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Preceptors: Prof.

Rita Sood
Prof. Padma M.V.
Dr. Rohit Bhatia

Speaker: Swastik Agrawal


 Introduction
 Epidemiology
 Etiology
 Pathophysiology
 Clinical presentation
 Investigations
 Differentiating acute bacterial from non bacterial
meningitis
 Prognostic markers
 Treatment
 Complications and outcome
 Prevention
 Summary
 Definition- Acute purulent infection within the
subarachnoid space.
 Meninges, subarachnoid space and brain parenchyma
frequently involved together-meningoencephalitis.
Pus covered
surface -
Leptomeninges
Incidence- 0.6-4/1,00,000 adults in developed nations.

Upto 10 times higher in developing nations.

Mortality 16% to 37% despite modern antibiotics.

Lancet Infect Dis 2007; 7:191–200


Lancet Neurol 2006; 5: 332–42
 Disease burden greatly reduced as a result of routine
immunization of children with Hib vaccine.

 Further reduction expected with wider usage of


pneumococcal and meningococcal vaccines.
 Proportion of cases in adults on the rise (≈ 56%)
Lancet Infect Dis 2007; 7:191–200
In poorer countries where routine vaccination has not been
implemented H. influenzae is still an important causative
organism.

C> ..

.. '" ... ,,
..

outine Hib implementation status


D Yes ..
!] No

'ti )
 In developed world MC organism in both children and
adults is S. pneumoniae ≈ 50%

 N. meningitidis ≈ 25%

 Group B Streptococcus ≈ 15%

 Listeria monocytogenes ≈10%

 H. influenzae < 10%

 Staphylococcal species and gram negative bacilli in


special circumstances.
Common causes of acute bacterial meningitis in resource poor settings
Lancet Neurol 2008; 7: 637–48

 Tubercular and cryptococcal meningitis common in HIV


 Maybe difficult to distinguish from acute bacterial
meningitis.
Age wise distribution of pathogens- 10 year study from
south India.

Indian Journal of Medical Microbiology, (2007) 25 (2):108-14


 S. pneumoniae: pneumococcal pneumonia, sinusitis
otitis media, alcoholism, diabetes
mellitus, asplenia, HIV,
hypogammaglobulinemia, complement
deficiency, head trauma,CSF
rhinorrhea.

 N. meningitidis: asplenia, complement deficiency.

 L. monocytogenes: neonates, elderly (>60 years),

pregnancy, immunodeficiency.
 H. influenzae: unvaccinated children and adults.

 Staphylococci: neurosurgical procedures, s.c.


Ommaya reservoirs, shunts etc.

 Enteric gram negative bacilli: diabetes, cirrhosis,


alcoholism, chronic UTI, craniotomy
 Pneumococci colonize the nasopharynx and compete
with resident flora.
 Balance effected by recent antibiotic usage, host
immunity, smoking, over crowding.
 Invade intravascular space via the nasal epithelium.
 Avoid phagocytosis and complement mediated
destruction mainly by virtue of polysaccharide capsule.
 Invade choroid plexus cells and gain access to CSF via
transcytosis.
 Low levels of complements, antibodies and leukocytes in
CSF allow rapid bacterial multiplication.
Lancet Neurol 2006; 5: 332–42
Invas ion o f SAS by pathogen ic bac ter ia

Mu ltip lication and lys is o f organ isms

Release o f bacter ia l ce ll wa ll componen ts (endo tox n


i , techo ci ac di )

Production of i nfl ammat ory cytoki nes like TNFα , IL-1β , and IL -6

Adherence of Alterations in Production o


Alt ered BBB ft
l eukocy l l it t ,
es to cerebra b ood exc a ory AA
permeabili ty
Hence neuronal injury can progress
endothe a ce s
li l ll
ow
fl reactive O and
i
N spec es
ilit f l ,
ll i j
even after CSF sterilization.
↑Permeab y o vesse s
ury Leakage
t i if o l p asma
Leukocytes enter CSF
degranu
l tt ia e and
l re ease
Ce
and
t
n

dea h pro e ns nto CSF cy ok nes

Exudate obstructs outf ow


l
& resorption o CSF and Cerebra
f l t
Infiltrat es vascu l fl l fl
a ure i schemial ↓ B ood ow ↑ B ood ow

