4. Definition
Bacterial meningitis -acute purulent infection within the subarachnoid
space.
CNS inflammatory reaction that may result in decreased consciousness,
seizures, raised ICP, and stroke.
The meninges, subarachnoid space, and brain parenchyma frequently
involved -Meningoencephalitis.
Bradley's- 7th Edition
5. • Suspected: Acute fever (>38 degree axillary or 38.5 degree rectal) with
-Neck stiffness
-Altered consciousness
-Other meningeal signs
WHO Case Definition
- WHO surveillance definition
6. WHO Case Definition
• Probable: Suspected + CSF showing at least one of the following:
-Turbid,
-Leukocytosis (>100/ml),
-Leukocytosis(>10/ml)with either elevated protein(>100 mg/dl) or
decreased glucose(<40 mg/dl).
- WHO surveillance definition
7. WHO Case Definition
• Confirmed: Identification of pathogenic bacteria in CSF or blood by
• Culture
• Gram staining
• Antigen detection
with clinical syndrome consistent.
- WHO surveillance definition
17. Jolt accentuation test
Exacerbation of existing headache on
having the patient rotate his head
horizontally @ 2-3 times/sec
Sensitivity of 97%, specificity of 60%
Kiss the knee test
Knees is kept down
Patient is asked to kiss the knee
Cannot perform the maneuver
due to stiffness of spine and
knees draws up abruptly
Lancet 2007
NEJM 2004
25. EPIDEMIOLOGY
• 80% of pyogenic meningitis cases occur in children
• Fatal in 50% of cases if untreated
• 8-15% patients die after early diagnosis and treatment.
• 10-20% have residual brain damage sequelae.
WHO surveillance
26. Risk Factors
• Age
• Infants are at higher risk .
• Community setting
• Overcrowded dormitories and military personnel –meningococcal meningitis
• Certain medical conditions
Diseases that weaken the immune system.
Ananthrayan Microbiology 8 th edition
27. Risk Factors
• Working with meningitis-causing pathogens
• Microbiologists
• Travel
• Meningitis belt in sub-Saharan Africa - meningococcal meningitis.
• Meningococcal meningitis - travellers Mecca during the annual Hajj and
Umrah pilgrimage.
Ananthrayan Microbiology 8 th edition
28. Transmission
• Germs can be contagious.( Not as contagious as diseases like the common
cold or the flu.)
• Exchange of respiratory and throat secretions (kissing).
• Listeria monocytogenes -contaminated food.
29. • Close contacts - with meningococcal or Haemophilus influenzae type b (Hib)
meningitis – Prophylaxis recquired.
• Close contacts of a person with meningitis caused by Streptococcus
pneumoniae, do not need antibiotics.
• Healthy people can carry the bacteria in their nose or throat without getting
sick.
Ananthrayan Microbiology 8 th edition
33. ETIOLOGY
Age Group Causes
Newborns Group B Streptococcus, Escherichia
coli, Listeria monocytogenes
Infants and Children Streptococcus pneumoniae, Neisseria
meningitidis, Haemophilus influenzae
type b
Adolescents and Young Adults Neisseria meningitidis, Streptococcus
pneumoniae
Older Adults Streptococcus pneumoniae, Neisseria
meningitidis, Listeria monocytogenes
Ananthrayan Microbiology 8 th edition
34. STREPTOCOCUS PNEUMONIAE
• Most common pathogen isolated in adults.
• Gram positive diplococci lanceolate shape
• Predisposing factors:
Pneumonia, sinusitis, otitismedia
Alcoholism, diabetes, splenctomy,
hypogammaglobulinemia, complement
deficiency
Basilar skull fracture with csf rhinorrhoea.
Ananthnarayan micobiology 8 th edition
Image courtesy Dr Nagarathna
35. HAEMOPHILUS INFLUENZAE
• Occurs mostly in children (6months to 4 years).
• Gram negative cocco-bacilli.
• Normal throat microbioata.
