Академический Документы
Профессиональный Документы
Культура Документы
meningococcal meningitis, pneumoccal meningitis, Ps. aeruginosa. Mixed bacterial infection with more
Listeria meningitis and meningoencephalitis, lumbar than one agent typically accounts for 1% of all cases of
puncture (LP), CSF, treatment for meningitis, anti- ABM and is seen in patients who are immuno-
biotic, dexamethasone and vaccine. For determining suppressed, have skull fracture or externally commu-
the levels of evidence for therapeutic interventions, the nicating dural stula, parameningeal source of infection
EFNS guideline was followed [1] (Table S1). Only (otitis and sinusitis) and previous neurosurgery.
research papers published in English were considered. Nosocomial bacterial meningitis is often caused by
Limitations of the search strategy include: non-ran- staphylococci (aureus and albus, including methicillin-
domized clinical data, lack of sensitivity and specicity, resistant strains) and Gram-negative bacilli. Entero-
small numbers of cohorts and casecontrol studies. bacteriaceae are the most common aetiological agent of
bacterial meningitis after neurosurgical procedures. The
present guideline will not address the treatment of
Background
nosocomial meningitis and neonatal meningitis.
Acute bacterial meningitis is a life-threatening neuro- Presently, S. pneumoniae has emerged as the single
logical emergency. Its estimated annual incidence is 25 most common cause of community-acquired bacterial
per 100 000 people in the Western world and a gure meningitis after post-natal life both in the developed and
that may be 10 times as high in the less developed developing countries [w5,w6]. S. pneumoniae is suscepti-
countries [w1]. ABM is one of top 10 causes of infec- ble to penicillins and cephalosporins although emergence
tion-related death worldwide [w2] and 3050% of its of penicillin and cephalosporin-resistant S. pneumoniae
survivors have permanent neurological sequelae has increased in the recent years [w7,w8,w9]. However, in
[w3,w4]. The causative organism of ABM can be reli- children as well as in adults, the severity of disease and the
ably predicted by the age of the patient, predisposing outcome of meningitis caused by penicillin-sensitive S.
factors, underlying diseases and immunological com- pneumoniae are similar to those caused by the penicillin-
petence. Streptococcus pneumoniae and Neisseria men- resistant strains [w10,w11].
ingitidis are the two most common aetiologic agents of
ABM in immunocompetent infants (>4 weeks) and
Early management of ABM
children, as well as in adults, comprising nearly 80% of
all cases, followed by Listeria monocytogenes and Early diagnosis and eective antibiotic treatment
staphylococci (Table S2). Gram-negative bacilli (Esc- remains the cornerstone of successful management of
herichia coli, Klebsiella, Enterobacter and Pseudomonas ABM. An understanding of the pathophysiological
aeruginosa) contribute to <10% of the cases. Haemo- time-table of ABM [2], as summarized in Panel 1, is
philus inuenzae meningitis caused by the capsular b essential for its successful and timely management.
strains (Hib) was the leading cause of meningitis in
infants and younger children but has become rare after
Clinical feaures of ABM
universal Hib immunization with an emergening trend
of H. Inuenzae meningitis caused by uncapsulated The suspicion of ABM is critically dependent on the early
strains. In immunocompromised patients, the most recognition of the meningitis syndrome. In a Dutch study
common agents causing ABM are S. pneumoniae, of adults presenting with community-acquired ABM, the
L. monocytogenes and Gram-negative bacilli, including sensitivity of the classic triad of fever, neck stiness and
Panel 1 Time line of ABM [2]
Pathophysiology
Phase 1 Phase 2 Phase 3
Release of pro-inammatory Subpial encephalopathy Breakdown in the Impaired CBF, rising Focal neuronal injury
cytokines from bacterial induced by cytokines blood-brain-barrier, intracranial pressure and
invasion and consequent and other chemical transendothelial vasculitis
inammation of Mediators emigration of leukocytes
subarachnoid space and development of
cerebral oedema
Clincal
Fever, headache Meningism, confusion, Impaired consciousness, Obtundation, seizures, focal Paralysis, cognitive
reduced CSF glucose elevated CSF pressure, neurological symptoms impairment coma,
increased CSF protein, and/signs (e.g. cranial possibly death in
focal symptoms nerve palsies) untreated cases
Panel 2 Differential diagnosis of acute bacterial meningitis practitioners with parenteral penicillin was associated
Other infective meningitis and meningoencephalitis
with an increased odds ratios for death [7.4, 95% con-
(viral, tuberculous, fungal, leptospiral and primary amoebic) dence interval (CI) 1.537.7] and complications in
