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CNS Infections Bacterial Meningitis

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									BACTERIAL
MENINGITIS
Gebre K. Tseggay, MD
 November 21, 2005
    MAJOR CHANGES IN EPIDEMIOLOGY
     OF MENINGITIS SINCE THE 1990’S
       mainly due to the introduction of Hib vaccine
   Dramatic drop in the number of H.influenzae meningitis cases

   Dramatic drop in the overall number of meningitis cases

   Shift in age of distribution of bacterial meningitis
        (median age was 15 months in 1986, but 25 yrs in 1995)

   Before the 1990’s: H. infl> S. pneumoniae> N. meningitidis

   Since the 1990’s: S. pneumoniae> N. meningitidis>>>H. infl.


                                                                 NEJM 1997;337:970-6
    Etiology Of Bacterial Meningitis In The US

                          Percentage of Total Cases
Organism                  (1978-81) (1985) (1995)
H. Influnezae               48        45       7
N. meningitidis             20        14      25
S. pneumoniae               13        18      47
Strep. agalactiae            3          6     12
Listeria m.                  2          3      8
Other                         8         14      -
Unknown                      6          -      -
JAMA.1985;253:1749-1754
JID.1990;162:1316-1323
NEJM.1997;337:970-976
    INCIDENCE OF BACTERIAL MENINGITIS IN
                  THE USA

                       Per 100,000 population            %
   S. pneumoniae            1.1                        47
   N. meningitidis          0.6                        25
   Group B Strep.           0.3                        12
   L. monocytogenes         0.2                         8
   H. influenzae            0.2                         7




                                                NEJM 1997;337:970-6
    CHANGES IN EPIDEMIOLOGY
             (cont’d)
   Increase in cases of MDR- S. pneumoniae.
     [Resulted in changes in empiric Rx]

   Clusters of cases of meningococcal meningitis in adolescents
    & young adults.
    [Resulted in change in recommendation for meningococcal vaccination]


   Cochlear implants and higher risk for bacterial meningitis.
    [Change in recommendation for Pneumococcal +/- Hib?]

   Decrease in pneumococcal invasive disease including
    meningitis after widespread use of of pediatric
    pneumococcal vaccine.
             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,
                  aerobic gram-negative bacilli
          ETIOLOGY OF BACTERIAL MENINGITIS
               BY PREDISPOSING CONDITION


Immunocompromised state: S. pneumoniae, N.
meningitidis, Listeria, aerobic GNR (including Ps.aeruginosa)


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
           OF BACTERIAL MENINGITIS
1.   Nasopharyngeal colonization
2.   Direct extension of bacteria.
        Parameningeal foci (sinusitis, mastoiditis, or
         brain abscess)
        Across skull defects/fracture
3.   From remote foci of infection
     (e.g., endocarditis, pneumonia, UTI…)
Brain with inflammatory exudate covering the
cortical hemispheres in purulent meningitis.




                       Cohen & Powderly: Infectious Diseases, 2nd ed., Copyright © 2004 Mosby
    CLINICAL PRESENTATION
Symptom or Sign                   Relative Frequency (% )
   FEVER                                         >90
   HEADACHE                                      >90
   NUCHAL RIGIDITY                               >85
   ALTERED MENTAL STATUS                         80
   BRUDZINSKI SIGN                               50
   KERNIG SIGN                                   50
   VOMITING                                      ~35
   SEIZURES                                      10-30
   FOCAL NEURO SIGNS                             10-30
   PAPILLEDEMA                                    <1
   PHOTOPHOBIA
   SKIN RASH (e.g., petechia/purpura in meningococcemia)
      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          HIV infection or AIDS, receiving
     state                      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/mm3
   Neutrophils                   >80%
   Protein                       >100 mg/dl
   Glucose                       <40 mg/dl
   CSF/serum glu ratio           <0.4
   Gram stain                    Positive in 50-80%
   Culture                       Positive in ~85%
   Bacterial antigen detection   Positive in 50-100%
            CSF ANALYSIS

