Recurrent Bacterial Meningitis in Pediatric Patients with Anatomical Defects

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Vol. 19, No. 2, August, 2011

□ 원 저 □

1)

Received : 25 April, 2011, Revised : 19 July, 2011, Accepted : 9 August, 2011,

Correspondence : Tae-Sung Ko, M.D.

Department of Pediatrics, Asan Medical Center Children s’ Hospital, University of Ulsan College of Medicine

Tel : +82.2-3010-3390, Fax : 82.2-473-3725 E-mail : [email protected]

Introduction

Bacterial meningitis is an acute infectious dis- ease associated with substantial morbidity and mortality rates. Recurrent bacterial meningitis

Recurrent Bacterial Meningitis in Pediatric Patients with Anatomical Defects

Eun Lee, M.D., Eun-Hye Lee, M.D.

^*

Mi-Sun Yum, M.D., and Tae-Sung Ko, M.D.

Department of Pediatrics, Asan Medical Center Children s Hospital, ’ University of Ulsan College of Medicine, Seoul, Korea,

Department of Pediatrics

^*

, Kyung Hee University School of Medicine, Seoul, Korea

= Abstract =

Purpose : Recurrent bacterial meningitis represents the reappearance of two or more episodes of meningitis by a different or same organism after an intervening period of full convalescence. Predisposing factors for recurrent bacterial meningitis include developmental or traumatic anatomical defects or immunodeficiencies. The purpose of this study was to characterize recurrent bacterial meningitis in children.

Methods : We identified 81 cases of bacterial meningitis diagnosed at the Asan Medical Center Children s Hospital between January 1999 and March 2009. We con’ - ducted retrospective reviews for children (below 18 years of age) with recurrent bacterial meningitis who had been diagnosed both by latex agglutination and positive cerebrospinal fluid (CSF) cultures.

Results : Among 81 cases, 4 patients were identified as having recurrent bacterial meningitis, among whom 13 episodes of meningitis were identified. Two episodes occurred in 2 patients, 2 in 1 patient, and 6 in 1 patient. Three patients had inner ear anomalies with CSF leakage and 1 patient had a traumatic CSF fistula, repre- senting predisposing factors. Of the 13 episodes,

Streptococcus pneumoniae

was the causative agent in 10 episodes and

Hemophilus influenzae

and

Streptococcus

.

mitis

were the other causative organisms. After the second case of meningitis, successful repair of CSF leakage prevented further development of meningitis in 3 patients.

Despite several repair operations for CSF leakage, 1 patient died of cerebral edema during the 6th episode of meningitis. In addition, 2 patients experienced further episodes of meningitis after vaccination against pneumococcus or

H. influenzae

type B in our study.

Conclusion : Identification and proper management of conditions that predispose children to recurrent bacterial meningitis are essential to prevent further, potentially lethal infections.

Key Words : Bacterial meningitis, Pediatric patients, Anatomical defect

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indicates meningitis occurring on 2 or more oc- casions of meningitis by a different or the same organism after an intervening period of convale- scence and full recovery

^1-3)

. The predisposing factors for recurrent bacterial meningitis can be broadly categorized into congenital and acquired conditions, or divided into anatomical abnorma- lities, immunodeficiencies, and chronic parame- ningeal infections

⁴⁾

. The aim of this study was to characterize recurrent bacterial meningitis in children with different predisposing factors. We describe here the children who experienced recurrent bacterial meningitis due to the pre- existing anatomical defects.

Materials and Methods

A retrospective study was performed to iden- tify children with a diagnosis of recurrent bac- terial meningitis, who were treated at Asan Me- dical Center Children s Hospital between January ’ 1999 and March 2009. Patients who were initially diagnosed and treated at other hospitals but were transferred to our hospital for further the- rapy were also included.

There is considerable confusion and disagree- ment about the definition and terminology used in relation to the recurrence of bacterial menin- gitis. Bacterial meningitis was defined by a com- patible clinical history and physical examination, as well as 1 of the following: a positive cerebro- spinal fluid (CSF) culture, a positive CSF antigen test, or a negative CSF culture with a finding of neutrophilic pleocytosis (CSF leukocytes >1,000/

uL). We recorded the patient s age, number of ’ meningitis episodes, and diagnostic investigations performed (CSF cultures and imaging work up).

