Suhail Allaqaband

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Acute Bacterial Meningitis

• Suhail Allaqaband
• Sinai Samaritan Medical Center
• Milwaukee, WI

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DEMOGRAPHY AND EPIDEMIOLOGY

• The highest incidence is among neonates, who are
  usually infected by bacteria found in the birth
  canal at the time of parturition.
• Group B streptococci (Streptococcus agalactiae)
  account for the majority of cases other causes
  include Listeria monocytogenes, E.coli, other
  Gram-negative bacilli, and enterococci.
• From age 1 to 23 months, the most common
  organisms are Streptococcus pneumoniae and
  Neisseria meningitidis

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• Children from the second to the fifth year used
  to have a high rate of infection caused by
  Haemophilus influenzae type b. However the wide
  use of protein-polysaccharide conjugated vaccines
  has dramatically reduced the incidence of this
  infection
• From age 2 through 18, N. meningitidis is the
  most common cause, accounting for more than
  one-half of cases, followed by S. pneumoniae
• In adults up to age 60, S. pneumoniae is most
  common followed by N. meningitis
• Over age 60, most cases are due to S. pneumoniae
  and less often L. monocytogenes

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Etiology - in Adults

• S. pneumoniae 30-50
• N. meningitidis 10-35
• H. influenzae 1-3
• G -ve bacilli 1-10
• Listeria species 5
• Streptococci 5
• Staphylococci 5-15

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Predisposing factors

• Most cases of meningitis occur when colonization
  by potential pathogens is followed by mucosal
  invasion of the nasopharynx
• However, some patients develop disease by direct
  extension of bacteria across a skull fracture in
  the area of the cribriform plate
• Other patients develop meningitis following
  systemic bacteremia as with endocarditis or a
  urinary tract infection or pneumonia
• Other predisposing conditions include asplenia,
  complement deficiency, corticosteroid excess, and
  HIV infection

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CLINICAL FEATURES

• The overwhelming majority of patients with
  bacterial meningitis have fever and headache
• Most patients have high fevers, but a small
  percentage have hypothermia
• CNS symptoms
• Some patients will have significant photophobia
  and/or clouding of the sensorium
• Changes in mentation and level of consciousness,
  seizures, and focal neurologic signs tend to
  appear later in the course of disease

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CLINICAL FEATURES

• Nuchal rigidity
• Passive or active flexion of the neck will
  usually result in an inability to touch the chin
  to the chest
• Tests to illustrate nuchal rigidity
• The Brudzinski sign refers to spontaneous flexion
  of the hips during attempted passive flexion of
  the neck
• The Kernig sign refers to the inability or
  reluctance to allow full extension of the knee
  when the hip is flexed 90 degrees

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CLINICAL FEATURES

• Other findings
• Some infectious agents, particularly N.
  meningitidis, can also cause characteristic skin
  manifestations, petechiae and palpable purpura
• If meningitis is the sequela of an infection
  elsewhere in the body, there may be features of
  that infection still present at the time of
  diagnosis of meningitis eg, otitis or sinusitis

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Differential Dx

• Viral - 40 of meningitis
• Fungal
• Tuberculous
• Spirochete
• Chemical / Drug induced
• Collagen Vascular Disease
• Parameningeal infection brain abscess, epidural
  abscess
• Subarachnoid hemorrhage
• Neuroleptic Malignant Syndrome

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LABORATORY FEATURES

• Most often the WBC count is elevated with a shift
  toward immature forms
• Platelets may be reduced if disseminated
  intravascular coagulation is present or in the
  face of meningococcal bacteremia
• Blood cultures are often positive, and can be
  very useful in the event that CSF cannot be
  obtained before the administration of
  antimicrobials
• At least one-half of patients with bacterial
  meningitis have positive blood cultures, with the
  lowest yield being obtained with meningococcus

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LABORATORY FEATURES

• CSF analysis The CSF can be diagnostic, and
  every patient with meningitis should have CSF
  obtained unless the procedure is contraindicated
• Chemistry and cytologic findings highly
  suggestive of bacterial meningitis include a CSF
  glucose concentration below 45 mg/dL, a protein
  concentration above 500 mg/dL, and a white blood
  cell count above 1000/mm3
• A Gram stain should also be obtained
• The Gram stain is positive in up to 10 percent of
  patients with negative CSF cultures and in up to
  80 percent of those with positive cultures

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Treatment and prevention of bacterial meningitis

• Suspected bacterial meningitis is a medical
  emergency and immediate diagnostic steps must be
  taken to establish the specific cause
• The mortality rate of untreated bacterial
  meningitis approaches 100 percent and, even with
  optimal therapy, there is a high failure rate
• Empiric treatment should be begun as soon as the
  diagnosis is suspected using bactericidal
  agent(s) that achieve significant levels in the
  CSF