PARAMETER    BACTERIAL              VIRAL
OPENING      200-500 mm H20         <250 mm H20
PRESSURE
WBC          1000-5000              <1000
             (mainly neutrophils)   (mainly lymphocytes)
GLUCOSE      <40 mg/dL              >45 mg/dL

PROTEIN      100-500 mg/dL          <200 mg/dL
  CSF PREDICTIVE OF BACTERIAL
MENINGITIS WITH 99% ACCURACY, IF:

  WBC count       >2,000
  Neutrophils     >1180
  Protein         >220 mg/dl
  Glucose         <34 mg/dl
  Glu (CSF/serum): <0.23


                                Spanos et al. JAMA 1989;262(19):2700-7
              What Specific CSF Diagnostic Tests Should Be Used
              to Determine the Bacterial Etiology of Meningitis?

   Gram Stain
   Latex Agglutination (the Practice Guideline Committee does not recommend
    routine use of this modality):
      Does not appear to modify the decision to administer antimicrobial therapy
      False-positive results have been reported
      Some would recommend it for patients with a negative CSF Gram stain
        result and may be most useful for the patient who has been pretreated with
        antimicrobial therapy and whose Gram stain and CSF culture results are
        negative.
   Polymerase Chain Reaction (PCR)
      Broad-based PCR may be useful for excluding the diagnosis of bacterial
        meningitis, with the potential for influencing decisions to initiate or
        discontinue antimicrobial therapy.
      Although PCR techniques appear to be promising for the etiologic diagnosis
        of bacterial meningitis, further refinements of the available techniques may
        lead to their use in patients with bacterial meningitis for whom the CSF
        Gram stain result is negative.
                                                                        CID 2004;39:1267-1284
What Laboratory Testing May Be Helpful in Distinguishing
            Bacterial from Viral Meningitis?
   CSF LACTATE:
      Not recommended in suspected community-acquired bacterial meningitis
      May be helpful in the postoperative neurosurgical patient,
      If CSF lactate concentrations are 4.0 mmol/L, initiation of empirical
       antimicrobial therapy should be considered pending results of additional studies.

   C-REACTIVE PROTEIN:
      Normal CRP has a high negative predictive value in the diagnosis of bacterial
       meningitis.
      Measurement of serum CRP concentration may be helpful in patients with CSF
       findings consistent with meningitis, but for whom the Gram stain is negative
       and you’re considering withholding antimicrobial therapy.

   PROCALCITONIN: At present, because measurement of serum procalcitonin
    concentrations is not readily available in clinical laboratories, recommendations on its
    use cannot be made at this time.

   PCR: Enterovirus-PCR (rapid, sensitivity 86-100% specificity 92-100%)
                                                                CID.2004;39:1267-1284
IS CSF CULTURE ALWAYS
 POSITIVE IN BACTERIAL
       MENINGITIS?
    BACTERIAL MENINGITIS CAN BE
        “CULTURE-NEGATIVE”
   10-15% of bacterial meningitidis are culture-neg.
   Pre-LP use of even oral antibiotics may lower
       Gram stain positivity by 20% &
       Culture positivity by 30%
   In children (S.pneumo, H.flu, N. mening.) in 90-
    100% of pts within 24-36h of “appropriate” antibiotic
    Rx:
       CSF became culture-negative
       No sig change in cell count/chemistry.

                                      Ped.ID J.1992 11 423-32
ARE NEUTROPHILIC PLEOCYTOSIS &
  LOW CSF GLUCOSE UNIQUE FOR
     BACTERIAL MENINGITIS?
NEUTROPHILIC PLEOCYTOSIS & LOW CSF GLUCOSE
       May Not Always Mean Bacterial Meningitis

    INFECTIONS:               NON-INFECTIOUS:
   Viral meningitis (early    Chemical-meningitis
    phase only)                 (contrast…)
   Some parameningeal         Behcet syndrome
    foci/ cerebritis
                               Drug –induced ( NSAIDs,
   Leakage of brain            Sulfa, INH, IVIG, OKT3…)
    abscess into ventricle
   Amebic
    meningoencephalitis
   TB meningitis (rarely,
    & usu. only early)
BACTERIAL MENINGITIS MAY NOT ALWAYS
   HAVE NEUTROPHILIC PLEOCYTOSIS?