Recurrent bacterial meningitis was defined as a recurrence if it was due to a different organism

from the first organism or if it was due to the same organism but occurred more than 3 weeks after the completion of therapy for the initial epi- sode. In addition, we included cases with two or more episodes of bacterial meningitis defined by abnormal CSF results if the episodes occurred a minimum of 3 weeks apart. Antibiotic treatment was considered successful if the patient was clinically well and CSF findings in addition to sterile culture were normal at the end of therapy.

Four episodes in 2 patients were diagnosed and treated at other hospitals. One culture ne- gative episode of bacterial meningitis which was diagnosed on the basis of a compatible clinical picture and marked pleocytosis despite negative blood and CSF cultures was included.

We did not perform immunologic investiga- tions in all patients because all patients had anatomical defects with CSF leakage. Cranial computerized tomography (CT) was conducted in all patients. A CT scan of the temporal bones, cranial magnetic resonance imaging (MRI) and CT cisternography were performed in selected cases according to clinical risk factors.

Results

Among 81 cases of acute bacterial meningitis during the study period

⁵⁾

, 4 patients (2 male and 2 female) were identified as having recurrent bacterial meningitis, resulting in a rate of recur- rent bacterial meningitis as 4.9%. Patient features are summarized in Table 1. Patient age during the first episode of meningitis ranged between 20 months and 7 years (mean: 52 months).

The time between the first episode of bacterial meningitis and the second episode of meningitis ranged between 2 months and 12 months (mean:

6.3 months). The etiology of recurrent bacterial

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meningitis was inner ear anomalies in 3 patients and a traumatic CSF fistula in 1 patient. CSF rhinorrhea was detected in 3 patients with inner ear anomalies and CSF otorrhea was detected in 1 patient with a traumatic CSF fistula. In a patient with a history of head trauma, the first episode of bacterial meningitis developed 6 months after the injury due to traumatic menin- goencephalocele. The total number of meningitis episodes in these patients was 13, with a range of 2-6 episodes per patient.

The causative agents for the 13 episodes of recurrent bacterial meningitis were Streptococcus pneumoniae in 10 episodes in 4 patients, S. mitis in 1 episode, and Hemophilus influenzae type B in 1 episode. In the remaining 1 episode of men- ingitis, no pathogen was proven in the CSF cul- ture.

In 3 of 4 patients, the clinical course was complicated by convulsions, a reduced level of consciousness requiring intubation, and cranial nerve dysfunction. The patient with 3 episodes of meningitis (Case 1) experienced cerebral

edema requiring craniectomy and loss of con- sciousness during hospitalization and she re- covered with cranial nerve II, III, IV, and VII dysfunction and voiding difficulty.

All patients were treated with antibiotics and surgery. In 12 of 13 episodes, antibiotic treat- ment over 10-14 days was sufficient for the treatment of bacterial meningitis. In the remaining 1 episode, the patient died from cerebral edema.

All of the patients were treated with a combina- tion of ceftriaxone and vancomycin, except 1 episode due to S. mitis , which was treated with cefotaxime after an antibiotic sensitivity test. An antibiotic susceptibility test for S. pneumoniae was performed in 5 episodes, and the results showed that 2 episodes were penicillin-resis- tant, 2 episodes were penicillin-sensitive, and 1 episode was penicillin-intermediate. A serial antibiotics sensitivity test performed in case 1 showed that penicillin-sensitive pneumococcal meningitis was followed by penicillin-resistant pneumococcal meningitis. After the second epi- sode of meningitis, successful repair of CSF lea-

Table 1. Summary of Four Cases of Recurrent Bacterial Meningitis at Asan Medical Center Children s Hospital.’

Case No.