Viral encephalitis survivors (5.0, CI 1.715.0) [4]. The adverse outcome
Brain abscess from pre-hospital antibiotic therapy was interpreted as
Spinal epidural abscess (cervical) indicative of more severe disease in these cases and lack
Parameningeal infection (cranial osteomyelitis, subdural empyema)
Aseptic meningitis (e.g. SLE, Behcets, sarcoidosis)
of supportive treatment before hospital admission. A
Chemical meningitis (e.g. after human IVIg therapy, recent multivariate regression analysis of a retrospective
subarachnoid haemorrhage) case study of 119 adults with ABM showed that time
from presentation to antibiotic administration of >6 h
was associated with an adjusted 8.4 times increased risk
altered mental status was found to be low, but almost of death (95% CI 1.740.9) [5]. Absence of the classical
all patients with ABM had at least two of the four triad of meningitis and delay in the diagnosistreatment
symptoms of headache, fever, neck stiness and altered sequence (transfer to institution, CT scan before LP,
mental status [3]. In children, irritability, refusal to antibiotics) were factors which were associated with the
eat, vomiting and seizures are often early symptoms. door-antibiotic time >6 h in this study. Delay in anti-
The level of consciousness in ABM is variable and may biotic administration beyond 3 h and penicillin-resis-
range from drowsiness, confusion, stupor to coma. tance were two major risk factors associated with
adverse outcome in adults with severe pneumococcal
meningitis [w12]. Despite relative paucity of controlled
Differential diagnosis
studies on the timing of antibiotics administration to
A high index of suspicion is required for the diagnosis the outcome of ABM, available data do point to a cut-
of ABM and a list of common dierential diagnosis is o period of 36 h beyond which there is a signicant
provided in Panel 2. increase in mortality.
In patients visiting to the hospital, empirical antibi-
otic treatment for ABM should be considered before
Initial management
CSF analysis only if LP is contraindicated (Panel 3), or
Examination of CSF by LP is an undisputable and the facility for rapid brain imaging (CT scan) prior to
indispensible part of assessment of patients who present LP is not immediately available. A normal CT scan in a
with symptoms and signs of meningitis unless the patient with clinical manifestations of cerebral hernia-
procedure is contraindicated by reasons of clinical tion does not guarantee absence of risk from the pro-
safety. Clearly, treatment in ABM will be initiated in cedure of LP [w13,w14,w15,w16]. In all cases of ABM,
the hospital setting for the majority of cases, and after
the diagnosis of bacterial meningitis is conrmed by the Panel 3 Contraindications for lumbar puncture in suspected acute
CSF formula obtained by LP. However, there will be bacterial meningitis
situations where the antibiotic treatment may have to
Absolute (lumbar puncture is not to be recommended)
be commenced on suspicion before it is possible to
Signs of raised intracranial pressure
conrm the diagnosis of ABM by CSF examination. (papilloedema, decrebrate posturing)
This could happen in a primary care setting where trans- Local skin infection in needle track
fer to a secondary care unit is probably to take some Evidence of obstructive hydrocephalus, cerebral oedema
time. Even in hospitalized patients, CSF analysis may or herniation in CT (or MR) scan of brain
Relative (appropriate therapeutic measures and/or investigations
have to be delayed because of clinical or logistic reasons.
are indicated before lumbar puncture)
There are no randomized controlled trials to deter- Sepsis or hypotension (systolic blood pressure <100 mmHg,
mine the outcome of bacterial meningitis based on diastolic blood pressure <60 mmHg): patients should be
timing of administration of the antibiotic. There are no stabilized rst
prospective casecontrol studies of the potential benet Coagulation disorder (disseminated intravascular coagulopathy,
platelet count <50 000/mm3, therapeutic use of warfarin):
of pre-hospital antibiotic treatment. The evidence is
appropriate correction rst
conicting between countries and pooled analysis of all Presence of focal neurological decit, especially when
the published results did not conrm the perceived posterior fossa lesion is suspecteda
advantage of pre-hospital antibiotic treatment in ABM Glasgow coma score of 8 or lessa
which may relate to dierences in sample size and Epileptic seizuresa
reporting bias [w11]. In a casecontrol study of 158 a
In all these cases, CT (or MR) scan of brain should be the rst
children (age group 016 years) with suspected menin- step. Isolated single cranial nerve palsy without papilloedema does
gococcal disease, pre-hospital treatment by general not necessarily contraindicate LP without brain imaging.
