Module: Pharmacology and Therapeutics III, (Therapeutics part) Coordinator: Dr. Arwa M. Amin Mostafa Academic Level: Undergraduate, B.Pharmacy School: Dubai Pharmacy College Year of first presented in Class: 2018 This presentation is for Educational purpose. It has no commercial value associated with it.

1. MENINGITIS
ARWA M. AMIN MOSTAFA
PHD, M.PHARM CLINICAL PHARM, DIP MANGT, B.PHARM.

2. Arwa M. Amin
WHAT WE WILL DISCUSS TODAY?
• What is Meningitis & Meninges?
• What is Encephalitis & Meningoencephalitis?
• What is CSF and what are the CSF functions?
• How does Meningitis infection spread?
• What is the pathogenesis of Meningitis?
• What are the common pathogens of Meningitis?
• What are the Complications of Meningitis?
• What are the risk factors of Meningitis?
• What are the Clinical Presentations of Meningitis?
• How to diagnose Meningitis?
• How to Manage Meningitis?
• How to Prevent Meningitis?

3. Arwa M. Amin
MENINGITIS
Meningitis is the inflammation of the Meninges (the membranes surrounding
the Brain and the Spinal Cord) usually due to infection. This includes the
Arachnoid Membrane, Subarachnoid Space, and Cerebrospinal Fluid (CSF).
• Meningitis may be caused by Viral, Bacterial, Fungal
or Parasite.
• Viral Meningitis is the Most Common Type.
• It is Less Severe than Bacterial Meningitis.
• Bacterial Meningitis is Severe and Deadly type of
Meningitis.
• It may progress to permanent Brain Damage,
Neurological Problems or Death.
• Fungal Meningitis: Very Rare and cause Chronic
Meningitis.
• Meningitis can be caused rarely by non-infectious
causes such as Cancer, Drug Reaction, and
Autoimmune Disease.

4. Arwa M. Amin
MENINGES
• Meninges consists of the Layers
membranes system which covers the
central nervous system (CNS).
• Meninges layers are the Dura mater,
the Arachnoid mater and the Pia mater.
• The Subarachnoid space which is
present between the Arachnoid mater
& Pia mater contains the cerebrospinal
fluid (CSF).

5. Arwa M. Amin
CSF & ITS FUNCTIONS
• The CSF is a clear and colorless body fluid which is produced by the Ependymal
Cells in the Choroid Plexuses of the Ventricles in the brain, and absorbed in the
Arachnoid granulations.
CSF Functions:
• Cushions the brain within the skull.
• CSF serves as Shock absorber for the CNS.
• Circulates Nutrients, Metabolites,
Neurotransmitters and Endocrine
substances filtered from the blood.
• Removes disposed waste products from the
brain.
• Serves as Chemical Buffer to maintain
constant ionic environment.

6. Arwa M. Amin
ENCEPHALITIS & MENINGOENCEPHALITIS
• Encephalitis is an acute inflammation of the brain due to infection.
• Encephalitis can be caused by the same infections that cause meningitis.
• Encephalitis has Milder symptoms than meningitis.
• Meningoencephalitis is an inflammation of both the Brain and the Meninges.

7. Arwa M. Amin
SPREAD OF MENINGITIS INFECTION
Bloodstream
Spread through
BBB from primary
infection site
Spread of Meningitis Infection
Airborne
Respiratory droplets
(Ears & Nasopharynx)
HematogenousHead trauma,
Neurosurgery
or Congenital
Meningeal defect
Food
Particularly, from Late
Spring to Fall; because
viruses causing
Meningitis Spread most
often during that time.
Listeria monocytogene
can spread through food
e.g. Meningomyelocele
BBB: Blood Brain Barrier

8. Arwa M. Amin
PATHOGENESIS OF MENINGITIS
Bacterial Meningitis starts
with a Nasopharyngeal
colonization by the
pathogenic bacterial
infection
Bacteria is
phagocytized into
the blood stream
In the CSF: Rapid
multiplication of the Bacteria
due to the availability of
Nutrients

9. Arwa M. Amin
PATHOGENESIS OF MENINGITIS
• When the infection invade the
CSF, an inflammatory response is
initiated by the immune system.
• The inflammation will lead to:
• Swelling of the brain tissues
• ↓↓ Blood flow to the vital areas
of the Brain.