   Partially   Rx’d bacterial
     Listeria
     some GNR...
    PRINCIPLES OF TREATMENT
     Suspected Bacterial meningitis

   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


                    Common pathogens                    Antimicrobial therapy
Patient’s Age
 <1 month       Streptococcus agalactiae,        Ampicillin plus cefotaxime or
                Escherichia coli, Listeria       ampicillin plus an aminoglycoside
                monocytogenes, Klebsiella
                species
 1 - 23 mos     Streptococcus pneumoniae,        Vancomycin plus a third-generation
                Neisseria meningitidis, S.       cephalosporin
                agalactiae, Haemophilus
                influenzae, E. coli

 2 - 50 yrs     N . meningitidis, S.             Vancomycin plus a third-generation
                pneumoniae                       cephalosporin

 >50 yrs        S.pneumoniae, N. meningitidis    Vancomycin plus ampicillin plus a
                L. monocytogenes, aerobic        third-generation cephalosporin
                gram-negative bacilli
                                       EMPIRIC THERAPY
Predisposing Common pathogens                        Antimicrobial therapy
factor
Basilar skull   S. pneumoniae, H. influenzae,        Vancomycin plus a third-
fracture        group A -hemolytic streptococci      generation cephalosporin

Penetrating     Staphylococcus aureus, coagulase- Vancomycin plus cefepime,
trauma          negative staphylococci (especially vancomycin plus ceftazidime, or
                Staphylococcus epidermidis),       vancomycin plus meropenem
                aerobic gram-negative bacilli
                (including Pseudomonas
                aeruginosa)
Post-        Aerobic gram-negative bacilli           Vancomycin plus cefepime,
neurosurgery (including P. aeruginosa), S .          vancomycin plus ceftazidime, or
             aureus, coagulase-negative              vancomycin plus meropenem
             staphylococci (especially S.
             epidermidis)
CSF shunt       Coagulase-negative staphylococci     Vancomycin plus cefepime,c
                (especially S. epidermidis), S.      vancomycin plus ceftazidime,c or
                aureus, aerobic gram-negative        vancomycin plus meropenemc
                bacilli (including P. aeruginosa),
                Propionibacterium acnes
                               SPECIFIC-RX
Microorganism                 Recommended Rx                                    Alternative therapies
Streptococcus               Vancomycin plus a                    Meropenem (C-III), fluoroquinolonec (B-II)
pneumoniae                  third-generation
                            cephalosporina,b

Neisseria                   Third-generation                     Penicillin G, ampicillin, chloramphenicol,
meningitidis                cephalosporina                       fluoroquinolone, aztreonam
Listeria      Ampicillind or penicillin                          Trimethoprim-sulfamethoxazole,
monocytogenes Gd                                                 meropenem (B-III)


Streptococcus               Ampicillind or penicillin            Third-generation cephalosporina (B-III)
agalactiae                  Gd
Haemophilus                 Third-generation                     Chloramphenicol, cefepime (A-I),
influenzae                  cephalosporina (A-I)                 meropenem (A-I), fluoroquinolone
Escherichia coli            Third-generation                     Cefepime, meropenem, aztreonam,
                            cephalosporina (A-II)                fluoroquinolone, trimethoprim-
.
    a Ceftriaxone or cefotaxime.
                                                                 sulfamethoxazole
    b Some experts would add rifampin if dexamethasone is also given (B-III).
    c Gatifloxaxin or moxifloxacin.
    d Addition of an aminoglycoside should be considered.
PATHOGEN
susceptibility           Standard therapy                  Alternative therapies
Streptococcus
pneumoniae
     Penicillin MIC

