
Escherichia coli
Enterococcus
Unknown
A. baumanii
Acinetobacter
baumanii
Streptococcus
pneumoniae
AB-5100H-11
AB-5100H
AB-5100H
AB-5100H
AB-5100H
AB-5100H
AB-5100H
AB-5100H
AB-5100H-11
CI22M
CI24RST
AB-5100H-11
AB-5100H-11
AB-5100H-11
CI24M
CI24M
AB-5100
AB-5100H
CI24M
Neither
Gusher
Neither
Perioperative leak
Gusher
Gusher
Perioperative leak
Gusher
Neither
Cerebrospinal Fluid
Leak or Gusher
Unknown
None
None
None
Common cavity
Unknown
Unknown
None
Unknown
Unknown
Neither
Neither
Neither
Neither
Unknown
Unknown
Neither
Neither
None
Enlarged vestibular
aqueduct
None
None
Mondinis malformation
Mondinis malformation
Unknown
Cochlear dysplasia
None
Radiographic
Evidence of Inner-Ear
Malformation
Neither
Neither
Meningitis
Neither
Neither
Neither
Meningitis
Neither
Neither
Meningitis
Both
Neither
Neither
Neither
Neither
Meningitis
Neither
Neither
Neither
Previous Meningitis
or Ventriculoperitoneal Shunt
Yes
Yes
Yes
Yes
No
Yes
Yes
No
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
Yes
No
Yes
Yes
No
Yes
Yes
No
Yes
No
Yes
Yes
Yes
Yes
No
No
Yes
Unknown
Unknown
Unknown
Yes
Yes
Yes
Yes
No
No
No
Unknown
No
No
No
No
No
No
No
History of
Recurrent History of
Signs of
Otitis
Tympanos- Acute Otitis
Media tomy Tubes
Media
of
3 yr 10 mo M
F
F
Implant Model
at Time of
Sex Causal Bacteria
Episode
3 yr
2 yr 4 mo
2 yr 1 mo
5 yr 3 mo
2 yr
23 mo
3 yr 7 mo
3 yr 9 mo
18 mo
16 mo
2 yr 1 mo
Age at
Time of
Episode
Table 2. Episodes of Postimplantation Bacterial Meningitis and Predisposing Factors in Children Who Received a Cochlear Implant in the United States between 1997 and 2002.*
The
medicine
10 mo
10 mo
12 mo
14 mo
14 mo
17 mo
19 mo
24 mo
36 mo
18
19
20
21
22
23
24
25
26
5 yr 11 mo F
5 yr 2 mo
3 yr 1 mo
3 yr 2 mo
6 yr 8 mo
3 yr 4 mo
2 yr 11 mo M
2 yr 2 mo
6 yr 6 mo
6 yr 3 mo
Unknown
Unknown
S. pneumoniae
S. pneumoniae
Unknown
H. influenzae
type b
S. pneumoniae
H. influenzae,
nontypeable
S. pneumoniae
S. pneumoniae
CI24M
CI22M
AB-5100H
CI24RST
AB-5100
AB-5100H
AB-5100H-11
AB-5100H
AB-5100H-11
C40+HS
Common cavity
None
Unknown
Mondinis malformation
None
None
None
None
None
Mondinis malformation
Neither
Neither
Gusher
Neither
Neither
Neither
Neither
Neither
Gusher
Neither
Meningitis
Neither
Neither
Neither
Neither
Neither
Neither
Neither
Neither
Ventriculoperitoneal
shunt
Yes
No
Yes
Yes
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
Unknown
No
Yes
Unknown
Yes
Yes
No
No
* Implant models AB-5100H and AB-5100H-11 (Advanced Bionics) include a positioner; the positioner is optional in model AB-5100 (Advanced Bionics). Patient 3 did not have a positioner
placed; Patient 23 did have a positioner placed. Models CI24M, CI24RST, and CI22M are manufactured by Cochlear Corporation, and model C40+HS is manufactured by MED-EL. Mondinis
malformation is defined as a small cochlea with an incomplete or no interscalar septum, with a normal or malformed vestibule and semicircular canals.
