Pyogenic and TB

Meningitis

Kishor K Adhikari
Intern, PAHS
Content
Meningitis: Introduction
Causes of Meningitis: Infective, non-infective
Normal CSF parameters
Viral Meningitis: in short
Bacterial Meningitis:
Aetiology: Most common causes
Clinical features
Treatment
TB meningitis
Clinical features and staging
Investigations
Treatment
Meningitis
Inflammation of the meninges around the brain and/or
spinal cord.

Acute infection of the meninges presents with a

characteristic combination of
pyrexia, headache and meningism

Meningism
Headache, photophobia, neck stiffness +/- signs of meningeal
irritation
Can occur with SAH
Diagnosis requires a lumbar puncture with
Measurement of opening pressure

Examination of cerebrospinal fluid (CSF) protein,

glucose, and cell count with differential, and

Gram stain with culture

CSF PCR
CSF Analysis

Kumar and Clark’s Clinical Manual, 8th edition

#Harrison
Viral Meningitis
Most common cause of meningitis  viruses
Most common virus:
 enteroviruses (echo, coxsackie, polio)
Usually benign and self limiting
Suspicion of Viral Meningitis
Nuchal rigidity is present in most cases but may be
mild and present only near the limit of neck
anteflexion

Constitutional signs can include malaise, myalgia,

anorexia, nausea and vomiting, abdominal pain,
and/or diarrhea
Patients often have mild lethargy or drowsiness

Not typical of viral meningitis : suggest the presence of

encephalitis or other alternative diagnoses

Profound alterations in consciousness, such as stupor, coma, or

marked confusion,

Seizures or focal neurologic signs or symptoms

Neuroimaging abnormalities indicative of brain parenchymal

involvement
 Viral Meningoencephalitis
Viral meningoencephalitis, and particularly herpes
simplex virus (HSV) encephalitis, can mimic the clinical
presentation of bacterial meningitis

HSV encephalitis typically presents with

headache,
fever,
altered consciousness,
focal neurologic deficits (e.g., dysphasia, hemiparesis), and
focal or generalized seizures
MRI abnormalities (other than meningeal enhancement)
are not seen in uncomplicated bacterial meningitis.

By contrast,

In HSV encephalitis

on T2-weighted, fluid-attenuated inversion recovery
(FLAIR) and diffusion-weighted MRI images,
high signal intensity lesions are seen in the orbitofrontal,
anterior, and medial temporal lobes in the majority of
patients within 48 h of symptom onset.
Bacterial (Pyogenic)
Meningitis
Bacterial (Pyogenic) Meningitis
A medical emergency

Therapy should not be delayed for diagnostic

measures because
prognosis hinges on rapid initiation of antimicrobial
treatment

Commonly N. meningitis, S. pneumonia, H.

influenzae
Bacterial Meningitis: Etiology
The organisms most often responsible for community-
acquired bacterial meningitis are (In USA)
Streptococcus pneumoniae (~50%),
Neisseria meningitidis (~25%),
group B streptococci (~15%) or, Streptococcus agalactiae,
Listeria monocytogenes (~10%).
Haemophilus influenzae type b <10% of cases of
bacterial meningitis in most series.
S. pneumoniae is the most common cause of
meningitis in adults >20 years of age
Harrison 19th edition
In Nepal:Studies
1. “Bacterial meningitis in children under 15 years of
age in nepal”
 Shrestha Rajani Ghaju, et al. : 2015
 May 2012- April 2013, descriptive study, TUTH,
Maharajgunj
 Gm stainging, culture and Latex agglutination test
 Result: most common cause: H. influenzae (38.9 %)
E. coli (16.7 %), N. meningitis (11.1%)
In Patan Hospital: Studies
1. “Aetiologies of central nervous system infections in adults in
Kathmandu, Nepal: A prospective hospital based study”
 Basnyat, et.al.
 Published on 8 August, 2013; Study from February 2009-April
2011.
 Adult patient (med. Age 30 yrs), admitted to PH, Dx by
molecular diagnostics, culture and serology.
 83 pt. included, etiology established in 38% (33 pt.)
 Bacterial: 13/87 (14%) N. meningitidis (6.8%) Strep.
pneumoniae (5.7%) Staph. aureus
 Enteroviruses (12/87, 13%), Herpes viruses (2/87)
 Japenese Encephalitis IgM 11 patient.
When to Suspect Bacterial Meningitis
Depressed level of consciousness (e.g., somnolence,
coma), seizures, or focal neurologic deficits do not
occur in viral meningitis
Treated empirically for bacterial and viral
meningoencephalitis.