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• Use of bactericidal agents
• Bactericidal therapy is generally necessary to
  cure meningitis
• Bacteriostatic drugs, such as clindamycin and
  tetracycline, are inadequate for meningitis
• Chloramphenicol is a bacteriostatic drug for most
  enteric Gram negative rods however, it is
  usually bactericidal for H. influenzae, N.
  meningitidis, and S. pneumoniae and has been
  extensively and successfully used to treat
  meningitis caused by these organisms

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• Choice of agent
• Selected third generation cephalosporins such as
  cefotaxime and ceftriaxone, have emerged as the
  beta-lactams of choice in the empiric treatment
  of meningitis
• These drugs have potent activity against the
  major pathogens of bacterial meningitis with the
  notable exception of listeria
• Ceftazidime, another third generation
  cephalosporin, is much less active against
  penicillin-resistant pneumococci than cefotaxime
  and ceftriaxone

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Treatment - Empiric

• Ceftriaxone 2 gm IV q12h or Cefotaxime 2 gm IV
  q4-6h
• plus Vancomycin 15 mg/kg q6h
• If gt 50 years, also add Ampicillin 2 gm IV q4h
  (for Listeria)

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THERAPY FOR SPECIFIC PATHOGENS

• Streptococcus pneumoniae
• The conventional approach to the treatment of
  pneumococcal meningitis was the administration of
  penicillin alone for two weeks at a dose of four
  million units intravenously every four hours
• Good results have also been obtained with third
  generation cephalosporins
• However, the problem of treating pneumococcal
  meningitis has recently been compounded by the
  widespread and increasingly common reports of
  pneumococcal strains resistant to penicillin

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• Cefotaxime or ceftriaxone can be used if the MIC
  for these drugs is less than 0.5 µg/mL
• It is recommended that vancomycin (2 g/day)
  should be given with cefotaxime or ceftriaxone in
  the initial treatment of pneumococcal meningitis
  if there has been beta-lactam resistance noted
  locally
• Vancomycin should be continued if there is high
  level penicillin resistance and an MIC gt0.5 µg/mL
  to third generation cephalosporins
• If corticosteroids are given, rifampin should be
  added as a third agent since it increases the
  efficacy of the other two drugs
• The usual duration of therapy is two weeks

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• Haemophilus influenzae
• A third generation cephalosporin is the drug of
  choice for H. influenzae meningitis
• Patients with H. influenzae meningitis should be
  treated for five to seven days
• For adults, a dose of 2 g every six hours of
  cefotaxime and 2 g every 12 hours of ceftriaxone
  is more than adequate therapy
• Pharyngeal colonization persists after curative
  therapy and may require a short course of
  rifampin if there are other children in the
  household at risk for invasive Haemophilus
  infection
• The recommended dose is 20 mg/kg per day (to a
  maximum of 600 mg/day) for four days

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• Neisseria meningitidis
• This infection is best treated with penicillin
• Although there are scattered case reports of N.
  meningitidis resistant to penicillin, such
  strains are still very rare
• A third-generation cephalosporin is an effective
  alternative to penicillin for meningococcal
  meningitis
• A five day duration of therapy is adequate
• However, when penicillin is used, there may still
  be pharyngeal colonization with the infecting
  strain. As a result, the index patient may need
  to take rifampin, a fluoroquinolone, or a
  cephalosporin

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• Listeria monocytogenes
• Listeria has been traditionally treated with
  ampicillin and gentamicin, as resistance to these
  drugs is quite rare
• Ampicillin is given in typical meningitis doses
  (2 g intravenously every four to six hours in
  adults) and gentamicin is used for synergy
• An alternative in penicillin-allergic patients is
  trimethoprim-sulfamethoxazole (dose of 10/50
  mg/kg per day in two or three divided doses)
• The usual duration of therapy is at least three
  weeks

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• Enteric Gram negative rods
• Prior to the availability of third generation
  cephalosporins, it was often necessary to instill
  an aminoglycoside antibiotic such as gentamicin
  directly into the cerebral ventricles
• It is now possible to cure these infections with
  high doses of third generation antibiotics
• A repeat CSF sample should be obtained for
  culture two to four days into therapy to help
  assess the efficacy of treatment
• The duration of therapy should be at least three
  weeks

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PREVENTION OF MENINGITIS Vaccines