Signs of acute otitis media on admission included ear drainage, a bulging tympanic membrane, or the receipt of antibiotics for acute otitis media.
In this child, the implant was removed during the hospitalization for meningitis.
The child died of meningitis.
Meningitis occurred after a second implant was placed; both implants were model AB-5100H.
10 mo
17
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Table 3. Incidence of All Cases of Bacterial Meningitis (Sporadic or Perioperative) and of Sporadic Meningitis
among Children Who Received a Cochlear Implant.*
Variable
Sporadic Meningitis
No. of
Cases
Incidence/100,000 Person-Yr
(95% CI)
No. of
Cases
Incidence/100,000 Person-Yr
(95% CI)
26
239.3 (156.4350.6)
17
161.8 (94.2259.0)
No
10
103.6 (49.7190.3)
53.3 (17.3124.4)
Yes
16
1332.7 (762.02163.6)
12
1060.3 (547.91851.5)
AB-5100H-11
1687.4 (678.63474.1)
1062.6 (289.62719.0)
AB-5100H
1146.2 (524.32175.0)
1059.7 (457.62087.2)
AB-5100
66.2 (8.0239.5)
33.8 (0.8188.9)
CI22M
159.5 (19.3575.9)
81.0 (2.0451.4)
CI24M
82.3 (17.0240.6)
28.1 (0.7156.6)
CI24RST
2072.5 (251.07469.9)
1102.9 (28.06132.2)
C40+HS
2660.8 (67.314,749.8)
2771.4 (70.215,359.8)
All children
Implant with a positioner
Implant model
Geographic region
Northeast
191.3 (52.1489.7)
98.8 (12.0356.5)
Midwest
264.6 (114.2521.3)
188.0 (75.6387.4)
South
11
285.6 (142.6511.0)
214.9 (92.8423.4)
West
163.9 (33.8479.2)
169.8 (35.0496.1)
19971998
59.9 (12.4174.8)
20.3 (0.5113.2)
19992000
11
252.6 (126.1451.8)
189.6 (81.8373.4)
20012002
12
802.2 (414.61401.0)
585.7 (253.01153.9)
1 yr
335.4 (144.8660.7)
217.8 (70.7508.3)
2 yr
262.3 (113.3516.8)
135.4 (36.8346.6)
3 yr
209.9 (68.2489.8)
173.3 (47.2443.6)
Year of implantation
Age at implantation
4 yr
61.8 (1.6344.3)
63.8 (1.6355.3)
5 yr
299.0 (81.5765.5)
231.2 (47.6675.7)
* Perioperative meningitis was defined as meningitis with an onset within 30 days after surgery, and sporadic meningitis
as that with an onset more than 30 days after surgery. CI denotes confidence interval.
Data are for models AB-5100H and AB-5100H-11 (Advanced Bionics); data on children who received model 5100H (Advanced Bionics), for which the use of a positioner was optional, were included in the group without a positioner, because
information on the use or nonuse of the positioner was not available for children who were not included in the casecontrol
investigation.
No cases were reported among children who received implant models CI24R(CS), who accounted for 1300 person-years,
C40+H, who accounted for 301 person-years, or C40+HGB, who accounted for 10 person-years.
A test for trend showed a significant increase over time: chi-square statistic for trend=19.9, with 1 df; P<0.001.
