cns infections 2013 -mk.pptx

7/29/2019 CNS infections 2013 -MK.pptx

1/54

Mahen Kothalawala


2/54

CNS infections Meningitis,

Encephalitis,

Parameningeal abscesses (subdural empyema andepidural abscess),

Brain abscesses,

&

CSF shunt infections.


3/54

Meningitis

is an inflammatory response to bacterial infection of thepia-arachnoid and CSF of the subarachnoid space


4/54

Epidemiology

Incidence is between 3-5 per 100,000

More than 2,000 deaths annually in the U.S.


5/54

Bacterial meningitis and other CNS infections areconsidered infectious disease emergencies that can causesignificant patient morbidity and mortality.


6/54

Mortality/Morbidity Bacterial meningitis -uniformly fatal before the antimicrobial

era.

overall mortality rate has decreased, but remains alarminglyhigh - - Higher in developing countries

Varies with the specific etiologic agent

S pneumoniae 19-26%

H influenzae - 3-6%

N meningitidis 3-13%,

L monocytogenes 15-29%


7/54

Survivors end up with complications

Children suffers mostly with complications


8/54

Morbidity associated with

complications

in children In adults

sensorineural hearing loss / Cranial nervepalsies

brain infarction,,

epilepsy hydrocephalus,

diffuse brain swelling

hydrocephalus,

cerebral vein thrombosis,

cerebral palsy

More with H.influenzae meningitis

**** Severe morbidity is associated with H.influenzae meningitis and TB

meningitis due to fibrinous exudates


9/54

Viral meningitis

Viral meningitis (without encephalitis) is less than 1%.

In patients with deficient humoral immunity (eg,agammaglobulinemia), enterovirus meningitis mayhave a fatal outcome.


10/54

Meningococcal

Meningitis belt - Faso, Chad, Ethiopia and Niger; in2002, the outbreaks occurring in

Burkina Faso, Ethiopia and Nigeraccounted for about 65% of cases


11/54

Crossing of the

BBB and entryinto the CSF

Bloodstreaminvasion

Nasopharyngealepithelial cell

invasion

Bacteremia with

intravascularsurvival

Nasopharyngealcolonization

Neisseria meningitides (meningococcus)and nasopharyngeal colonization with S

pneumoniae (pneumococcus).

Survival andMultiplication in

the subarachnoidspace

Pathogenesis of Meningitis


12/54

Retrograde flowto meningesthrough the

olfactory bulb

Nasopharyngealepithelial cell

invasion

MeningitisFree living

amoeba in naturalresovoires

Pathogenesis of Meningitis

eg,Naegleria fowleri,


13/54

Meningitis

Spread along the

CSF fistuloustract

Colonizing bacteria insinuses/auditorycanal otitismedia, congenital

malformations, trauma, directinoculation during intracranial

manipulation

Pathogenesis of Post traumatic/Neurosutgery Meningitis


14/54

Pathogenesis cont.With in the CNS, the infectious agents likely survive as

immunoglobulins, neutrophils, complement components

absent or activity limited

replication of infectious agents remain uncontrolled triggersthe cascade of meningeal inf lammation

Increased CSF concentrations of TNF-alpha, IL-1, IL-6, andIL-8 are characteristic findings in patients with bacterial

meningitis


15/54

Treatment using rapidly bactericidal agents maytransiently worsen the patients condition due to rapidrelease of pyrogenic substances in to CSF

Increase of proinflammatory mediators


16/54

Specific Pathogens

A P d i P h


17/54

Age group Predominant Pathogen

Age 0-4 weeks S agalactiae (group B streptococci)E coli K1L monocytogenes

Age 4-12 weeks S agalactiaeE coliH influenzaeS pneumoniae

N meningitidis

Age 3 months to 18

years

N meningitidis (worldwide epidemic strains A,B,C W135)

S .pneumoniaeH influenzae

Age 18-50 years S pneumoniaeN meningitidisH influenzae

Age older than 50 years S pneumoniaeN meningitidisL monocytogenesAerobic gram-negative bacilli

Immunocompromisedstate

S pneumoniaeN meningitidis

L monocytogenesAerobic ram-ne ative bacilli


18/54

***Direct extension from the throat or nasal or ear colonization an give rise to post

traumatic meningitis

Intracranial manipulation, includingneurosurgery

Staphylococcus aureusCoagulase-negative staphylococciAerobic gram-negative bacilli,includingPseudomonas aeruginosa