Obstruc ve and
ti cytotox c edema stroke
commun cating hydrocepha us
vasogenic edema Interstitia
i l edema l i i zures ,
se

↑ CP
DEA I
DEATTHH
Coma
Symptoms
Fever (75-95o/o)
Headache (80-95%)
Photophobia (30-50%)
Vomiting (90% of 10% of adults)
children;
Signs
Neck stiffness (50-90%)
Confusio (75-85%)
nKernig' sign*
s (5%)signst
Brudzinski'
s
Focal (5%) deficit {20-30%)
neurological
Fits (15-30%)
Rash (10-
Common signs and symptoms of acute bacterial meningitis
15%)
Lancet Neurol 2008; 7: 637–48
Right 3rd nerve palsy and severe herpes labialis in a patient of
acute bacterial meningitis
 Classic triad of fever, neck stiffness, and altered
sensorium seen in only 2/3rd of adults.

 More common in pneumococcal than other bacterial


meningitis.

 1 of the 3 elements present in almost all patients.

 Absence of all 3 rules out acute meningitis with


sensitivity of 99-100%.

 Usually history is of 24 to 48 hours.


Rash most commonly seen with meningococcal
disease (92% of meningitis cases with rash).

Presence of shock, rash or clustering of cases should


raise suspicion of meningococcemia.

Petechial skin rash that accompanies Fine petechial rash in disseminated infection and
meningitis due to Neisseria meningitidis. meningitis due to Staphylococcus aureus
 Kernig’s and Brudzinski’s sign have poor sensitivity
(5%) with high specificity (95%)

 Nuchal rigidity has low sensitivity (30%) and


specificity (68%).
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% in a small study, never


been further evaluated extensively.

Lancet Infect Dis 2007; 7:191–200

N Engl
J Med 2004;351:1849-59.
 ↑ TLC (mean 10,600/cc vs 8900/cc).
 ↓Platelet counts- systemic infection, sepsis.
 **Hyponatremia (serum Na < 135mEq/l) seen in 30%
cases.
- Severe (Na <130) in 6%. (resolves spontaneously)
- More common with L. monocytogenes and in
patients with symptoms > 24 hours.
 Blood culture- should be taken immediately, before
starting antibiotics. Positive in 74% cases.
**QJ Med 2007;100:37-
 Acute inflammatory markers - ESR, CRP and
Procalcitonin elevated : distinguish acute bacterial from
non bacterial meningitis.

 Diagnostic lumbar puncture - performed in all cases


unless specific contraindications present-

i) local infection at puncture site


ii) subdural abscess
iii) bleeding diathesis
iv) septic shock- diastolic BP < 60 mm of Hg
v) mass lesion/ ventricular obstruction/ brain shift on
cranial imaging
Indications for cranial imaging before L.P.

 Non contrast CT scan of the head before L.P. is


indicated if one of the following is present:

i. New onset seizure (within one week of presentation)


ii. Immunocompromised state
iii. Papilledema
iv. Focal neurological signs (excluding hearing loss)
v. Moderate to severe impairment of consciousness
(GCS <10)

 Absence of all these features has 97% negative


predictive value for an intra cranial abnormality that
would preclude a lumbar puncture
N Engl J Med 2004;351:1849-59.
Lancet Neurol 2006; 5: 332–42
Meningeal
enhancement in
Bacterial
meningitis.
Analysis of CSF- typical findings in bacterial meningitis
Opening >180 mm water in 90% cases
pressure

WBC 10-10,000/cc, predominantly neutrophils


(>100cells/cc in 90% cases)
RBC Absent in non traumatic tap

Glucose <40 mg/dl in 60% cases

CSF/blood <0.4 in 60% cases


glucose
Protein >45mg/dl (in 90% cases)

Gram’s stain Positive in > 60%

Culture Positive in > 80%

Latex + in pneumococcal, meningococcal, Harrison's


Principles of
agglutination H. influenza, E.coli, Gr B streptococcus Internal Medicine,
17th ed
Limulus lysates + in gram negative meningitis

PCR for Research test


bacterial DNA
Cell type Cell count Glucose Protein

Normal Lymphocytes 0-4 >60% of < 0.45


blood mg/dl
glucose
Viral Lymphocytes 10-2000 Normal Normal

Bacterial Polymorphs 1000-5000 Decreased Increased

Tubercular Lymphocytes/ 50-5000 Decreased Increased


polymorphs
Fungal Lymphocytes 50-500 Decreased Increased

CSF findings in infectious meningitis


Methods to improve diagnostic yield of microbiology

 Examine CSF before or shortly after antibiotics started.