      <0.1 g/mL       Penicillin G or ampicillin   Third-generation cephalosporin,
                                                   chloramphenicol
      0.1-1.0 g/mL    Third-generation             Cefepime (B-II), meropenem
                      cephalosporin
      > 2.0 g/mL      Vancomycin plus a            Fluoroquinolone
                      third-generation
                      cephalosporin
   Cefotaxime or      Vancomycin plus a            Fluoroquinolone
    ceftriaxone       third-generation
  MIC 1.0 g/mL
        >             cephalosporin
Neisseria
meningitidis
    Penicillin MIC
      <0.1 g/mL       Penicillin G or ampicillin   Third-generation cephalosporin,
                                                   chloramphenicol
PATHOGEN             STANDARD RX                  ALTERNATIVE RX

Listeria             Ampicillin or penicillin G   Trimethoprim-sulfamethoxazole,
monocytogenes                                     meropenem
Strep. agalactiae    Ampicillin or penicillin G   Third-generation cephalosporin

E. coli and other    Third-generation             Aztreonam, fluoroquinolone,
Enterobacteriaceae   cephalosporin                meropenem, trimethoprim-
                                                  sulfamethoxazole, ampicillin
Pseudomonas          Cefepime or ceftazidime Aztreonam ciprofloxacin, meropenem
aeruginosa           (consider plus              (consider plus aminoglycoside)
                     aminoglycoside)
Haemophilus
influenzae
    B -Lactamase     Ampicillin                   Third-generation cephalosporin,
.   negative                                      cefepime, chloramphenicol,
                                                  fluoroquinolone
    B -Lactamase     Third-generation             Cefepime, chloramphenicol,
    positive         cephalosporin                fluoroquinolone
PATHOGEN                STANDARD RX               ALTERNATIVE RX


Staphylococcus
aureus
Methicillin             Nafcillin or oxacillin    Vancomycin, meropenem
susceptible
Methicillin resistant   Vancomycin (consider      Trimethoprim-sulfamethoxazole,
                        adding rifampin)          linezolid (consider adding rifampin)
Staphylococcus          Vancomycin                Linezolid
epidermidis
Enterococcus
species
Ampicillin              Ampicillin + gentamicin                     ...
susceptible
Ampicillin resistant    Vanc + gentamicin                           ...


Ampicillin and          Linezolid                                   ...
vancomycin
resistant
                          In adults
                      Total daily dose
                      (dosing interval in
Antimicrobial agent   hours)
Amikacin              15 mg/kg (8)
Ampicillin            12 g (4)
Aztreonam             6-8g (6-8)
Cefepime              6 g (8)
Cefotaxime            8-12g(4-6)
Ceftazidime           6 g (8)
Ceftriaxone           4g (12-24)
Chloramphenicol       4-6 g (6)
Ciprofloxacin         800-1200mg (8-12)
Gatifloxacin          400 mg (24)
                                            CID.2004;39:1267-1284
 Antimicrobial agent    Total daily dose (dosing
                          interval in hours)
Gentamicin             5 mg/kg (8)
Meropenem              6 g (8)
Moxifloxacin           400 mg (24)
Nafcillin              12 g (4)
Oxacillin              12 g (4)
Penicillin G           24 mU (4)
Rifampin               600 mg (24)
                                        9
Tobramycin             5 mg/kg (8)
TMP-SMZ                10-20 mg/kg (6-12)
Vancomycin             30-45 mg/kg (8-12)
                                              CID   2004;39:1267-1284
                                           Duration of
Microorganism                            therapy (days)

Neisseria meningitidis                                     7

Haemophilus influenzae                                     7

Streptococcus pneumoniae                              10-14

Streptococcus agalactiae                              14-21

Aerobic gram-negative bacilli                             21

Listeria monocytogenes                                  >21
                                Clinical Infectious Diseases   2004;39:1267-1284
           BACTERIAL MENINGITIS
              CASE FATALITY
                       (%)
   S. pneumoniae       21
   L. monocytogenes    15
   Group B Strep.      7
   H. influenzae       6
   N. meningitidis     3



                                   NEJM 1997;337:970-6
                       (based on 248 cases from 4 states, in 1995)
               ROLE OF STEROIDS
   Decrease subarachnoid space inflammatory response to
    abx-induced bacterial lysis

   Significant reduction in deafness in pediatric H.
    influenzae & pneumococcal meningitis (JAMA 1997; 278:925).
   In adults, reasonable to use steroids:
      for pts with evidence of cerebral edema.
      for adult with pneumococcal meningitis
                                                       (Nov 14, 2002 issue of NEJM)



    Give immediately before or with the 1st dose of antibiotic.
    Dexamethasone dose: 0.15 mg/kg q6 x 2-4 days
            Dexamethasone in Adults with Bacterial Meningitis
Jan de Gans, et.al., for the European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators




                                                            NEJM 2002. 347:1549-1556. (Nov. 14, 2002)
        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.