Basilar skull fracture S pneumoniae

H influenzaeGroup A streptococci

CSF shunts Coagulase-negative staphylococciS aureusAerobic gram-negative bacilli


19/54

Other causes

Bacteraemic infectionof Salmonella, Brucella andStaphylococcus aureus can cuase meningitis

Gram Negative meningitis in overwhelming infectionsdue to Strogyloides / Hyper infection due toStrongyloides stercorhalis

Leptospira and Treponema

Protozoa Acanthomoeba and Naeglaria fowleri Fungi Histoplasma and

Nematodes Angyostrogilus cantonensis


20/54

Clinical diagnosis unreliable- symptoms unreliable specially extremesof age

The efficacy of treatment (CNS) infections -depends on the accuracy ofthe etiologic diagnosis.

requires the best specimen at the appropriate time,

transporting it to the laboratory under optimum conditions,

processing the specimen efficiently and timely manner,

and selecting the tests necessary to identify the spectrum of possibleetiologies


21/54

Clinical signKernig's sign sensitivity, 5%; likelihood ratio for a positive test result

[LR(+)], 0.97)

Brudzinski's sign (sensitivity, 5%; LR(+), 0.97),

Nuchal rigidity (sensitivity, 30%; LR(+), 0.94)

Degree of meningealinflamation

6 up to 100 Clinical signs are unreliable

Inbetween Unreliable(>/=1000 WBCs/mL of CSF Nuchal rigidity shows diagnostic value- sensitivity

100% and negative predictive value 100%


22/54

Diagnosis

Should not be delayed

Inform laboratory

Initial report based on Cell count and Direct smear Cytospin method gives more positive yield than

traditional overlaying

Gram stain can be considered as the gold standard


23/54

Diagnosis Is established by investigation of CSF obtained from

lumbar puncture,

Cysternal puncture or ventricular puncture orfontanelle taps possible not done routinely

Exclude raised intracranial pressure before performingthe procedure due to possibility of herniation

Place of CT/ MRI to exclude SOL

When, contraindication +, diagnosis established usingother means Blood culture, WBC/DC, CRP togetherwith symptoms


24/54

Additional factors for success Communication between the clinician and laboratory-

about clinical notes, Patient condition, antibiotictherapy, Patient delay and Doctor delay

Seasonal prevalence of infectious diseases, forenteroviruses and arboviruses,

the epidemiology of emerging diseases such as West

Nile virus, and the immune status of the patient canbeis helpful.


25/54

Specimen collection and

transportationtimingAll specimens should be collected prior to the

initiation of antimicrobials

If therapy initiated action to nullify it-Innoculating itto broth media 1:5 ratio< specially for cerebral abcess

Specimens for diagnosis of CNS


26/54

Specimens for diagnosis of CNS

infections

Disease Specimen Quantity Note

Meningitis Cerebrospinal fluid

(CSF)

Mininmum of 1 mL/culture 1 to 2 mL [PCR]), 1 mL \antibody test

For M. tuberculosis, anddimorphic and filamentous fungirequire repeat CSF or largevolumes (10 to 20 mL) of

ventricular CSF.Blood 5 to 10ml as for bloodculture

Encephalitis or brainabscess

Abscessmaterial orirrigation

fluid

0.5 to 1.0 mL per culturerequest preferred

1 to 10 mL can be added to bloodculture medium antimicrobial

effect- dilution of 1 :5 or 1:10

Tissue 0.5 cc preferred minced /gently ground. Minceonly if filamentous fungi

expected.

Subdural

empyemaor epidural

Abscess

material /irrigation

0.51.0 mL per culture

request preferred

Small volumes of pus diluted

(ratio of 1:2) with sterile saline toallow washing of material from


27/54

Collection and transportationSpecimen Container Transport/Storage Conditions

Cerebrospinalfluid (CSF)

Sterile tube. Room temperature. Ice/Refrigeration aredetrimental to some bacteria and

anaerobes. For PCR 4 Cfor


28/54

Collection of CSF

Cerebrospinal fluid collected by lumbar puncture is theroutine specimen for diagnosis of meningitis

Strict aseptic techniques

Three or four containers depending on tests requested

But should have separate tubes for Gram stain/culture,

Biochemistry and glucose level- accompanied by bloodsample for RBS

Never to keep it in refrigerator


29/54

Which tube for microbiology?Any tube possible

First tube- Theoretically risk of contamination -epithelium or blood from skin and soft tissuecapillaries ruptured during the punctur

In practice, total volume of fluid is more importantthan the tube cultured.