 Submit large volume of CSF ( >5 ml) for microbiology.
 Gram stain and inoculation for culture as soon as possible.
 Centrifuge at high force ( 3000g) for 20 min and stain and
culture the deposit.
 Subculture after 24 hr inoculation in brain heart infusion
broth at 37°C with 5% CO2.
 Storage/ transport of CSF – incubate at 37°C if available or
at room temperature.
 Do not refrigerate.
Turbid CSF with fibrous spider clot after 1 hour in pyogenic meningitis
Gram positive diplococci of S. Neutrophils and gram negative bacilli in
pneumoniae in CSF.
CSF of an elderly patient of E. coli
meningitis

Gram negative diplococci of Gram negative rods- H. influenza


meningococci in CSF
 CSF latex agglutination for pneumococcal and
meningococcal antigen - specificity of 95-100%.

 Sensitivity 70-100% for pneumococci, 30-70% for


meningococcci.

 Pneumolysin in CSF - detected by Cowan 1


Staphylococccal protein A co-agglutination method.

 Sensitivity and specificity of 91 and 92% respectively.


Indian J Med Res 119, February 2004, pp 75-78
 CSF C reactive protein (CRP)- rapid test by latex slide
agglutination method, available as a kit.
 Positive when value > 6μg/ml.
 Sensitivity of 84% and specificity of 100% in
distinguishing acute bacterial from aseptic meningitis.
Indian Pediatrics, Vol. 32-June 1995

 Semi quantitative measurement of glucose and protein


using urinary dipsticks may be acceptable if lab. facilities
unavailable.

 It is able to differentiate abnormal from normal CSF in


97% and viral from bacterial meningitis in 98% cases.
Lancet Neurol 2008; 7: 637–48
Study of 151 adults with acute meningitis-

Comparison between ABM and NBM on biological variables

American Journal of Emergency Medicine (2007) 25, 179–184


- . .
-
Sensit Specif PP NP PL NL Accur
ivity icity V V R R acy
Eirergency 0.8 0. OJ 0. 3.8 0. 0.
physician 9 77 I 96 6 14 79
CSF 0.5 0. 0. 0. 8.3 0. 0.
leukocyte
CSF/blood 0*
0.3 94
0.4 53
0. 94
0. 3*
0.5 53
1.6 71
0.1
rount
glucose
CSF ratio 0.7
3*
0.6 0.
2*
0. 0.
07
0. 0.
82
0. 3.1
7*
10. 0.
0*
0. 0.•
0.
1
% CSF
protein 83* 75
94 30
58 96
96 2
50* 29
39 71
75
leukocyte
Serum 0.7 0. 0.
1.0 0. 3.0 0. 0.
Serum 0. 1.0 >10 0.9
CRP
PCT 8
87 74
0* 28
0• 96
99 0*0 30
23 75
9*
PPV irdieab.~ valoc; NPV, ircdkt \'Bl PLR, ixisitivc ratio; NLR, negative
po~tivc
* P < predictive o:gativc
.05 vs crocrgcncy ivc theue;
physkian; likelihood
th~oold valoo forlikelihood ratio.was
each variaNc
dctcrmimxl by the ROC ewvc (Tabk 4).
Comparison of the efficiency of the emergency physician and various biological results

American Journal of Emergency Medicine (2007) 25, 179–184


bacterial meningitis (contd.)

Threshold values for each variable determined by the AUC

American Journal of Emergency Medicine (2007) 25, 179–184


Bacterial meningitis score (BMS)
Points

Predictor Present Absent

CSF Gram stain 2 0

CSF protein > 80mg/dl 1 0

CSF ANC>1000/cc 1 0

Peripheral blood ANC > 1 0


10,000/cc
Seizures at or before 1 0
presentation
JAMA. 2007;297:52-60
 Risk of bacterial meningitis is very low (0.1%) with BMS
0 and it increases as the score increases:-
– 3% with score 1
– 27% with score 2
– 70% with score 3
– 95% with score ≥ 4

 It has a negative predictive value of 99.9% for acute


bacterial meningitis.