 Some authorities would initiate dexamethasone in all adults
  because the etiology of meningitis is not always ascertained at initial
  evaluation, although the data are inadequate to recommend adjunctive dexamethasone to
   adults with meningitis caused by other bacterial pathogens
     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;39:1267-1284
      What Are the Indications for Repeated Lumbar Puncture
              in Patients with Bacterial Meningitis?
•Not indicated routinely in patients with bacterial meningitis who have responded
appropriately to antimicrobial therapy,
• Repeated CSF analysis should be performed in:
    • Any patient who has not responded clinically after 48h of appropriate antimicrobials
          This is especially true for the patient with pneumococcal meningitis caused by
          penicillin-or cephalosporin-resistant strains, especially for those who have also received
          adjunctive dexamethasone therapy.

     • Neonate with meningitis due to gram-negative bacilli should have repeated LPs
         •To document CSF sterilization, because the duration of antimicrobial therapy is
         determined, in part, by the result.

     • In patients with CSF shunt infections
          •The presence of a drainage catheter after shunt removal allows for monitoring of CSF
          parameters to ensure that the infection is responding to appropriate antimicrobial therapy
          and drainage).




                                                                              CID   2004;39:1267-1284
            PREVENTION OF BACTERIA
                 MENINGITIS
   Isolation of index patient
       Droplet precautions
       For 24 hrs after 1st dose of appropriate abx)

   Post-exposure prophylaxis
   Vaccination
    POST-EXPOSURE PROPHYLAXIS
   Candidates:
      Household members
      Day care center contacts
      Direct exposure to pt’s oral secretion ( as in kissing,
       mouth-to-mouth , intubation/ET tube management)
      Index patient (if not treated w 3rd gen cephalosporins)


   Regimen:
      Meningococcus: Rifampin, ciprofloxacin, or ceftriaxone
      Hempohilus influenzae serotype b: Rifampin.
                           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.
   Who Should Be Vaccinated with the NEW
       MENINGOCOCCAL VACCINE
                (Menactra)
•Children aged 11-12 years

•Previously unvaccinated adolescents before entering high school or at
age 15 (whichever comes first)

•All first-year college students living in dormitories

•Other high-risk groups, such as those with underlying medical conditions
or travelers to areas with high rates of meningococcal disease, such as
Africa and India.

•Other adolescents who choose to get the vaccine to reduce their risk

"As the vaccine supply increases, CDC hopes, within three years, to recommend routine
vaccination [for] all adolescents beginning at 11 years of age," per CDC's news release
       FDA and CDC Issue Alert on Menactra Meningococcal Vaccine
                     and Guillain Barre Syndrome

• FDA and CDC alerted consumers and health care providers to five reports of
Guillain Barre Syndrome (GBS) following administration of Meningococcal
Conjugate Vaccine (trade name Menactra).

• It is not known yet whether these cases were caused by the vaccine or are
coincidental.

• Prelicensure studies conducted by Sanofi Pasteur of more than 7000 recipients
of Menactra showed no GBS cases.

• CDC conducted a rapid study using available health care organization
databases and found that no cases of GBS have been reported to date among
110,000 Menactra recipients.


