SNS Review
Complications and treatment of bacterial meningitis
■ H.-W. Pfister, R. Paul, S. Kastenbauer, U. Koedel
Depar tment of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich (D)
Summary
Pfister H-W, Paul R, Kastenbauer S, Koedel U.
Complications and treatment of bacterial menin-
gitis. Schweiz Arch Neurol Psychiatr 2003;154:
169–73.
The prognosis of bacterial (purulent) meningitis
depends on early diagnosis and prompt initiation
of antibiotic therapy. However, despite the im-
provement of antimicrobial therapy during the last
decades, mortality rate and sequelae due to bac-
terial meningitis remain unacceptably high. For
example, the mortality rate of meningitis due to
Streptococcus pneumoniae, the organism most
often responsible for bacterial meningitis in adults,
has remained relatively unchanged during the
last decades and is still as high as 20–30%. The un-
favourable courses of bacterial meningitis are
often due to intracranial complications including
brain oedema, cerebrovascular arterial or venous
involvement, and hydrocephalus. These complica-
tions usually lead to an increased intracranial
pressure. Patients with bacterial meningitis may
require adjunctive therapy including administra-
tion of hyperosmolar agents, hyperventilation or
ventricular drainage. Anticoagulation with dose-
adjusted intravenous heparin should be considered
in patients with meningitis-associated septic ve-
nous sinus thrombosis proven by MRI, MR angio-
graphy or cerebral angiography.
Recently, a prospective, randomised, multicen-
tre, double-blind trial (performed by de Gans
and van de Beek) in adults with acute bacterial
meningitis showed a beneficial effect of dexa-
methasone (10 mg was administered 15 to 20
minutes before or with the first dose of antibiotic
Correspondence:
Hans-Walter Pfister, MD
Depar tment of Neurology
Klinikum Grosshadern
Ludwig-Maximilians-University
Marchioninistrasse 15
D-81377 Munich
e-mail: Pfister@nefo.med.uni-muenchen.de
169 SCHWEIZER ARCHIV FÜR NEUROLOGIE UND PSYCHIATRIE
and was given every 6 hours for 4 days) compared
with placebo. Treatment with dexamethasone was
associated with a significant reduction in the risk
of an unfavourable outcome, and a significant
reduction in mortality. Among the patients with
pneumococcal meningitis, 14% of the dexametha-
sone group died, as compared with 34% of the
placebo group. Gastrointestinal bleeding occurred
in 2 patients of the dexamethasone group and in
5 patients of the placebo group. Based on these
data the use of dexamethasone is recommended in
adult patients with suspected bacterial meningitis,
i.e. in patients with clinical suspicion plus cloudy
cerebrospinal fluid, detection of bacteria in
the cerebrospinal fluid (CSF) by microscopy of
a Gram’s stained smear or a CSF cell count of
more than 1000 cells/µ l.
Keywords: bacterial meningitis; dexamethasone;
pneumococcal meningitis; brain oedema
Clinical aspects of bacterial meningitis
The spectrum of meningeal microorganisms caus-
ing bacterial meningitis is mainly dependent on
the age of the patient, predisposing factors and
underlying diseases. The most common aetiolo-
gical agents of bacterial meningitis in adults and
children are Neisseria meningitidis and Strepto-
coccus pneumoniae. Listeria monocytogenes is seen
especially in neonates, the elderly and immuno-
compromised patients with bacterial meningitis.
Gram-negative Enterobacteriaceae cause 10% of
the overall cases of bacterial meningitis; however,
they are the aetiologic agents in 60 to 70% of all
cases of meningitis following a neurosurgical pro-
cedure and are a common cause of meningitis in the
elderly and adults debilitated by chronic illness.
The most common agents causing bacterial menin-
gitis in newborns are group B streptococci (Strep-
tococcus agalactiae).
Bacterial meningitis is clinically characterised
by stiff neck, headache, fever, photophobia,
malaise, vomiting, alteration of consciousness,
seizures, confusion, irritability and, rarely, acute
154 ■ 4/2003
Table 1 Possible findings on CT (or MRI) in patients with bacterial
meningitis.