 Validated only in age group of 29 days to19 years. Not


applicable to adults and neonates.
JAMA. 2007;297:52-60
Indicators of poor prognosis in a case of bacterial
meningitis are:-
1. Evidence of systemic compromise – tachycardia
(HR>120 bpm), low blood pressure, positive blood
culture, raised ESR, low platelet count.

2. Low CSF leukocyte count (<100/cc).

3. Low score on GCS

4. Advanced age
5. Predisposing conditions like immunocompromised
state, pneumonia, otitis, sinusitis.

6. Cranial nerve palsy

7. Pneumococcal meningitis- 6 times higher chance of


unfavorable outcome compared to meningococcal
meningitis.
Lancet Infect Dis 2007; 7:191–200
N Engl J Med 2004;351:1849-59.
 A bedside risk score to identify individuals with
high risk of adverse outcome that can be used
within 1 hour of presentation has been
developed using both a derivation cohort (696
cases) and a validation cohort (301 cases).

 22 variables were studied and 6 were found to


have a significant bearing on outcome.
Ann Neurol 2008;63:90–97
 This score helps to decide level of care required
and for informing the patient and his/her
relatives about the prognosis.
 Antibiotics are the mainstay of treatment.
 Should be given as early as possible.
 Delay >3 hours independently associated with mortality
Lancet Infect Dis 2007; 7:191–200

Q J Med 2005; 98:291–298


100

90

ao
70

l
s
8
60

"
·"i" 50
a ,o
x8
v
JO

20

10

- -
0
1910 1920 19)0 9~0
] 1%0 1970 1980 1990

=l
Pn-eumoco«.,;1 ~tallin Thl,d·genet.1tl
M1'1$erum ~emiurty on
S.pneum0tiioe • mt.rathec;;.,lly ceph,tosporin
Thlfd
genero1t1on
ctph;,losporln-
.. v.:incomyc:i n

=l
Chl0t1mpl,enic Th!rd·1tntr1;k)
ol n
< eph:1!~porir1
H. influ1n10. Sutfona.mid
es

Penidllin (.-impicitlin} +third-generation


Trutment for [ c:tphalosporin
N. meningilidis

Figure. MortaUty Rates Associated with Community.Acquired Bacterial Meningitis over the Past 90 Years.
Initial empirical antibiotics
Predisposing Common bacterial Antimicrobial
factor pathogens therapy
Age
<1 Streptococcus agalactiae, Escherichiacoli, Ampicillin plus cefotaxime or ampicillin
month Listeria plus an
monocytogenes, Klebsiel/a species aminoglycosidea third-generation
1-23 Vancomycin
months Streptococcus
S. aga/actiae,pneumoniae,
HaemophilusNeisseria
E plus ceohalosporn':"
2-50 influenzae,
meningitidis, coli Vancomycin a third-generation
years N . S.meningitidis,S.
pneumoniae, N.pneumoniae
L. plus cephalospom'"
>50 years meningitidis, monocytogenes, Vancomycin arnpicillin plus a third-
aerobic gram-negative plus generation
Head trauma
bacilli cephelosoori
Basilar skull S. pneumoniae, H. influenzae, group A p- Vancomycin
n':" plus a third-generation
fracture hemolytic cephalosporin"
Penetrating streptococci Vancomycin plus cefepime, vancomycin plus
trauma Staphylococcus aureus. coaqulase-neqetive ceftazi•
staphylo- cocci (especially Staphylococcus dime. or vancomycin plus meropenem
epidennidis}.aer• obic gram-negative bacilli
Postneurosurg (including Pseudomonas aeruginosa} Vancomycin plus cefepime, vancomycin plus
ery Aerobic gram-negative bacilli {including P ceftazi•
aeruginosa}, S . aureus, coagulase-negative dime, or vancomycin plus meropenem
CSF staphylococci (es• pecially S. epidermidis} Vancomycin plus cetepime," vancomycin plus
shunt Coagulase--negative staphylococci {especially ceftazi•
S. epi- dennidis}, S. aureus. aerobic gram- dime," or vancomycin plus meropenern?
negative bacilli (including P aeruginosa},
Propionibacteriumacnes Clinical Infectious Diseases 2004; 39:1267–84
Dosage
Total daily (dosing interval in hours)
dose
Neonates, age in days

