1. Drugs used in Meningitis Prof. M. Alhumayyd

2. Objectives At the end of the lecture , students should :
Describe briefly common types of meningitis
Describe the principles of treatment
List the name of antibiotics used for treatment of meningitis
Describe the mechanism of action & adverse effects of the individual drugs

3. Definition
Meningitis is an inflammation of the protective membranes covering the brain and the spinal cord (meninges).

4. Causes Infectious Non-infectious Viruses Bacteria
e.g,spread of cancer to meninges(malignant meningitis),etc.

5. Bacterial meningitis Is a serious , life threatening disease.
May lead to serious long –term consequences (e.g. deafness, epilepsy, limb loss,hydrocephalus & cognitive deficits).

6. CAUSES OF BACTERIAL MENINGITIS
Neisseria meningitidis**
Streptococcus pneumoniae**
Haemophilus influenzae
Staphylococcus aureus
Pseudomonas aeruginosae
Listeria monocytogenes
Mycobacterium tuberculosis(tuberculous meningitis)

7. SYMPTOMS OF BACTRIAL MENINGITIS
High fever*
Severe headache*
Stiff neck*
Irritability
Seizures
Vomiting

8. Treatment of Meningitis
Antibiotics
Antibiotic selected must penetrate adequately into the CSF.
Regimen chosen must have potent activity against known or suspected pathogens & exert a bactericidal effect.(Empiric?)

9. Carbapenems ( Imipenem )
Antibiotics for Treatment of Bacterial Meningitis 1.Inhibitors of cell wall synthesis (β-Lactams)
PENICILLINS
Cephalosporins
Carbapenems ( Imipenem )

10. Penicillins Mechanism of action
Inhibit bacterial cell wall synthesis by inhibiting the peptidoglycan layer of bacterial cell wall (bactericidal).

11. Narrow Spectrum Penicillin
Penicillin G
Narrow spectrum
Destroyed by gastric acidity
Inactivated by β- lactamase
Short acting ( 4-6 hrs )

12. Are acid stable (effective orally ).
Extended Spectrum Penicillins
(Amoxicillin, Ampicillin)
Effective against G⁺ & G¯ bacteria.
Inactivated by β- lactamase enzyme(given with β-lactamase inhibitors, Clavulanic acid and salbactam)
Are acid stable (effective orally ).
Can also be given parenterally (I.V or I.M)
Amoxicillin is better absorbed from the gut & not affected by food.

13. Adverse effects of penicillins
Hypersen-sitivity
Diarrhea
Nephritis
Neurotoxi-city

14. Cephalosporins 3rd generation Ceftriaxone
Both of them are given by intravenous infusion
Ceftazidime
Ceftriaxone

15. Mechanism of action
Inhibit bacterial cell wall synthesis

16. Bacterial Spectrum of 3rd Generation Cephalosporins
Highly effective against Gm –ve bacilli
Pseudomonas ( ceftazidime)
Highly resistant to β- lactamase

17. Adverse effects Allergy Thrombophl-ebitis Superinfect-ions
Renal toxicity
Superinfect-ions

18. Carbapenems Imipenem/cilastatin
Inhibits bacterial cell wall synthesis(bactericidal).
Has a wide spectrum of activity(aerobic & anaerobic G⁺ & G¯ bacteria, including pseudomonads)
Resistant to most β lactamases

19. Pharmacokinetics Not absorbed orally, taken by I.V.
Inactivated by dehydropeptidases in renal tubules, so it is given with an inhibitor cilastatin for clinical use.
Penetrates body tissues and fluids including C.S.F.

20. Adverse effects Nausea, vomiting, diarrhea
Skin rash and reaction at the site of infusion
High doses may cause seizure in patients with renal failure
Patients allergic to penicillins may be allergic to carbapenems .

21. Other inhibitor of cell wall synthesis

22. Vancomycin Bactericidal Cell wall inhibitor Poorly absorbed orally
Given intravenously

23. Vancomycin Active only against Gm⁺ ve bacteria
Used in combination with3rd generation cephalosporins for treatment of meningitis caused by penicillin resistant pneumococci.
Used against Methicillin resistant S. aureus (MRSA).
May be combined with ampicillin or ceftazidime as an initial therapy of meningitis in infant, elderly and immunocompromised patients .

24. Adverse Effects Phlebitis at site of injection Ototoxicity
Nephrotoxicity
Histamine release (flushing of upper body) [red man ( red neck ) syndrome] and hypotension (minimized if injected slowly).

25. Prevention better than cure
Haemophilus influenzae type b (Hib) bacterium, a leading cause of bacterial meningitis in children.
Pneumococcal polysaccharide vaccine (PPSV) Protects against meningitis caused by S. pneumoniae in children and adults.
Meningococcal conjugate vaccine
people going to Hajj.