30/54

CSF Examinations

Macroscopy color,clotting etc

Complete count

Differential count Gram stain of direct smear

Culture

Biochemistry sugar difference and proteins

PCR when indicated


31/54

CSF Macroscopy


32/54

Color of CSF supernatant Conditions or causes

Purulent Pyogenic meningitis

Yellow Blood breakdown productsHyperbilirubinemiaCSF protein >=150 mg per dL (1.5 g per L)>100,000 red blood cells per mm3

Orange Blood breakdown productsHigh carotenoid ingestion

Pink Blood breakdown products

Green HyperbilirubinemiaPurulent CSF

Brown Meningeal melanomatosis


33/54

Normal CSF values

Cell component Age Category Normal Value

Leukocytes Neonates 0 30 cells X 10 / L

1 to 4 yr old 0 20 X 10 / L

5 to puberty 0 10 X 10 / L

Erythrocytes Newborn 0 675 X10 / LAdults 0 10 X10 / L

Protein Neonates 0.7 g/l

Adults 0.2 0.4 g/l

Glucose > 60% of RBS value is considerednormal

Bacterial or viral counts should be considered where leukocyte counts arenear the upper normal value5 WBCs per mm3 (normal value)


34/54

differential diagnosis of various

forms of meningitisDiagnosis Pressure Cells

(10 / l)PMN Glucose

ratioProtein(g/ l)

Lactate(mmol/l)

normal < 20 cm 1-2 < 1 > .5 < 0.45 (1545mg/dl) < 2

Acutepyogenic

>20 cm >1000 > 50% < .4(>.2)

> 1(100 mg) > 4

Chronic variable > 1000 Vary < .4 > 0.45 > 2

Aseptic(Viral)

< 20 cm < 1000 .4 Vary < 2


35/54

As CSF is hypotonic, WBCs lyse with the time.

Process, immediately

87% of Patients with meningitis 1000 /mm WBCs

99% of Patients with meningitis 100 per mm3

More likely to have viral meningitis 100 per mm3


36/54

Lymphocytes : PMN

CSF, PMN:L ratio is unreliable for diagnosis ofmeningitis

Viral meningitis may show lymphocytosis butinitially PMN predominates

Neutropaenics no or less PMN response


37/54

Presence of RBCs Indicates intra cerebral ,SAH or traumatic tap

Presence of RBCs make interpretation of CSF analysisdifficult

But, rarely obscures it

Inspecting first and third lumbar puncture samples if RBC count different - Traumatic tap

WBC:RBC ratio of 1:500 to 1:1000 is considered normal CSF obtain > 12 hrs post ICH may have WBC counts up

to 500 X 10 /l - due to inflammation


38/54

Direct smear Gram stain


39/54

a Gram stain of the cytospin CSF has a sensitivity of90% if the LP is carried out before the administrationof antibiotics.


40/54

Effects of antibiotics in CSF culture

and Direct smears In a retrospective review of 128 children with bacterial

meningitis, Kanegaye et al. (2001)

compared 39 patients who received empiricantimicrobial therapy before LP with 55 whounderwent LP before receiving antimicrobial therapy

Treatment Group - Bacterialsterilization

Treatment group

Meningococcus sterilization occurredwithin 2 hrs

Up to 24 to 48 hrs CSF cellular andbiocheical parameters remained unchained

Pneumococcus sterilization occurredwithin 4 hours


41/54

Condition Diagnostic test Sensitivity (%) Specificity(%)

Bacterial meningitis Cytospin Gram stain 6090 100

Culture 90 100

Antigen detectionassays * 50100 100

Tuberculous meningitis Acid-fast stain 1022 100

Culture3888 100

PCR 2785 95100

Effect of antibiotic treatment oncerebrospinal fluid. Am J ClinPathol 1983; 80:386-387.
http://www.mdconsult.com/das/book/body/91685783-9/0/1209/94.htmlhttp://www.mdconsult.com/das/book/body/91685783-9/0/1209/94.html


42/54

Blood cultures 50 to 80% patients with meningitis has accompanied

bacteremias - blood cultures would be useful to isolationof organisms more than CSF growth