                                                              September 30, 2005
 CRITERIA FOR OUTPATIENT ANTIMICROBIAL THERAPY IN
        PATIENTS WITH BACTERIAL MENINGITIS

• Inpatient antimicrobial therapy for > 6 days
• Absence of fever for at least 24- 48 h prior to initiation of outpatient therapy
• No significant neurologic dysfunction, focal findings, or seizure activity
• Clinical stability or improving condition
• Ability to take fluids by mouth
• Access to home health nursing for antimicrobial administration
• Reliable intravenous line and infusion device (if needed)
• Daily availability of a physician

• Established plan for physician visits, nurse visits, laboratory monitoring, and
emergencies
• Patient and/or family compliance with the program
• Safe environment with access to a telephone, utilities, food, and refrigerator


                                                                  CID   2004;39:1267-1284
                        REVIEW
   Most common cause overall….
   CT?
   Duration of Rx…
   Steroids for…
   Most deadly…
   Isolation for…. How long?
   Chemoprophylaxis
       For which pathogens?
       Which contacts?
       What Regimen?
   Vaccination?
MANAGEMENT
DO YOU WANT MORE SLIDES ON
   BACTERIAL MENINGITIS??
                                  SHUNT INFECTION
 Removal of all components of the infected shunt, external drainage, +abx
COAG-NEGATIVE STAPH.:
   1. If normal CSF findings, and a negative CSF culture results after externalization,
      the patient can be reshunted on the 3rd day after removal.
   2. If CSF abnormalities are present and a coagulase-negative staphylococcus is
      isolated, 7 days of antimicrobial therapy are recommended prior to reshunting as
      long as additional CSF culture results are negative and the ventricular protein
      concentration is appropriate (<200 mg/dL);
   3. If additional culture results are positive, abx are continued until CSF culture
      results remain negative for 10 consecutive days before a new CSF shunt is placed.
STAPH. AUREUS :
   10 days of negative culture results are recommended prior to reshunting .

GRAM-NEGATIVE BACILLI:
   10-14 day course of antimicrobial therapy should be used, although longer durations
      may be needed depending on the clinical response.

[Some experts also suggest that consideration be given to a 3-day period off antimicrobial
   therapy to verify clearing of the infection prior to shunt reimplantation; although this
   approach is optional, it may not be necessary for all patients].
                      Neisseria Meningitidis
   5-15% asymptomatic nasopharyngeal colonization.
   Transmission by air-droplets, kissing, sharing saliva…
   Most common cause of meningitis in children and young adults , with
    overall mortality rate of 3- 13%.
   Causes epidemics in the “meningitis belt.”
   Predisposing Factors :
       Deficiencies in the terminal complement components (C5-C9)
       Splenectomy
       Crowding (military recruits, college dormitory, Hajj…). Tarvel.
       College freshmen in dormitory>>dormitory >> freshman>>college
        students overall.
      Rates of meningococcal disease, by risk
   group--United States, Sept. 1998--Aug. 1999

Risk group                       Rate per 100,000
Children aged 2-5 years                      1.7
Persons aged 18-23 years                     1.4
Non-college students aged 18-23 years        1.5
College students                             0.6
Undergraduates                               0.7
Freshmen                                     1.8
Dormitory residents                          2.2
Freshmen living in dormitories               4.6

MMWR 2000,49(RR-7)1-20
         Meningococcal Meningitis
   Penicillin (or 3rd gen cephalosporin)
   Resistance to penicillin still very rare
   If penicillin used for Rx, eradication of
    pharyngeal colonization of index case advisable
   Duration of Rx, 7 days
   Chemoprophylaxis for close contacts
   Droplet isolation (for 24h after 1st dose of abx)
           Streptococcus Pneumoniae
   Most common cause of bacterial meningitis in the
    US, with mortality rate of 19 to 26%.
       Often from contiguous or distant foci of infection (e.g.,
        pneumonia, otitis media, mastoiditis, sinusitis,
        endocarditis, or after head trauma w CSF leak).
   Predisposing factors:
       Anatomic or functional asplenia, multiple myeloma,
        hypogammaglobulinemia, alcoholism, malnutrition,
        chronic liver or renal disease, malignancy, and diabetes
        mellitus.
               Pneumococcal Meningitis
   Before MICs: Vancomycin + 3rd gen cephalosporin
   If PSSP: Penicillin (or 3rd gen cephalosporin) alone
   If PRSP(CTX-S): 3rd gen cephalosporin
   If PRSP&CTX-R: Vancomycin +3rd gen cephalosp