CT (or MRI) findings
brain oedema
hydrocephalus
brain infarction
signs of venous sinus thrombosis
parameningeal infectious foci (bone window technique),
e.g. sinusitis, mastoiditis
intracranial free air due to a dural leak
meningeal and ventricular ependymal enhancement
basal purulent exudate
brain abscess or subdural empyema (leading secondarily
to bacterial meningitis)
Table 2 Cerebral complications in adults with bacterial meningitis.
complication
brain oedema with the risk of herniation
cerebrovascular involvement
cerebral ar terial complications: ar teriitis,
vasospasm, focal cor tical hyperper fusion,
disturbed cerebral autoregulation
septic sinus thrombosis (in par ticular
of the superior sagittal sinus) and cor tical
venous thrombosis
hydrocephalus
vestibulocochlear involvement
(hearing impairment, vestibulopathy)
cranial ner ve palsies
cerebritis
sterile subdural effusiona
rarely as a consequence of meningitis:
brain abscess, subdural empyema
a
especially in infants
psychosis. Focal neurologic signs (e.g., hemi- or
tetraparesis, ataxia, aphasia, visual field defects)
are found in approximately 10–15% of the patients.
Cranial nerve palsies, usually of the 3rd, 6th, 7th or
8th cranial nerve, are detectable in approximately
10% of the patients. Hearing impairment, most
often due to purulent labyrinthitis, is a well-known
sequela of acute bacterial meningitis.
Diagnosis of acute bacterial meningitis is based
on (a) identification of the bacterial pathogen
in the cerebrospinal fluid (CSF), microscopy of a
Gram’s stained smear or antigen detection using
latex particle agglutination test, and/or (b) elevat-
ed CSF cell count of more than 1000 white blood
cells/µl and CSF consisting of more than 60% poly-
morphonuclear leukocytes, an elevated total pro-
170 SCHWEIZER ARCHIV FÜR NEUROLOGIE UND PSYCHIATRIE
tein content (>120 mg/dl) and a low CSF glucose
concentration (usually a ratio of CSF: blood glu-
cose of less than 0.3).
Cranial CT (or MRI) may identify several ab-
normalities in patients with bacterial meningitis
(table 1). Cerebrovascular involvement may be
detected by MRI (diffusion imaging), MR angio-
graphy and transcranial Doppler sonography
(TCD). TCD may be useful in diagnosing and
monitoring the involvement of great arteries at
the base of the brain [1]. In addition, MRI may
reveal septic sinus thrombosis.
Cerebral and systemic complications arising
during the acute phase of the disease are respon-
sible both for the mortality and the long-term
sequelae caused by bacterial meningitis (table 2)
[2].
Cerebrovascular involvement, both of arteries
(arteriitis, vasospasm) and veins (septic sinus ve-
frequency
nous thrombosis) may lead to infarction with se-
10–15% vere irreversible cerebral damage and an increase
15–20% in intracranial pressure due to cytotoxic oedema
[3]. In addition to oedema, increased intracranial
blood volume due to disturbed cerebrovascular
autoregulation or septic venous sinus thrombosis
may lead to life-threatening elevation of intra-
cranial pressure with the risk of herniation. There
is a risk of cortical necrosis when cerebral perfu-
10–15%
sion pressure (defined as the difference between
10–20% systemic mean arterial blood pressure and intra-
cranial pressure) decreases as a result of increased
ca 10%
intracranial pressure and systemic hypotension.
<10% Interstitial oedema may occur due to transepen-
ca 2% dymal movement of CSF from the ventricular sys-
tem into the surrounding brain parenchyma as a
consequence of obstructive hydrocephalus.