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Table 4. Incidence of Bacterial Meningitis among Children Who Received Implant Models Including a Positioner
as Compared with Those Who Received Other Models, 19992002.*
Months of
Follow-up
Incidence-Rate Ratio
(95% CI)
No. of
Cases
Incidence/
100,000 Person-Yr
(95% CI)
No. of
Cases
Incidence/
100,000 Person-Yr
(95% CI)
5818 (158014,841)
1528 (3164472)
3.8 (0.625.9)
1.13.0
3676 (11948579)
0 (0948)
Undefined (2.6infinity)
3.16.0
526 (132932)
0 (0673)
Undefined (0.1infinity)
6.112.0
922 (1902697)
205 (25739)
4.5 (0.554.0)
12.118.0
870 (1063140)
121 (3675)
7.2 (0.4423.8)
18.124.0
701 (183896)
150 (4837)
4.7 (0.1365.6)
1.0
* This analysis was limited to children who received an implant after the devices including a positioner became available
in 1999; three children in the cohort who had meningitis in 1997 or 1998 were excluded from the analysis. Confidence intervals for incidence rates and incidence-rate ratios were calculated according to the exact method under the assumption
that the number of cases is a Poisson random variable.
Data are for models AB-5100H and AB-5100H-11 (Advanced Bionics); data on children who received model 5100H (Advanced Bionics), for which the use of a positioner was optional, were included in the group without a positioner, because
information on the use or nonuse of the positioner was not available for children who were not included in the casecontrol
investigation.
In instances in which the incidence-rate ratio was undefined, the lower limit for the 95 percent confidence interval was
calculated according to exact methods.
discussion
The incidence of bacterial meningitis caused by
S. pneumoniae in our study population of children
who received cochlear implants when they were less
than six years of age was more than 30 times the incidence of pneumococcal meningitis among children in that age group in the general U.S. popula-
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All Meningitis
Univariate Analysis
Univariate
Analysis
(N=26)
Multivariate
Analysis
(N=26)
Perioperative
Meningitis
(N=9)
Sporadic
Meningitis
(N=17)
S. pneumoniae
Meningitis
(N=15)
5.6 (2.413.4)
18.4 (3.4120.3)
1.0 (0.14.8)
4.9 (0.444.9)
3.2 (0.519.7)
2.4 (0.511.4)
9.7 (3.031.1)
1.8 (0.29.4)
14.0 (1.0138.5)
1.7 (0.28.8)
6.0 (1.723.1)
14.7 (1.7119.8)
1.8 (0.29.4)
3.2 (0.810.7)
7.2 (1.040.9)
3.0 (0.513.1)
7.1 (0.3126.1)
3.9 (0.328.8)
5.9 (0.168.2)
2.9 (0.131.9)
7.2 (0.655.1)
2.2 (0.67.8)
2.2 (0.95.2)
3.8 (0.819.8)
1.7 (0.55.2)
2.0 (0.66.8)
2.7 (0.3127.1)
3.7 (0.816.3)
2.3 (0.521.5)
1.4 (0.28.4)
2.3 (0.67.3)
4.9 (0.727.0)
1.3 (0.16.2)
3.3 (0.712.7)
* Perioperative meningitis was defined as meningitis with an onset within 30 days after surgery, and sporadic meningitis as that with an onset
more than 30 days after surgery. There were 199 controls included in all analyses. Univariate results included in this table are limited to those
that were associated with any subcategory of meningitis with a two-sided P value of less than 0.1.
Fishers exact methods were not used, because the expected numbers in the contingency tables were greater than 5.
There were no patients with a malformation only.
There were no patients with a leak only.
All patients had otitis media before implantation.
are unclear. Possible explanations include the larger cochleostomy required for the insertion of both
the electrode and the positioner, the presence of an
additional foreign body in the inner ear, trauma to
the fragile anatomy of the inner ear caused by the
wedging of the positioner into place,14 deficient formation of a fibrous-tissue seal at the site of the cochleostomy,3 and a combination of these factors. A
further complication for the comparison of types of
implants is that the choice of a particular implant
could be based on certain characteristics of the patient. For example, product labeling for the implants
with positioners states that their use is contraindicated in people with ossification of the cochlea.
Overall, the risk of meningitis decreased rapidly after the perioperative period. The incidence of
meningitis among children with an implant that
included a positioner remained higher than that
among children with other types of implants for the
duration of follow-up. However, only a few cases
were identified during each period, and such small
numbers result in imprecise estimates; continued
follow-up is needed in order to estimate the incidence of meningitis more than 24 months after implantation.
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