   Steroids in children & adults
   If on vanc, and steroids have to be used, add rifampin?
   For PRSP: re-LP in few days for response.
   Duration of Rx 10-14 days
             Haemophilus Influenzae

   Meningitis usually seen in children <6 years (peak 6-
    12mo).
   Capsular type b causes >90% of invasive disease.
   Meningitis in above 6 yrs usually associated with:
    sinusitis, otitis, pneumonia, sickle cell disease,
    splenectomy, DM, alcoholism, immuno-deficiency, or
    head trauma w csf leak.
   Causes 7% of meningitis cases in US
   Mortality 3-6%.
          H. influenzae meningitis
   Ceftriaxone or cefotaxime
   Steroids in chldren
   Duration of Rx: 5-7 days
   Chemoprophylaxis of close contacts.
   Droplet precaution (in pediatric cases, x 24h of abx)
                Listeria monocytogenes
   May be isolated from dust, soil, water, sewage, and
    decaying vegetable matter. Usually foodborne infections
    (contaminated cole slaw, raw vegetables, milk, cheese...)

   Causes 8% of cases of bacterial meningitis in the US,
    mortality rate of 15-29%. (Seizures, focal signs,
    rhomboencephalitis common)
   Meningitis most common in neonates/elderly, alcoholics,
    malignancy, corticosteroid Rx.
   Other predisposing factors: DM, liver disease, chronic
    renal disease, collagen-vascular diseases, & conditions
    with Fe overload.
              Streptococcus agalactiae
   Asymptomatic vaginal or rectal colonization in 15 to 35% of
    pregnant women .
   Most common cause of meningitis in newborns
   Mostly vertical transmission (but some horizontal
    transmission from the hands of nursery personnel)
   Can also cause meningitis in ADULTS. Risk factors in adults
    include: age>60 years, diabetes mellitus, pregnancy/the postpartum
    state, cardiac disease, collagen-vascular diseases, malignancy, alcoholism,
    hepatic failure, renal failure, previous stroke, neurogenic bladder,
    decubitus ulcers, and corticosteroid therapy.
                       Staphylococci

   Staphylococcus aureus (&/or coag-neg Staph) meningitis is
    mainly postneurosurgical, CSF shunts, or post-trauma.
   Community-acquired S. aureus meningitis can be seen in
    patients with sinusitis, endocarditis, osteomyelitis, and
    pneumonia.
   Other underlying conditions include diabetes mellitus,
    alcoholism, hemodialysis, injection drug use, and malignancies
         Aerobic Gram-Negative Bacilli
   Increasingly important cause of bacterial meningitis
    (e.g., Klebsiella spp., E. coli, Serratia marcescens, Pseudomonas
    aeruginosa, Salmonella spp.)
   Usually after head trauma or neurosurgery.
   May be seen in neonates, the elderly, immuno-
    suppressed patients, and pts with gram-negative sepsis.
   Seen w the hyperinfection syndrome of disseminated
    strongyloidiasis
         Garm negative meningitis
   Ceftazidime (or Cefepime or meropenem) + an
    aminoglycoside
   Re-LP for proof of response, in 2-4 days?
   Duration of Rx: 21 days
           BACTERIAL MENINGITIS
             COMPLICATIONS

   Death ( Pneumococcal> Listeria> Meningococcal)
   Deafness (5-10%)
   Mental retardation (4.2%)
   Seizures( 4.2%)
   Paresis/spasticity (3.5%)


Poorest prognosis: >60, seizure `24h, obtunded/coma
              COMPLICATIONS OF BACTERIAL
                     MENINGITIS
Immediate
     Coma
        Loss of airway reflexes
        Seizures
        Cerebral edema
        Vasomotor collapse
        Disseminated intravascular coagulation (DIC)
        Respiratory arrest
        Dehydration
        Pericardial effusion
        Death