Antimicrobial agent o- 8-28" Infants and children Adults


Amikacio? 15-20
"78
mg/kg 30 mg/kg (8) 20-30 mg/kg (8) 15 mg/kg (8)
Ampicillin (12)
150 mg/kg (8) 200 mg/kg (6-8 @oo mg/kg [2 g:ill)
Aztreonam 1fil) 6-8 g (6-8)
Cefepime 150 mg/kg (8) 6 g (8)
Cefotaxime 100-150 mg/kg (8-12) 150-200 mg/kg (6-8) 225-300 mg/kg (6-8) 8-12 g (4-6)
~hazidimi) 100-150 mg/kg (8- 150 mg/kg (BJ g (8)
[c fqiaxone"l 12) @=jgo mg/)5g,(12- 4g,{1ki@
Chloramphenicol 25 mg/kg (24) 50 mg/kg (12-24) 24), 4-6 g (6,C
Ciprofloxacin 75-100 mg/kg (6)
800-1200 mg (8-
Gatifloxacin 12)
Gentamicinb 5 mg/kg (12) 7.5 mg/kg 7.5 mg/kg (8) 400 mg (24)d
Meropenem (Bl 120 mg/kg (8) 5 mg/kg (8)
Moxifloxacin 6 g (8)
Nafcillin 75 mg/kg (8-12) 100-150 mg/kg (6-8) 200 mg/kg (6) 400 mg (24)d
Oxacillin 75 mg/kg (8-12) 150-200 mg/kg (6-8) 200 mg/kg (6) 9--12 g (4)
Penicillin G 0.15 mU/kg (8- 0.2 mU/kg (6-8) 0.3 mU/kg (4-6) 9--12 g (4)
Rifampin 12) 10-20 mg/kg (12) 10-20 mg/kg (12-24)9 24 mu (4)
Iobrarnvcin'' 5 mg/kg 7.5 mg/kg (8) 7.5 mg/kg (8) 600 mg (24)
TMP-SMz! (12) 5 mg/kg (8)
10-20 mg/kg (6-12)
Vancom cing 20-30 m /kg (8-12) 30-45 mg!!<g (6-8) 60 mg!!<g(6) 10-20 mg/kg (6-12)
30-4539:1267–84
Clinical Infectious Diseases 2004; mg/kg (8-12)
 These recommendations are based on the US
microbiological antibiotic susceptibility patterns.

 The Netherlands national guidelines recommend


monotherapy with penicillin in patients 16-60 years
based on low incidence of penicillin resistance locally.

 No India/ SE Asia specific guidelines available.


Organism specific antibiotics
Microorganism susceptibility Standard therapy Alternative
. therapies
Streptococcus pneumoniae
Penicillin MIC
<0.1 µg/ml Penicillin G or ampicillin Third-generation cephalosporin, • chloramphenicol
0.1-1.0 µg/mlb Third.generation cephalosporin" Cefepime (B-lll. meropenem (B-
;;,,2.0 µg/ml Vancomycin plus a Fluoroquinolone 11) (B-11)
third.generation cephalosporin'r" "
Cefotaxime or ceftriaxone Vancomycin plus a third.generation Fluoroquinolone (B-
MIC ;;,,1.0 µg/ml cephalosporin'r" " 11)
Neisseria meningitidis
Penicillin MIC
<0.1 µg/ml Penicillin G or ampicillin Third-qeneration cephalosporin,8 chloramphenicol
0.1-1.0 µg/ml Third-qeneration cephalosporin" Chloramphenicol fluoroquinolone meropenem
Listeria monocytogenes Ampicillin or penicillin G9 .Trimethoprim-sulfamethoxazole.
. meropenem (B-111)
Streptococcus agalactiae Ampicillin or penicillin G9 Third-qeneration cephalosporin" (B-111)
Escherichia coli and Third.generation cephalosporin (A- Aztreonam. fluoroquinolone. meropenem. trimethoprim•
other Enterobacteriaceae'' 11) sulfamethoxazole. ampicillin
Pseudomonas aeruginosag Cefepime" or ceftazidime9 (A-Ill Aztreonam," ciprofloxacin." meropenem"
Haemophilus influenzae
13-Lactamase negative Ampicillin Third-generation oephalosporin, • cefepime, chlor•
amphenicol, fluoroquinolone
P-lactamase positive Third.generation cephalosporin (A- Cefepime (A-1), chloramphenicol,
Staphylococcus aureus 1) fluoroquinolone
Methicillin susceptible Nafcillin or Vancomycin, meropenem (B-
Methicillin resistant oxacillin 111) linezolid (8-
Staphylococcus epidermidis Vancomycin1 Trimethoprim- 111)
Enterococcus species Vancomycin1 sulfamethoxazole, Linezolid
Ampicillin susceptible Ampicillin plus gentamicin (B-111)
Ampicillin resistant Vancomycin plus gentamicin
Ampicillin and vancomycin resistant Linezolid (B-111)

