Meningitis drug treatment

Useful for Interns and Post graduates.
Doses of drugs referred from Harrison textbook of internal medicine

1. PHARMACO THERAPY OF MENINGITIS

2. BACTERIAL MENINGITIS Causative organism: Streptococcus pneumoniae ,  Neisseria meningitidis ,  Haemophilus influenzae  type b ( Hib ), group B  Streptococcus ,  Listeria monocytogenes

3. Empirical therapy for Bacterial meningitis

4. ANTIBIOTIC THERAPY BASED ON SPECIFIC PATHOGENS

5. Pathogenic bacilli ANTIBIOTICS DOSAGE DURATION Streptococci pneumoniae Penicillin-G 20-24 million units/day i.v . 4 th hourly 10-14 days Pn resistant Ceftriaxone Cefotaxime Cefepime Vancomycin 4 gms /day i.v . BD 12 gms /day i.v .4 th hrly 6 gms /day i.v.8 th hrly 2 gms /day iv BD Neisseria meningitidis Pn -G Ceftriaxone Cefotaxime 7 days Haemophilus influenzae Ceftriaxone Cefotaxime Cefepime 7 days

6. Listeria Monocytogenes Ampicillin Sulfamethoxazole And trimethoprim 12 gm/day iv 4 th hrly 50-100 mg/kg/day 6 th hrly 10-20 mg/kg/day 3 weeks Gram negative bailli Ceftriaxone cefotaxime 3 weeks Pseudomonas Cetazidime Cefepime Meropenam 6 gm/day 8 th hrly 6 gm/day 8 th hrly 3 gm/day 8 th hrly 3 weeks Staphylococci epidermidis Vancomycin Linezolid 2 gms /day iv BD 21 days

7. Dexamethasone 0.15 mg/kg every 6 hours for 2-4 days adjunctive treatment for bacterial meningitis improves outcome by attenuating the detrimental effects of host defenses ( eg , inflammatory response to the bacterial products and the products of neutrophil activation).

8. Intrathecal antibiotics Considered in patients with nosocomial meningitis ( eg , meningitis developing after neurosurgery or placement of an external ventricular catheter) that does not respond to IV antibiotics.  Daily doses: Vancomycin : 5-20 mg Gentamicin : 1-2 mg in infants and children, 4–8 mg in adults Amikacin : 30 mg 

9. Mechanism of Action  Interferes with bacterial cell wall synthesis PEPTIDOGLYCAN LAYER N- ACETYL MURAMIC ACID (NAM) N- ACETYL GLUCOSAMINE (NAG) AMINO ACID CHAINS

10. β- Lactam Antibiotic X - Inhibition of cross (P -l e i n n ic k il i l n in g ) PENICILLIN BINDING PROTEINS (PBPs) (ANIM A T I ON)

11. Mechanism of Action Cross-linking is blocked by: X - cleavage of terminal D-alanine X - transpeptidation of 5- glycine chain residues Inhibiting cell wall synthesis DAMAGES cell High osmotic pressure inside cell and low osmotic pressure outside causes cell to BURST due to a weak and unstable cell wall Bactericidal

12. Resistance to penicillin Inactivation of β lactam ring by β lactamases . Modification of penicillin binding proteins(PBP) Reduction of peniillin permeability to reach PBP: Pseudomonas aeruginosa block penicillin transfer across outer membrane via porin mutants.

13. Hypersensitivity- rash, itching, urticaria, fever wheezing, angioneurotic edema, serum sickness, exfoliative dermatitis (less common) Anaphylaxis (rare, but fatal)

14. Adverse Effects Superinfections Rare with PnG Bowel, respiratory and cutaneous microflora can undergo changes Jarisch- Herxheimer Reaction Shivering, fever, myalgia, exacerbation of lesions, vascular collapse Seen in syphilitic patients injected with Penicillin Due to sudden release of spirochetal lytic products Symptomatic treatment with aspirin and sedation

15. Vancomycin Glycopeptide antibiotic Active against MRSA , enterococci,clostridium difficile,C.tetani,Listeria and Bacillus anthracis . Effective against Gram positive bacteria .