10. Arwa M. Amin
Non-polio enteroviruses
COMMON PATHOGENS OF MENINGITIS
Viral Pathogens:
• Non-polio enteroviruses
• The most common virus
causing meningitis
• Other viruses:
• Mumps virus
• Herpes viruses
• Measles viruses
• Influenza virus
• Lymphocytic choriomeningitis
virus
Influenza virus
Mumps virus Herpes virus
Lymphocytic
choriomeningitis virus

11. Arwa M. Amin
COMMON PATHOGENS OF MENINGITIS
Bacterial Pathogens:
• Streptococcus pneumonia (G +)
• Common cause of Bacterial Meningitis
• Group B Streptococcus (GBS) (G +)
• Haemophilus Influenza (G -)
• Neisseria meningitidis (G -)
• Meningococcal Meningitis
• Listeria monocytogenes (G +)
• Mycobacterium tuberculosis
Neisseria meningitidis
Listeria monocytogenes

12. Arwa M. Amin
COMMON PATHOGENS OF MENINGITIS
Fungal Pathogens:
• Cryptococcus Neoformans
• Most often in HIV patients
• Coccidioides immitis
• Blastomyces dermatitidis
• Histoplasma Capsulatum
• Aspergillus Fumigatus
• Candida Albicans
• Sporothrix schenckii
Aspergillus Fumigatus

13. Arwa M. Amin
COMPLICATIONS OF MENINGITIS
• Cerebraledema
• Braindamage
• Brain Abscess
• Venous sinus thrombosis
• Hydrocephalus
• Septicemia
• HearinglossorDeafness
• Seizures
• MentalRetardation
• MultiorganFailure

14. Arwa M. Amin
RISK FACTORS OF MENINGITIS
• Age
• Children < 5 years (particularly < 2 years)
• Meningitis is severe in babies < 1 month
• Travel
• Sub-Saharan Africa, particularly during dry season
• Makah during Hajj & Umrah
• Large group communities (Schools, Campuses)
• Immunocompromised subjects
• Immunocompromised subjects also suffer severe
meningitis
• Passive & Active exposure to cigarette smoke
• Presence of Cochlear implant that includes a
positioner

15. Arwa M. Amin
RISK FACTORS OF MENINGITIS
• Age
• Children < 5 years (particularly < 2 years)
• Meningitis is severe in babies < 1 month
• Travel
• Sub-Saharan Africa, particularly during dry season
• Makah during Hajj & Umrah
• Large group communities (Schools, Campuses)
• Immunocompromised subjects
• Immunocompromised subjects also suffer severe
meningitis
• Passive & Active exposure to cigarette smoke
• Presence of Cochlear implant that includes a
positioner
↑↑ Risk of Bacterial
Meningitis

16. Arwa M. Amin
CLINICAL PRESENTATIONS OF MENINGITIS
Signs & Symptoms of Meningitis* in Adults:
• High Fever
• Severe Headache (not similar to usual headache)
• Drowsiness.
• Confusion
• Sleepiness
• Stiff neck
• Sensitivity to light
• Skin Rash
• Vomiting
• Loss of appetite
• Seizures (Less common)
Note*: Symptoms of Viral Meningitis are milder than Bacterial Meningitis

17. Arwa M. Amin
CLINICAL PRESENTATIONS OF MENINGITIS
Signs & Symptoms of Meningitis in Infants:
• High Fever
• Stiffness in babies body and neck.
• Inactivity or sluggishness
• Sleepiness or Irritability
• Poor feeding
• Constant Crying
• Bulging fontanel

18. Arwa M. Amin
CLINICAL PRESENTATIONS OF MENINGITIS

19. Kernig’s sign is one of the physically
demonstrable sign of meningitis. It is
demonstrated by placing the patient in Supine
position then flexing the hip to 90 degrees.
• Severe stiffness of the
hamstrings causes resistance to straighten
the leg when flexed to 90 degrees.
DIAGNOSIS OF MENINGITIS
Diagnosis:
Besides the signs & symptoms of Meningitis, nick stiffness is manifested by two
signs; Kernig’s and Brudzinski's signs
Kernig’s sign :
https://www.youtube.com/watch?v=rRZRhVflCvQ

20. DIAGNOSIS OF MENINGITIS
Brudzinski's neck sign is one of the physically
demonstrable sign of meningitis. It is
demonstrated by flexing the neck.
• Severe neck stiffness where the
Forward Flexion of the neck causes
involuntary flexion of the knee and hip.
Brudzinski's sign:
https://www.youtube.com/watch?v=LicL5tndjW0

21. Arwa M. Amin
DIAGNOSIS OF MENINGITIS
• Besides the Physical examination, Lumbar Puncture is
important to confirm the diagnosis of Meningitis and
identify the infecting pathogen.
• Lumbar Puncture has to be performed to obtain CSF
sample for laboratory assessment.
• CSF will be examined for pressure, gross visual
turbidity, cell count (RBCs, WBCs), glucose
concentration and protein concentration.
• Culture and gram stain of CSF

