MENINGITIS

Omaid Hayat Khan

Assistant Professor
Faculty of Pharmacy
The University of Lahore
CONTENT
• INTRODUCTION

• ANATOMY & PHYSIOLOGY

• PATHOPHYSIOLOGY

• ETIOLOGY

• TREATMENT/ MANAGEMENT
 INTRODUCTION
◦ Meningitis is the inflammation of the meninges (especially the two inner layers
called leptomeninges).

◦ Meninges are a set of three protective layers covering the brain & spinal
cord.
◦ Dura mater
◦ Arachnoid mater
Leptomeninges
◦ Pia Mater

◦ Between the leptomeninges is the sub-arachnoid space which holds the

cerebrospinal fluid (CSF).
◦ Encephalitis ~ inflammation of the brain
◦ Meningitis ~ inflammation of the leptomeninges
◦ Meningoencephalitis ~ Inflammation of both meninges and brain.
◦ Brain abscess ~ a pus-filled pocket of infected material in your brain.
 CSF & BBB
◦ Cerebrospinal fluid (CSF) is a clear watery liquid
which is pumped around the brain and spinal cord,
cushioning them from impact and bathing them with
nutrients.
◦ In 1 microliter CSF, there are ~5 WBC
◦ In 1 deciliter CSF, 70% of neutrophils and 30% of
monocytes with few PMN cells (e.g. neutrophils)
◦ Proteins 15-50 mg
◦ Glucose ~45-100 mg
◦ CSF pressure < 15 mmHg
◦ CSF quantity ~150 ml dynamically.
◦ 500 ml of CSF produced daily and ~350 ml is
reabsorbed into blood.
◦ Blood Brain Barrier: endothelial cells in blood vessels
are so tightly bound to each other that there is no
space in between them, therefore anything that has
to pass, have to pass through the cells themselves.
 Newborns
Etiology & triggers Bacterial causes
•
•
Group B Streptococci
E. Coli
◦ Autoimmune diseases ~ Lupus
• Listeria monocytogenes

◦ ADRs with some Medications which are intrathecally

injected into CSF Children & teens
◦ Infections (most common) • Neisseria meningitidis
◦ Bacteria • Streptococcus pneumoniae
◦ Virus
◦ enterovirus, herpes simplex, HIV are most common.
◦ Vericella zoster, mumps, lymphocytic choriomeningitis are
less common. Adults & elderly
◦ Fungus
◦ Cryptococcus genuses
• Streptococcus pneumoniae
In immunocompromised • Listeria monocytogenes
◦ Coccidioides genuses
individuals
◦ Mycobacterium tuberculosis
◦ P. falciparum

A common characteristic of most CNS bacterial pathogens (eg, H. influenzae, Escherichia coli, and N. meningitidis) is the presence of an
extensive polysaccharide capsule that is resistant to neutrophil phagocytosis and complement opsonization.

Introduction of H. influenza (Hib) and pneumococcal vaccines have significantly decreased the infant mortality rates.

Passive and active exposure to cigarette smoke and the presence of a cochlear implant that includes a positioner, both increase the risk
of bacterial meningitis.
 Pathophysiology
◦ Direct spread
◦ Through overlying skin • Colonization
◦ Up through nose (sinuses) • Invasion
◦ Anatomical defect • Immune evasion
◦ Congenital ~ Spina bifidia
◦ Acquired ~ Skull Fracture
• Meningeal invasion
◦ Hematogenous spread
◦ Moves through the blood into endothelial cells of BBB and enters CSF.
◦ They must bind to the surface receptors to enter otherwise; they must find areas of damage or more vulnerable spots like the choroid
plexus.

◦ Once in CSF, microbes multiply and WBC become activated and start releasing cytokines which attracts more WBCs and 1
microliter of CSF start having 1000’s of WBCs, however, criteria of having meningitis is having WBC more than 5 per
microliter.
◦ More immune cells attract more fluid into CSF raising CSF pressure above 200 mmH2O, glucose conc. falls less than 2/3rd
of blood glucose, & protein levels increase to over 50 mg/dL.
◦ Proteolytic products and toxic oxygen radicals cause an alteration of the blood–brain barrier, whereas platelet-activating
factor activates coagulation, and arachidonic acid metabolites stimulate vasodilation. These events lead to cerebral edema,
elevated intracranial pressure, cerebrospinal fluid (CSF) pleocytosis, decreased cerebral blood flow, cerebral ischemia, and
death.
 CLINICAL PRESENTATION
• > 100 WBCs/uL
Bacterial • > 90% PMNs