• Predisposing factors:
URTI, otitis media, sinusinitis, splenectomy and
hypogammaglobulonemia.
Ananthnarayan micobiology 8 th edition
36. Nesseriae meningitidis
• Occurs in children (age 2 years to 5 years )
• Gram negative diplococci
• 10 % of people are healthy nasopharygeal carriers.
• Infection starts as sore throat and appearance of rash.
• Predisposing factors:
URTI, splenectomy, complement deficiency, hypogammaglobulinemia.
Ananthnarayan micobiology 8 th edition
37. LISTERIA MONOCYTOGENES
• Occurs in neonates, pregnant, old age
and immunocompromised.
• Gram positive flagellated bacilli
• Infected by food contaminated by Listeria.
• Ex: milk, soft cheese, canned food, meat.
Ananthnarayan micobiology 8 th edition
38. GRAM NEGATIVE BACILLI
• Prevalent in all age groups.
• Eg. E coli, Klebsiella, Salmonella
• Predisposing factors:
Diabetes, cirrohosis of liver,
Chronic alcoholism, chronic UTI
Head trauma with csf rhinorrhoea
Otitis media, sinusitis
Ananthnarayan micobiology 8 th edition
39. OTHERS
• Staph aureus
• Gram positive coccus in clusters
• Predisposing factors:
Invasive neurosurgical procedure:
particularly shunting procedure for
hydrocephalus and intrathecal
chemotherapy.
Ananthnarayan micobiology 8 th edition
Image courtesy Dr Nagarathna
40. OTHERS
• Meningitis complicating endocarditis
(HACEK GROUP-Haemophillus,
Actinobacillus, Cardiobacterium, Eikenella,
Kingella)and enterococcus.
• Group B Streptococcus: Neonates or older
individuals.
43. LABORATORY
• WBC count- elevated with a shift toward immature forms
• Platelets – reduced.
• DIC - meningococcal bacteremia.
• 50% - have positive blood cultures,
Ananthnarayan micobiology 8 th edition
44. Recommended criteria for CT scan prior to LP
Criterion Comments
Immuno-compromised
state
HIV, immuno-suppresants or transplants
History of CNS disease Mass lesions, stroke or focal infection
New onset seizure Within one week of presentation
Papilledema Absence of venous pulsation
Focal neurological deficits Gaze palsy, arm or leg drifts, non-reactive pupil
Abnormal level of
consciousness
Revised according to new IDSA guideline and is removed from the criteria
IDSA guidelines B – II
45. CONTRAINDICATIONS OF LP
NEURO ICU BOOK 2 ND EDITION
• Relative
Platelet count less 20-40 K/ ml
Thienopyridine therapy
•Absolute
Non communicative hydrocephalous
Uncorrected bleeding diathesis
Platelet count < 20 K/ml
Local skin infection
Spinal stenosis or spinal cord compression
above the level of LP
Spino cranial developmental abnormalities
47. LABORATORY
• CSF analysis – every patient with meningitis
should have CSF unless LP is contraindicated .
• Volume -2-3 ml
• (Mycobacterial/fungal 10-15 ml)
• Storage –room temperature
49. • CSF glucose-
• <45 mg/dl-bacterial(Bonadio1992).
• CSF glucose/serum glucose <0.4 bacterial: sensitivity 91% and
specificity 96%(Genton et al 1990).