22. Arwa M. Amin
DIAGNOSIS OF MENINGITIS
• Contraindications of Lumbar Puncture:
• Increased intracranial pressure (ICP)
• Skin Infection near the puncture site
• Brain Abscess
• Acute Spinal cord trauma
• Deteriorating consciousness
• Coagulopathy
• Significant Cardiorespiratory compromise
• Thrombocytopenia (↓↓ platelets)

23. Arwa M. Amin
DIAGNOSIS OF MENINGITIS: CSF FINDINGS
Tuberculous
Meningitis
Fungal
Meningitis
Viral MeningitisBacterial
Meningitis
Normal CSFParameter
↑↑↑↑Normal↑↑< 150 mm H2OPressure
ClearClearClearCloudyClear/TransparentGross visual
turbidity
Pleocytosis*
Lymphocytes
Pleocytosis*
Lymphocytes
Pleocytosis*
Lymphocytes
Pleocytosis*
Neutrophils
2 - 4 mm3
Monocytes
WBCs count
Differential**
↓↓↓↓Normal↓↓45 – 80 mg/dL
(2/3 of serum)
Glucose conc.
↑↑↑↑slightly ↑↑↑15 – 50 mg/dLProtein conc.
AFSIISNA+ Bacterial
presence
NAGm stain/IIS***
AFS**** Bacterial
culture
*Pleocytosis: ↑↑ WBCs, **Differential: Predominant Cell type in Differential,***IIS: India Ink stain ****AFS: Acid fast staining

24. Arwa M. Amin
DIAGNOSIS OF MENINGITIS
• Polymerase Chain Reaction (PCR)
• To diagnose meningitis caused by Neisseria meningitidis,
Streptococcus pneumoniae, and Haemophilus influenzae.
• PCR of the CSF is used to indicate viral meningitis infections.
• Latex Fixation, Latex coagglutination, Enzyme Immunoassay
• Rapid identification of several bacterial causes of meningitis,
including Neisseria meningitidis, Streptococcus pneumoniae,
and Haemophilus influenzae.
• Cryptococcal Antigen Testing
• Indication of cryptococcosis.

25. Arwa M. Amin
DIAGNOSIS OF MENINGITIS
• Other Laboratory Tests:
• Blood Culture.
• CBC
• Inflammatory markers: ESR, CRP
• Blood Electrolytes: Na, K, why?
• Hyponatremia may happen in Bacterial Meningitis
• Head CT
• Chest X-Ray
• To look for signs of infection in the child’s lungs
CBC: Complete Blood Count, CT: Computed Tomography, CRP: C-Reactive Protein, ESR: Erythrocyte sedimentation rate

26. Arwa M. Amin
MANAGEMENT OF MENINGITIS
Meningitis, particularly Bacterial Meningitis requires Urgent and Fast Medical
Intervention.
 Goals of Meningitis Treatment:
To Provide Urgent Supportive Care and ameliorate Symptoms
To Eradicate Infection
Initiate appropriate Antimicrobial Therapy ASAP
To Prevent Meningitis Complications (Morbidity and Mortality)
ASAP: as soon as possible

27. Arwa M. Amin
MANAGEMENT OF MENINGITIS
AB: Antibiotics
Meningitis Management
Supportive &
Symptomatic
Adjunctive
TherapyAntimicrobial
• AB
• Antiviral
• Fluids & Electrolytes
• Antipyretics
• Analgesics
• Dexamethasone
• Mannitol
• Anticonvulsant
• Introducing AB
directly to CSF

28. Arwa M. Amin
MANAGEMENT OF MENINGITIS
Supportive Treatment:
Encourage Bed Rest
Reassure adequate oral fluids intake to treat dehydration
 Provide IV fluids if oral is not suitable
Provide Electrolytes (Na, K)
Symptomatic Treatment
 Antipyretic & Analgesics Therapy for fever & Headache
 Acetaminophen and/or Ibuprofen
 Avoid using Aspirin in Children

29. Arwa M. Amin
MANAGEMENT OF MENINGITIS
Factors affecting Antimicrobial selection for Meningitis:
 Age
 Infant? Child? Young adult? Old?
 Infecting Pathogen
 What is the suspected pathogen? is it Bacterial? Viral? Fungal? T.B.?
 Gm stain results
 Presence of Meningitis Complications and Concomitant Medical Conditions
 Penetration of the Antimicrobial agent through BBB to ensure adequate antimicrobial
concentration in the CSF.
 AB should be Bactericidal.
Antimicrobial Therapy for Meningitis