Fever and either headache, stiff neck, or an altered level

of consciousness will be present in nearly every patient
with bacterial meningitis.
Seizures occur as part of the initial presentation of
bacterial meningitis or during the course of the illness
in 20–40% of patients

Raised ICP is an expected complication of bacterial

meningitis
the major cause of obtundation and coma in this disease
Risk (Predisposing) Factors
Pneumococcal Meningitis
Most important is pneumococcal pneumonia

Additional risk factors:

coexisting acute or chronic pneumococcal sinusitis
otitis media,
alcoholism,
diabetes,
splenectomy,
hypogammaglobulinemia,
complement deficiency,
head trauma with basilar skull fracture and
CSF rhinorrhea
Meningococcal Meningitis
Incidence of Meningococcal Meningitis declining
withRoutine immunization
Quadrivalent (serogroups A, C, W-135, and Y) meningococcal
glycoconjugate vaccine to 11- to 18-year-olds

The vaccine does not contain serogroup B

 which is responsible for one-third of cases of meningococcal
disease

deficiencies of any of the complement components, including

properdin are highly susceptible to meningococcal infections
Listeria monocytogens
L. monocytogenes is an increasingly important
cause of meningitis in
neonates (<1 month of age),
pregnant women,
Individuals >60 years,
immunocompromised individuals of all ages

Infection is acquired by ingesting foods contaminated

by Listeria.
H. Influenza b
H. influenzae type b (Hib) meningitis in children has
declined dramatically since the introduction of the
Hib conjugate vaccine
rare cases of Hib meningitis in vaccinated children have
been reported

Causes meningitis in unvaccinated children and older

adults

Non-b H. influenzae is an emerging pathogen.

Bacterial Meningitis (C/F)
Headache, drowsiness, fever and neck stiffness are the
usual presenting features

Severe cases comatose, focal neurological signs

 90% of pt. with Meningococcal meningitis: 2 of following

Fever
Neck stiffness
Altered consciousness
Rash
Rash:
A nonblanching rash (petechial or purpuric) develops in >80% of cases
of meningococcal disease

Usually initially blanching (macule, maculopapule, or urticaria)

indistinguishable from more common viral rashes

Rash of meningococcal infection becomes petechial or frankly

purpuric over the hours after onset

Some patients (including those with overwhelming sepsis)

may have no rash
Chronic meningococcaemia
rare condition

patient can be unwell for weeks or even months

recurrent fever, sweating, joint pains and transient rash

usually occurs in the middle-aged and elderly, and in

those who have previously had a splenectomy
In pneumococcal and Haemophilus infections
Associated otitis media

Pneumococcal meningitis
Associated with pneumonia commonly in elderly,
alcoholic, and non functioning spleen .

Listeria monocytogens: in immunosuppressed,

diabetic, alcoholic, pregnancy
Bacterial Meningitis: Treatment
Supportive measures and antimicrobial therapy

Oxygen therapy or elective endotracheal intubation

In cases with shock, aggressive fluid resuscitation with

inotropic support may be necessary to maintain cardiac
output

Metabolic derangements, including hypoglycemia, acidosis,

hypokalemia, hypocalcemia, hypomagnesemia,
hypophosphatemia, anemia, and coagulopathy, should be
anticipated and corrected
Specific Antimicrobial Therapy
Meningococcal Meningitis
Choice for susceptible strain Penicillin G
Resistant strain cefotaxime or Ceftriaxone
Resistant to penicillin/Ampicillin

For uncomplicated meningococcal meningitis 7-day course of is

adequate.