• CSF protein-
• >55 mg/dl-bacterial/fungal/tubercular(Bonadio 1990)
50. • CSF cytology-
• Neutrophil 80-95%
• 10%patient- lymphocytic predominance(>50%lymp/monocyte)
(Tunken et al)
• FALSE POSITIVE-ICH/SAH
• Correction formula-Actual WBC-WBC in bloodxRBC in CSF/RBC in
blood
• Seizure –Transient pleocytocis (Neutrophillic with WBC <80 )
51. FALSE NEGATIVE CSF
• Prolonged storage
• 32% decrease after 1hr
• 50% decrease after 2hr (Gray et al 1992)
• Septic shock and systemic infection (Heckenberg et al2008)
• 10-15% of pyogenic meningitis CSF WBC <100 (Durandet al1993)
52. Cerebrospinal Fluid Parameter Typical Finding
Opening pressure 200-500 mm H2O
White blood cell count
1000-5000/mm3 (range <100 to
>10,000)
Percentage of neutrophils ≥80%
Protein 100-500 mg/dL
Glucose ≤40 mg/dL
CSF-to-serum glucose ratio ≤0.4
Gram stain Positive in 60%-90%
Culture Positive in 70%-85%
Polymerase chain reaction Promising*
53. Gram stain
• Rapid- in 60%–90% of patients with CABM
• Specificity of 97%
• Correlates with the CSF concentration of bacteria
• 103 (CFU)/mL - positive microscopy 25%
• 1105 CFU/mL- lead to positive microscopy 97%
IDSA GUIDELINES OF PYOGENIC MENINGITIS
54. • The probability of visualizing bacteria, up to 100-fold by using cytospin.
• Likelihood also depends on the specific bacterial pathogen causing
meningitis.
• 90% -Streptococcus pneumoniae,
• 86%- Haemophilus influenzae,
• 75% - Neisseria meningitidis,
• 50% - gram-negative bacilli,
• 33% - Listeria monocytogenes have positive Gram stain results.
IDSA GUIDELINES OF PYOGENIC MENINGITIS
56. Determination of lactate concentration
• CSF lactate recommendation - not received prior antimicrobial therapy.
False positive
• Cerebral hypoxia/ischemia,
• anaerobic glycolysis,
• metabolism of CSF leukocytes
Not recommended suspected CABM (D-III).
• Superior to CSF/blood glucose in bacterial meningitis in postoperative
neurosurgical patient.
IDSA GUIDELINES OF PYOGENIC MENINGITIS
57. • 4.0 mmol/L CSF lactate concentrations-
• Distinguishes bacterial from a nonbacterial meningeal syndrome.
• Empirical antimicrobial therapy - If CSF lactate > 4.0 mmol/L (B-II).
IDSA GUIDELINES OF PYOGENIC MENINGITIS
Determination of lactate concentration
58. Determination of Chloride Concentration
A moderate decrease - pyogenic meningitis,
Severe decrease - tuberculous meningitis (no consensus criteria for cut off
mark)
Spinal fluid chlorides normal-in encephalitis and the viral meningitides
H. W. GIERSON, M.D., and G. J. OWENS. M.D., Los Angeles
59. Determination of C-reactive protein (CRP)
concentration
• Serum CRP - Gram stain negative bacterial meningitis.
• Sensitivity -96%,Specificity - 93%, Negative predictive value - 99%.
• Serum CRP concentration- helpful in CSF Gram stain negative meningitis
physician is considering withholding antimicrobial therapy. (B-II)
IDSA GUIDELINES OF PYOGENIC MENINGITIS
60. Determination of procalcitonin concentration
• Differentiating b/w bacterial and viral meningitis.
• Serum -10.2 ng/mL sensitivity and specificity up to 100% - bacterial
meningitis.
• At present, recommendations on its use cannot be made at this time (C-II).
(Because measurement of serum procalcitonin concentrations is not readily
available in clinical laboratories)
IDSA GUIDELINES OF PYOGENIC MENINGITIS
61. PCR
• Amplify DNA -N. meningitidis, S. pneumoniae , H. influenzae type b, S.
agalactiae, and L. monocytogenes
• Sensitivity - 100%, specificity - 98.2%
• PPV - 98.2%, NPV - 100%.
• In patients with bacterial meningitis for whom the CSF Gram stain result is
negative (B-II).
ESCMID GUIDELINESOF PYOGENIC MENINGITIS
62. Latex agglutination
• Utilize serum bacterial antibodies or commercially available antisera-
against the capsular polysaccharides of pathogens.
• Simple and rapid (results are available in 15 min).
