Bagian Ilmu Penyakit Saraf Journal Reading

Fakultas Kedokteran September 2019

Universitas Pattimura

MENINGITIS IN ADULTS: DIAGNOSIS AND MANAGEMENT

Mathilda I. Uniplaita
NIM. 2018-84-060

Pembimbing :
dr. Parningotan Y. Silalahi, Sp.S

DIBAWAKAN DALAM RANGKA TUGAS KEPANITERAAN KLINIK

BAGIAN ILMU PENYAKIT SARAF
FAKULTAS KEDOKTERAN
UNIVERSITAS PATTIMURA
AMBON
Abstract
Introduction
Bacterial meningitis is a potentially catastrophic infectious
disease associated with substantial mortality and a risk of
permanent disability in survivors.

Despite ongoing advances in diagnostic methods and

treatment strategies, mortality remains as high as 30% in
pneumococcal meningitis and 5–10% in meningococcal
meningitis.

This article will focus on diagnostic and management issues

that a clinician will face when dealing with a suspected case
of community-acquired bacterial meningitis in an adult.
Diagnosis: Clinical features and clues to the
responsible pathogen
A patient who presents with recent onset of
headache, fever, neck stiffness or altered
mental state would prompt most clinicians to
consider the possibility of meningitis.
Con’t
Meningitis due to Neisseria meningitidis may
begin with an influenza with symptoms such
as fever, muscle aches and vomiting, before
meningitis becomes clinically apparent.
Con’t
Meningitis due to Streptococcus
pneumoniae should be suspected in
patients with predisposing conditions, such
as otitis media, sinusitis, mastoiditis,
cerebrospinal fluid (CSF) leak, cochlear
implants, asplenia, human
immunodeficiency virus (HIV) infection or
other immunosuppressive conditions or
medications.
Con’t
Patients at risk of Listeria monocytogenes
meningitis include those aged ≥ 50, those
taking long term glucocorticoids or other
immunosuppressive drugs and those with
diabetes, alcoholism, cirrhosis, end-stage
renal failure, malignancy, HIV infection or
organ transplantation.
Neuroimaging: Computed tomography before lumbar puncture is not usually
required

CT prior to LP should not be performed for most

patients for several reasons.
1. First, and most importantly, if a patient is not
pretreated with antibiotics, the sequence of CT
followed by LP followed by antibiotics.
2. Second, the yield of CT is low in patients who
do not have clinical features of raised intra-
cranial pressure (ICP), with 97% having a
normal result.
Con’t
3. Third, if a patient is pretreated with
antibiotics prior to CT and LP, the yield of
CSF culture will be significantly decreased,
although a diagnosis can often still be
obtained through polymerase chain reaction
(PCR) testing.
Con’t
CT prior to LP is recommended for patients
who have one or more clinical features that
increase the probability of having raised ICP,
to attempt to identify those most at risk of
brain herniation following LP.
CSF analysis
CSF analysis is of vital importance in suspected
meningitis as clinical characteristics alone are
unable to distinguish meningitis from other
diagnoses, and bacterial from non bacterial
aetiologies.