Management of an adult patient with bacterial
meningitis
In patients with clinical signs and symptoms sug-
gesting acute bacterial meningitis, a lumbar punc-
ture should be performed immediately after the
initial clinical examination. After drawing a single
blood culture, antibiotic therapy is immediately
started (dexamethasone treatment see below). In
patients who are unconscious and have focal neuro-
logic deficits (e.g. hemiparesis), a CT scan should
be performed prior to lumbar puncture. These
patients receive an initial antibiotic dose immedi-
ately after drawing a single blood culture, prior
to any other diagnostic procedure. Afterwards
CT scanning and CSF examination should be
performed as soon as possible. Contraindications
to lumbar puncture are clinical signs of cerebral
154 ■ 4/2003
Table 3 Initial empiric antibiotic therapy of bacterial meningitis of adults.

clinical setting typical pathogen recommended antibiotics

healthy, immunocompetent, S. pneumoniae, N. meningitidis, 3rd generation cephalosporina

community-acquired L. monocytogenes plus ampicillinb
nosocomial (e.g. postneurosurger y gram-negative Enterobacteriaceae, ceftazidime (or meropenem)
or posttraumatic brain injur y) P. aeruginosa, staphylococci plus vancomycinc
ventriculitis, shunt-infection Staph. epidermidis, Staph. aureus, ceftazidime (or meropenem)
gram-negative Enterobacteriaceae, plus vancomycinc
P. aeruginosa
immunocompromised or older patients L. monocytogenes, gram-negative 3rd generation cephalosporin plus
(impaired cellular immunity) Enterobacteriaceae, P. aeruginosa, ampicillin
pneumococci
a e.g. ceftriaxone oder cefotaxime
b In some areas increasing resistance rates of pneumococci against penicillin have been repor ted in the last years,
in par ticular in Hungar y, Spain, Australia, South-Africa and in some areas of the US. The initial treatment in these areas
consists of ceftriaxone plus vancomycin or ceftriaxone plus rifampicin.
c Alternative antibiotics: linezolide, fosfomycin, rifampicin (according to susceptibility tests).

herniation (e.g. unconsciousness, a unilaterally Adjunctive therapy

dilated and unreactive pupil, decerebrate move-
ments) or a focal mass lesion (e.g. large, space-
occupying brain abscess) on CT. The presence of a
parameningeal infectious focus such as sinusitis
or mastoiditis should also be investigated by CT,
including the bone window technique (see table 1).
In addition, clinical examination by an otolaryn-
gologist should be performed. If a parameningeal
focus (e.g. otitis, mastoiditis, sinusitis) is identified
as a possible origin of bacterial meningitis, drainage
is required as soon as possible. If antibiotic therapy
has to be started without microbiologic confir-
mation, empiric therapy is initiated under con-
sideration of the patient’s age, predisposing factors,
underlying diseases and the most probable me-
ningeal pathogens (table 3). Importantly, the sen-
sitivity of the causative pathogen against the anti-
biotic regimen administered must be confirmed by
in vitro testing and antibiotic coverage must be
adjusted to the sensitivity results.
Patients with clinically suspected meningococ-
cal meningitis (e.g. petechial rash, gram-negative
diplococci on Gram’s stained smear of the CSF)
have to be isolated for the first 24 hours after
initiation of antibiotic therapy.
Treatment of bacterial meningitis due to Strep-
tococcus pneumoniae, H. influenzae, and group B
streptococci usually consists of intravenous admi-
nistration of antibiotics for 10 to 14 days. Some
clinical observations have suggested that shorter
courses of 7 days may be adequate for uncom-
plicated meningococcal meningitis. For antibiotic
treatment of meningitis due to L. monocytogenes
and gram-negative Enterobacteriaceae, a treatment
duration of 3 to 4 weeks may be required.
Recently, a meta-analysis of 11 randomised clinical
trials since 1988 using dexamethasone as adjunctive
therapy in bacterial meningitis was performed [4].