• Sensitivity
1. 78%–100% for H. influenzae type b,
2. 67%–100% for S. pneumoniae,
3. 69%–100% for Streptococcus agalactiae,
4. 50%–93% for N. meningitidis.
ESCMID GUIDELINESOF PYOGENIC MENINGITIS
63. • Negative test does not rule out infection.
• Routine use of latex agglutination - No consensus opinion
• IDSA does not recommend - for the bacterial etiology of meningitis (D-II),
although for negative CSF Gram stain result (C-II).
• Latex agglutination- useful for the patient pre-treated with antimicrobial
therapy(B-III).
ESCMID GUIDELINESOF PYOGENIC MENINGITIS
64. Limulus lysate assay
• Lysate - from the amebocyte of the horseshoe crab: Limulus
polyphemus.
• For suspected gram-negative meningitis.
• Positive test result suggests the presence of endotoxin.
• Not sensitive as screening for gram-negative meningitis in neonates.
ESCMID GUIDELINESOF PYOGENIC MENINGITIS
65. • Does not distinguish between specific gram-negative organisms.
• Negative test result does not rule out gram negative meningitis.
• IDSA do not recommend routine use (D-II)
67. TREATMENT GUIDELINES
Step 1. Suspect of bacterial meningitis
a) Ceftrixone 2 gm iv 12 hourly / Cefotaxime 2 gm iv 6 hourly
b) Probable meningo-coccal sepsis – single dose of ciprofloxacin 500 mg orally (to eliminate carrier state)
Step 2. Review after gram stain
i. Pneumococcus
a) Continue as step 1 a
b) Suspected penicillin resistance – add vancomycin 20 mg/kg 12 hourly
c) Alternatively add rifampicin 600 mg iv or orally 12 hourly
ii. Neisseria meninigitidis - continue as step 1 a
iii. Listeria – Contine as step1 a, add ampicillin / amoxycillin 2 gm iv 4 hourly
iv. Gram negative bacilli – continue as step 1 a, meropenem 2 gm iv 8 hourly
MANUAL OF MEDICAL MICROBIOLOGY
68. MANUAL OF MEDICAL MICROBIOLOGY
Step 3. When culture / PCR reports available
i. Pneumococcus confirmed –
a) Penicillin sensitive – continue as step 1a (switch to benzylpenicillin 2.4 gm iv 4 hourly)
b) Penicillin resistant but cephalosporin sensitive – continue as step 1 a
c) Penicillin and cephalosporin resistant – add vancomycin
d) Treat for 14 days in case of antibiotic resistance or incomplete recovery by treatment
ii. Nisseria – continue as step 1 a
iii. Listeria – switch to ampi/amoxycillin, alternatively cotrimoxazole (in case of anaphylaxis to beta
lactams)
iv. Haemophilus – Continue as step 1 a
v. Enterobacteriacae – continue as step 2.
69. (VINCENT et al NEJM.1997)
Factors influencing the bactericidal activity in CSF
Factors increasing activities
•Small molecular size
•Low degree of protein binding
•Low degree of ionization in
physiological pH
•High solubility in lipids
Factors reducing activities
•Low pH of fluids
•High proteins
•High temperature
71. Empirical therapy for pyogenic meningitis
Predisposing Factor Antimicrobial therapy
Age Neonate Ampicillin plus cefotaxime; or ampicillin plus an
aminoglycoside
Infant (1-23 months) Vancomycin plus a third or fourth generation
cephalosporina
Children & adults (2-50 years) Vancomycin plus a third or fourth generation
cephalosporina,b
Adults (>50 years) Vancomycin plus ampicillin plus a third or fourth
generation cephalosporina
Immuno-compromised state Vancomycin plus ampicillin plus either cefepime
or meropenem
Basilar skull fracture Vancomycin plus a third or fourth generation
cephalosporina
Head trauma Vancomycin plus either ceftazidime or
meropenem
a Cefotaxime or ceftriaxone or cefepime
b Add ampicillin if meningitis caused by Listeria monocytogenes is suspected
72. DURATION OF ANTIBIOTIC THERAPY
Microorganism Duration of therapy
Neisseria meningitidis 7
Haemophilus Influenzae 7
Streoptococcus pneumoniae 10-14
Streptococcus agalactiae 14-21
Aerobic gram negative bacilli -a 21
Listeria monocytogenes > 21
a Duration in the neonate is 2 weeks beyond the first sterile CSF culture or > 3
weeks, whichever is longer
IDSA GUIDELINES OF PYOGENIC MENINGITIS
73. Steroid
Infants and children
• Evidence supports - dexamethasone with H. influenzae type b meningitis (A-I).