CSF analysis should be performed within 1 h of

the presumptive diagnosis of meningitis without
awaiting further investigations, such as platelet
count or coagulation studies.
Con’t
Appearance and opening pressure
• Appearance of the CSF should be noted;
cloudy or turbid fluid suggests a significant
concentration of leukocytes in the sample
• In bacterial meningitis, opening pressure is
typically >20 cm H2O, although other
factors, such as patient anxiety and
positioning, may artifactually elevate this.
Gram stain
• A Gram stain should be rapidly performed.
The presence of Gram-positive cocci
suggests S. pneumoniae, Gram- negative
diplococci N. meningitidis and Gram-
positive bacilli L. monocytogenes.
• The likelihood of a positive Gram stain
ranges from 25% to 97% and is highly
correlated with the concentration of
bacterial colony-forming units in the CSF.
Cell counts and chemistry
• Meningitis is confirmed when the leukocyte count
in the CSF exceeds 5 cells/μL.
• A leukocyte count of ≥1000 cells/μL with a
neutrophilic predominance is highly suggestive of
bacterial meningitis,1 whereas <1000 cells/μL
with a lymphocytic predominance is more
consistent with viral meningitis, tuberculous
meningitis (TBM) or cryptococcal meningitis.
Con’t
Bacterial meningitis due to L.
monocytogenes is an important exception,
with approximately 60% of cases having a
leukocyte count of <1000 cells/μL, which
may be lymphocytic.
If a traumatic tap occurs, the leukocyte
count should be corrected by deducting one
leukocyte for every 500–1000 red cells in
the CSF.
Con’t
Culture
The sensitivity of culture is 60–90% for
CSF collected before antibiotic
treatment has been started, with
positive results generally available
within 24–48 h.
Bacterial antigen testing
Many laboratories offer BAT (Bacterial
Antigen Test) on CSF samples, most often
for the detection of S. pneumoniae. The
pneumococcal BAT has been reported to
have a specificity in excess of 95% for
pneumococcal meningitis and a sensitivity
ranging between 67% and 100%.
Polymerase chain reaction
Multiplex PCR assays can detect the
presence of many important bacterial and
viral pathogens in CSF, including N.
meningitidis, S. pneumoniae, enteroviruses,
HSV, VZV and mumps virus, with sensitivity
and specificity ≥90%.
Aseptic meningitis: not synonymous with viral
meningitis
• Viral meningitis is most commonly caused by the
entero viruses and is self limiting, although HSV
or VZV meningitis may warrant antiviral therapy
in some circumstances.
• Not all patients with aseptic meningitis have viral
meningitis, and it is important to consider other
causes if a viral aetiology is not confirmed by
PCR.
• Listeria meningitis may present with symptoms
and CSF parameters that mimic viral meningitis.
Management
In bacterial meningitis, prompt treatment is
life-saving. For patients who present to
primary care with suspected meningococcal
disease, pre-hospital treatment with
parenteral benzylpenicillin or ceftriaxone has
been advocated. Early consultation with an
infectious diseases physician may improve
patient outcomes.
Con’t
On arrival at hospital, the patient should be
placed in droplet precautions to prevent
potential nosocomial transmission of
meningococcal infection and resuscitated as
required. Blood and, ideally, CSF cultures
should be quickly obtained, following which
dexamethasone and antibiotics should be
given, aiming for administration within 1 h of
admission.
Empirical therapy
• Most guidelines recommend dexamethasone plus
ceftriaxone in the initial empirical treatment of community
acquired bacterial meningitis in adults.
• In Australia, the inclusion of vancomycin in the initial

empirical regimen is recommended for patients with known

or suspected otitis media or sinusitis, for those who have
been treated with beta lactam antibiotics recently and for
those with Gram-positive cocci in the CSF or with a
positive pneumococcal BAT.
Con’t
• An anti-Listeria agent should also be added for