Age at last episode

Sex No. of epoisode

Age at initial diagnosis

Organism

Vaccination (age at vaccination)

Underlying causes

CSF

leakage Complications 1

2

3

4

29 months

68 months

5 years

9 years F

F

M

M 3

2

6

2

20 months

63 months

4 years

8 years

S. pneumoniae (2 episodes)

No growth (1 episode) S. pneumoniae

(2 episodes)

S. pneumoniae (4 episodes) H. influenzae

type B (1 episode)

S. mitis (1 episode) S. pneumoniae

(2 episodes)

7-valent (24 mo) 23-valent

(28 mo) 23-valent

(46 mo)

Hib (49 mo) 23-valent

(51 mo)

(-)

Congenital inner ear malformation

Cochlear implantation Congenital inner ear malformation

Skull fracture (+)

(+)

Facial palsy, Voiding difficulty, Cortical blindness

(-)

Hearing disturbance,

Seizure, Death

Seizure

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kage prevented further development of meningitis in 3 patients. But one patient died from cerebral edema and increased intracranial pressure se- condary to fulminant pneumococcal meningitis.

In 3 cases (Cases 1-3), patients experienceed further episodes of pneumococcal meningitis al- though they received vaccination for pneumo- coccus. In cases 1 and 3, 23-polyvalent vacci- nation against S. pneumoniae was performed after the first attack of S. pneumoniae menin- gitis, but those 2 patients experienced repeated S. pneumoniae meningitis episodes thereafter.

Among them, one patient experienced no further episode of H. influenzae meningitis after the vaccination against H. influenzae .

Discussion

Acute bacterial meningitis is often caused by blood-borne bacteria, but recurrent bacterial meningitis results from defects or imperfections of host defense mechanisms, allowing bacteria to reach the central nervous system, or a defect in the external covering of the leptomeninges and skull. The frequency of recurrent meningitis has not been estimated accurately, but some retrospective studies have suggested that as many as 5-6% of patients develop recurrent bacterial meningitis

³⁾

. In this study, bacterial meningitis recurred in 5% of the patients.

Predisposing factors for recurrent bacterial meningitis include CSF leakage resulting from a congenital CSF fistula, a traumatic or surgical CSF fistula, and several immunodeficiencies such as immunoglobulin deficiencies, comple- ment deficiencies, and splenic dysfunction

⁴⁾

. In our case series, all patients had anatomical de- fects, rather than immunodeficiencies; 3 of 4 patients experienced recurrent bacterial menin-

gitis due to a malformed inner ear, and the re- maining 1 patient experienced recurrent men- ingitis due to traumatic meningoencephalocele.

Although these inner ear malformations occur during early fetal life, the first episode of bac- terial meningitis at school age does not exclude a congenital defect. Some case reports have de- scribed the occurrence of recurrent bacterial meningitis after cochlear implantation

^6-8)

. In case 2, cochlear implantation was performed in the right ear, and recurrent bacterial meningitis oc- curred as a result of a left perilymphatic fistula.

Although in case 4, the patient developed the first episode of bacterial meningitis 6 months after a traffic accident, an interval of several years between trauma and the first episode of meningitis does not rule out CSF leakage

⁹⁾

. In cases of recurrent bacterial meningitis, it is important to question and examine the patient carefully to identify possible underlying struc- tural lesions, or immunodeficiencies, or to rule out congenital anomalies of the ear, to enable effective treatment. Identification and proper management of conditions that predispose chil- dren to recurrent bacterial meningitis are es- sential to prevent further lethal infections. Also, prompt recognition and repair of the anatomical defect with dural closure prevents further epi- sodes of meningitis and ensures a good outcome for neurological development.

Inner ear defects may present with either

otorrhea or rhinorrhea and should be suspected

in all patients with recurrent meningitis. Otogenic

CSF rhinorrhea is difficult to diagnose in young

children and infants and is frequently misdiag-

nosed, because CSF rhinorrhea can be indistin-

guishable from normal nasal discharge

¹⁰⁾

. Tradi-

tional testing of nasal discharge or middle ear

fluid for its glucose content is unreliable and may

(5)

soon be replaced by testing for 2-transferrin, β which is found only in the CSF

¹¹⁾

.

Brain CT scan and CT cisternography are currently the most reliable technique for the ac- curate localization of CSF leakage

¹²⁾

. Also, to- mography allows a more efficient and complete circumferential survey than a planar imaging, and is particularly useful for cases in which the location of the leak is unknown or unusual. Brain MR imaging is also helpful in detecting CSF leakage or herniated tissues in a patient with no active CSF leakage

^{13, 14)}

.

