Bacterial

Meningitis
Dr. Dinesh kumar Reddy
What We'll
Discuss
TOPIC OUTLINE

Definition
Common Organisms and Etiology
Pathogenesis
Clinical features and Pathophysiology
Management
Treatment

BACTREIAL MENINGITIS
 DEFINITION
MENINGITIS IS AN ACUTE
INFLAMMATION OF THE
MENINGES COVERING THE
BRAIN AND SPINAL CORD.
BACTERIAL MENINGITIS IS AN ACUTE PURULENT INFECTION
WITHIN THE SUBARACHNOID SPACE (SAS)
 H,influenza type B
7.4%

Listeria monocytogenes

Common
9.3%

group B streptococci S.pneumoniae

causative
organisms
13.9% 46.3%

N.meningitidis causes recurring

epidemics of meningitis
N.meningitidis
23.1%

Harrisons; 20th edition

 ETIOLOGY

Neonates(<3) Children Adults Elderly(>65)

Group B Pneumococcus
Streptococcus Pneumococcus
Meningococcus Pneumococcus
  N.meningitidis
Escherichia coli H.influenza Meningococcus
  Type B
Listeria L.monocytogenes
monocytogenes

Lancet 2003; 361: 2139–48 BACTERIAL MENINGITIS

If no organism can be
isolated with routine
culture and sensitivity
assays of CSF, the
condition is called Aseptic
meningitis
The etiology is likely viral (e.g. Enterovirus, HIV and HSV),
tuberculous meningitis (M.tuberculosis), Lyme disease
(Borrelia spp.), parasitic infections (e.g. Taenia
solium, Toxoplasma gondii), and malignancy.
Risk factors for pathogen entry:

# chronic and debilitating diseases (diabetes, cirrhosis, or

alcoholism and in those with chronic urinary tract
infections)

# Otitis, mastoiditis, and sinusitis

# Neurosurgical procedures, particularly craniotomy, and

head trauma associated with CSF rhinorrhea or otorrhea

# Endocarditis

#Asplenia
PATHOGENESIS OF

MENINGITIS

Ther Adv Neurol Disord. 2009; 2(6):401-412.

Clinical features and Pathophysiology
Symptom Signs Mechanism
Endogenous cytokines (released during the immune
response to the invading pathogens) affect the
Chills, rigors Fever (T>38°) thermoregulatory neurons of the hypothalamus,
changing the central regulation of body temperature.

Invading viruses or bacteria produce exogenous

substances (pyrogens) that can also re-set
the hypothalamic thermal set point.

Nuchal Brudzinski Flexion of the spine leads to stretching of the

rigidity (neck sign and meninges.
stiffness) Kernig sign In meningitis, traction on the inflamed meninges
is painful, resulting in limited range of motion
through the spine (especially in the cervical spine)

Petechial rash Meningococcemia (due to N. meningitidis)

Clinical features and Pathophysiology
Symptom Signs Mechanism

Altered Decreased Gl ↑ ICP → brain herniation → damage to the reticular

mental status asgow Coma formation ( governs consciousness)
Scale (GCS)

Focal Examples: Cytotoxic edema and ↑ ICP lead to neuronal

neurological cranial nerve damage.
deficits, e.g. palsies,
vision loss hemiparesis,
Signs or symptoms depend on the affected area
hypertonia,
(cerebrum, cerebellum, brainstem, etc.)
nystagmus

Nausea and ↑ ICP stimulates the area postrema (vomiting centre),

vomiting causing nausea and vomiting.
Clinical features and Pathophysiology
Symptom Signs Mechanism

Inflammation in the brain alters membrane

Seizures permeability, lowering the seizure threshold. Exact
seizure pathophysiology is unknown.

Headache Jolt Bacterial exotoxins, cytokines, and ↑ ICP

accentuation of stimulate nociceptors in the meninges (cerebral
headache:
tissue itself lacks nerve endings that generate
headache
pain sensation).
worse when
patient
vigorously
shakes head

Due to meningeal irritation. Mechanisms unclear;

Photophobia pathways are thought to involve the trigeminal nerve.
In the pediatric population, all of the above signs and symptoms are
applicable. Additional signs and symptoms in children include:

Bulging fontanelles
Bones of the skull do not form sutures until age 2
↑ ICP → meninges protrude through gaps in skull bones

Jaundice
Impaired bilirubin excretion
Exact mechanism unclear, associated with sepsis

Reduced feeds, irritability, lethargy, and toxic appearance

Fever, shock and cerebral edema can lead to such manifestations in
children
 Classic triad of Meningitis

Fever Headache Nuchal rigidity

This classic triad may not be present in every person with Meningitis

NOT to be confused
with MENINGISM
MENINGISMUS OR
PSEUDOMENINGITIS
Non meningitic irritation of the meninges, usually
associated with acute febrile illness.
The triad is nuchal
rigidity, photophobia and headache
 MANAGEMENT OF
BACTERIAL MENINGITIS IN
ADULTS AND CHILDREN
Initial Management approach
Once there is suspicion of acute bacterial meningitis, blood
samples must be obtained for culture and a lumbar puncture
performed immediately to determine whether the CSF is
consistent with the clinical diagnosis.