patients with risk factors for Listeria meningitis

(age ≥ 50, long-term use of glucocorticoids or
other immunosuppressive drugs, diabetes,
alcoholism, cirrhosis, end-stage renal failure,
malignancy, HIV infection and organ
transplantation).
Con’t
Benzylpenicillin and trimethoprim/
sulfamethoxazole are active against L.
monocytogenes, but ceftriaxone and
vancomycin are not.
Dexamethasone
• Dexamethasone reduces cerebral
inflammation, oedema and ICP in
experimental models of bacterial
meningitis.
• Guidelines recommend the empirical use of
10 mg dexamethasone intravenously (IV)
every 6 h in patients with bacterial
meningitis.
Con’t
• Dexamethasone should be started before
or at the same time as the first antibiotic
dose in order to attenuate cerebral
inflammation caused by antibiotic-mediated
bacteriolysis.
Con’t
• If pneumococcal meningitis is diagnosed,
treatment with dexamethasone should be
continued for 4 days. Dexamethasone can
be stopped if meningococcal meningitis is
diagnosed.
• Dexamethasone should also be stopped if
Listeria meningitis is diagnosed as there is
evidence that patients who receive this
treatment have a higher mortality rate than
those who do not.
Con’t
Antibiotic
Because almost all strains of N. meningitidis
and many strains of S. pneumoniae are
sensitive to ceftriaxone, most guidelines
recommend 2 g ceftriaxone IV every 12 h.
It is important to note that ceftriaxone
provides no cover for L. monocytogenes.
Con’t
Con’t
Con’t
Because CSF concentrations of ceftriaxone
may not be sufficient to treat S. pneumoniae
strains with reduced susceptibility to
ceftriaxone, the supplementation of initial
therapy with vancomycin should be
considered.
Other considerations
Many patients with bacterial meningitis are
critically unwell and will require support in the
intensive care unit.
For adults with pneumococcal meningitis,
predisposing conditions, such as otitis media,
sinusitis or mastoiditis, should be sought and
managed in conjunction with otorhinolaryngology if
required.
Direct therapy
Once a presumptive microbiological diagnosis has
been provided by Gram stain or confirmed by
culture or PCR, further therapy can be directed at
the identified pathogen.
Streptococcus pneumoniae
• For pneumococcal meningitis, a 10–14-day course
of IV therapy should be completed, with
dexamethasone given during the first 4 days.
• In patients infected with ceftriaxone-susceptible
strains, vancomycin can be discontinued and
treatment continued with 2 g ceftriaxone IV every
12 h.
• If the isolate is penicillin-susceptible, clinicians
may consider changing to 2.4 g benzylpenicillin IV
every 4 h to avoid continuing with an
unnecessarily broad- spectrum agent.
Con’t
• If the isolate is ceftriaxone-intermediate or
-resistant, options include continuing
ceftriaxone and vancomycin if the patient
has responded well to initial therapy (with
consideration of the addition of rifampicin)
or changing to 400 mg moxifloxacin IV
every 24 h.
Neisseria meningitidis
• A dose of 1.8 g benzylpenicillin IV every 4 h should
be used for the treatment of meningococcal
meningitis in Australia and New Zealand.
• Ceftriaxone can be used for patients with immediate
penicillin hypersensitivity and moxifloxacin or
ciprofloxacin used for patients with severe T cell-
mediated reactions to penicillins.
• Patients with meningococcal disease should be
placed in droplet precautions until 24 h of antibiotic
therapy has been given.
Con’t
• Options for non-pregnant persons include
ciprofloxacin (a single 500 mg oral dose) or
rifampicin (600 mg orally twice/day for 2 days)
• Rifampicin should be avoided in women taking
the oral contraceptive pill or in patients for
whom there are other important drug
interactions.
• Ceftriaxone (a single intramuscular dose of
250 mg) is the preferred option for pregnant
women.
Listeria monocytogenes
• A dose of 2.4 g benzylpenicillin IV every 4 h
(or 2 g amoxicillin IV every 4 h) is the
treatment of choice for meningitis caused by L.
monocytogenes.
• Trimethoprim/sulfamethoxazole can be used
for patients with penicillin allergy.
• Dexamethasone should be discontinued
immediately if L. monocytogenes has been
identified, because of the worse outcome in
patients who receive dexamethasone.
Viral meningitis
• Symptomatic treatment alone is
reasonable, although 7–10 days of antiviral
treatment (with acyclovir, valacyclovir or
famciclovir) has been shown to improve
neurological outcomes in
immunocompromised hosts.
Deteriorating patients
• Neuroimaging is indicated in patients who fail to
improve or in whom neurological abnormalities or
seizures develop, to evaluate for hydrocephalus,
venous sinus thrombosis, subdural empyema or
intracerebral abscess.
• Repeat LP should be considered in those who fail
to improve after 48 h of treatment and who have
unremarkable neuro- imaging; this is particularly
important for patients with meningitis caused by a
strain of S. pneumoniae with reduced
susceptibility to ceftriaxone.
Primary prevention
• Childhood vaccination against
Haemophilus influenzae serotype b has led
to the near-complete elimination of
meningitis.
• Vaccination has reduced the rates of
pneumococcal meningitis in children and
adults.
TERIMA KASIH 