Central Nervous System Infection

Transcription

1 Central Nervous System Infection Lingyun Shao Department of Infectious Diseases Huashan Hospital, Fudan University

2 Definition Meningitis: an inflammation of the arachnoid membrane, the pia mater, and the intervening cerebrospinal fluid (CSF). The inflammatory process extends throughout the subarachnoid space around the brain and spinal cord and involves the ventricles.

3 Anatomy

4 Meningies

5 1. Bacterial Meningitis (Purulent Meningitis) 化脓性脑膜炎

6 Definition Bacterial meningitis is usually an acute bacterial infection that evokes a polymorphonuclear response in CSF

7 Epidemiology & Etiology

8 Causes of bacterial meningitis in adults

9 ETIOLOGY OF BACTERIAL MENINGITIS BY AGE <1 month Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species 1-23 mos Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli 2-50 yrs N. meningitidis, S. pneumoniae >50 yrs S.pneumoniae, N. meningitidis, L. monocytogenes, gram-negative bacilli

10 ETIOLOGY OF BACTERIAL MENINGITIS BY PREDISPOSING CONDITION Immunocompromised state: S. pneumoniae, N. meningitidis, Listeria, aerobic GNR Basilar skull fracture: S. pneumoniae, H. influenzae, betahemolytic strep group A Head trauma or post-neurosurgery: S. aureus, S. epidermidis, aerobic GNR CSF shunt: S. epidermidis, S. aureus, aerobic GNR, Propionibacterium acnes

11 Pathogenesis

12 Routes for bacterial invasion of the meninges

13 Pathogenesis Organism Neisseria meningitidis Streptococcus pneumoniae Listeria monocytogenes Haemophilus influenzae Staphylococcus aureus Staphylococcus epidermidis Nasopharynx Nasopharynx or direct extension across skull fracture (cerebrospinal rhinorrhea) GI tract, placenta Nasopharynx Site of entry Bacteremia, skin, or foreign body Skin or foreign body

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15 Brain with inflammatory exudate covering the cortical hemispheres in purulent meningitis.

16 Pathology Bacterial Meningitis: Infection of the pia mater and arachnoid, the subarachnoid space, the ventricular system, and the CSF Infectious agents: Meningococcus (Neisseria meningitidis) pneumococcus (streptococcus pneumoniae) URI---blood borne---cns entry Inflammatory response by meninges, CSF, ventricles Neutrophils migrate producing exudate that plugs off CSF flow around the brain and spinal cord

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18 Clinical manifestations

19 Symptoms Acute-onset fever Generalized headache Vomiting An antecedent or accompanying upper respiratory tract infection or nonspecific febrile illness, acute otitis, or pneumonia The illness usually progresses rapidly, with the development of confusion, obtundation, and loss of consciousness

20 Physical signs Stiff neck Kernig s sign Brudzinski s sign

21 a combination of two of four symptoms is found in 95% of patients Headache Fever stiff neck altered mental status

22 Initial symptoms and signs Symptoms or signs Relative frequency Headache 90% Fever 90% Meningismus 85% Altered sensorium >80% Kernig s or Brudzinski signs 50% Focal findings 10-20%

23 Neurologic Findings Cranial nerve abnormalities the third, fourth, sixth, or seventh nerve Increased CSF pressure is associated with seizures, vomiting, sixth and third nerve dysfunction, abnormal reflexes

24 Diagnosis

25 CONFIRMATION OF SUSPECTED BACTERIAL MENINGITIS Lumbar puncture ASAP If LP has to be delayed for any reason, send blood culture and start empiric antibiotics Who should undergo CT prior to lumbar puncture?

26 Who should undergo CT prior to lumbar puncture? Criterion Immunocompromised state History of CNS disease New onset seizure Papilledema Abnormal level of consciousness Comment HIV infection or AIDS, receiving immunosuppressive therapy, or after transplantation Mass lesion, stroke, or focal infection Within 1 week of presentation; some authorities would not perform a lumbar puncture on patients with prolonged seizures or would delay lumbar puncture for 30 min in patients with short, convulsive seizures Presence of venous pulsations suggests absence of increased intracranial pressure Focal neurologic deficit Including dilated nonreactive pupil, abnormalities of ocular motility, abnormal visual fields, gaze palsy, arm or leg drift...

27 DIAGNOSIS - CSF Examination Typical CSF in Patients with Bacterial Meningitis Opening pressure mmh 2 O White blood cell count /μL Neutrophils >80% Protein >1000 mg/l Glucose <400mg/L CSF/serum glu ratio <0.4 Gram stain Positive in 50-80% Culture Positive in ~85%

28 CSF Profiles in Central Nervous System Infections

29 Special Testing Procedures PCR: Broad-range PCR with CSF in patients: antimicrobial therapy was begun before lumbar puncture when cultures are negative and a bacterial origin is still suspected Specific real-time PCR Latex agglutination test

30 Differential Diagnosis Viral meningitis, tuberculous meningitis Acute subarachnoid hemorrhage

31 Treatment

32 PRINCIPLES OF TREATMENT Prompt initiation of treatment. Bactericidal agents, with adequate CSF levels. Empiric Rx (based on age and predisposing factors) Specific Rx (based on Gram-stain or antigen). Include steroids where indicated

