pharmacotheraputics-II

1. MENINGITIS

2. ⮞ Infection predominantly involves the subarachnoid space---
MENINGITIS.
⮞ Brain tissue directly involved is called as ENCEPHALITIS.
⮞ Focal bacterial,fungal,parasitic infection involving brain tissue –
CEREBRITIS –absence of capsule,ABSCESS presence of
capsule.
⮞ Nuchal rigidity (STIFF NECK ) – pathognomonic sign of
meningeal irritation-resistance to passive flexion.
⮞ Classical signs of meningeal irritation –
KERNIG’S,BRUDZINSKI’S sign.

3. ⮞ MENINGISM :the symptoms and signs of meningeal irritation
assosciated with acute febrile illness or dehydration without actual
infection of the meninges…also called
meningismus…PSEUDOMENINGITIS.

4. ⮞ Immunocompromised
⮞ Very young or elderly.
⮞ Severely depressed mental state.
⮞ False positive – cervical spine disease..

5. ⮞ It is an emergency.
⮞ Empirical antibiotics to be started.
⮞ Do CT scan/MRI in case of immunocompromised,recent head
trauma,focal neurological deficits ---LP – but AB not to be
delayed.
⮞ No depressed level of consciousness –think of viral meningitis.
⮞ Immunocompetent ,consciousness good –can be treated on
OP basis.
⮞ Failure of a patient to improve < 48 hrs – reevaluate the
patient,repeat LP ,lab studies and neurological examination.

7. ⮞ It is an acute purulent infection within the subarachnoid space.
⮞
CNS INFLAMMATION
SEIZURES
INTRACRANI
AL
PRESSURE
STROKE
CONSCIOUSNESS

8. ⮞ Most common orgnaisms responsible for community
acquired bacterial meningitis
⮞ S.pneumoniae 50%
⮞ N.meningitidis 25%
⮞ Group B streptococci - 15%
⮞ Listeria monocytogenes 10%
⮞ Hemophilus influenzae 10%

10. Fever
Headache
Neck stifness

11. ⮞ PNEUMOCOCCAL –
 from pneumonia,otitis
media,alcoholism,diabetes,splenectomy,hypogammaglobu
linemia,complement deficiency,head trauma.
 20% mortality depsite antimicrobial Rx.
⮞ N.meningitidis -25% of all cases.
 Petechiae or purpuric skin rash.
 Fulminant –death within hours
⮞ ENTERIC gram negative – chronic debilitating diseases.
⮞ S.agalacticae -- >50 yrs of age.
⮞ L.monocytogenes –ingestion of food contaminated.

12. • ⮞ Invasive meningeal disease
• ⮞ Depends on bacterial virulence factor ,host immune
defense mechanisms
• ⮞ Deficiency of complement Highly susceptible
–asymptomatic carrier.

13. Bacteria
Colonize
Nasophrayngeal
epithelial cells
Intravascular
space
Polysaccharide
capsule
Avoids
phagocytosis
Intraventricular
Choroid plexus
Gain access
To CSF
Multiply,absence of
Immune defences
Inflammatory
reaction
Lysis of
bacteria,cyto
kines
TNF
,IL1
COMPLICATIONS

14. ⮞ Much of the pathophysiology is due to direct consequence of
chemokines,cytokines.
TNF
IL1
Vascular
permeabilitiy
Vasogenic
edema
Exudate in
CSF
Obstructive
hydrocephalus
Increased
Leukocyte adherence
Leakage into
CSF
Degranulation
of neutrophils
chemokines
Excitatory
Aminoacids
Death Of brain
cells

16. ⮞ Decreased level of consciousness >75%
⮞ Nausea,vomiting,photphobia common
⮞ Classical triad –less sensitivity
⮞ Only two may be present nearly in all cases.
⮞ Seizure –initial presentation in 20-40% cases
⮞ Focal –focal arterial ischemia,cortical venous
thrombosis,focal edema
⮞ GTCS– hyponatremia,anoxia,high dose penicillin.
⮞ RAISED ICP- >90 % have CSF pressure – 180mmH20
⮞ 20% -- 400mm H20
⮞ Rash of meningococcemia – diffuse,petechial;

