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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

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bacterial meningitis


Gebre K. Tseggay, MD

November 21, 2005

MAJORCHANGESINEPIDEMIOLOGYOFMENINGITISSINCETHE1990’Smainly 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
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 --




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.



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
  • Nasopharyngeal colonization
  • Direct extension of bacteria.
    • Parameningeal foci (sinusitis, mastoiditis, or brain abscess)
    • Across skull defects/fracture
  • 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 SignRelative Frequency (%)

  • FEVER>90
  • VOMITING ~35
  • SEIZURES 10-30
  • 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?
diagnosis csf examination typical csf in patients with bacterial meningitis
DIAGNOSIS - CSF ExaminationTypical 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 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
What Laboratory Testing May Be Helpful in Distinguishing Bacterial from Viral Meningitis?
    • Not recommended in suspected community-acquired bacterial meningitis
    • May be helpful in thepostoperative neurosurgicalpatient,
    • If CSF lactate concentrations are 4.0 mmol/L, initiation of empirical antimicrobial therapy should be considered pending results of additional studies.
    • Normal CRP has ahigh negative predictivevalue 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
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 by20% &
      • 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

neutrophilic pleocytosis low csf glucose may not always mean bacterial meningitis

Viral meningitis (early phase only)

Some parameningeal foci/ cerebritis

Leakage of brain abscess into ventricle

Amebic meningoencephalitis

TB meningitis (rarely, & usu. only early)


Chemical-meningitis (contrast…)

Behcet syndrome

Drug –induced ( NSAIDs, Sulfa, INH, IVIG, OKT3…)

bacterial meningitis may not always have neutrophilic pleocytosis
  • Partially Rx’d bacterial
  • Listeria
  • some GNR...
principles of treatment suspected bacterial meningitis
PRINCIPLES OF TREATMENTSuspected 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

. a Ceftriaxoneor cefotaxime.b Some experts wouldadd rifampin if dexamethasoneis also given (B-III).cGatifloxaxinor moxifloxacin.d Addition of anaminoglycoside should be considered.




  • 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,, 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
Use of Adjunctive Dexamethasone Therapy in Pediatric Patients with Bacterial Meningitis
  • Infants and Children
  • Use in H. influenzae typeb 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 routinelyin patients with bacterial meningitiswho have responded appropriately to antimicrobial therapy,
  • Repeated CSF analysis should be performed in:
    • Any patientwho has not responded clinically after 48h of appropriate antimicrobialsThis 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 bacillishould 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.
  • 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
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 Vaccineand 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
  • 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?


  • Removal of all components of the infected shunt, external drainage, +abx


    • If normal CSF findings, and a negative CSF culture results after externalization, the patient can be reshunted on the 3rd day after removal.
    • 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);
    • 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.


    • 10 days of negative culture results are recommended prior to reshunting .


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)


Crowding (military recruits, college dormitory, Hajj…). Tarvel.

College freshmen in dormitory>>dormitory >> freshman>>college students overall.

Neisseria Meningitidis
rates of meningococcal disease by risk group united states sept 1998 aug 1999
Rates of meningococcal disease, by risk group--United States, Sept. 1998--Aug. 1999

Risk groupRate 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


Dormitory residents 2.2

Freshmen living in dormitories 4.6

MMWR 2000,49(RR-7)1-20

meningococcal meningitis
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
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, orafter 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
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
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
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
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
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.
  • Staphylococcus aureus (&/or coag-neg Staph) meningitis is mainly postneurosurgical, CSF shunts, or post-trauma.
  • Community-acquiredS. 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
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
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


  • ComaLoss of airway reflexesSeizuresCerebral edemaVasomotor collapseDisseminated intravascular coagulation (DIC)Respiratory arrestDehydrationPericardial effusionDeath


  • Seizure disorderFocal paralysisSubdural effusionHydrocephalusIntellectual deficitsSensorineural hearing lossAtaxiaBlindnessBilateral adrenal hemorrhageDeath
complications of bacterial meningitis75
  • 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)

NOTE.     Thereare no specific datathat define the exactdose of an antimicrobialagent that should beadministered by the intraventricularroute. a Most studies have useda 10-mg or 20-mgdose.b Usual daily dose is1    2 mg for infantsand children and 4    8mg for adults.c The usualdaily intraventricular dose is30 mg.d Dosage in childrenis 2 mg daily.e Dosageof 5    10 mg every48    72 h in onestudy [112].

recurrent meningitis

Anatomic defect/CSF leak

Parameningeal infection

Immunologic (Ig def, asplenia, complement def...)


Endogenous: cranio-pharyngioma, epidermid cyst.

Drugs, Behcet, SLE, Mollaret...


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 anormal 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.


  • 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