• A spectacular reduction in H. influenzae
  meningitis has been associated with the near
  universal use of a vaccine against this organism
  in developed countries since 1987
• There has been a 94 percent reduction in H.
  influenzae meningitis between 1987 and 1995
• Pneumococcal vaccine administered to the
  chronically ill and elderly is probably useful in
  reducing the overall incidence of pneumococcal
  infections. However, its role in the prevention
  of meningitis is as yet undetermined

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Vaccines

• Meningococcal vaccines are active against many
  strains of N. meningitidis
• However, the majority of meningococcal infections
  in the United States are caused by type b
  meningococcus for which there is no vaccine
• Vaccines for other types (notably type a) are
  recommended for travelers and American military
  personnel to countries with epidemic meningitis
• Immunization against meningococci is not
  warranted as postexposure prophylaxis

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Chemoprophylaxis

• There is a role for chemoprophylaxis to prevent
  spread of meningococcal and haemophilus
  meningitis but not for pneumococcal disease
• The use of antimicrobial therapy to eradicate
  pharyngeal carriage of meningococci is widely
  accepted to prevent development of disease in
  close contacts and to eradicate pharyngeal
  carriage
• Rifampin 600 mg PO every 12 h for a total of four
  doses is recommended
• Ciprofloxacin, in a single dose of 500 mg PO, is
  equally effective and can be used in patients
  over the age of 18

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Role Of Steroids

• The addition of antiinflammatory agents has been
  attempted as an adjuvant in the treatment of
  meningitis
• Early administration of corticosteroids such as
  dexamethasone for pediatric meningitis has shown
  no survival advantage, but there is a reduction
  in the incidence of severe neurologic
  complications and deafness
• A meta-analysis of five such studies in children
  showed a relative risk of bilateral deafness of
  4.1 and of late neurological sequelae of 3.9 in
  controls compared to children treated with
  steroids

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• A second meta-analysis of trials of meningitis in
  children evaluated the findings according to
  organism
• For H. influenzae type b meningitis,
  dexamethasone therapy was associated with a
  significant reduction in deafness
• For pneumococcal meningitis, dexamethasone was
  effective only if given early in this setting,
  there was a significant reduction in hearing loss
• Two days of therapy was as effective and less
  toxic than longer courses of steroid
  administration
• Dexamethasone as adjunctive therapy in bacterial
  meningitis. A meta-analysis of randomized
  clinical trials since 1988. JAMA 1997 278925

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• There is no consensus regarding the utility of
  corticosteroid therapy in adults
• The Infectious Disease Society of America
  considers adjuvant corticosteroids for meningitis
  to be unsupported for routine use in adults but
  supports them for H. influenzae infections in
  children
• Guidelines for the use of systemic
  glucocorticoids in the management of selected
  infections.
• J Infect Dis 1992 1651

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MORTALITY RATE AND LATE SEQUELAE

• The prognosis of meningitis is linked to age and
  the presence of underlying disease
• Bacterial meningitis accompanying advanced liver
  disease, HIV infection, or organ transplantation
  is likely to be associated with more morbidity
  and mortality
• In addition, the prognosis and complications
  differ in children and adults

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• The mortality rates are lowest in children
• A meta-analysis of prospectively enrolled cohorts
  of children in developed countries showed a 4.8
  percent mortality from 1955 to 1993
• The mortality rate varied by organism, ranging
  from 3.8 for H. influenzae to 7.5 percent for N.
  meningitidis to 15.3 for S. pneumoniae
• 83.6 percent of the surviving children had
  apparently complete recovery
• The most common sequelae were
• Deafness 10.5 percent.
• Bilateral severe or profound deafness 5.1
  percent.
• Mental retardation 4.2 percent.
• Spasticity and/or paresis 3.5 percent.
• Seizures 4.2 percent.

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• Complications are more common in adults
• A series of 86 adults with meningitis, for
  example, showed a mortality rate of 18.6 percent
  with a complication rate of 50 percent
• The most common problems were
• Cerebrovascular involvement 15.1 percent.
• Cerebral edema 14 percent.
• Hydrocephalus 11.6 percent.
• Septic shock 11.6 percent.
• Disseminated intravascular coagulation 8.1
  percent.
• Acute respiratory distress syndrome 3.5
  percent.
• Spectrum of complications during bacterial
  meningitis in adults. Results of a prospective
  clinical study. Arch Neurol 1993 50575

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• A second review of bacterial meningitis in adults
  from 1962 to 1988 found a mortality rate of 25
  percent that did not vary during the 26 years of
  the study
• As in children, there was a higher rate of death
  due to S. pneumoniae (37 percent) as compared to
  N. meningitidis (13 percent) and listeria (10
  percent)
• Acute bacterial meningitis in adults.
• N Engl J Med 1993 32821.