Tuberculosis • 50-500 WBC/uL

meningitis • >80% lymphocytes Acute meningitis

• 10-1000 WBCs/uL
Viral • >50% lymphocytes, <20% PMNs

• 10-500 WBC/uL
Fungal • > 50% lymphocytes Chronic meningitis
 Signs & Symptoms
◦ Kernig’s Sign
◦ Brudzinski Sign
◦ Triad
◦ Headache
◦ Fever
◦ Nuchal rigidity
◦ Photophobia ~ discomfort with bright lights
◦ Phonophobia ~ Discomfort with loud sounds
◦ Meningoencephalitis
◦ Altered mental status
◦ Seizures
◦ Clinical signs and symptoms in young children
may include bulging fontanelle, apneas,
purpuric rash, and convulsions, in addition to
those just mentioned.
 Brudzinski Neck Sign

Diagnosis
◦ Kernig’s Sign
◦ Brudzinski Sign
◦ Lumber puncture ~ between L3-L4
◦ Gram stain and culture of the CSF are the most important
laboratory tests performed for bacterial meningitis. When
performed before antibiotic therapy is initiated, Gram stain
Kernig’s Sign is both rapid and sensitive and can confirm the diagnosis of
bacterial meningitis in 75% to 90% of cases.

◦ Polymerase chain reaction (PCR)

◦ N. meningitidis, S. pneumoniae, and H. influenzae type b
(Hib)
◦ HIV, Enterovirus, HSV, tuberculosis (also acid-fast staining)

◦ Western blot ~ Borrelia burgdorferi

◦ Thin blood smear ~ malaria
 CLINICAL
TOOL
ALERT
Treatment is recommended when
one or more criteria are present. An
elevated CSF protein of 50 mg/dL
or more and a CSF glucose
concentration less than 50% of the
simultaneously obtained peripheral
value suggest bacterial meningitis
 Treatment
Goals of Treatment: Pharmacological Treatment

❑ Eradication of infection with amelioration of signs ◦ Empiric antimicrobial therapy should be

and symptoms instituted as soon as possible to eradicate the
❑ preventing morbidity and mortality, causative organism
❑ initiating appropriate antimicrobials,
❑ providing supportive care, and
◦ Antimicrobial therapy should last at least 48 to
72 hours or until the diagnosis of bacterial
❑ preventing disease through timely introduction of
vaccination and chemoprophylaxis. meningitis can be ruled out.

◦ The administration of fluids, electrolytes, ◦ Once a pathogen is identified, antibiotic therapy

antipyretics, analgesia, and other supportive should be tailored to the specific pathogen.
measures are particularly important for patients ◦ The first dose of antibiotic should not be
presenting with acute bacterial meningitis. withheld even when lumbar puncture is delayed,
or neuroimaging is being performed.
 BACTERIAL
MENINGITIS
TREATMENT
With increased meningeal inflammation,
there will be greater antibiotic
penetration. Problems of CSF
penetration were traditionally overcome
by direct instillation of antibiotics
intrathecally, intracisternally, or
intraventricularly. Advantages of direct
instillation, however, must be weighed
against the risks of invasive CNS
procedures. Intrathecal administration of
antibiotics is unlikely to produce
therapeutic concentrations in the
ventricles possibly owing to the
unidirectional flow of CSF.
 Empiric MENINGITIS

therapy: Therapy for common pathogens

Neisseria meningitides Haemophilus Streptococcus Adjunctive

Streptococcus pneumonia
Neonate younger than 1 influenzae agalactiae corticosteroid
7 days
month: 10-14 days 7 days 14-21 days therapy
Ampicillin +
aminoglycosides
MIC to penicillin = or < 0.1 mcg/ml MIC to penicillin = or < 0.1 mcg/ml Beta lactamase negative: Penicillin G Dexamethasone 0.15 mg/kg q6h
Ampicillin + cefotaxime for 2-4 days give 10-20 minutes
Penicillin G 4 million units IV q4h Penicillin G Ampicillin Ampicillin
Infants (1-23 months): before or at same time as
Ampicillin Alternative: Alternative: antibiotics
Ampicillin 2g IV q4h
3 rd gen. cephalosporin
Alternative: cefotaxime 2g IV every 4-6 cefotaxime 2g IV every 4-6
Alternative 3rd generation cephalosporins cefotaxime 2g Cryptococcal meningitis
Cefotaxime OR hrs hrs
IV every 4-6 hrs OR Ceftriaxone 2g IV q12h 3 rd generation cephalosporins
ceftriaxone
OR Ceftriaxone 2g IV q12h OR 2-3 weeks
OR cefotaxime 2g IV every 4-6 hrs
+ vancomycin
OR Cefepime 2g IV Q8h Ceftriaxone 2g IV q12h
Patient severely penicillin allergic: OR Ceftriaxone 2g IV q12h
 