The index case and all close contacts should receive

chemoprophylaxis with a 2-day regimen of rifampin
600 mg every 12 h for 2 days in adults and
10 mg/kg every 12 h for 2 days in children >1 year
Rifampin is not recommended in pregnant women
Alternatively, Adults can be
treated with one dose of azithromycin (500 mg) or one
intramuscular dose of ceftriaxone (250 mg)
Pneumococcal Meningitis
Initiated with a cephalosporin (ceftriaxone,
cefotaxime, or cefepime) and vancomycin

Cephalosporin MICs ≤0.5 μg/mL (Sensitive), treatment

with cefotaxime or ceftriaxone is usually adequate

For Cephalosporin MIC >1 μg/mL (Intermediate

Resistant) vancomycin is the antibiotic of choice
Rifampin can be added to vancomycin for its synergistic
effect
A 2-week course of intravenous antimicrobial therapy is
recommended for pneumococcal meningitis

Patients with S. pneumoniae meningitis should have a

repeat LP performed 24–36 h after the initiation of
antimicrobial therapy
 To document sterilization of the CSF
Failure to sterilize the CSF after 24–36 h of antibiotic
therapy should be considered presumptive evidence of
antibiotic resistance

Patients with penicillin- and cephalosporin- resistant

strains of S. pneumoniae who do not respond to intravenous
vancomycin alone
 may benefit from the addition of intraventricular vancomycin
Listeria Meningitis
Ampicillin for at least 3 weeks

Gentamicin is added in critically ill patients (2 mg/kg

loading dose, then 7.5 mg/kg per day given every 8 h
and adjusted for serum levels and renal function).

The combination of trimethoprim (10–20 mg/kg per

day) and sulfamethoxazole (50–100 mg/kg per day)
given every 6 h may provide an alternative in
penicillin-allergic patients.
Staphylococcal Meningitis
Susceptible strains of S. aureus or coagulase-negative
staphylococci
treated with nafcillin

Methicillin resistant staphylococci and for patients allergic to

penicillin
Vancomycin is the drug of choice

If the CSF is not sterilized after 48 h of intravenous

vancomycin therapy
then either intraventricular or intrathecal vancomycin, 20 mg
once daily, can be added.
Gram Negative Bacillary Meningitis
The third-generation cephalosporins— cefotaxime,
ceftriaxone, and ceftazidime—are equally efficacious
Except for Pseudomonas
Should be treated with ceftazidime, cefepime, or
meropenem

A 3-week course of intravenous antibiotic therapy is

recommended for meningitis due to gram-negative
bacilli.
Adjunctive Treatment
The release of bacterial cell-wall components by
bactericidal antibiotics
leads to the production of the inflammatory cytokines
IL-1β and TNF-α in the subarachnoid space

Dexamethasone
Inhibit the synthesis of IL-1β and TNF-α decreasing CSF
outflow resistance, and stabilizing the blood-brain
barrier
The rationale for giving dexamethasone 20 min
before antibiotic therapy
Inhibits the production of TNF-α by macrophages and
microglia only if it is administered before these cells are
activated by endotoxin

Dexamethasone does not alter TNF-α production once it

has been induced
Efficacious in meningitis due to H. influenzae, S.
pneumoniae, and N. meningitidis
decreases meningeal inflammation and
neurologic sequelae such as the incidence of
sensorineural hearing loss decreases

Dexamethasone (10 mg intravenously) is administered

15–20 min before the first dose of an antimicrobial
agent, and the same dose repeated every 6 h for 4 days
Therapy with dexamethasone should ideally be
started 20 min before, or not later than concurrent
with, the first dose of antibiotics

It is unlikely to be of significant benefit if started >6 h

after antimicrobial therapy has been initiated
 Point to be Noted
Dexamethasone may decrease the penetration of
vancomycin into CSF, and it delays the sterilization of CSF
in experimental models of S. pneumoniae meningitis.