In Haemophilus influenzae meningitis in children,
dexamethasone reduced severe hearing loss over-
all. In pneumococcal meningitis, only studies in
which dexamethasone was given early suggested
protection, which was significant for severe hear-
ing loss and approached significance for any neuro-
logical or hearing deficit. Outcomes were similar
in studies that used 2 days versus 3 or 4 days of
dexamethasone therapy. In contrast, a prospective,
randomised, double-blind study in 598 children
with bacterial meningitis (study centre: Malawi)
did not show superiority of dexamethasone com-
pared with placebo [5]. Recently, a prospective,
randomised, multicentre, double-blind trial of
adjuvant therapy with dexamethasone, as com-
pared with placebo, in 301 adults with acute
bacterial meningitis was performed [6]. Dexa-
methasone (10 mg) or placebo was administered
15 to 20 minutes before or with the first dose of
antibiotic and was given every 6 hours for 4 days.
The primary outcome measure was the score on
the Glasgow Outcome Scale at 8 weeks (a score of
5, indicating a favourable outcome, a score of 1 to
4, indicating an unfavourable outcome).Treatment
with dexamethasone was associated with a signifi-
cant reduction in the risk of an unfavourable out-
come and also a significant reduction in mortality.
Among the patients with pneumococcal menin-
gitis, there were unfavourable outcomes in 26%
of the dexamethasone group, as compared with
52% of the placebo group. Gastrointestinal bleed-
ing occurred in 2 patients of the dexamethasone

171 SCHWEIZER ARCHIV FÜR NEUROLOGIE UND PSYCHIATRIE 154 ■ 4/2003

Table 4 Chemoprophylaxis of meningococcal meningitis.a
antibiotic
age group dosage
rifampin (Rifa®)
adults 600 mg ever y 12 hours
for 2 days po
infants ≥ 1 month 10 mg/kg ever y 12 hours
for 2 days po
infants <1 month 5 mg/kg ever y 12 hours
for 2 days po
ciprofloxacin (Ciprobay®)
adults 500 mg as single dose po
ceftriaxone (Rocephin®)
adults and children 250 mg as single dose im (or iv)
≥ 15 years
children <15 years 125 mg as single dose im (or iv)
a
Rifampin and ciprofloxacin should not be prescribed during
pregnancy. Fur thermore, the use of ciprofloxacin is not
recommended for children and adolescents (<18 years).
group and in 5 patients of the placebo group. Based
on these data the use of dexamethasone is recom-
mended in adult patients with suspected bacterial
meningitis (e.g. clinical suspicion plus cloudy cere-
brospinal fluid, detection of bacteria in the cere-
brospinal fluid by microscopy of a Gram’s stained
smear or a CSF cell count of more than 1000
cells/µ l). The subgroup analyses revealed that
dexamethasone was protective only for patients
with pneumococcal meningitis but not for others,
e.g. with meningococcal disease [6]. The patient’s
level of consciousness might be an important guide
to a decision to administer corticosteroids, since the
beneficial effect of dexamethasone was limited to
the group of the more severely ill patients (Glas-
gow Coma Score <12). The questions of whether
to administer adjunctive dexamethasone to less
severely ill patients or patients who are strongly
suspected to suffer from meningococcal meningitis
are important, because animal studies of experi-
mental meningitis have shown that adjuvant dexa-
methasone causes aggravation of hippocampal
neuronal apoptosis and learning deficits [7, 8].This
concern should therefore be addressed by neuro-
psychological testing of survivors of meningitis.
We do not currently know whether early dexa-
methasone will be able to prevent cerebrovascular
arterial complications.
Corticosteroids are not recommended for the
therapy of meningitis following infective endo-
carditis or in newborns with bacterial meningitis.
Increased intracranial pressure may be man-
aged by elevation of the head of the bed to 30°,
172 SCHWEIZER ARCHIV FÜR NEUROLOGIE UND PSYCHIATRIE
hyperventilation to maintain a pCO2 concentration
between 32 and 35 torr and the intravenous admi-
nistration of hyperosmolar agents (e.g. 20% manni-
tol). Stuporous or comatose patients may benefit
from intracranial pressure monitoring to control
this therapy [9]. If meningitis-associated hydro-
cephalus is diagnosed, CT scan follow-up inves-
tigations or ventricular drainage should be per-
formed, depending on the patient’s level of
consciousness and the degree of ventricular dilata-
tion on CT. Anticoagulation of septic venous sinus
thrombosis in bacterial meningitis is controversial.