Children & adults (2-50 OR Chloramphenicol 1-1.5g  
OR Chloramphenicol 1-1.5g IV q6h Amphotericin B 0.7 1.0 mg/kg/day
 years) Vancomycin + Rifampin 300mg PO TID OR IV q6h
(If pt penicillin allergic) Listeria +
3 rd gen. cephalosporin Chloramphenicol 1-1.5g IV q6h OR Fluoroquinolone
  monocytogenes Flucytocin 100 mg/kg/day (6days)
Cefotaxime OR    
Beta lactamase positive:
If ceftriaxone resistance or high level penicillin resistance:  
MIC to penicillin of 0.1 – 1.0 mcg/ml OR
ceftriaxone +   21 days or more
Vancomycin added 3 rd  3 rd generation cephalosporins Fluconazole 400-800 mg/day
vancomycin   generation cephalosporins
  cefotaxime 2g IV every 4-6 hrs (6weeks)
Older adults >50 years:  cefotaxime 2g IV every 4-6 hrs Penicillin G
OR OR
MIC TO PENICILLIN OF 0.1-1.0 MIC TO PENICILLIN OF 2.0 mcg/
3 rd gen. cephalosporin Ampicillin 2g V q4h + systemic
mcg/ml ml or greater: Ceftriaxone 2g IV q12h Ceftriaxone 2g IV q12h
Cefotaxime OR rd
3 generation cephalosporins Vancomycin 15-20 mg/kg IV every ALTERNATIVE: Alternative:
aminoglycoside. Viral meningitis
ceftriaxone + 8-12h Alternative:
cefotaxime 2g IV every 4-6 hrs Chloramphenicol 1-1.5g IV q6h Cefepime 2g IV Q8h
vancomycin + ampicillin
+ Trimethoprim/
OR OR OR
  rd
3 generation cephalosporins sulfamethoxazole 5mg/kg IV
Penetrating head trauma, Ceftriaxone 2g IV q12h Meropenem 2g IV q8h Chloramphenicol 1-1.5g IV q6h
every 6-12h
neuro surgery or CSF cefotaxime 2g IV every 4-6 hrs
Alternative; OR OR Herpes simplex
shunt: OR Or meningoencephalitis
Cefepime 2g IV q8h Fluoroquinolone Fluoroquinolone
Vancomycin + cefepime / Ceftriaxone 2g IV q12h Meropenem Acyclovir 10 mg/kg IV q8h
OR    
ceftazidime/ meropenem Alternative:  
Meropenem 2g IV q8h      
Moxifloxacin 400mg IV q24h  
     
 

 
 Dexamethasone as an Adjunctive
Treatment for Meningitis
◦ In addition to antibiotics, dexamethasone is a commonly used therapy for the treatment of pediatric meningitis.
◦ Current recommendations call for the use of adjunctive dexamethasone in infants and children with H. influenzae
meningitis.

◦ The recommended IV dose is 0.15 mg/kg every 6 hours for 2 to 4 days, initiated 10 to 20 minutes prior to or
concomitant with, but not after, the first dose of antimicrobials. Clinical outcome is unlikely to improve if
dexamethasone is given after the first dose of antimicrobial and should therefore be avoided.
◦ If adjunctive dexamethasone is used, careful monitoring of signs and symptoms of gastrointestinal (GI) bleeding
and hyperglycemia should be employed.
 ◦ Make a list of Gram positive and gram-negative
bacteria causing meningitis and common drugs
Assignment recommended as first line therapy for each.
◦ Also, find common side effects &
contraindications attached with these antibiotics.
 REFERENCES
• DiPiro, J. T. (2017). Pharmacotherapy handbook. 10th Edition. B. G. Wells, T. L. Schwinghammer, C. V. DiPiro, & M. H.
Education (Eds.). McGraw-Hill Medical.
• Cereberal cortex nervous system infections Notes, Osmosis.org Date accessed: 24-04-2022, URL: https://www.
osmosis.org/notes/Cerebral_cortex_nervous_system_infections#page-1
• Bacterial Meningitis Score for Children, MDCalc.com Date retrieved: 26-04-2022, URL: https://www.mdcalc.com/
bacterial-meningitis-score-children