Clinical Infectious Diseases 2004; 39:1267–84


Duration of antibiotic therapy

Clinical Infectious Diseases 2004; 39:1267–84

 WHO recommendation – 5 day antibiotic therapy


 To be extended if-
– Immunocompromise
– Persistent fever
– Persistent seizures
– Coma Lancet Neurol 2008; 7: 637–48
 Mortality and rate of neurological sequelae remain high
despite appropriate antimicrobial therapy.

 Due to adverse effects of inflammatory cytokines.

 Corticosteroids act by
– inhibiting synthesis of IL-1 and TNF at m-RNA level
– decreasing CSF outflow resistance and
– stabilizing the BBB.

 Once macrophages and microglia activated and TNF


production induced, steroids have less effect.
 Hence steroids to be given early, with or before 1st dose
of antibiotics to have maximum effect.

 Duration of this window of opportunity not described.

 Dose- Dexamethasone 0.15 mg/kg I.V. 6t hourly for 4


h
days is the most widely recommended dose.

 2 day regimen with 0.4 mg/kg 12th hourly shown to be


equally efficacious in one study(Syrogiannopoulos,1994)
 Cochrane review- beneficial effect of steroids in adults
from both high and low income countries and children
from high income countries.
 Children from low income countries had neither benefit
nor harm.
 Overall case fatality decreased (RR 0.83), specially in
pneumococcal group (RR 0.42).
 10 adult patients need to be treated with steroids to
prevent one mortality.
 Lower rate of long term neurological sequelae (RR 0.67)
 Lower rate of short term neurological sequelae in high
income countries ( RR 0.56).
Cochrane Database of Systematic Reviews
2007, Issue 1. Art. No.: CD004405.
Comparison 01. All patients

No. of No. of
Outcome title studies participants Statistical method Effect size

01 Mortality 20 2750 Relacive Risk (Fixed) CI 0.83 [0.71, 0.99)


02 Severe heating loss 14 1747 95% CI 0.65 [0.47, 0.91
Relacive Risk (Fixed) CI 0.86 [0.68, )
03 Short-term neurological 10 1175
95% 1.08)
sequelae
Relacive Risk (Fixed)
04 Long-term neurological 10 1163 Relacive
95% Risk (Fixed) CI 0.67 [0.45, 1.00)
sequelae 95%
05 Adverse events 15 1484 Relative Risk (Fixed) 95% CI 1.08 [0.90,
1.29)

Comparison 02. Children

No. of No. of
Outcome title studies participants Statistical method Effect size
01 Mortality 15 2074 Relacive Risk (Fixed) 95% CI 0.99 [0.81, 1.20)
02 Severe hearing loss 13 1383 Relacive Risk (Fixed) 95% CI 0.61 [0.44, 0.86)