• Dexamethasone - (10–20 min prior)
• first antimicrobial dose at 0.15 mg/kg every 6 h for 2–4 days.
• Should not be given to who have already received antimicrobial therapy (A-I).
Ogunlesi TA, Odigwe CC, Oladapo OT et al
74. Steroid
Infants and children
• Pneumococcal meningitis - controversial (C-II).
• 2003 IDSA on the use of steroids for pneumococcal meningitis is as follows:
• “For infants and children 6 weeks -, adjunctive therapy with dexamethasone
may be considered after weighing the potential benefits and possible risks.
Ogunlesi TA, Odigwe CC, Oladapo OT et al
75. Steroid
Adults
• IDSA recommends use of dexamethasone in adults with suspected or proven
pneumococcal meningitis (A-I).
• Continued if the CSF Gram stain reveals gram-positive diplococci, or if blood or
CSF cultures are positive for S. pneumoniae.
Ogunlesi TA, Odigwe CC, Oladapo OT et al
76. Steroid
Adults
• Adjunctive dexamethasone may be harmful -pneumococcal meningitis caused
by highly penicillin- or cephalosporin-resistant strains
• Diminished inflammatory response induced by dexamethasone might reduce
CSF vancomycin penetration and delay CSF sterilization.
Ogunlesi TA, Odigwe CC, Oladapo OT et al
77. Prophylactic anticonvulsants
• Seizure frequency 5-27 % (varies with aetiology)
• Pneumococcal 24 %
• Meningococcal 5 %
• Risk factors for seizures
1. Tachycardia
2. Low GCS
3. Focal abnormalities
No consensus criteria, no data to suggest to use of prophylactic
anticonvulsants NeuroICU 2nd edition
78. • Principles of antimicrobial therapy - same
• Direct instillation into the ventricles through
1. external ventriculostomy
2. shunt reservoir - occasionally needed in shunt infections (A-III).
• Antimicrobial agents are not approved - US FDA.
SHUNT INFECTION
79. • Doses can be determined by calculation of the “inhibitory quotient.”
• Sample of CSF is withdrawn to obtain the trough CSF concentration.
• Inhibitory quotient - trough CSF concentration / MIC of the agent for isolated b
pathogen.
• It should > 10–20 for consistent CSF sterilization.(BIII)
IDSA GUIDELINES OF PYOGENIC MENINGITIS
80. • Shunt removal and component of external drainage with
appropriate antibiotic in ventriculitis (A-II).
• Timing of shunt re-implantation - depends
1. Isolated microorganism,
2. Extent of infection
3. CSF findings (B-II)
SHUNT REMOVAL OF DIRECT SHUNT INFECTION
IDSA GUIDELINES OF PYOGENIC MENINGITIS
81. • If culture positive antibiotics therapy until CSF culture results
remain negative for 10 consecutive days
• Duration of antibiotics (no consensus guidelines)
gram negative bacilli 10-14 days
Coagulase negative staph 7 days
Staph aureus – 14 – 21 days
IDSA GUIDELINES OF PYOGENIC MENINGITIS
82. PARTIALLY TREATED PYOGENIC MENINGITIS
• CSF pressure normal or elevated
• WBC 5-10000 PMN predominant (mononuclear if pre-treated for extended
period)
• Protein 100-500 mg/dl
• Glucose normal or decreased
• Gram stain, antigen agglutination test can be normal
• PCR and culture recommended (A-III)
• Treatment – no consensus guidelines of treatment.To treat as new case
Ananthnarayan micobiology 8 th edition
83. • Yes
Not reponding clinically after 48 h of appropriate antimicrobial therapy (AIII).
