Meningitis

Encephalitis
Brain abscess

Diagnosis and Treatment Update

Germaine Daley BSc, MSc (Clinical Microbiology)
germaine.daley@aaims.edu.jm
germaine.daley02@uwimona.edu.jm

Objectives
Infections of the Nervous
System
Meningitis
Encephalitis
Brain absess

C. Nolts

Infections of the Nervous

System
Can include infections of the
meninges (meningitis), the general
brain parenchyma(encephalitis), or a
focalized infection of the brain
parenchyma (brain absess)
General Sx are fever and headache.
Other Sx will exist depending on the
etiology/nature.

Infections of the Nervous

System
Untreated or improperly
treated=high mortality
Neonates, young people, adults, old
people, and
immunocompromised(HIV) are
distinctly different populations and
this categorization is essential

Definitions
Meningitis
inflammation of the
meninges
Encephalitis
infection of the
brain parenchyma
Meningoencephaliti
s inflammation of
brain + meninges
Aseptic meningitis
inflammation of
meninges with
sterile CSF

Common causes of
meningitis
#1 cause:
S. pneumoniae- in adults, very prevalent in others
N. meningitidis-in young people, characteristic
rash
S. agalactiae (GBS)-in neonates

Other prominent causes:

Listeria-in children<2, old
Viruses
S. aureus-in postop pts
Cryptococcus-in pts w/HIV

Other important cause of meningitis

More rare
Rickettsia-RMSF
Borrelia-Lyme disease
T. pallidum-Neurosyphilis
M. tuberculosis-TB meningitis
Naegleria-Primary amoebic
meningoencephalitis (PAME)
Angiostrongylus cantonensis(most
common cause of eosinophilic
meningitis)

Meningitis
Infection and inflammation of the
meningeal lining
Sx: Fever, headache, stiff
neck/nuchal rigidty, nausea,
vinittng, photophobia, +Kernig sign
(hip flex/Knee extension),
+Brudzinski sign (involuntary leg
lifting), rash
Keep a eye out for rash! Do a very
thorough dermatological

Meningitis
Dx Technically, best first diagnostic
step is lumbar puncture w/CSF
analysis.
However, if the pt shows any
physical signs of elevated
ICP(papilledema), focal Sx, confusion,
or is immunocompromised, the best
first step is a CT.
The most accurate test is a CSF
culture, which takes forever.

Symptoms of meningitis
Fever
Altered consciousness, irritability,
photophobia
Vomiting, poor appetite
Seizures 20 - 30%
Bulging fontanel 30%
Stiff neck or nuchal rigidity
Meningismus (stiff neck + Brudzinski +
Kernig signs)

Clinical signs of meningeal irritation

Supine

Diagnosis lumbar puncture

Contraindications:
Respiratory distress (positioning)
ICP reported to increase risk of herniation
Cellulitis at area of tap
Bleeding disorder

CSF evaluation
Protein
Glucose
Condition
WBC
(mg/dL) (mg/dL)
Normal
<7, lymphs mainly 5-45
>50
Bacterial, 100 60K PMNs 100-500 Low
acute
Bacterial, 1 10,000
Low to
100+
part rxd
normal
TB
10 500
100-500 <50
Fungal
25 500
25-500 <50
Viral
<1000
50-100 Normal

Reading a CSF analysis

Three major factors: protein, glucose,
and cell count
Protein-Will be elevated in all cases
of meningitis, septic or aseptic.a
negative protein is not consistent w/
any kind of meningitis
Glucose-Normal(40) suggest nonbacterial cause. However, will ofrtn
be low in cryptococcal

Reading a CSF analysis

Cell count-Most important. Normal is
<5 cells/ml
Bacrerial=1000s of neutrophils/PMNs
Viral(and some others)=100s of
lymphocytes

Staining(India Ink, AFB, Gram),

serology, immunological studies
(VDRL), and staining can be useful
too.