17. ⮞ CSF analysis
⮞ Blood cultures
⮞ CT scan/MRI --- LP
⮞ Latex agglutination – S.pneumoniae,N.meningitidis
⮞ Lumulus lysate –gram negative
⮞ In case of immunocompetent,no h/o head trauma,no
evidence of papilledema –LP without CT scan
⮞ AB therapy to be started hrs before LP –no change in
analysis,or visualization of organisms

19. ⮞ CSF glucose may be zero –
⮞ CSF/serum glucose corrects for hyperglycemia
⮞ CSF/s.glucose < 0.6
⮞ CSF/s.glucose < 0.4 – bacterial, fungal, tuberculosis,
carcinomatosis
⮞ 30 min to several hours to reach equilbrium with blood glucose levels
–so can start 50 ml of 50 % D.
⮞ PCR –useful in pretreated pts,gram stain negative
⮞ MRI >CT for cerebral edema
⮞ Diffuse meningeal enhancement --gadolinium – increased
permeability of BBB.

21. ⮞ HSV mimics bacterial meningitis –differentiated by
CSF,EEG,neuroimaging.
⮞ RICKETTESIAL- rash—petechiae—necrosis—
gangrene,distal
⮞ Non infectious – SAH,Chemical meningitis
⮞ Uveomeningeal syndrome – VogtKoyangiHarada syndrome
⮞ Subacute –M.tuberculosis,c.noeformans,h.capsulatum

22. ⮞ BEGIN AB < 60 min
⮞ Empirical treatment –dexamethasone,cefotaxime or
ceftriaxone,vancomycin,azithromycin,acyclovir,doxycycline.
⮞ Post op cases –
ceftazidime,cefepime,meropenem,vancomycin
⮞ Then change according to culture reports

24. ⮞ PENICILLIN G is DOC
⮞ In case of resistance – Ceftriaxone,cefotaxime
⮞ Uncomplicated course--7 day course.
⮞ All close contacts should receive chemoprophylaxis – 2 day
regimen of rifampicin 600 mg every 12 hrs *
2days/ciprofloxacin 750 mg od/azithromyxin 500 mg
OD/ceftriaxone 250 mg OD
⮞ Who are close contacts --- nasopharyngeal
secretions,kissing,toys,beverages use.

25. ⮞ Cephalosporin plus vancomycin
⮞ If resistance – vancomycin
⮞ Rifampin can be added synergistic action
⮞ 2 week course
⮞ Repeat LP after 24-36 hrs –sterilization of CSF –if not
introventricular vancomycin

26. ⮞ Ampicillin for 3 weeks
⮞ Gentamicin 2mg/kg/d loading – 7.5 mg/kg/d every 8hrs
⮞ TMP SMX –every 6hrs
⮞ STAPHYLOCOCCAL –vancomycin
⮞ Gram negative – 3 weeks of third generation
cephalosporin.

28. ⮞ Dexamethasone – decreases synthesis of IL1,TNF,stabilises
BBB
⮞ 20 min before AB Rx
⮞ Inhibits TNF production by macrophages only before
activated by endotoxin.
⮞ Decreases penetration of vancomycin into CSF.
⮞ 10 mg IV 30 min before AB every 6hrs -4 days.

29. ⮞ Elevate head end of bed 30-45
⮞ Intubation
⮞ Hyperventilation PaCo2 – 25-30 mm Hg
⮞ mannitol

30. ⮞ 20% mortality –pneumococcal
⮞ 15% - listerias
⮞ 3-7% h.infleunzae,gram negative.

31. ⮞ Decreased level of consciousness at admission
⮞ Seziures < 24 hrs of onset
⮞ Raised ICP
⮞ Young age,>50 yrs
⮞ Mechanical ventilation
⮞ Delay in treatment
⮞ <40 mg /dl -glucose
⮞ >300 mg/dl -protein