Combined therapy of pediatric bacterial meningitis with the use of corticosteroids and antibacterials: a bibliographical review

COMBINED THERAPY OF PEDIATRIC BACTERIAL MENINGITIS WITH THE USE

OF CORTICOSTEROIDS AND ANTIBACTERIALS: A BIBLIOGRAPHICAL REVIEW

Terapia combinada da meningite bacteriana pediátrica com o uso de corticoesteroides e

antibacterianos: uma revisão bibliográfica

Anna Bárbara Ribeiro de Araújo¹

Raquel Santos Oliveira² Folmer Quintão Torres1 Jânio Eduardo Siqueira2 Joanilva Ribeiro Lopes3

Abstract: Bacterial meningitis in childhood is an infection that requires special care and immediate

intervention, as it can cause severe sequelae in the child, which can lead to death. The idea of the use of

corticosteroids and antibacterial in the combined therapy of this infection is discussed. The objective of the

present article was to present a review of the literature with a detailed approach regarding the combined

therapy of bacterial meningitis, through corticotherapy and its effects on the child. After analyzing the

articles, it was concluded that the results of corticosteroid use in bacterial meningitis are still controversial,

since there is no consensus of its benefits in the combined therapy of meningitis. There is a need for a larger

number of studies to evaluate the efficacy of corticosteroids in the therapy of this infection and its action on

other etiological agents, that is, the therapy should be broad-spectrum; not only for Haemophilus influenzae

type B.

Keywords: Bacterial meningitis; Corticosteroid; Anti-bacterial; Combination therapy.

________________

Corresponding author: Anna Bárbara Ribeiro de Araújo. E-mail: [email protected]

1 Faculdade de Minas.

2 Superior Instituto Superior de Educação Ibituruna. 3 Universidade Estadual de Montes Claros.

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Resumo: Meningite bacteriana na infância é uma infecção que necessita de cuidados especiais e de

intervenção imediata, pois pode causar sequelas graves na criança, podendo levar ao óbito. Discute-se a

ideia do uso de corticoesteroide e dos antibacterianos na terapia combinada dessa infecção. O objetivo do

presente artigo foi apresentar uma revisão de literatura com uma abordagem detalhada em relação à terapia

combinada da meningite bacteriana, através da corticoterapia e de seus efeitos na criança. Após análise

dos artigos, concluiu-se que os resultados do uso de corticoesteroide na meningite bacteriana ainda são

controversos, pelo fato de não haver um consenso de seus benefícios na terapia combinada da meningite.

Verifica-se a necessidade de um número maior de pesquisas para avaliar a eficácia da corticoterapia na

terapêutica dessa infecção e sua ação em outros agentes etiológicos, ou seja, a terapia deve ser de amplo

espectro; não somente para o Haemophilus influenzae tipo B.

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INTRODUCTION

Bacterial meningitis is an infection that

affects the Central Nervous System (CNS) with

a prevalence of 0.9 to 2.6 per 100,000 per year in

adults in developed countries and higher incidence

in underdeveloped countries. Streptococcus

pneumoniae (pneumococcus) is the most frequent

agent of meningitis caused by bacteria acquired

in the community in 70% of cases in adults.

_In

children younger than 5 years of age, the bacterial

infection is also the main cause of meningitis and,

among the main pathogenic agents, gram-positive

bacteria, especially, S. pneumoniae is responsible

for about 6% of cases. Long-term sequelae,

including blindness, deafness, cerebral palsy,

seizures, disabilities, hydrocephalus are still high

after recovery and present in approximately

25-50% of survivors.

.

The pathophysiology of neurological

injuries is due to the severity of inflammation in the

cerebrospinal fluid (CSF) which can be alleviated

with the use of systemic corticosteroids .

The etiology in children depends on the age,

the immunity and epidemiology. Younger than 1

month to 3 months old: (Neonatal pathogens from the

intestinal and maternal urinary flora): Streptococcus

agalactiae (grupo B), Gram-negative Bacillus (E.

coli, Klebsiela), listeria and enterococcus. From 3

months old: Streptococcus pneumoniae, Neisseria

meningitidis and Haemophilus influenzae type B.

The diagnosis of this infection in children

is based mainly on clinical evaluation of the patient

and exams, through the analysis of the cerebrospinal

fluid (CSF) except when there are contra-indications;

identification of the antigen by polymerase chain

reaction (PCR), computed tomography of the skull

to assess the brain impairment.

In this context, due to the importance

of bacterial meningitis in childhood by being an

infection which needs special care and immediate

intervention, besides causing serious consequences

for the child, and may lead to death, the goal of

this article is to present a literature review with

a detailed approach in relation to the combined

therapy of bacterial meningitis, through the

corticotherapy and its effects on the child, from a

bibliographic research of scientific articles available

in the databases Virtual Library of Health, PubMed,

UpToDate and JAMA.

LITERATURE REVIEW

The combination therapy of bacterial

meningitis must be started from the moment it is

diagnosed, as it can cause serious consequences,

such as the intracranial hypertension. The

antibacterials are the treatment of choice, and

cephalosporins of 3° generation the most used.

In addition, the corticoesteroids are also used in

order to avoid the progression of neurological

complications, although there are controversies

about its use.

The corticoesteroid dexamethasone is

commonly used prior to administration of the

antibacterial in meningitis, because it acts in reducing

the inflammatory response against bacteria killed

by another therapy. The dead bacteria

releasepro-inflammatory cykines which may lead to a harmful

reaction for the patient, however, the corticoesteroid

improves the prognosis and outcome of infection.