30. Arwa M. Amin
MANAGEMENT OF MENINGITIS
Management of Viral Meningitis:
 Viral Meningitis is Mild and Self Limiting.
 Symptoms improves within 7 – 10 days.
 Treatment should focus on Supportive and Symptomatic Treatment.
 AB does not treat Viral Meningitis, however, AB can be given until Bacterial
Meningitis is ruled out.
 Antiviral such as Acyclovir IV can be provided if Herpesvirus or Varicella
zoster are suspected.
 Follow-up, re-evaluate and assess improvement within 1-2 days.
AB: Antibiotics

31. Arwa M. Amin
MANAGEMENT OF MENINGITIS
Commonly used AB for Bacterial Meningitis
• 3rd generation Cephalosporins
• Activity against: Gm - > Gm +
• Active against pneumococci,
Haemophilus Influenza, Neisseria
Meningitidis & Gram negative
Bacilli
• Ceftriaxone IV 2 g q 12 h
• Cefotaxime IV 2 g q 4 - 6 h
• Penicillin G
• To cover penicillin sensitive
pneumococcal meningitis.
• 4 millions units q 4 h
CrCl: Creatinine Clearance
• Ampicillin
• To cover Listeria monocytogenes
• 2g IV Q 4 h
• Vancomycin
• 15 -20 mg/Kg q 8-12 h
• Indicated for:
• Patient with Resistant
staphylococci infection
• Patients who failed to respond
to penicillins and
cephalosporins

32. Arwa M. Amin
MANAGEMENT OF MENINGITIS
Empiric Antimicrobial Therapy for Bacterial Meningitis
Empiric AB TherapyMost Likely OrganismsAge
Ampicillin + Cefotaxime or
Ampicillin + Aminoglycoside
S. agalactiae, Gram-negative enterics
L. monocytogenes
< 1 month
Vancomycin + 3rd generation
Cephalosporin (Cefotaxime
or Ceftriaxone)
S. pneumoniae, N. meningitidis, H.
influenzae, S. agalactiae
1 – 23 months
Vancomycin + 3rd generation
cephalosporin (Cefotaxime
or Ceftriaxone)
N. meningitidis, S. pneumoniae2 – 50 years
Vancomycin + Ampicillin +
3rd generation Cephalosporin
(Cefotaxime or Ceftriaxone)
S. pneumoniae, N. meningitidis, Gram-
negative enterics, L. monocytogenes
> 50 years

33. Arwa M. Amin
MANAGEMENT OF MENINGITIS
Management of Fungal Meningitis:
 Fungal Meningitis causes Chronic Meningitis.
 Treatment is with long course of Antifungal:
 Amphotericin B, 0.7 to 1 mg/kg/day
Maintain adequate Hydration and monitor Renal Function
 Flucytosine, 25 mg/kg/q 6 h
Consider TDM to avoid bone marrow suppression
 Repeated Lumbar puncture or Lumbar drain are recommended to relief
the ↑↑ ICP.
TDM: Therapeutic Drug Monitoring, ICP: intracranial Pressure

34. Arwa M. Amin
MANAGEMENT OF MENINGITIS
Adjunctive Therapy for Meningitis
Steroids; Dexamethasone IV
• To reduce inflammatory response in bacterial meningitis.
• To decrease complications of bacterial meningitis such as cerebral edema
and elevated ICP.
• Should be initiated with the 1st dose of Antimicrobial or 10 to 20 minutes
prior to it but Not after it.
• Dose (0.15mg/Kg every 6 hours for 2 to 4 days)
Mannitol IV (1g/Kg)
• To reduce ICP
• To decrease Cerebral edema
Anticonvulsant or Sedative Therapy
• Phenytoin, Diazepam or Barbiturates
• To treat seizures if present
• To reduce restlessness ICP: Intracranial Pressure

35. Arwa M. Amin
PREVENTING MENINGITIS
• Ensure proper Meningitis Immunization
(Vaccination):
• Bacterial vaccines: Meningococcal Vaccines, Hib
Vaccine & Pneumococcal vaccine
• Viral Vaccines: Influenza vaccine, Varicella,
Measles & Mumps.
• Ensure Proper Hygiene.
• Wash your hands every time you go to public
places and Hospitals
• Disinfect frequently touched surfaces.

36. Arwa M. Amin
PREVENTING MENINGITIS
• Avoid sharing cups, drinks, lip stick and
personal utilities.
• Eat Healthy and avoid food prepared
uncleanly.
• Avoid Passive and active smoking
• Use masks in crowded spaces and cover
your face when you sneeze and cough.

37. Arwa M. Amin
PREVENTING MENINGITIS
• Chemoprophylaxis AB Therapy can be provided for Close contact (Intimate
contacts) with Neisseria Meningitidis infected Patient:
• Rifampin
• Ceftriaxone
• Ciprofloxacin
• Azithromycin

38. Arwa M. Amin