16. Mechanism of Action of Vancomycin Vancomycin binds to the D-alanyl-D-alanine dipeptide on the peptide side chain of newly synthesized peptidoglycan subunits, preventing them from being incorporated into the cell wall by penicillin-binding proteins (PBPs). In many vancomycin-resistant strains of enterococci, the D-alanyl-D-alanine dipeptide is replaced with D-alanyl-D-lactate, which is not recognized by vancomycin. Thus, the peptidoglycan subunit is appropriately incorporated into the cell wall.

17. Adverse effects Nephrotoxic . Concentration dependant nerve deafness. Red man syndrome: Rapid i.v injection cause chills,fever,urticaria and intense flushing.(release histamine by action on mast cells)

18. Linezolid Oxazolidinones . Active against MRSA,VRSA,VRE ,penicillin resistant str.pyogenes,M.tuberculosis,listeria,clos tridia and Bacillus anthracis . Linezolid is a MAO inhibitor,interactions with SSRI Iis expected.

19. Mechanism of action Linezolid inhibits bacterial protein synthesis. It binds to 23 S fraction (P site) of 50 S ribosome and interfere with formation of t RNA -70 S initiation complex. Stops protein synthesis before it starts. Resistance: Mutation of 23 S ribosomal RNA.

20. VIRAL MENINGITIS

21. Herpes simplex meningitis Seriously ill patients - receive IV acyclovir (15–30 mg/kg per day tds ), followed by an oral drug acyclovir (800 mg, five times daily) or valacyclovir (1000 mg tid ) for 7–14 days. Patients with HIV meningitis should receive highly active antiretroviral therapy.

22. Cytomegalovirus meningitis Ganciclovir is given in an induction dosage of 5 mg/kg IV every 12 hours and a maintenance dosage of 5 mg/kg every 24 hours - 21 days Foscarnet is given in an induction dosage of 60 mg/kg IV every 8 hours and a maintenance dosage of 90-120 mg/kg IV every 24 hours - 21 days

23. ACYCLOVIR

24. Adverse effects Acylovir Oral: headache,nausea,malaise , cns effects. IV: rashes,sweating,emesis and fall in B.P. Reversible neurological manifestations ( tremor,lethargy,haallucination,convulsions and coma) ascribed to high doses. Ganciclovir Bonemarrow suppression,fever,rash,vomiting,neuropsychiatric disturbances.

25. Fungal meningitis causes Cryptococcus C immitis H capsulatum Candida  species S schenckii  (rarely)

26. Cryptococcal meningitis For initial therapy in these cases, amphotericin B (0.7-1 mg/kg/day IV) for at least 2 weeks, with flucytosine (100 mg/kg orally) in 4 divided doses. Coccidioides immitis The preferred treatment for meningitis caused by  C immitis  is oral fluconazole (400 mg/day). Candidial meningitis amphotericin B (0.7 mg/kg/day). Flucytosine (25 mg/kg every 6 hours) is usually added. treatment is continued for a minimum of 4 weeks after the complete resolution of symptoms .  

27. H capsulatum  meningitis Liposomal amphotericin B (5 mg/kg/day iv over 4-6 weeks), followed by oral itraconazole (200-300 mg 2 or 3 times daily for at least 1 year. Sporothrix schenckii Amphotericin B itraconazole (200 mg twice daily) is recommended as step-down therapy  -12 months of therapy.

28. AMPHOTERICIN B Mechanism of action It binds to fungal cell membrane sterol and alters the permeability of fungal cell membrane by forming pores Na, k,Mg ,H leak out cell death

29. FLUCONAZOLE

30. FLUCYTOSINE

31. Uses Cryptococcosis –synergistic action with amphotericin B,Candidiasis Cromoblastomycosis Adverse effects GIT effects Bone marrow depression

32. TUBERCULAR MENINGITIS TREATMENT

33. Neuro syphilis Treatment: Penicillin G I8-24 million units i.v . Daily ( 4 th hrly ) for 10-14 days often followed with IM penicillin G benzathine (2.4 million U).  Lyme Meningitis Borrelia burgdorferi Treatment: Ceftriaxone (2 g/day for 14-28 days). The alternative therapy is penicillin G (20 million U/day for 14-28 days). 

34. THANK YOU