1. Meningitis

2. Bacterial Viral ( aseptic) TB Fungal Chemical Parasitic ? Carcinomatous

3. Meningitis Definition –Bacterial meningitis is an inflammatory response to bacterial infection of the pia- arachnoid and CSF of the subarachnoid space Epidemiology –Incidence is between 3-5 per 100,000 –More than 2,000 deaths annually in the U.S. –Relative frequency of bacterial species varies with age.

4. Meningitis Epidemiology –Neonates (< 1 Month) Gm (-) bacilli 50-60% Grp B Strep 20-40% Listeria sp. 2-10% H. influenza 0-3% S. pneumo 0-5%

5. Meningitis Epidemiology –Children (1 month to 15 years) H. influenzae40-60% –Declining dramatically in many geographic regions N. meningitidis25-40% S. pneumo10-20%

6. Meningitis Epidemiology –Adults (> 15 years) S. pneumo30-50% N. Meningitidis10-35% –Major cause in epidemics Gm (-) Bacilli1-10% –Elderly S. aureus5-15% H. influenzae1-3% –>60 include Listeria, E. coli, Pseudomonas

7. Meningitis Pathogenesis –Majority of cases are hematogenous in origin –Organisms have virulence factors that allow bypassing of normal defenses Proteases Polysaccharidases

8. Meningitis Pathology and Pathogenesis –Sequential steps allow the pathogen into the CSF Nasopharyngeal colonization Nasopharyngeal epithelial cell invasion Bloodstream invasion Bacteremia with intravascular survival Crossing of the BBB and entry into the CSF Survival and replication in the subarachnoid space

9. Meningitis Pathology –Hallmark Exudate in the subarachnoid space Accumulation of exudate in the dependent areas of the brain Large numbers of PMN’s Within 2-3 days inflammation in the walls of the small and medium-sized blood vessels Blockage of normal CSF pathways and blockage of the normal absorption may lead to obstructive hydrocephalus

10. Meningitis Clinical Manifestations –HA –Fever –Meningismus –Cerebral dysfunction Confusion, delirium, decreased level of consciousness –N/V –Photophobia

11. Meningitis Clinical Manifestations – Nuchal rigidity –Kernig’s Pt supine with flexed knee has increased pain with passive extension of the same leg –Brudzinski’s Supine pt with neck flexed will raise knees to take pressure off of the meninges Present in 50% of acute bacterial meningitis cases –Cranial Nerve Palsies IV, VI, VII –Seizures

12. Meningitis Clinical Manifestations - Meningococcemia –Prominent rash Diffuse purpuric lesions principally involving the extremities –Fever, hypotension, DIC –History of terminal complement deficiency –Classic findings often absent Neonates Elderly

13. Meningitis

14. Diagnosis –Assess for increased ICP Papilledema Focal neurologic findings –Defer LP until CT scan or MRI obtained if any of above present –If suspect meningitis and awaiting neuroimaging Obtain BC’s and start empiric Abx

15. Meningitis Papilledema

16. Obtain CT scan before lumbar puncture in patients with: Immunucompromised state History of CNS disease New onset seizures Papilledema Altered level of consciousness Focal neurologic signs

17. Obtain blood cultures and give empiric antibiotics if LP is delayed

18. LP-CSF Tube # 1 Protein & Glucose Tube # 2 Gram stain & Culture Tube # 3 Cell count & differential Tube # 4 Store ( PCR, viral studies etc)

19. Meningitis Diagnosis –CSF Findings : Opening pressure Appearance Cell count & differential Glucose Protein Gram stain & culture

20. Opening pressure: high, > 200 mmH20 Cloudy 1000-5000 cells/mm3 with a neutrophil predominance of about 80-95% <40mg/dl and less than 2/3 of the serum glucose Protein elevated

22. Meningitis Diagnosis –Rapid Tests CIE (Counter immunoelectrophoresis/ latex agglut.) PCR –CT/MRI Little role in DIAGNOSIS of menigitis Obtain if suspect increased ICP

23. Meningitis Diagnosis –Additional Tests CBC w/ diff Blood cultures CXR Electrolytes and renal function

24. Meningitis Differential Diagnosis –CNS infections (abscess, encephalitis) –Viral/ Tb/ Lyme meningitis –Ricketsial infections –Cerebral vasculitis –Subarachnoid hemorrhage –Neurosyphilis

25. Meningitis Treatment –Emergent empirical antimicrobial therapy Based on age and underlying disease status –Empiric antibiotic regimines Neonates (<3 months) –Ampicillin plus a third generation cephalosporin Children –Third generation cephalosporin ( alternative -ampicillin and chloramphenicol) Young adults –Third generation cephalosporin (Ceftriaxone) + Vancomycin

26. Meningitis Treatment –Empiric Antibiotic Regimines Older adults –Ampicillin in combination with third generation ceph. Postneurosurgical Pt’s –Vancomycin plus ceftazidime until cultures are available

28. Meningitis Treatment –N. Meningitidis High dose Pen G –S. pneumoniae Ceftriaxone For areas with high level resistance –Vancomycin plus third generation cephalosporin or rifampin

29. Meningitis Treatment –Gm (-) Enterics Third generation cephalosporins –L. monocytogenes Ampicillin –S. aureus Vancomycin or Nafcillin –S. epidermidis Vancomycin

30. Meningitis Treatment –Duration of Treatment Dependent on infecting organism –Average of 10-14 days –Gm (-) bacilli for 3 weeks

31. Meningitis Treatment –Steroids –Shortly before or along with antibiotics. Do not give steroids after antibiotic treatment. –de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347:1549-56.

32. Meningitis Prognosis –Pneumococcal Meningitis Associated with the highest mortality rate –20-30% Permanent neurologic sequelae –1/3 of pts –Hearing loss –Mental retardation –Seizures –Cerebral Palsy

33. Meningitis Vaccinations –Asplenic pts should have had a pneumoccocal vaccine prior to their splenectomy –Vaccines available for H. influenza –Prophylaxis for N. meningitidis contacts Rifampin

34. Meningitis Conclusion –Meningitis is an infectious disease emergency –Mortality is often high but can be prevented with appropriate medical therapy –If you consider meningitis in your differential, you are committed to an LP and empiric antibiotics