When to order a CT scan of the

head prior to Lumbar
puncture?
If clinical
presentation is IF there is a significant interval
consistent between establishing the diagnosis of
bacterial meningitis and initiating
with a CNS mass appropriate therapy
lesion or another
cause of increased
ICP a CT scan of
the head is done Blood samples must be obtained for
culture and appropriate antimicrobial
prior to lumbar and adjunctive therapy given prior to
puncture lumbar puncture or before the patient is
sent for CT

BACTERIAL MENINGITIS
 Suspicion for bacterial meningitis

Immunocompromise, history of selected cns diseases, new onset seizures,

papilledema,Altered conciousness or FND, or delay in performance of a lumbar

A puncture

Blood culture stat

Blood culture and

D lumbar Puncture stat

Dexamethasone + emperical AMT

U Dexamethasone + emperical AMT Negaative CT scan of

the head
CSF findings c/w
L bacterial Meningitis Perform Lumbar
Puncture

T Positive Gram Stain

Dexamethasone + Dexamethasone +
emperical AMT Targeted AMT

Clinical Infectious Diseases, Volume 39, Issue 9, 1 November 2004

C Suspicion for bacterial meningitis

H Immunocompromise, history of selected cns diseases, papilledema,or selected FND,

or delay in performance of a lumbar puncture

I Blood culture and Blood culture STAT

L
lumbar Puncture STAT

Dexamethasone +

D
Dexamethasone + emperical AMT
emperical AMT
Negaative CT scan of
R CSF findings c/w
bacterial Meningitis
the head

E Continue Therapy
Perform Lumbar
Puncture

N
Clinical Infectious Diseases, Volume 39, Issue 9, 1 November 2004
 Specific CSF Diagnostic Tests Should Be Used
to Determine the Bacterial Etiology of Meningitis
The diagnosis of bacterial meningitis rests on CSF examination performed after
lumbar puncture

Opening pressure--- >180mm h20

White blood ---10/μL to 10,000/μL
RBCs ---Absent in nontraumatic tap
Glucose---<40 mg/dL
CSF/serum glucose---<0.4
Harrisons 20th ed Table-133-2
Protein--->45 mg/dL
CSF/serum glucose ratio corrects for hyperglycemia that may mask a relative decrease in the CSF glucose
concentration
CSF appearance may be cloudy, depending on the presence of significant concentrations of WBCs,
RBCs, bacteria, and/or protein
Gram stain.

Gram stain examination of CSF permits a rapid, accurate

identification of the causative bacterium in 60%–90% of
patients with community-acquired bacterial meningitis, and
it has a specificity of >97%

Latex agglutination.
They utilize serum containing bacterial antibodies or commercially
available antisera directed against the capsular polysaccharides of
meningeal pathogens
Limulus lysate.

Lysate prepared from the amebocyte of the horseshoe crab,

Limulus polyphemus, has been suggested as a useful test for
patients with suspected gram-negative meningitis

PCR.

Broad-based PCR may be useful for excluding the diagnosis of

bacterial meningitis, with the potential for influencing decisions to
initiate or discontinue antimicrobial therapy.
Laboratory tests to distinguish Bacterial from Viral Meningitis
CSF findings consistent with a diagnosis of bacterial meningitis, but in
whom the CSF Gram stain and culture results are negative certain
tests can help.
Lactate concentration - CSF lactate concentrations of >4.2mmol/L are
considered to be a positive discriminative factor for bacterial
meningitis

C-reactive protein (CRP) concentration- Not a diagnostic test for

bacterial meningitis. Several Acute-phase reactants are useful in the
diagnosis of acute bacterial meningitis

procalcitonin concentration-Elevated serum concentrations of the

polypeptide procalcitonin, are observed in patients with severe
bacterial infection
PCR.
Treatment

EMPERICAL ANTIMICROBIAL THERAPY

SPECIFIC ANTIMICROBIAL THERAPY

OTHER DRUGS
GOAL OF TREATMENT

Begin antibiotic therapy within 60 min of a patient’s arrival in

the emergency room

To maintain cerebral perfusion pressure by preserving the mean arterial

pressure (e.g. fluid resuscitation)

And normalizing Intracranial Pressure( By elevating the head, hyperventilation,

controlling seizure activity; hyperventilation causes hypocapnia-mediated
cerebral vasoconstriction)
Cerebral perfusion pressure = Mean arterial pressure – ICP

Mainstay of treatment for bacterial

meningitis is antibiotics; choice of
antibiotic depends on the organism
isolated from blood and CNS
cultures
Clin Infect Dis. (2004) 39 (9):1267-1284
 Combination of dexamethasone, a third- or
fourth-generation cephalosporin (e.g.,
ceftriaxone, cefotaxime, or cefepime), and
vancomycin,
+
Emperical
Therapy Acyclovir, as HSV encephalitis is the leading
disease in the differential diagnosis,

&

Doxycycline during tick season to treat tick-

borne bacterial infections.