blood cultures must be obtained rst before any treat- istered as empirical therapy for ABM and may be
ment is administered. The time taken for antibiotic commenced immediately [IIIA].
therapy ideally should coincide with or occur immedi- In patients with known history of severe beta-lactam
ately before the administration of adjunctive dexa- allergy, vancomycin should be administered as the
methasone therapy for suspected pneumococcal and alternative for pneumococcal meningitis and chl-
H. inuenzae meningitis. The choice of empirical anti- oramphenicol for meningococcal meningitis [IVC].
biotic in ABM may be inuenced by a number of In regions with known or suspected penicillin-resis-
factors, including patients age, systemic symptoms and tant strains of pneumococcus, high dose vancomycin
local pattern of bacterial resistance. A recent Cochrane should be used in combination with a third-genera-
Database review however, found no clinically impor- tion cephalosporin [IVC].
tant dierence between the third-generation cephalo- Patients with risk factors for Listerial meningitis (old
sporins (ceftriaxone or cefotaxime) and conventional age, immunosuppressed and/or signs of rhomben-
antibiotics (penicillin or ampicillinchloramphenicol or cephalitis) should receive IV amoxicillin in addition
chloramphenicol) as the empirical therapy in the to a third-generation cephalosporin as the empirical
treatment of ABM [6]. treatment of ABM initially [IVC].
Dexamethasone in high doses may be appropriate as
an adjunctive therapy and should be given shortly
Recommendation
before or with the rst dose of antibiotics (see
The Task Force recommends (Flow chart) that all Adjunctive therapy on ABM).
patients with suspected ABM should be hospitalized All ABM patients should be managed as medical
as soon as possible [III A]. Care of patients with emergencies and when available, treated in neuro-
suspected ABM should be considered as an emer- logical intensive care units.
gency and fast-tracked for rapid assessment and
treatment. We propose the following timeline for
Investigations in ABM
management of ABM: admission to hospital within
rst 90 min of making contact with health service; The primary purpose of investigations in ABM is to
and assessment and treatment commenced within conrm the diagnosis and to identify the causal
60 min of hospital admission, and no longer than 3 h bacteria. The recommended specic laboratory tests for
after contact with health service [IVC]. patients with suspected ABM are listed in Panel 4. In
Pre-hospital antibiotic treatment should only be ini- uncomplicated meningitis, plain CT and MR scans are
tiated for patients with strong suspicion of dissemi- often normal. Contrast scans may show abnormal
nated meningococcal infection (meningococcemia) enhancement of basal cisterns and subarachnoid space
because of the unpredictable risk of early circulatory (involving convexity, falx, tentorium, base of the brain)
collapse from adrenocortical necrosis (Waterhouse because of the presence of inammatory exudates
Fredrichsen syndrome). For other patients, rapid pre- [w17,w18,w19]; some MRI methods may have high
admission antibiotic therapy should be considered sensitivity [w20].
only if a delay in excess of 90 min in hospital transfer An increased CSF-opening pressure, high number of
is anticipated [IIIC]. polymorphonuclear leukocytes and raised protein con-
LP and CSF analysis is the specic investigation centration, together with decreased CSF:plasma ratio
required for diagnosis and management of ABM. of glucose (<0.3) are characteristic ndings supportive
Therefore, if diagnosis of bacterial meningitis is sus- of ABM (Panel 5). Listerial meningitis may have CSF
pected and there are no clinical contraindications, ndings identical to chronic tuberculous or fungal
LP should be performed as soon as safely possible meningitis [w22,w23,w24,w25].