CSF Gram stain

Hemophilus influenza
(H flu)

Strep pneumoniae

Not addressed
Indwelling CNS catheters
S/P cranial surgery
Anatomic defects predisposing to
meningitis
Immunocompromised patients
Abscesses

Bacterial meningitis
3 - 8 month olds at highest risk
66% of cases occur in children <5
years old

Bacterial meningitis Organisms

Neonates

Most caused by Group B Streptococci

E coli, enterococci, Klebsiella,
Enterobacter, Samonella, Serratia,
Listeria

Older infants and children

Neisseria meningitidis, S. pneumoniae,
tuberculosis, H. influenzae

Bacterial meningitis Clinical

course

Fever
Malaise
Vomiting
Alteration in mental status
Shock
Disseminated intravascular coagulation
(DIC)
Cerebral edema
Vital signs
Level of mentation

Increased intracranial
pressure (ICP)
Papilledema
Cushings triad
Bradycardia
Hypertension
Irregular
respiration

ICP monitor (not

routine)
Changes in pupils

 ICP treatment
3% NaCl, 5 cc/kg over
~20 minutes
May utilize
osmotherapy - if serum
osms <320
Mild hyperventilation
PaCO2 <28 may cause
regional ischemia
Typically keep PaCO2
32-38 torr

Elevate HOB 30o

Meningitis - Fluid
management
Restore intravascular volume &
perfusion
Monitor serum Na+ (osmolality, urine
Na+):

If serum Na+ <135 mEq/L then fluid

restrict (~2/3x), liberalize as Na+
improves
If severely hyponatremic, give 3% NaCl

SIADH

4 - 88% in bacterial meningitis

9 - 64% in viral meningitis

Diabetes insipidus
Cerebral salt wasting

Meningitis - Treatment
duration

Neonates: 14 21 days
Gram negative meningitis: 21 days
Pneumococcal, H flu: 10 days
Meningococcal: 7 days

Bacterial Meningitis - Treatment

Neonatal (<3 mo)
Ampicillin (covers Listeria)
+
Cefotaxime
High CSF levels
Less toxicity than aminoglycosides
No drug levels to follow
Not excreted in bile not inhibit bowel
flora

Meningitis - Acute
complications
Hydrocephalus
Subdural effusion
or empyema
~30%
Stroke
Abscess
Dural sinus
thrombophlebitis

Bacterial meningitis Outcomes

Neonates: ~20% mortality
Older infants and children:
<10% mortality
33% neurologic abnormalities at
discharge
11% abnormalities 5 years later

Sensorineural hearing loss 2 - 29%

Bacterial meningitis children

Strep pneumoniae
Neisseria meningitidis
TB
Hemophilus influenza

Pneumococcal meningitis

Empiric Treatment
Common cause

Neonates < 1
month of age

Child/Teen

Adults

E. coli

Streptococcus
pneumoniae

Streptococcus
pneumoniae

Listeria
monocytogenes
e

Neisseria
meningitidis

Streptococcus
algalactiae
Empiric
treatment

Ampicillin
+Cefotaxime

Cefotaxime+
Vancomycin

Cefotaxime+
Vancomycin

Antibiotic susceptibility
Susceptible
Non-susceptible
Resistant

Pneumococcal resistance

Strep pneumococcus - most common

cause of invasive bacterial infections in
children >2 months old
Incidence of PCN-, cefotaxime- &
ceftriaxone-nonsusceptible isolates has
d to ~40%
Strains resistant to PCN, cephalosporins,
and other -lactam antibiotics often
resistant to trimethoprimsulfamethoxazole (Bactrim, Septra),
erythromycin, chloramphenicol,
tetracycline

Mechanism of resistance
PCN-binding proteins synthesize
peptidoglycan for new cell wall
formation
PCN, cephalosporins, and other lactam antibiotics kill S pneumoniae by
binding irreversibly to PCN-binding
proteins located in the bacterial cell
wall
Chromosomal changes can cause the
binding affinity for the -lactam
antibiotics to decrease

Pneumococcal meningitis
Mgmt
Vancomycin + cefotaxime or
ceftriaxone, if > 1 month old
If hypersensitive (allergic) to -lactam
antibiotics, use vancomycin + rifampin
D/C vancomycin once testing shows
PCN-susceptibility
Consider adding rifampin if susceptible
& condition not improving, or
cefotaxime or ceftriaxone MIC high
Not vancomycin alone