To assure reliable penetration of vancomycin into the CSF,

children and adults are treated with vancomycin in a dose
of 45–60 mg/kg per day.

Alternatively, vancomycin can be administered by the

intraventricular route.
Tubercular Meningitis
Tubercular Meningitis
Seen in those born in endemic areas and in the
immunocompromised

Occurs shortly after a primary infection in childhood

or as part of miliary tuberculosis
accounts for ~6% of extrapulmonary cases
1 % of all TB cases
Clinical Features
Subacute febrile illness progresses through 3 phases
1. Prodromal phases: lasts 2-3 wks
 Insidious onset of malaise, lasitude, headache, low grade
fever, personality change

2. Meningitic phase: more pronounced neurologic features

 Meningism, protracted headache, vomiting, lethargy,
confusion and varying degree of CN involvement

3. Paralytic phases: advanced illness with delirium, stupor,

coma, seizure, multiple CN palsies, dense hemiplegia
Onset is much slower than in other bacterial meningitis –
over 2–8 weeks

If untreated it is fatal in a few weeks (5-8 weeks of

symptoms onset)

Complete recovery is usual if treatment is started at stage I

When treatment is initiated later the rate of death or

serious neurological deficit may be as high as 30%.
Meningeal involvement is pronounced at the base of
the brain
paresis of cranial nerves (ocular nerves in particular) is a
frequent finding, and
involvement of cerebral arteries may produce focal
ischemia
Investigations
CSF
Increased pressure
Clear, but if allowed to stand fine clot (spider web)
form
High leukocyte count (up to 1000/μL)predominantly
lymphocytes
 but sometimes with a predominance of neutrophils in the early
stage;
There is a rise in protein, 1–8 g/L (100–800 mg/dL);
Marked fall in glucose (<45% in 80% patient)
CXR: abnormality is seen in ~50% patient (focal lesion
to milliary pattern)

Culture of CSF is diagnostic in up to 80% of cases

remains the gold standard

Real time automated nucleic acid amplification (the

Xpert MTB/RIF assay)
Sensitivity of up to 80%
preferred initial diagnostic option
Treatment
Clinical outcome depends greatly on stage at which
treatment is initiated

# ATT: 9 to 12 months therapy recommended

(depending on clinical response)
2 months +7 to 10 months

# If Pyrazinamide is not tolerated/contraindicated 

treatment extended to 18 months #Upto date
If MDR TB infection
No guidelines for duration of therapy
Advisable to extend duration of therapy to 18-24 months
 Severity of illness
 Rate of clinical response
 Immune status of patient

Patient assumed to be non-infectious after 2 weeks of

therapy
Adjunctive Glucocorticoids
Recommended to all children and adults
Exception: adults with early mild stage I manifestation

Specific clinical indication:

CSF opening pressure more than 400 cm H2O or CT evidence of
cerebral edema

Patient who demonstrate “therapeutic paradox” exacerbation of

clinical signs(fever, change in mentation) after initiating ATT

Spinal block (CSF protein>500 mg/dl)

CT head: marked basilar enhancement or moderate or advancing
hydrocephalus
Intracerebral tuberculoma.
Glucocorticoid Regimen
Dexamethasone or Prednison
Dexamethasone:
 <25 kg  total 8mg/day
 > 25kg and adults 12 mg/day

 For 3 weeks then tapper off gradually over the

following 3-4 weeks

Prednisolone:
 3-4 mg/kg/d for children
 60 mg/day for adults

 For 3 weeks then tapper off over next 3 weeks

# Upto date 23.6
References
Harrison’s Principle of Internal Medicine, 19th edition
Davidsons Principle and Practice of Medicine, 22nd
edition
Washington’s Manual of Medical Therapeutics, 34th
edition, 2014
Uptodate 23.6
Thank You