[IIIC]. The identication of the causal bacteria depends on
In patients with symptoms and signs suggestive of staining (Table S3) and culture of CSF, which should
raised intracranial pressure or with high risk of cere- always be tested in freshly obtained samples. Gram
bral herniations following LP (imaging evidence of stain is used most widely and has the best predictive
intracranial mass lesion, obstructive hydrocephalus or value, but it is probably less sensitive.
midline shift), diagnostic LP should be postponed [IA]. Identication of bacteria in CSF staining depends
In a patient with suspected ABM in whom LP is both on the bacterial concentration and the specic
being delayed or postponed, antibiotic therapy organism [w30]. The percentage of positive cultures
should be commenced immediately after collecting (sensitivity) is variable and ranges between 50 and 90%
blood sample for culture. IV or IM Benzyl Penicillin, for ABM [w23,w24,w31]. A variable percentage of
or IV Cefotaxime or Ceftriaxone should be admin- positive cultures are because of contaminanting
Rapidly
Yes evolving skin No
rash ?
60 min Hospital
admission
90 min Is LP clinically
Yes No
safe?
Is CT facility
readily
available?
Yes
Review
120 min 1. Commence on empiric antibiotics (see Table)
imaging.
No 2. Add dexamethasone if focal neurological deficit
Proceed to
No 3. Add acyclovir if HSE is a possibility
LP?
No
Yes
Safety of LP
reconfirmed by a
neurologist?
Yes Stabilise patient
Definitive Imaging
(MR)
Delayed LP (if
312 h
safely possible)
1224 h Review results. Confirm choice of antibiotics, continuation of steroids and duration of antibiotic therapy
2448 h Response to
Yes therapy No
satisfactory?
Reassess clinical,
Continue
imaging and
treatment
laboratory data
Flow chart Flow chart of emergency management of patients with suspected bacterial meningitis. ABM, acute bacterial meningitis; DIC,
disseminated intravascular coagulation; GCS, Glasgow Coma Scale; HSE, herpes simplex encephalitis; LP, lumbar puncture.
organisms but not responsible for the meningeal infec- tive predictive value: 99%); (b) increased CSF lactate
tion [w31]. In patients with ABM, the probability of a [w34,w35] (sensitivity: 8690%, specicity: 5598%,
negative CSF culture in previously treated patients is positive predictive value: 1996%, negative predictive
increased compared with non-treated patients (odds value: 9498%); and (c) high CSF ferritin [w36,w37,w38]
ratio 16; 95% CI 1.45764.68; P = 0.01) [w32]. In (sensitivity: 9296%,specicity: 81100%).
ABM, the likelihood of diagnostic yield in CSF micro- Several rapid methods for detecting components of
biology is highest before antibiotic treatment. Three bacteria in CSF have been based on bacterial antigen
other helpful and indirect diagnostic markers of ABM detection, counterimmunoelectrophoresis, coagglutina-
are: (a) elevated serum C-reactive protein (quantied) in tion, latex agglutination and ELISA. The average
children [w33] (sensitivity: 96%, specicity: 93%, nega- ecacy of these tests have been: sensitivity: 6090%,
meningitis should be treated with benzyl penicillin or a 4 hourly or Ceftriaxone 2 g 12 hourly or Cefotaxime
third-generation cephalosporin, or chloramphenicol if 2 g 68 hourly.
there is a history of life-threatening beta-lactam allergy. Alternative therapy; Meropenem 2 g 8 hourly [IVC]
Listeria is intrinsically resistant to the cephalosporins or Vancomycin 60 mg/kg/24 hourly as continuous
and suspected listerial meningitis should be treated with infusion (adjusted for creatinine clearance) after
high dose IV ampicillin or amoxicillin usually in con- 15 mg/kg loading dose aiming for serum levels of
junction with IV gentamicin (12 mg/kg 8 h) for the rst 1525 mg/l) plus Rifampicin 600 mg 12 hourly
710 days which is synergistic in vivo, or with high dose [IVC] or,
IV cotrimoxazole when there is history of penicillin al- Moxioxacin 400 mg daily [IVC]