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broad spectrum for all etiological agents, as the

Committee of Infectious Diseases of the American

Academy of Pediatrics (AAP) claims that the

treatment with dexamethasone may be beneficial

in children with meningitis caused by Haemophilus

influenzae type B (Hib) if administered before

or concurrent with the first dose of antimicrobial

therapy.

Ygberget al.

_{(2016) observed the effects of}

the use of Glucocorticosteroids in combination

therapy of bacterial meningitis in a retrospective

study of 10 years with 44 children with this

infection. All children received cefotaxime as

empirical antibiotic, 26 received betamethasone,

14 received dexamethasone and 4 used other

Glucocorticosteroids. The children who received

powerful and suitable Glucocorticosteroids -

betamethasone or dexamethasone had auditory

deficit significantly smaller in relation to those who

used another or no corticosteroid (18% versus 50%;

P = 0.032). At the end of the study, it was concluded

that corticosteroids reduce hearing deficits and

neurological sequelae after bacterial meningitis in

all ages. On the other hand, Kaplan et al.

_{(2014), in}

their work, report that in a meta-analysis of 2015

which included 2511 children it was discovered

that the administration of dexamethasone did not

interfere in mortality, but reduced the incidence

of severe hearing loss in children with bacterial

meningitis, but those whose etiological agent was

the Haemophilus influenzae type B.

According to Ogunlesi et al.

_{(2015), the}

administration of adjuvant corticosteroids reduced

the risk of death among neonates with bacterial

meningitis; although there is a trend toward an

increase or worsening the results in relation to

sensorineural deafness at two years of age, however,

this difference is not statistically significant.

However, dexamethasone is not indicated in the

combination therapy of bacterial meningitis in

infants less than six weeks or with congenital

or acquired abnormalities of the central nervous

system. Also, it is not indicated in combination

therapy of patients in whom is suspicious of entereic,

non-bacterial or gram-negative meningitis. If begun

before the diagnosis, the corticotherapy should be

stopped as soon as the diagnosis of enteric,

non-bacterial or gram-negative meningitis is confirmed.

In addition, studies demonstratedf that

the corticoesteroids may have toxic effects to the

cultures in cortical and hippocampus neurons. The

corticotherapy increases hippocampal apoptosis

and leads to learning disabilities.

_Moreover,

Engelen-Lee et al.1 (2016), report in their article an

experimental study of pneumococcal meningitis in

which was identified apoptosis in the hippocampus

of rats treated with dexamethasone in association

with the deficiency of learning.

FINAL CONSIDERATIONS

After the articles analsys, it was concluded

that the results of using corticosteroid in bacterial

meningitis asre still controversial, due to the fact

that there is no consensnus of its benefits when it

comes to combination therapy in meningitis. There

is a need for a larger number of studies to evaluate

the efficacy of corticosteroids in the therapy of this

infection and its action on other etiological agents,

that is, the therapy should be broad-spectrum; not

only for Haemophilus influenzae type B.

There are no conflicts of interests.

REFERENCES

1.

ENGELEN-LEE, J. Y. et al. Pneumococcal

9.

GUDINA, E. K. et al. Adjunctive dexamethasone

therapy in unconfirmed bacterial meningitis

in resource limited settings: is it a risk worth

taking?. BMC neurology, v. 16, n. 1, p. 153,

2016.

10.

SAMKAR, A. V. et al. Streptococcus suis

meningitis: a systematic review and

meta-analysis. PLoS Negl Trop Dis, v. 9, n. 10,

p.41-91, 2015.

11.

WENZEL, M. et al. Corticosteroid-induced

meningococcal meningitis in a patient with

chronic meningococcemia. JAMA dermatology,

v. 150, n. 7, p. 752-755, 2014.

12.

BARTT, R. Acute bacterial and viral

meningitis. CONTINUUM: Lifelong Learning

in Neurology, v. 18, n. 6, p. 1255-1270, 2012.

13.

MACONOCHIE, I. K.; BHAUMIK, S. Fluid

therapy for acute bacterial meningitis. Cochrane

Database Syst Rev, v. 5, 2014.

(meningene-path). Acta neuropathologica

communications, v. 4, n. 1, p. 26, 2016.

2.

DU, K. X. et al. Effects of dexamethasone on

aquaporin-4 expression in brain tissue of rat

with bacterial meningitis. International journal

of clinical and experimental pathology, v. 8, n.

3, p. 3090, 2015.

3.

CARDOSO, D. N. S. Meningite bacteriana

aguda. Revista de pediatria SOPERJ, v. 13, n.

2, p. 72-76, 2012.

4.

SHAO, M. et al. The role of adjunctive

dexamethasone in the treatment of bacterial

meningitis: an updated systematic

meta-analysis. Patient preference and adherence, v.

10, p. 1243, 2016.

5. KAPLAN, S. L. et al. Bacterial meningitis in

children: Dexamethasone and other measures

to prevent neurologic complications.

Waltham

(MA): UpToDate, 2014.

6.

YGBERG, S. et al. A ten-year retrospective case

series of glucocorticoid treatment of bacterial

meningitis in children. Acta Paediatrica, v.

105, n. 8, p. 979-982, 2016.

7.

OGUNLESI, T. A.; ODIGWE, C. C.;

OLADAPO, O. T. Adjuvant corticosteroids

for reducing death in neonatal bacterial

meningitis. The Cochrane Library, 2015.

8.

BERNARDO, W. M.; AIRES, F. T.; DE SÁ,

F. P. Eficácia da associação de dexametasona à

antibioticoterapia em pacientes pediátricos com

meningite bacteriana. Revista da Associação