central nervous system infection - fudan...
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Central Nervous System Infection
Lingyun Shao Department of Infectious Diseases
Huashan Hospital, Fudan University
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.
Anatomy
Meningies
1. Bacterial Meningitis (Purulent Meningitis)
化脓性脑膜炎
Definition
• Bacterial meningitis is usually an acute bacterial infection that evokes a polymorphonuclear response in CSF
Epidemiology & Etiology
Causes of bacterial meningitis in adults
<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
ETIOLOGY OF BACTERIAL MENINGITIS BY AGE
ETIOLOGY OF BACTERIAL MENINGITIS BY PREDISPOSING CONDITION
Immunocompromised state: S. pneumoniae, N. meningitidis, Listeria, aerobic GNR
Basilar skull fracture: S. pneumoniae, H. influenzae, beta-hemolytic strep group A
Head trauma or post-neurosurgery: S. aureus, S. epidermidis, aerobic GNR
CSF shunt: S. epidermidis, S. aureus, aerobic GNR, Propionibacterium acnes
Pathogenesis
Routes for bacterial invasion of the meninges
Neisseria meningitidis Nasopharynx
Streptococcus pneumoniae Nasopharynx or direct extension across skull fracture (cerebrospinal rhinorrhea)
Listeria monocytogenes GI tract, placenta
Haemophilus influenzae Nasopharynx
Staphylococcus aureus Bacteremia, skin, or foreign body
Staphylococcus epidermidis Skin or foreign body
Organism Site of entry
Pathogenesis
Brain with inflammatory exudate covering the cortical hemispheres in purulent meningitis.
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
Clinical manifestations
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
Physical signs
• Stiff neck • Kernig’s sign • Brudzinski’s sign
• a combination of two of four symptoms is found in 95% of patients – Headache – Fever – stiff neck – altered mental status
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%
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
Diagnosis
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?
Who should undergo CT prior to lumbar puncture?
Criterion Comment Immunocompromised state
HIV infection or AIDS, receiving immunosuppressive therapy, or after transplantation
History of CNS disease Mass lesion, stroke, or focal infection New onset seizure 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
Papilledema Presence of venous pulsations suggests absence of increased intracranial pressure
Abnormal level of consciousness
...
Focal neurologic deficit Including dilated nonreactive pupil, abnormalities of ocular motility, abnormal visual fields, gaze palsy, arm or leg drift
DIAGNOSIS - CSF Examination Typical CSF in Patients with Bacterial Meningitis
• Opening pressure 200-500 mmH2O • White blood cell count 1000-5000/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%
CSF Profiles in Central Nervous System Infections
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
Differential Diagnosis
• Viral meningitis, tuberculous meningitis • Acute subarachnoid hemorrhage
Treatment
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
EMPIRIC THERAPY Patient’s Age Common pathogens Antimicrobial therapy
<1 month Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species
Ampicillin plus cefotaxime
1 - 23 mos Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli
Vancomycin plus a third-generation cephalosporin
2 - 50 yrs N . meningitidis, S. pneumoniae
Vancomycin plus a third-generation cephalosporin
>50 yrs S.pneumoniae, N. meningitidis L. monocytogenes, aerobic gram-negative bacilli
Vancomycin plus ampicillin plus a third-generation cephalosporin
EMPIRIC THERAPY Predisposing factor
Common pathogens Antimicrobial therapy
Basilar skull fracture
S. pneumoniae, H. influenzae, group A -hemolytic streptococci
Vancomycin plus a third-generation cephalosporin
Penetrating trauma
Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic gram-negative bacilli (including Pseudomonas aeruginosa)
Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem
Post- neurosurgery
Aerobic gram-negative bacilli (including P. aeruginosa), S . aureus, coagulase-negative staphylococci (especially S. epidermidis)
Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem
CSF shunt 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
SPEC
IFIC
-RX
Microorganism Duration of
therapy (days)
Neisseria meningitidis
7
Haemophilus influenzae
7
Streptococcus pneumoniae
10-14
Streptococcus agalactiae
14-21
Gram-negative bacilli
>21
Listeria monocytogenes
21
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
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 gram-positive 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 third-generation cephalosporin may be reasonable pending culture results and in vitro susceptibility testing , in patients with suspected pneumococcal meningitis who receive adjunctive dexamethasone.
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.
Use of Adjunctive Dexamethasone Therapy in Pediatric Patients with Bacterial Meningitis
CID 2004;39:1267-1284
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%
Prevention
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.
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
2. Viral Meningitis 病毒性脑膜炎
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
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
CSF Profiles in Central Nervous System Infections
Special Testing Procedures
• Polymerase chain reaction (PCR) for HSV-1 and HSV-2 in
• Enterovirus PCR
Treatment
• Mainly observation
• Symptomatic treatment: e.g. 20% mannitol
• Administer antibiotics if CSF contains PMNs
• Self-limiting disease, lasts 7 to 10 days
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