lergy [w52,w54,w57]. The doses for common antibiotics ii. Pneumococcus with reduced susceptibility to
in children are provided in Table S4. penicillin or cephalosporins;
There are no randomized controlled trials on the Ceftriaxone or Cefotaxime plus Vancomycin
treatment of staphylococcal meningitis which is usually Rifampicin [IV]. Alternative therapy Moxioxacin,
nosocomial (e.g. shunt infection). Linezolid has been Meropenem or Linezolid 600 mg combined with
used in a number of case reports with good success and Rifampicin [IV]
pharmacokinetics are persuasive and may be an option iii. Menigococcal meningitis
for the treatment of methicillin-resistant staphylococcal Benzyl Penicillin or Ceftriaxone or Cefotaxime [IV]
meningitis and ventriculitis [w58]. Lizezolid however Alternative therapy; Meropenem or Chloram-
requires to be used with caution, because of adverse phenicol or Moxioxacin [IVC]
events and drug interactions, particularly in the inten- iv. Haemophilus infuenzae type B
sive care when vasoactive agents are used. The use of Ceftriaxone or Cefotaxime [IVC]
intrathecal or intraventricular antibiotics is to be con- Alternative therapy; IV ChloramphenicolAmpicil-
sidered in patients who fail conventional treatment. lin/Amoxicillin [IVC]
Intraventricular vancomycin may achieve better CSF v. Listerial meningitis
concentration as compared with intravenous route and Ampicillin or Amoxicillin 2 g 4 hourly
the addition of intrathecal or intrventricular amino- Gentamicin 12 mg 8 hourly for the rst 7
glycosides as an additional agent is an option for pa- 10 days [IVC]
tients with Gram-negative bacillary meningitis who do Alternative therapy, TrimethoprimSulfamethoxaz-
not respond well to monotherapy. ole 1020 mg/kg 612 hourly or Meropenem [IV]
vi. Staphylococcal species; Flucloxacillin 2 g 4 hourly
[IV] or
Recommendation
Vancomycin if penicillin allergy is suspected [IV].
Initial antibiotic treatment of ABM should be par- Rifampicin should also be considered in addition to
enteral [IA]. either agent, and Linezolid for methicillin-resistant
staphylococcal meningitis [IVC].
vii. Gram-negative Enterobacteriaceae
Empirical antibiotic therapy in suspected ABM
Ceftriaxone or Cefotaxime or Meropenem
Ceftriaxone 2 g 1224 hourly or Cefotaxime 2 g viii. Pseudomonal meningitis
68 hourly [IIIB] Meropenem Gentamicin
Alternative therapy; Meropenem 2 g 8 hourly [IIIC] or
Chloramphenicol 1 g 6 hourly.
Duration of therapy
If penicillin or cephalosporin-resistant pneumococcus is
suspected, use Ceftriaxone or Cefotaxime plus Vanco- The optimum duration of therapy in ABM is not
mycin 60 mg/kg/24 hourly (adjusted for creatinine known. In a prospective, observational study of
clearance) after loading dose of 15 mg/kg [IVA]. meningococcal disease in adults from New Zealand,
Ampicillin/Amoxicillin 2 g 4 hourly if Listeria is sus- which had a majority of cases with meningitis, a 3-
pected [IVA]. day course of IV benzyl penicillin was successful
[w59]. Amongst children with uncomplicated ABM,
7 days of ceftriaxone was found to be equivalent to
Pathogen specific therapy
10 days in India [w60] and 4 days was found to be
i. Penicillin-sensitive Pneumococcal meningitis (and equivalent to 7 days in Chile [w61]. In a Swiss mul-
including other sensitive Streptococcal species); ticentre study in children short course therapy (7 days
Benzyl Penicillin 250 000 U/kg/day (equivalent to or less) was equivalent to 812 days of treatment with
2.4 g 4 hourly) [IVA] or Ampicillin/Amoxicillin 2 g ceftriaxone [w62]. Two single doses of intramuscular
oily chloramphenicol separated by 48 h were found in trials. The rationale for using corticosteroids was that
African children to be equivalent to 8 days parenteral the treatment would attenuate subarachnoid space
ampicillin [w63]. In the absence of controlled clinical inammation and vasogenic oedema in meningitis that
trials in adults, the recommended duration of antibi- may have potentially serious and damaging eects [2].