Specially where LP is contraindicated

Blood culturesVolume 20ml or as

recommended by themanufactures

Collected before antibiotic therapy> 2 cultures taken from different sites or three cultures with

in 24 hrsInnoculate into broth medium at a ratio of >1:5

When suspecting Dimorphic fungi or cryptococcus blodshould be colected to tube containing lysis solution for lysiscentrifugation


43/54

Utilityof Gram stain for diagnosis of Pyogenic

meningitis

Etiology Sensitivity

All common etiologiesno previous antibiotics 75% to 90%

All common etiologiesantimicrobial therapyprior to lumbar puncture

40% to 60%

Streptococcus pneumoniae without antibiotics 90%

Neisseria meningitidis - 75%

Haemophilus influenzae 86%

Listeria monocytogenes


44/54

Unfortunately the positivity rate of gram staining andcultures remain low between 25- 40% as against therate of 80-85% from the developed world


45/54

Partially treated meningitis

As the early symptoms and signs - non-specific, up to 50% receiveoralantibiotics.

This delay the presentation to hospital &

CSF findings altered; - Gram stain and growth of organism

may benegative

Antibiotics rarely interfere with CSFprotein/glucose andmolecular diagnosis (PCR).

In partially treated meningitis request for PCR and bacterialantigens - not affectedby prior antibiotic administration.


46/54

Tuberculuos meningitisAFB positive only in 3%

Cobweb formation is seen 2/3 cases

Ratio of albumin to globulin changes can be used asscreening method(Nl ratio 6:1)Abnormal in TBMchanges can be predicted with eletrophoresis(Modified Levinsons test


47/54

Use of Bacterial Antigen Testing The use of rapid bacterial antigen detection in CSF and other body

fluids has come under question. Rarely does a positive result alter therapy, and test performance is

similar to that of the Gram's stain.

Two contemporary approaches are advocated for bacterial antigentesting. The first recommends testing only those specimens with abnormal CSF

parameters (cell count, protein, glucose).[35] This approach results in a68% reduction in the number of antigen tests performed.

Although positive CSF cultures occur when white blood cell count,glucose, and protein values are within normal ranges, this is unusual

and does not justify testing all CSF for bacterial antigen. Another approach eliminates antigen testing, except in a few limited,

specific cases, such as prior antimicrobial therapy when culture resultsare negative after 24 to 48 hours of incubation.
http://c/Users/Panora/Desktop/Diagnosis%20of%20CNS%20infections.htmlhttp://c/Users/Panora/Desktop/Diagnosis%20of%20CNS%20infections.htmlhttp://c/Users/Panora/Desktop/Diagnosis%20of%20CNS%20infections.html


48/54

latex particle agglutination tests , have similarsensitivities to Gram stain or culture

of doubtful benefit when used routinely,

but sometimes identify organisms in patients withpartially treated bacterial meningitis and negativeGram stain and culture.

Cultures for bacteria and fungi should always beperformed, even in patients already treated withantibiotics.


49/54

Use of Culture


50/54

Culture media Incubation

For routinely encountering pathogens Good quality Blood A,chocolate Agar eithersheep or HBA -

24 to 48 hrs in 3-5% CO

Facultative anaerobes Broth media

Anaerobes from cerebral abscesses thioglycollate or choppedmeat broth,

Extendedincubation- onlywhen requested

Yeast and fungi Use of lysiscentrifugation method

Only whenrequested

********Culturing technique and media hardly ever changed over the years


51/54

Emerging issues


52/54

Methods of rapid diagnosis

Emergence of antibiotic resistant Pathogens


53/54

PCR

Broad range of PCRs N.meningitidis,

H.influenzae,Streptococcus pneumoniae

PCR of blood Buffy coat provide higher yield for N.meningitidis

Agents of Aseptic meningitis Rapid RealTime PCRfor entero viruses available results in 60 min


54/54

Antibiotic resistance

worldwide increase in infection withpenicillin andcephalosporin resistant strains ofS pneumoniae,

caused by either alteration in the penicillinbinding

proteins (Mosaic PBP)

Incidence increasing Europe, South Africa, Asia, and theUnited States.

American Academy of Pediatrics recommended

combination therapy, initially with vancomycin and either

cefotaximeor ceftriaxone for all children 1 month of age orolder withdefinite or probable bacterial meningitis.

N. meningitis less susceptible strains

cns infections 2013 -mk.pptx

Documents