33 EMPIRIC THERAPY Patient s Age Common pathogens Antimicrobial therapy <1 month Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species 1-23 mos Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli 2-50 yrs N. meningitidis, S. pneumoniae >50 yrs S.pneumoniae, N. meningitidis L. monocytogenes, aerobic gram-negative bacilli Ampicillin plus cefotaxime Vancomycin plus a third-generation cephalosporin Vancomycin plus a third-generation cephalosporin Vancomycin plus ampicillin plus a third-generation cephalosporin

34 Predisposing factor Basilar skull fracture Common pathogens S. pneumoniae, H. influenzae, group A -hemolytic streptococci EMPIRIC THERAPY Antimicrobial therapy Vancomycin plus a thirdgeneration cephalosporin Penetrating trauma Postneurosurgery CSF shunt Staphylococcus aureus, coagulasenegative staphylococci (especially Staphylococcus epidermidis), aerobic gram-negative bacilli (including Pseudomonas aeruginosa) Aerobic gram-negative bacilli (including P. aeruginosa), S. aureus, coagulase-negative staphylococci (especially S. epidermidis) Coagulase-negative staphylococci (especially S. epidermidis), S. aureus, aerobic gram-negative bacilli (including P. aeruginosa), Propionibacterium acnes Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem

35 SPECIFIC-RX

36 Microorganism Duration of therapy (days) Neisseria meningitidis 7 Haemophilus influenzae 7 Streptococcus pneumoniae Streptococcus agalactiae Gram-negative bacilli >21 Listeria monocytogenes 21

37 ROLE OF STEROIDS Decrease subarachnoid space inflammatory response to abx-induced bacterial lysis Significant reduction in deafness in pediatric H. influenzae & pneumococcal meningitis In adults, reasonable to use steroids: for pts with evidence of cerebral edema. for adult with pneumococcal meningitis

38 Use of Adjunctive Dexamethasone Therapy in Adults with Bacterial Meningitis In suspected or proven pneumococcal meningitis cases. Dexamethasone should only be continued if the CSF Gram stain reveals grampositive diplococci, or if blood or CSF cultures are positive for S. pneumoniae. Adjunctive dexamethasone should not be given to adult patients who have already received antimicrobial therapy, because administration of dexamethasone in this circumstance is unlikely to improve patient outcome. Addition of rifampin to the empirical combination of vancomycin plus a thirdgeneration cephalosporin may be reasonable pending culture results and in vitro susceptibility testing, in patients with suspected pneumococcal meningitis who receive adjunctive dexamethasone.

39 Use of Adjunctive Dexamethasone Therapy in Pediatric Patients with Bacterial Meningitis Infants and Children Use in H. influenzae type b meningitis. For pneumococcal meningitis, controversial. Neonates Insufficient data to make a recommendation on the use of adjunctive dexamethasone. CID 2004;39:

40 Prognosis Prompt treatment of bacterial meningitis usually results in rapid recovery of neurologic function The mortality rate for community-acquired bacterial meningitis in adults varies With current antimicrobial therapy, the mortality rate for H. influenzae meningitis is less than 5% meningococcal meningitis is approximately 10% pneumococcal meningitis is approximately 20% L. monocytogenes meningitis 20 to 30%

41 Prevention

42 Vaccination Hib vaccine. Has had major impact in incidence of pediatric Hib meningitis Pneumococcal vaccine. For chronically ill and elderly, & now universal use in children. PCV-7. Use of PCV-7 for children has been an effective means of preventing disease in older adults (JAMA. Vol. 294 No. 16, October 26, 2005 ) Meningococcal vaccine Effective vs serotype A, C, Y, W135 Major reduction of disease in military recruits Recommended for travelers to endemic areas. Offered to college students, specially those residing in dormitory A new quadrivalent vaccine (Menactra) was recently approved.

43 Summary Headache, fever, stiff neck, confusion, vomiting are typical clinical manifestations of purulent meningitis Findings on CSF analysis are strikingly abnormal Antimicrobial therapy should be initiated promptly in this life-threatening emergency

44 2. Viral Meningitis 病毒性脑膜炎

45 Definition Viral meningitis is caused primarily by the non-polio enteroviruses, echoviruses, and coxsackieviruses In temperate climates, infections occur mainly in the warmer months of the year, usually during the summer and early fall In tropical climates, the infection occurs year round

46 Primary clinical manifestations Fever, headache and photophobia, stiff neck No loss of consciousness Conjunctivitis, maculopapular rash, and occasionally with echovirus, petechial rash Epstein Barr virus and cytomegalovirus

47 CSF Profiles in Central Nervous System Infections

48 Special Testing Procedures Polymerase chain reaction (PCR) for HSV-1 and HSV-2 in Enterovirus PCR

49 Treatment Mainly observation Symptomatic treatment: e.g. 20% mannitol Administer antibiotics if CSF contains PMNs Self-limiting disease, lasts 7 to 10 days

50 THANKS!