Comparison 03. Adults

1o. of No. of
Outcome title studies participants Statistical method Effect size

O I Mortality 5 623 Relative Risk (Fixed) 95% 0.57 (0.40, 0.81


02 Shorr-term 3 339 CI 0.42 J(0.22,
neurological se uelae Relative Risk (Fixed) 95% 0.78)
Cl
Cochrane Database of Systematic
Reviews
2007, Issue 1. Art. No.: CD004405.
Comparison 05. Income of
countries
No. No.
Outcome title of of
studies Statistical Effect
method size
participants
01 Mortality - all 2 275 Relat Ris (Fixe 95 Cl 0.8 [0.7 0.9
patients 0 0 ive k d) % Cl 3 1, 9]
02 Severe hearing loss - 1 17 Relac Ri (Fixe 95 C 0.6 [0.4 0.9
all patients 4 47 ive sk d) % l 5 7, 1]
03 Mortality·
Shore-termchildren 1 11 Relati Ris (Fixe 95 0.8 1.0
04 15 2074 Relative Risk (Fixed) 95% [0.6
Cl
neurological 0 75 ve k d) % 6 8]
0.99 [0.81, 1.20]
05 Severe hearing 1 13 Relati Ris (Fixe 95 C 8,
0.6 [0.4 0.8
sequelae
loss - all
- children 1 3,95%6]
06 Short-term neurological 2 11 7 ve k d)
836 %Relacive
l Risk (Fixed)
CIpatients 0.99 [0.77, 1.26]
07sequelae -children
Severe hearing loss 1 66 Relati Ris (Fixe 95 C 0.8 [0.5 1.3
in children 1 0 ve k d) % l 6 7, 0]
due to non-
Heamophilus infl
uenzae species
Cochrane Database of Systematic Reviews
2007, Issue 1. Art. No.: CD004405.
 Randomized controlled trial of 301 adult patients from
the Netherlands -

Distribution of scores on Glasgow outcome


scale at eight weeks
N Engl J Med, Vol. 347, N o. 20
DEXAMETHASON PucEeo RELATIVE
°'1TOOMEANO CULTUAE E GROUP RISK p
RESULTS GROUP l95o/o VALUE
noJlotal no. (%) Cllt

Unfavorable
outcome 23/157 (15) 36/144 (25) 0.59 (0.37-0.94) 0.03
Srnprocouus
All patients p11e111111111iae 15/58 (26) 26/50 (52) 0.50 (0.30-0.83)
0.006
Ntisuria mmi11Bitidis 4/50 (8) 5/47 ( 0.75 (0.21-2.63) 0.74
Other bacteria 2/12 ( 1/17 11) 2.83 (0.29-27.8) 0.55
Negauve bacterial culture; 2/37 17) 4/30 (6) 0.41 (0.08- 0.40
Death (S) (13) 2.06)
All 11/157(7 21/144 0.48 (0.24-0.96) 0.04
S. pnmmo11ine
patients ) 8/58 (14) (15)
17/50 (34) 0.41 (0.19-0.86)
N.
0.02 2/50 (4) 1/47 (2) 1.88(0.76-20.1) 1.00
mmi119itidis
Other bacteria 1/12 (8) 1/17 (6) 1.42(0.10-20.5) 1.00
Negative bacterial culture 0/37 2/30 (7) 0.20
Focal neurologic
abnormalities 18/143 (13) 24/119 (20) 0.62 (0.36- 0.13
All patients 11/49 (22) 11/33 (33) 1.09) 0.32
S. pnmmoniae 3/46 (7) 5/44 (11) 0.67 (0.33-1.37) 0.48
N. mmingitidis 3/11 (27) 3/16 (19) 0.57 (0.15- 0.66
Other bacteria 1/37 (3) 5/26 (19) 2.26) 0.07
Negative bacterial culture 1.45 (0.36-5.92)
Hearing loss 13/143 (9) 14/119(12) 0.77
0.14 (0.38-1.58)
(0.02- 0.54
All patients 7/49 (14) 7/33 (21) 0.67
1.13) (0.25-1.69) 0.55
S. pnmnumiae 3/46 (7) 5/44 (11) 0.57 (0.15- 0.48
N. mmingitidis 2/11 (18) 1/16 (6) 2.26) 0.55
Ocher bacteria 1/37 (3) 1/26 (4) 2.91 (0.30-28.3) 1.00
Negative bacterial culture 0.70 (0.05-10.7)

Outcome at eight weeks according to culture results

N Engl J Med, Vol. 347, N o. 20


RCT from Vietnam of 435 cases - no benefit in mortality at 1
month or mortality and disability at 6 months.
Significant increase in mortality in probable bacterial
meningitis cases probably due to a number of TBM cases in
this subgroup

N Engl J Med 2007;357:2431-40.


 RCT of 465 adult cases in Malawi - no difference in
mortality or disability, even in proven pneumococcal
meningitis patients.

N Engl J Med 2007;357:2441-50.


 90% of study population were HIV positive.