otic therapy in ABM is based on current standards of In 1988, published results of two-double blind, placebo-
practice and in most cases with early and uncompli- controlled trials of dexamethasone as adjunctive treat-
cated ABM, the shorter range of therapy would be ment of bacterial meningitis in infants and older chil-
appropriate. dren showed convincing benet from steroid therapy
(decreased incidence of sensorineural hearing loss in the
treated children with Hib meningitis) [w65]. In two
Recommendation
subsequent trials in paediatric patients, dexamethasone
Unspecied bacterial meningitis 1014 days [IVC]. given before or with the rst dose of antibiotic signi-
Pneumococcal meningitis 1014 days [IVA]. cantly reduced one or more neurological sequelae
Meningococcal meningitis 57 days [IVA]. [w66,w67]. In 1997, a meta-analysis of all randomized
Hib meningitis 714 days [IVB]. clinical trials since 1988 using dexamethasone as
Listerial meningitis 21 days [IVB]. adjunctive therapy in bacterial meningitis concluded that
Gram-negative bacillary and Pseudomonal menin- steroid treatment beneted Hib meningitis and when
gitis: 2128 days [IVB]. commenced with or before parenteral antibiotics, showed
benet for children with pneumococcal meningitis [w68].
A large prospective, open trial of dexamethasone in
Monitoring treatment
adults showed a benet of dexamethasone therapy in a
In general, if clinical condition does not improve by subgroup of patients with pneumococcal meningitis
48 h after commencing appropriate antibiotics (and [w69]. Another multi-centre double blind, randomized
dexamethasone when indicated), the following consid- trial of dexamethasone treatment for severe bacterial
erations should be given: meningitis in adults proved inconclusive because the
raised intracranial pressure from cerebral oedema or trial was stopped prematurely because of the emergence
obstructive hydrocephalus of penicillin-resistant S. pneumoniae [w70]. A placebo-
vascular complications (arteritis or venous sinus controlled double blind trial of dexamethasone in 40
thrombosis) adult patients from India concluded that the steroid
inappropriate antibiotic treatment reduced neurological complications because
poor antibiotic penetration (e.g. vancomycin if of meningitis but secondary fever, gastrointestinal
patient on dexamethasone) manifestations and neuropsychiatric symptoms were
wrong diagnosis common side eects in the treated group [w71].
epileptic seizures (e.g. non-convulsive status) Results of a double blind, placebo-controlled, ran-
metabolic complications (e.g. SIADH) domized European trial of dexamethasone in 301 adult
persistence of source of primary infection (e.g. pneu- patients with ABM in adults showed that early steroid
monia, bacterial endocarditis, mastoiditis or otitis) use (before or with rst dose of antibiotics) is associated
Risk scores for unfavourable outcome in ABM have with an improved survival and signicantly better out-
been recently validated both in adults [8] and children come in these patients as measured by the Glasgow
[9] and may be useful as prognostic tools. In a Outcome Scale at 8 weeks [10]. The benet was by far
retrospective study, disturbed level of consciousness most convincing in patients with pneumococcal menin-
and higher age at the time of admission were found to gitis who were given dexamethasone (10 mg 6 hourly for
be risk factors for developing hydrocephalus in the rst 4 days) beginning before or with the rst dose of the
early phase of ABM [w64]. CT or MR scans of brain antibiotic. The benet of adjuvant dexamethasone in this
can identify areas of ischaemia or infarction, brain trial was not undermined by any increase in the incidence
abscess. subdural empyema, signs of venous sinus of severe neurological disability in patients who survived,
thrombosis, hydrocephalus and ventriculitis [IIIB]. or by any serious steroid-induced complications.
The positive outcome of the European dexametha-
sone trial in adult bacterial meningitis contrasted
Adjunctive therapy of ABM
sharply with the results of a randomized controlled trial
of adjuvant dexamethasone in 598 children with bac-
Corticosteroids
terial meningitis from Malawi [w72]. The Malawi trial
Of all the adjunctive treatments in ABM, only corti- failed to demonstrate any treatment benet in terms of
costeroids have been properly evaluated in clinical survival or neurological outcome. A recently published
trial of dexamethasone in adult patients with bacterial There is insucient evidence to recommend the use of
meningitis from Malawi [w73] reached very similar dexamethasone in pharmacological doses after anti-
conclusions. In this trial, mortality was exceptionally biotic therapy has begun. Dose and duration of
high in both groups of patients receiving dexametha- therapy with corticosteroids in such cases should be
sone (56% of 233 patients) or placebo (53% of 232 guided by specic clinical indications in individual
patients) at 40 days and there was also no dierence in patients (e.g. physiological doses of steroids in cases
disability rates or hearing loss between these groups at of adrenal insuciency because of meningococcemia,
6 months. Nearly 90% patients in this study were pharmacological doses of steroids for raised intra-
seropositive for HIV infection. The results of the Viet- cranial pressure).