Delayed
         Seizure disorder
          Focal paralysis
          Subdural effusion
          Hydrocephalus
          Intellectual deficits
          Sensorineural hearing loss
          Ataxia
          Blindness
          Bilateral adrenal hemorrhage
          Death
    COMPLICATIONS of BACTERIAL
           MENINGITIS
   Cerebral infarction from occlusion of
    inflammed vessels (focal neurologic signs, seizures,
    AMS..)
   Brain edema from disturbance of
    cerebrovascular autoregulation, leakage of fluid
    from damaged vessels, cytotoxic edema from
    damaged barin cells, or dural sinus thrombosis
    which impede blood drainage from brain)
   Obstruction of flow of CSF (hydrocephalus)
            Recommended dosages of antimicrobial agents
             administered by the intraventricular route (A-
                                  III).
                                                 Daily
                                           intraventricular
                  Antimicrobial agent          dose, mg
                      Vancomycin                             5 20
                      Gentamicin                             1 8
                      Tobramycin                             5 20
                      Amikacin                               5 50
                      Polymyxin B                              5
                      Colistin                                 10
                      Quinupristin/dalfopristin              2 5
                      Teicoplanin                            5 40


NOTE. There are no specific data that define the exact dose of an antimicrobial agent that should be
administered by the intraventricular route.
  a Most studies have used a 10-mg or 20-mg dose.
  b Usual daily dose is 1   2 mg for infants and children and 4 8 mg for adults.
  c The usual daily intraventricular dose is 30 mg.
  d Dosage in children is 2 mg daily.
   e
  RECURRENT MENINGITIS
Bacterial:                  Chemical:
 Anatomic defect/CSF       Endogenous: cranio-
  leak                        pharyngioma, epidermid
 Parameningeal infection     cyst.
 Immunologic (Ig def,      Drugs, Behcet, SLE,
  asplenia, complement        Mollaret...
  def...)
Hasbun et al. NEJM 2001: 345 (24): 1727
Hasbun et al. NEJM 2001: 345 (24): 1727-33
  What Laboratory Testing May Be Helpful in Distinguishing Bacterial from Viral
                                     Meningitis?
CSF Lactate
•Not recommended for patients with suspected community-acquired bacterial meningitis
•However, measurement of CSF lactate concentrations was found to be superior to use of the ratio of
CSF to blood glucose for the diagnosis of bacterial meningitis in postoperative neurosurgical patients,
in which a CSF concentration of 4.0 mmol/ L was used as a cutoff value for the diagnosis…
Therefore, in the postoperative neurosurgical patient, initiation of empirical antimicrobial therapy
should be considered if CSF lactate concentrations are > 4.0 mmol/L, pending results of additional
studies.
C-reactive Protein
Measurement of serum CRP concentration may be helpful in patients with CSF findings consistent
with meningitis, but for whom the Gram stain result is negative and the physician is considering
withholding antimicrobial therapy, on the basis of the data showing that a normal CRP has a high
negative predictive value in the diagnosis of bacterial meningitis.
Procalcitonin
At present, because measurement of serum procalcitonin concentrations is not readily available in
clinical laboratories, recommendations on its use cannot be made at this time (C-II).
Polymerase Chain Reaction
In patients who present with acute meningitis, an important diagnostic consideration is whether the
patient has enteroviral meningitis. Rapid detection of enteroviruses by PCR has emerged as a valuable
technique that may be helpful in establishing the diagnosis of enteroviral meningitis.
                                                   IMPACT OF PCV-7




            Annual Incidence of Invasive Pneumococcal Disease by Age Group for
            Adults >50 Years—Active Bacterial Core Surveillance, 1998-2003
Percentage reductions from 1998-1999 to 2002-2003: for persons aged 85 years, –28% (95% confidence interval [CI], –36% to –
19%); 75-84 years, –35% (95% CI, –41% to –28%); 65-74 years, –29% (95% CI, –36% to –21%); and 50-64 years, –17% (95% CI,
–24% to –11%). Percentage reductions were significant (P<.001) in each age group. PCV-7 indicates 7-valent pneumococcal
conjugate vaccine.
                              JAMA. Vol. 294 No. 16, October 26, 2005
JAMA. Vol. 294 No. 16, October 26, 2005
JAMA. Vol. 294 No. 16, October 26, 2005

								
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