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
 Leakage of brain abscess  Drug –induced ( NSAIDs,
into ventricle Sulfa, INH, IVIG, OKT3…)
 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-
. sulfamethoxazole
     a Ceftriaxone or cefotaxime.
     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 MIC 1.0 third-generation
 >

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)  
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
 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 1 st 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.
 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