namese trial of dexamethasone in bacterial meningitis By reducing subarachnoid space inammation and
[w74], was however more favourable for the steroid- blood brain barrier permeability, steroids may lower
treated patients with proven ABM. In this trial, 435 CSF penetration of antibiotics and patients receiving
subjects older than 14 years were randomly assigned to vancomycin for penicillin-resistant pneumococcal
receive 0.4 mg/kg of dexamethasone (n = 217) or meningitis require close clinical and CSF monitoring.
placebo (n = 218) every 12 h for 4 days commencing
shortly before the administration of antibiotics in most
Other symptomatic and adjunctive therapies
cases with meningitis caused by S. suis (which is similar
to S. pneumoniae). Circulatory shock as part of severe sepsis or in
Taken together, results of these trials conrm the ear- meningococcemia should be handled in neurointensive
lier view [2] that longer use (for 4 days) of dexamethasone care unit. Treatment should consist of a 30 head-
in pharmacological doses is not appropriate if patients up position, head midline, minimal suction, deep
are probably to be immunocompromised or have a ten- sedation, normo- or moderate hypothermia and strict
taive diagnosis of ABM unsupported by appropriate avoidance of hypercapnia [11]. Head elevation and
investigations. The role of dexamethasone as an adjunc- hyperosmolar agents are recommended for the
tive therapy in ABM is clearly maximal in those who are management of cerebral oedema but have never been
not signicantly immunosuppressed and have a con- systematically evaluated in the context of bacterial
rmed microbiological diagnosis of ABM. In the context meningitis. As a hyperosmolar agent, 20% mannitol
of the bacterial aetiology of ABM, evidence conrms its may be given intravenously either as a bolus injection of
therapeutic benet in cases with pneumococcal and Hib 1 g/kg over 1015 min, repeated at 46 h intervals, or
meningitis. Wider use of high dose dexamethasone in in smaller but frequent doses (0.25 mg/kg every 23 h),
ABM because of other bacterial aetiologies is currently to maintain a target serum osmolality of 315
proposed [w75,w76], but its therapeutic benet is not 320 mOsm/l [IVC]. CSF pressure monitoring may be
conclusive across all groups of patients. helpful in cases where CSF drainage (ventricular) is
under consideration for obstructive hydrocephalus, and
the decision to perform the procedure should be based
Recommendation
on patients level of consciousness and the degree of
Adjuvant dexamethasone is recommended with or ventricular dilatation visualized in brain imaging (CT
shortly before the rst parenteral dose of antibiotic in or MRI) [IVC]. Seizures are frequent in ABM and are
all previously well and non-immunosuppressed adults associated with severe inammation, structural brain
with pneumococcal meningitis at a dose of 10 mg lesion and pneumococcal meningitis, may increase
every 6 h for 4 days [IA] and children at a dose of mortality [12] and should be treated with a parenteral
0.15 mg/kg every 6 h for 4 days for Hib and pneu- anticonvulsant, such as phenytoin (fosphenytoin)
mococcal meningitis [IA]. [IIIB]. Prophylactic anticoagulation to prevent deep
In all patients with clinically suspected pneumococcal vein thrombosis may be considered in patients who do
(or Hib) meningitis (early focal neurological signs), we not have coagulaopathy and are considered to be at a
recommend that dexamethasone is given with the rst high risk of deep vein thrombosis (e.g. obesity and
dose of empirical antibiotic therapy as above [IVC]. recent hip surgery). Heparin was considered benecial
In ABM because of other bacterial aetiology, routine in a retrospective study of patients with septic
use of high dose dexamethasone is not presently cavernous sinus thrombosis [w77]; however, experience
recommended [IA]. with therapeutic anticoagulation for venous sinus
If dexamethasone was initiated on clinical suspicion thrombosis in ABM is limited and is best reserved for
of ABM, which was subsequently proven to be patients who deteriorate neurologically because of
inaccurate by CSF microbiolgy, the treatment should venous sinus thrombosis and require close monitoring
be promptly withdrawn. of coagulation prole and brain imaging [IVC].
occur, all household members should have their vacci- Please note: Blackwell Publishing are not responsible
nation status evaluated. Prophylaxis with rifampicin is for the content or functionality of any supplementary
recommended and unimmunized children should be materials supplied by the authors. Any queries (other
vaccinated against Hib. than missing material) should be directed to the corre-
sponding author for the article.