Indicated pneumococcal meningitis caused by -resistant strains
Neonates meningitis gram-negative bacilli -repeated lumbar punctures to
document CSF sterilization
• No
document CSF sterilization
improvement of CSF parameters
REPEAT LUMBAR PUNCTURE
84. OPD TREATMENT GUIDELINES
Inpatient antimicrobial therapy for > 6 days
Absence of fever for at least 24-48 hours prior to initiation of outpatient therapy
No significant neurologic dysfunction, focal findings, seizure activity
Clinical stability or improving condition
Ability to take fluids by mouth
Access to home health nursing home for antimicrobial administration
IDSA GUIDELINES OF PYOGENIC MENINGITIS
85. OPD TREATMENT GUIDELINES
Reliable intravenous line and infusion device (if needed)
Daily availability of a physician
Established plans 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
IDSA GUIDELINES OF PYOGENIC MENINGITIS
87. • Complications more in adults
• The most common deficits:
• Cerebrovascular involvement – 15.1 percent.
• Cerebral edema – 14 percent.
• Hydrocephalus – 11.6 percent.
• Septic shock – 11.6 percent.
• Disseminated intravascular coagulation – 8.1 percent.
• Acute respiratory distress syndrome – 3.5 percent.
(Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study. Arch
Neurol 1993; 50:575)
Prognosis
88. SEQUELAE
• Most common sequelae
1. Deafness – 10.5 percent.
2. Bilateral severe or profound deafness – 5.1 percent.
3. Mental retardation – 4.2 percent.
4. Spasticity and/or paresis – 3.5 percent.
5. Seizures – 4.2 percent.
89. MORTALITY
• The mortality rates lowest in children in developed countries showed
a 4.8 percent mortality from 1955 to 1993
• 3.8% for H. Influenzae
• 7.5% for N. Meningitidis
• 15.3% for S. pneumoniae
WHO surveillance data
90. Chemoprophylaxis Regimens for Meningococcal Disease
Age Group Antibiotic Regimen for Chemoprophylaxis
Infants aged 1 month or less Rifampin 5 mg/kg q12h for 2 days
Children and infants older than 1 month Rifampin 10 mg/kg q12h for 2 days
Children less than 15 years of age Ceftriaxone 125 mg intramuscularly once
Adults Ceftriaxone 250 mg intramuscularly once
or
Ciprofloxacin 500 mg once*
or
Rifampin 600 mg PO BID for 2 days
91. FOLLOW UP
• In children and adults testing of hearing loss should be performed
during admission (LEVEL A) and during follow up (LEVEL C).
• In case of hearing loss patient should be referred to ENT specialist
performing cochlear implant.(LEVEL A).
• Routine neuropsychological examination is not recommended, if
cognitive decline occurs neuropsychological examination and
rehabilitation is indicated (LEVEL B).
ESCIMID GUIDELINES OF MENINGITIS
92.
93. Sample collection box Department of Clinical
Microbiology
CSF testing in Department of Clinical Microbiology
102. NIMHANS EXPERIENCE
• Cell counts should be performed on un-centrifuged CSF specimen
(Nagarathna et al)
• Clot in CSF invalidates the CSF cell count (Nagarathna et al)
• Management of the patients should be based on immediate gram
stain and cell count (Nagarathna et al)
• Gram negative organisms are the most common cause of post-
operative meningitis (Dwarkanath et al)
103. TAKE HOME MESSAGE
• Pyogenic meningitis is a common cause of febrile encephalopathy.
• Classic triad is seen in only 30-40% .
• Csf for febrile encephalopathy is mandatory unless contraindicated.
• Prompt treatment leads to reduction in morbidity and mortality.
• Vaccination forms the important component of prophylaxis.