Vancomycin use in
pneumococcal meningitis
Combination therapy since late 90s
At initiation Baseline urinalysis
BUN and creatinine

Enters the CSF in the presence of

inflamed meninges within 3 hours
Should not be used as solo agent,
but with cephalosporin for synergy

Infection control precautions

(invasive pneumococcus)
CDC recommends Standard Precautions
Airborne, Droplet, Contact are NOT
recommended
Nasopharyngeal cultures of family
members and contacts is NOT
recommended
No isolation of contacts
No chemoprophylaxis for contacts

Meningococcal meningitis
Neisseria meningitidis
~10 - 15% with chronic throat carriage
Outbreaks in households, high schools,
dorms
Accounts for <5% of cases

2,400 - 3,000 cases occur in the USA

each year
Peaks <2 years of age & 15-24 years

Meningococcal disease
Can cause purulent conjunctivitis, septic
arthritis, sepsis +/- meningitis
Diagnose presence of organism (Gram
negative diplococci) via:
CSF Gram stain, culture
Sputum culture
CSF (not urine) Latex agglutination
Petechial scrapings
Buffy coat Gram stain

Meningococcemia
Petechiae/Purpuric rash

Meningococcemia - Purpura
fulminans

Waterhouse-Freidrichsen syndrome
A very feared complication of
meningiococcemia.
Bacterial haemorrhage into the adrenal
glands, resulting in acute, severe adrenal
insufficiency.
Sx include hypotension, hyponaturenia,
hyperkalemia, TCP, and Sx of sepsis.
The only Tx is with (3rd gen cephalosporins
Condition often fatal

Meningococcemia - Isolation
Capable of transmitting organism up to
24 hours after initiation of appropriate
therapy
Droplet precautions x 24 hours, then no
isolation
Incubation period 1 - 10 days, usually
<4 days

Meningococcemia Treatment
Antibitotic resistance rare
Antibitotics:
PCN
Cefotaxime or Ceftriaxone

Patient should get rifampin prior to

discharge

Meningococcal disease - Care takers

Day care where child attends >25 h/wk,
kids are >2 years old, & 2 cases have
occurred
Day care where kids not all vaccinated
Persons who have had intimate
contact w/ oral secretions prior &
during 1st 24 h of antibiotics
Intimate contact 300-800x risk
(kissing, eating/ drinking utensils, mouth-to-mouth,
suctioning, intubating)

Meningococcemia Prophylaxis

No randomized controlled trials of

effectiveness
Treat within 24 hours of exposure
Vaccinate affected population, if
outbreak

Meningococcemia Prophylaxis
Rifampin
Urine, tears, soft contact lenses orange; OCPs
ineffective
<1 mo 5 mg/kg PO Q 12 x 2 days
>1 mo 10 mg/kg (max 600 mg) PO Q 12 x 2
days

Ceftriaxone
12 y 125 mg IM x 1 dose
>12 y 250 mg IM x 1 dose

Ciprofloxacin
18 y 500 mg PO x 1 dose

Meningococcal meningitis Outcomes

Substantial morbidity: 11% - 9% of
survivors have sequelae
Neurologic disability
Limb loss
Hearing loss

10% case-fatality ratio for

meningococcal sepsis
1% mortality if meningitis alone

Charlotte Noltz

TB meningitis
Children 6 months 6 years
Local microscopic granulomas on
meninges
Meningitis may present weeks to
months after primary pulmonary
process
CSF:
Profoundly low glucose
High protein
Acid-fast bacteria (AFB stain)
PCR

Steroids + antimicrobials

Aseptic vs. partially treated bacterial

meningitis
Aseptic much more common
Gram stain positive CSF:

90 - 100% in young patients

50 - 68% positive in older children

If CSF fails to show organisms in a

pretreated patient, then very unlikely
that organism is resistant

Viral meningitis

Summer, fall
Severe headache
Vomiting
Fever
Stiff neck
CSF - pleocytosis (monos), NL protein,
NL glucose

Etiology viral meningitis

Enteroviruses
predominate

Spring, summer Less common:

Mumps
Oral-fecal route
HIV
initial GI
symptoms
Lymphocytic
choriomeningitis
Meningitic
symptoms
HSV-2
appear 7-10
days after
exposure

Other causes of aseptic

meningitis
Leptospira
Young adults
Late summer, fall
Conjunctivitis, splenomegaly, jaundice,
rash
Exposure to animal urine

Lyme Disease (Borrelia burgdorferi)

Spring-late fall
Rash, cranial nerve involvement

Viral meningitis - Treatment

Supportive
No antibiotics
Analgesia
Fever control
Often feel better after LP
No isolation - Standard precautions

Viral meningitis - Outcomes

Adverse outcomes rare
Infants <1 year have higher incidence
of speech & language delay

Meningoencephalitis etiology
Herpes simplex type 1
Rabies
Arthropod-borne
St. Louis encephalitis
La Crosse encephalitis
Eastern equine encephalitis
Western equine encephalitis
West Nile

Common cause of
encephalitis
VIRUS
HSV
CMV(AIDSpts)
VZV
West Nile

Encephalitis
Infection and inflammation of the brain
parenchyma resulting in neurological
dysfunction. Infection often extends to
the meningeal space
Sx: Fever, headache, nausea, vomiting,
nuchal Sx, confusion, behavioral
disturbances, AMS (altered mental
status)

Encephalitis
Will appear very similar to meningitis
and often wont be differentiated
until the LP
Dx: Best first step in daignosis is a
CT, CSF is often needed to
differentiate from meningitis.
Analysis will show viral picture (high
protein, high lymphocytes, normal
glucose)

Encephalitis
Tx: Intravenous empiric therapy
should commence immediately.
Acyclovir is generally sufficient
Adjunctive steroids(dexamethasone)
Ganciclovir or foscarnet should be
added for pts suspected of CMV
encephalitis (HIV/AIDS,
immunocompromised)

Encephalitis
Seizures precautions are appropriate
in pts w/elevated ICP
Scheduled benzodiazepine(lorazepam)
Diuritic (furosemide, mannitol)

Close contact should be treated

prophylactically with ciprofloxacin or
rifampin)

Herpes simplex 1
encephalitis
Symptoms
Depressed level of consciousness
Blood tinged CSF
Temporal lobe focus on CT scan or EEG
+ PCR
Neonates typically will have cutaneous
vessicles

Treatment - IV acyclovir

West Nile Virus

Via bite of infected mosquito
Incubation period 3 - 14 days
1 in 150 infected persons get
encephalitis
4% of those are <20 years of age

H/A, fever, neck stiffness, stupor,

coma, convulsions, weakness, &
paralysis
Supportive therapy
Mortality 9%

West Nile Virus

MMWR Dec 2002 51;1129-33

Causes of brain absess

Polymicrobial
Streptococci
Bacteroides (anaerobic)
Enterobacteria
Staphylococcus

Brain Abscess
Focal infection (abscess) of the brain
parenchyma
Sx: Fever, headache, nausea. Vomiting, focal
deficits (weakness, ataxia, hemiparesia,
dyslexia, etc), papilledema, seizures
Dx: Best first step in diagnosis is a CT, which
will clearly display the abscess. Most
accurate test is a aspiration biopsy

Brain Abscess
Knowledge of the bacteria present in
the abscess is critical for appropriate
care of pt, due to variability.
Nevertheless, empiric therapy should
not be delayed.

Brain Abscess Tx
Staphylococcus & Streptococci- IV
betalactam(PCN, Naficilin)
Bacteroides (anaerobic)-Clindamycin
or metronidazole
Enterobacteria-third gen
cephalosporin ceftriaxone or
cefotaxime

Brain Absess
Tx if the pt has HIV: Surgery is
generally not necessary. Tx the pt
presumably for Toxoplasmosis with
pyrimethamine and sulfadiazine.
Should respond in 10-14 days

Summary
Antibiotics ASAP, even if LP not yet done
Vanco + cephalosporin until some identification
known
CSF, Latex, exam

Isolate if bacterial x 24 hours, Universal Precautions

Monitor for status changes
Pupils, LOC, HR, BP, resp
Seizures
Hemodynamics
DIC, coagulopathy
Fluid, electrolyte issues