BACTERIAL MENINGITIS
PREDISPOSING FACTOR ANTIMICROBIAL
THERAPY

Age
Ampicillin + Cefotaxime
< 1 month or Ampicillin + an
Aminoglycoside

Vancomycin + a third-
1-23 months generation
Cephalosporin

Vancomycin + a third-
2-50 years generation
Cephalosporin

Vancomycin + ampicillin
>50 years + a third-generation
cephalosporin
PREDISPOSING FACTOR ANTIMICROBIAL
THERAPY

Head trauma
Vancomycin + a third-
Basilar skull fracture gen cephalosporin

Vancomycin +cefepime,
vanc + ceftazidime, or
Penetrating trauma vancomycin +
meropenem

Post neurosurgery Vancomycin +cefepime,

vancomycin +
ceftazidime, vancomycin
+ meropenem
CSF shunt
Specific
Antimicrobial
Therapy
Once a bacterial pathogen is isolated and in vitro susceptibility
testing is performed, antimicrobial treatment should be modified for
optimal therapy

BACTERIAL MENINGITIS
ORGANISM STANDARD
THERAPY

Streptococcus pneumoniae
Penicillin G
Penicillin-sensitive
Ceftriaxone /
Penicillin-intermediate cefotaxime / cefepime
Ceftriaxone or
Penicillin-resistant cefotaxime or cefepime

Nisseria Meningitidis
Penicillin-sensitive Penicillin G or ampicillin

Penicillin-resistant Ceftriaxone/ cefotaxime

ORGANISM STANDARD
THERAPY

Gram-negative bacilli
Ceftriaxone /cefotaxime
(except Pseudomonas spp.)

Ceftazidime /
Pseudomonas aeruginosa meropenem

Staphylococci spp
Methicillin-sensitive Penicillin G or ampicillin

Methicillin-resistant Ceftriaxone/ cefotaxime

ORGANISM STANDARD
THERAPY

Listeria monocytogenes Ampicillin + gentamicin

Haemophilus influenzae Ceftriaxone /

cefotaxime / cefepime

Streptococcus agalactiae Penicillin G or ampicillin

Bacteroides fragilis Metronidazole

DURATION OF ANTIMICROBIAL THERAPY BASED ON ISOLATED
PATHOGEN

Microorganism Duration of therapy

Neisseria meningitidis 7 days

Haemophilus influenzae 7 days
Streptococcus pneumoniae 10–14 days
Streptococcus agalactiae 14-21 days
Aerobic gram-negative bacillia 21 days
Listeria monocytogenes >21 days
Indications for Repeated
Lumbar Puncture

Repeated CSF analysis should be performed,for any

patient who has not responded clinically 48 h after
appropriate antimicrobial therapy

Criteria to be used for Outpatient

Antimicrobial Therapy ??
Inpatient antimicrobial therapy for >6 days
Absence of fever for at least 24–48 h prior to initiation of
outpatient therapy
No significant neurologic dysfunction, focal findings, or
seizure activity
Clinical stability or improving condition
Ability to take fluids by mouth
Access to home health nursing for antimicrobial
administration
Reliable intravenous line and infusion device (if needed)
Daily availability of a physician
Established plan for physician visits, nurse visits, laboratory
monitoring, and emergencies
Patient and/or family compliance with the program
Why should Dexamethasone be used as an
adjunctive therapy for Bacterial
Meningitis??
Release of bacterial cell-wall components by bactericidal antibiotics
leads to the production of the inflammatory cytokines IL-1β and TNF-α
in the SAS

Dexamethasone exerts its beneficial effect by inhibiting the

synthesis of IL-1β and TNF-α at the level of mRNA, decreasing CSF
outflow resistance, and stabilizing the BBB

Dexamethasone should be given 20 min before

antibiotic therapy
WHEN TO ADMIT
• PATIENTS WITH SUSPECTED ACUTE MENINGITIS, ENCEPHALITIS, AND BRAIN OR
PARASPINOUS ABSCESS SHOULD BE ADMITTED FOR URGENT EVALUATION AND
TREATMENT.

• THERE IS LESS URGENCY TO ADMIT PATIENTS WITH CHRONIC MENINGITIS; THESE

PATIENTS MAY BE ADMITTED TO EXPEDITE DIAGNOSTIC PROCEDURES AND
COORDINATE CARE, PARTICULARLY IF NO DIAGNOSIS HAS BEEN MADE IN THE
OUTPATIENT SETTING.

BACTERIAL MENINGITIS
WHEN TO REFER

• PATIENTS WITH SUSPECTED HOSPITAL-ACQUIRED MENINGITIS (EG, IN PATIENTS

WHO HAVE UNDERGONE RECENT NEUROSURGERY OR EPIDURAL OR PARASPINAL
CORTICOSTEROID INJECTION).

• PATIENTS WITH RECURRENT MENINGITIS

BACTERIAL MENINGITIS
References
JAMA. 1999 Jul 14;282(2):175-81.

N Engl J Med 2004; 351:1849-1859.

Ther Adv Neurol Disord. 2009; 2(6):401-412.

Lancet 2003; 361: 2139–48.

Clin Infect Dis. (2004) 39 (9):1267-1284.

Harrisons principles of clinical medicine 20th edition

Thank
you.