There are no prospective controlled clinical stud-
ies, but anticoagulation with dose-adjusted intra-
venous heparin should be considered in patients
with meningitis-associated septic venous sinus
thrombosis proven by MRI or cerebral angio-
graphy. Anticonvulsants are given to treat seizures,
e.g. rapid intravenous phenytoin administration.
MR angiographic studies and transcranial
Doppler sonography recordings in patients with
bacterial meningitis and focal neurologic deficits
may reveal vasospasm of the large arteries at the
base of the brain resembling vasospasm following
subarachnoid haemorrhage. In these patients,
hypervolaemic therapy or nimodipine therapy
should be considered; however, these therapeutic
approaches have not been scientifically proven.
Several therapeutic agents, which may limit
meningeal inflammation, have shown beneficial
effects in animal models of bacterial meningitis
(in particular of the rat, rabbit and mouse). These
anti-inflammatory agents include antioxidants, in-
hibitors of matrix metalloproteinases and caspases
[10]. These agents have not yet been investigated
in humans with bacterial meningitis, but some
show promising beneficial effects in experimental
models.
Chemoprophylaxis of meningococcal
meningitis
Eradication of bacterial pathogens from the
nasopharynx by chemoprophylaxis may prevent
secondary cases of meningococcal meningitis.
Prophylaxis for meningococcal meningitis is re-
commended for all people sleeping in the same
household and engaging in saliva-exchanging
contacts and all persons who probably had contact
with oropharyngeal secretions of the index patient.
Rifampin is the drug most often recommended
for chemoprophylaxis of meningococcal menin-
gitis; alternative drugs are ceftriaxone and cipro-
floxacin (table 4).
154 ■ 4/2003
 References
1 Haring HP, Rötzer HK, Reindl H, Berek K, Kampfl A,
Pfausler B, et al. Time course of cerebral blood flow
velocity in central ner vous system infections.
Arch Neurol 1993;50:98–101.
2 Pfister HW, Feiden W, Einhäupl KM. The spectrum of
complications during bacterial meningitis in adults:
results of a prospective clinical study.
Arch Neurol 1993;50:575–80.
3 Roos KL. Bacterial meningitis. In: Roos KL, editor.
Central Ner vous Infectious Diseases and Therapy.
New York: Marcel Dekker; 1997. p. 99–126.
4 McIntyre PB, Berkey CS, King SM, Schaad UB, Kilpi T,
Kanra GY, et al. Dexamethasone as adjunctive therapy
in bacterial meningitis. A meta-analysis of randomized
clinical trials since 1988. JAMA 1997;278:925–31.
5 Molyneux EM, Walsh AL, Forsyth H, Tembo M,
Mwenechanya J, Kay B, et al. Dexamethasone treatment
in childhood bacterial meningitis in Malawi: a randomised
controlled trial. Lancet 2002;360:211–8.
173 SCHWEIZER ARCHIV FÜR NEUROLOGIE UND PSYCHIATRIE
6 De Gans J, van de Beek D. Dexamethasone in adults
with bacterial meningitis.
N Engl J Med 2002;347:1549–56.
7 Nau R, Brück W. Neuronal injur y in bacterial meningitis:
mechanisms and implications for therapy.
Trends Neurosci 2002;25:38–45.
8 Meli DN, Christen S, Leib SL, Tauber MG. Current
concepts in the pathogenesis of meningitis caused
by Streptococcus pneumoniae.
Curr Opin Infect Dis 2002;15:253–7.
9 Winkler F, Kastenbauer S, Yousry TA, Maerz U, Pfister HW.
Discrepancy between cranial CT scan and clinically
relevant raised intracranial pressure (ICP) in adults with
pneumococcal meningitis: should ICP monitoring be
per formed early? J Neurol 2002;249:1292–7.
10 Koedel U, Scheld WM, Pfister HW. Pathogenesis and
pathophysiology of pneumococcal meningitis.
Lancet Infect Dis 2002;2:721–36.
154 ■ 4/2003