After identification of the predisposing condi- tions, prompt antibiotic treatment is essential for any case of suspected bacterial meningitis and improves outcome. Initial selection of anti- biotics is made empirically, prior to the availa- bility of definite culture results, based on the incidence and susceptibility pattern in the pop- ulation.

The organism that causes recurrent meningitis may be the same as that in a previous attack or it may be different. The type of organism responsible for recurrent bacterial meningitis strongly correlates with the site of the defect, as the route of infection is a direct extension of the nasopharyngeal flora to the meninges. In cases of CSF leakage, the organism of recurrent meningitis is most frequently S. pneumoniae, followed by Nesseria meningitis and H. influenzae

15, 16)

. In our study, all 4 patients experienced meningitis due to S. pneumoniae , ranging in inci- dence from at least 2 times to at most 4 times.

Among the numerous causative organisms, S.

pneumoniae meningitis has the highest case- fatality rate (about 20%) for community-acquired meningitis in developed countries

¹⁷⁾

. S. pneu - moniae meningitis is associated with a higher mortality (14-30%) rate as well as more de-

vastating neurologic sequelae than other causa- tive agents

^18-20)

. The risk for sequelae or death is greatest for, but not confined to, those pati- ents who have seizures and focal neurologic signs, deteriorating consciousness in hospital, hypotension, and S. pneumoniae infection

^{21, 22)}

. In case 1, the patient experienced cortical blind- ness, seizure and voiding difficulty after the first episode of S. pneumoniae meningitis.

The role of immunization for the prevention of bacterial meningitis in patients with predis- posing factors is controversial

²³⁾

. Two large ef- ficacy trials of conjugate pneumococcal vaccines against invasive pneumococcal disease demon- strated clinically significant efficacy against serotype-specific invasive pneumoccocal disease

20)

. However, some reports have shown that prophylactic antibiotics are not useful in pre- venting meningitis after skull fracture

²⁴⁾

.

In conclusion, predisposing factors should be investigated in patients with recurrent bacterial meningitis and prompt antibiotic treatment and repair of the defects is essential for the good outcomes.

요 약

해부학적 결함을 가진 소아 환아에서의 재발성 세균성 뇌수막염

이 은 ㆍ 이은혜

^*

ㆍ 염미선 ㆍ 고태성

서울아산병원 소아청소년병원 소아청소년과

경희대학교 의과대학 소아과학교실^*

목 적 : 개 이상의 서로 다른 원인균 또는 주 이 2 3 상의 회복기 후 동일한 원인균에 의한 뇌수막염 발

생시 재발성 뇌수막염이라 한다 이의 원인으로는 .

발달적 이상 사고 이후 해부학적 결함 또는 면역 결 ,

핍이 있다 소아에서 발생하는 재발성 뇌수막염의 .

빈도 특징 및 원인은 정확히 알려져 있지 않은 바이 ,

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다 이에 저자는 소아에서 발생하는 재발성 뇌수막 . 염의 발생 빈도 임상적 특징 및 원인을 분석하여 재 , 발성 뇌수막염 환아의 진단 및 치료에 도움이 되고 자 본 연구를 시행하였다.

방 법 : 1999 년 월부터 1 2009 3 월까지 서울 아산

병원에서 뇌수막염으로 진단 및 치료 받은 81 명의

환자 중 뇌척수액의 배양 및 라텍스 응고 검사에서

재발성 뇌수막염으로 진단된 명의 환자를 대상으로 4

하였다 이들에 대한 분석은 의무 기록지를 통하여 .

후향적 고찰을 시행하였다.

결 과 : 명의 환자들에서 총 4 13 번의 뇌수막염이 발생하였고 (2-6 / ) 회 명 이 중 10 번이 Streptococ- cus pneumoniae 가 원인이었다 원인으로는 . 4 명의

환자 중 명이 선천성 내이 구조의 이상으로 진단되 3

었고 명은 사고 후 뇌척수액 누공을 보이고 있었다 1 . 결 론 : 재발성 뇌수막염은 선천성 및 후천적 재발 원인에 대한 면밀한 검사가 반드시 필요하고 조기 적극적인 치료가 필수적이다.

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