Recommendation
References
All cases of suspected meningococcal or Hib menin-
gitis should be reported urgently to the local public 1. Brainin M, Barnes M, Baron J-C, et al. Guidance for the
preparation of neurological management guidelines by
health authorities [IVC].
EFNS scientic task forces-revised recommendations
Chemoprophylaxis with either oral rifampicin 2004. European Journal of Neurology 2004; 11: 16.
(600 mg 12 hourly for 48 h), ciprooxacin (500 mg 2. Chaudhuri A. Adjuvant dexamethasone use in acute
single dose) or ceftriaxone (IV or IM injection of a bacterial meningitis. Lancet Neurology 2004; 3: 5461.
single 1 g dose) should be given to those adults with 3. Van de Beek D, de Gans J, Spanjaard L, et al. Clinical
features and prognostic factors in adults with bacterial
meningococcal infection who were treated without a
meningitis. New England Journal of Medicine 2004; 351:
third-generation cephalosporin [IVC]. 18491859.
Chemoprophylaxis with either Rifampicin, Cipro- 4. Harnden A, Ninis N, Thompson M, et al. Parenteral
oxacin or Ceftriaxone should be given to house- penicillin for children with meningococcal disease before
hold or close contacts of patients with suspected or hospital admission: casecontrol study. British Medical
Journal 2006; 332: 12951298.
proven meningococcal or Haemophilus infection
5. Proulx N, Frechette D, Toye B, Chan J, Kravcik S.
[IVC]. Delays in the administration of antibiotics are associated
A therapeutic 7-day course of Phenoxymethyl Peni- with mortality from acute bacterial meninigitis. QJM
cillin or Amoxicillin should be considered in addition 2005; 98: 291298.
to chemoprophylaxis for any household or close 6. Prasad K, Kumar A, Gupta PK, Singhal T. Third gen-
eration cephalosporins versus conventional antibiotics for
contact of a patient with meningococcal disease aged
treating acute bacterial meningitis. Cochrane database of
<15 years [IVC]. systematic reviews 2004; CD001832.
Chemoprophylaxis for meningococcal meningitis is 7. Richard JD, Wolff M, Lachareade JC, et al. Levels of
rarely indicated for health-care workers and is only vancomycin in cerebrospinal uid of adult patients
recommended in situations where there has been receiving adjunctive corticosteroids to treat pneumococcal
meningitis: a prospective multicentre observation study.
mouth to mouth contact or direct exposure to infec-
Clinical Infectious Diseases 2007; 44: 250255.
tious droplets from a patient with meningococcal 8. Weisfelt M, van de Beek D, Spanjaard L, et al. A risk
disease [IVC]. score for unfavourable outcome in adults with bacterial
Immunization with Meningococcal or H. inuenzae meningitis. Annals of Neurology 2008; 63: 9097.
type B vaccine should be considered in the public 9. Dubos F, De la Rocque F, Levy C, et al. Sensitivity of the
bacterial meningitis score in 889 children with bacterial
health management of an outbreak [IVC].
meningitis. Journal of Paediatrics 2008; 152: 378382.
Primary vaccination against N. meningitidis and 10. de Gans J, van de Beck D. Dexamethasone in adults with
H. inuenzae type B infection should be given to all at bacterial meningitis. New England Journal of Medicine
risk groups [IVC]. 2002; 347: 15491556.
Vaccination against N. meningitides type C and 11. Nadel S, Kroll JS. Diagnosis and management of me-
ningococcal disease: the need for centralized care. FEMS
H. inuenzae type B should be given to all children
microbiology reviews 2007; 31: 7183.
as part of the normal childhood immunization 12. Zoons E, Weisfelt M, de Gans J, et al. Seizures in adults
schedule [IVC]. with bacterial meningitis. Neurology 2008; doi:10.1212/
01.wnl.0000288178.91614.5d.
13. Kastenbauer S, Pster HW. Pneumococcal meningitis in
Supplementary material adults: spectrum of complications and prognostic factors
in a series of 87 cases. Brain 2003; 126: 10151025.
The full (unabridged) version of this article is available
as supplementary material as part of the online article
from: http://www.blackwell-synergy.com/doi/abs/10.1111/
j.1468-1331.2008.02193.x
(This link will take you to the article abstract).