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

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 MURAMICACID
(NAM)
N- ACETYL GLUCOSAMINE
(NAG)
AMINO ACID CHAINS

10. β- Lactam Antibiotic
X - Inhibition of cross(P-leinnickililning)
PENICILLIN BINDING PROTEINS
(PBPs)
(ANIMATION)

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

31. FLUCONAZOLE

32. FLUCYTOSINE

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

34. TUBERCULAR MENINGITIS TREATMENT

35. 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).

36. THANK YOU