 Since these patients already have an attenuated host


response, corticosteroids may not confer any advantage.
N Engl J Med 2007;357:2441-50

 As per these studies routine use of steroids in


developing countries with high incidence of HIV and
tuberculosis is questionable.
 Potential adverse effects of corticosteroids were not
found to be higher in dexamethasone treated patients.

N Engl J M ed, Vol. 347, N o. 20


 No evidence to indicate that short term steroid use
worsens neurocognitive consequences of meningitis by
hippocampal neuron apoptosis.

 Dexamethasone reduces vancomycin levels in CSF


and delays CSF sterilization. Careful observation of
such patients is needed.
 Treatment of raised ICP –
- Head end elevation (30°-45°)
- IV mannitol (25-100 g 4t hourly)
h
- Intubation and hyperventilation (PaCO2 25- mm
30
of Hg). Maintain ICP below 20 mm of Hg.

 Maintain blood pressure and urine output.


 Aggressive fluid resuscitation to be avoided for
fear of hyponatremia.
 Drugs aimed at down regulating inflammatory mediators
and pathways responsible for neuronal injury in bacterial
meningitis are at the experimental level .

Effects of adjuvant therapies on experimental bacterial meningitis

Lancet Neurol 2006; 5: 332–42


Suspicion of bacterial meningitis

Immunocompromised, H/O CNS disease, new onset seizures, focal deficits, papilledema, altered sensorium ,
delay in performing lumbar puncture.

No Yes

Blood culture and lumbar puncture STAT Blood culture STAT

Dexamethasone + empirical Dexamethasone + empirical


antibiotic therapy
antibiotic therapy

No CT scan head
Consider alternate
diagnosis CSF c/w pyogenic meningitis?
No C/I to
t lumbar puncture
Yes
Perform lumbar puncture
CSF gram stain positive?

Yes
No

Dexamethasone + empirical Dexamethasone + targeted


Dexamethaso
antibiotic therapy antibioti therapy
antibiotic
Lancet Neurol 2006; 5: 332–42
Cerebral abscess
Cerebral abscess
Gross:
Enlarged lateral ventricles
in a patient with
hydrocephalus - treated by
placing two shunts.
Dilation of the cerebral
ventricles (Hydrocephalus).
25 21%
. 19%
'~ 20 -
u
0 *
°E~ -
.-..
14%
13%
~ ·.: 15 .
ca. ·•en
'.: - - -
12%
10%
""-" . ~
o ~ 10 -
~ E
-0 5%
-
0 4%
V'I
·a. 5- ~
UJ ~

0- . . . .

Cause of death

Lancet Neurol 2006; 5: 123–29


Lancet Neurol 2006; 5: 332–42
 Vaccination and chemoprophylaxis useful for prevention.

 Chemoprophylaxis reserved for meningococcal


disease.

 Only for close contacts, to be given as early as possible.

Clinical Infectious Diseases 2004; 39:1267–84


 Meningococcal vaccine – quadrivalent polysaccharide
vaccine against serotypes A,C,Y and W 135.
 Indications-
- Control type C outbreaks
- Travelers to endemic regions
- Asplenia and terminal complement deficiency
 Single dose, repeated in 3-5 years after age of 2 years.

Meningo-
coccal
vaccine
introduced
 Pneumococcal vaccine - 23 valent polysaccharide
vaccine.
 Indications- asplenia, immunodeficiency, DM, CRF,
nephrotic syndrome, CLD, malignancies etc.
 2 doses 1-2 months apart after age of 2 years
 One time revaccination after 5 years if age < 65 years.

 H. influenzae type b vaccine - conjugate vaccine.


 Indication- Routine immunization of all children.
 3 doses 2 months apart starting at 2 months age.
 Booster at 15 months age.
 Most common organisms are S. pneumoniae and N.
meningitidis.
 Absence of clinical triad, Kerning's and Brudzinski's sign
do not rule out acute bacterial meningitis.
 Start antibiotics early, before lumbar puncture if need be.
 Empirical antibiotics based on age, predisposing
condition and geographical resistance patterns.
 Give dexamethasone with or before 1s dose of antibiotic.
t
 Imaging not needed before lumbar puncture in all cases.
 Absence of typical CSF findings do not rule out acute
bacterial meningitis.
Thank You