bacterial_and_viral_meningitis

8/14/2019 bacterial_and_viral_meningitis

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ACUTE BACTERIALMENINGITIS

ACUTE BACTERIAL MENINGITISBacterial meningitis

is an acute purulent infectionwithin the subarachnoid space.

associated with a CNS

inflammatory reaction decreasedconsciousness

seizures

raised intracranialpressure (ICP)

stroke

Meningoencephalitis:

meninges

subarachnoid space

brain parenchyma


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EPIDEMIOLOGY

Bacterial meningitis is the mostcommon form of suppurative

CNS infection

a dramatic decline in the incidenceof meningitis due to Haemophilus

in.uenzae, and a smaller decline inthat due to Neisseria meningitidis,following the introduction andincreasingly widespread use ofvaccines for both these organisms

organisms most commonlyresponsible for community-acquired bacterial meningitis:

Streptococcuspneumoniae (50%)

N. meningitidis (25%)

group B streptococci(15%)

Listeria monocytogenes(10%)

H. infuenzae (10%)

ETIOLOGYS. pneumoniae

is the most common cause ofmeningitis in adults

20 years of age

nearly half the reportedcases

Predisposing conditions thatincrease the risk of pneumococcalmeningitis:

pneumococcalpneumonia

coexisting acute orchronic pneumococcal

sinusitis or otitis media

alcoholism

diabetes

splenectomy

hypogammaglobulinemia,

complement de.ciency

head trauma with basilarskull fracture and CSFrhinorrhea.

Mortality remains 20% despiteantibiotic therapy.

N. meningitidis

25% of all cases of bacterialmeningitis

60% of cases in children and youngadults between the ages of 2 and20.

Pathognomonic: the presence ofpetechial or purpuric skin lesions

the disease is fulminant,progressing to death within hoursof symptom onset.

initiated by nasopharyngealcolonization

asymptomatic carrierstate

invasive meningococcaldisease.

Individuals with deficiencies of anyof the complement components,

including properdin, are highlysusceptible to meningococcalinfections.

Enteric gram-negative bacilli

increasingly common cause ofmeningitis in individuals withchronic and debilitating diseases

Gram-negative meningitis can alsocomplicate neurosurgicalprocedures, particularlycraniotomy.

Group B streptococcus, or S.agalactiae

previously responsible formeningitis predominantly inneonates

increasing frequency in individuals50 years of age, particularly thosewith underlying diseases.

L. monocytogenes

increasingly important cause ofmeningitis in neonates (1 month ofage)

pregnant women

individuals 60 years andimmunocompromised individuals ofall ages

Infection is acquired by ingestingfoods contaminated by Listeria:contaminated coleslaw, milk, soft cheeses,and several types of ready-to-eat foods


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including delicatessen meat and uncookedhotdogs.

H. influenzae type b

Meningitis in children has declineddramatically since the introductionof the Hib conjugate vaccine

causes meningitis in unvaccinatedchildren and adults

Staphylococcus aureus andcoagulase-negativestaphylococci

important causes of meningitis thatfollows Invasive neurosurgicalprocedures

shunting procedures forhydrocephalus

complication of the useof subcutaneous Ommayareservoirs for administration ofintrathecal chemotherapy.

PATHOPHYSIOLOGY

The most common bacteria thatcause meningitis, S. pneumoniaeand N.meningitidis,

colonize the nasopharynxattach to

nasopharyngeal epithelial cellstransported across epithelial cells

(membrane-bound vacuoles)intravascular space or invade the

intravascularspace by creating separations in theapical tight

junctions of columnar epithelial cells

bloodstreambacteria avoidphagocytosis by neutrophils andclassic complementmediatedbactericidal activity because of thepresence of a polysaccharide

capsulereach the intraventricular

choroid plexus directly infect choroid

plexus epithelial cells gain access tothe CSF

*S. pneumoniae, - can adhere tocerebral capillary endothelial cells andsubsequently migratethrough or between these cells toreach theCSF

Bacteria are able to multiply rapidlywithin CSF. Reasons:

1. Prevention of the effectiveopsonization of bacteria

Normal CSF contains fewwhite blood cells (WBCs)

small amounts ofcomplement proteins and

immunoglobulins.2. Phagocytosis of bacteria is furtherimpaired by the fluid nature of CSF

critical event: INFLAMMATORYREACTION induced by the invadingbacteria

1. Lysis of bacteria with thesubsequentrelease of cell-wall (LPS, techoic &peptidoglycan) components into thesubarachnoid space

- induce meningealin.ammation by stimulating theproduction of in.ammatorycytokines and chemokines bymicroglia, astrocytes, monocytes,microvascular endothelial cells,and CSF leukocytes

2. Formation of a purulent exudate inthe subarachnoid space

- cytokines including tumornecrosis factor (TNF) and

interleukin (IL) 1 increase in CSFprotein concentration and

leukocytosis

bacteremia and the inflammatorycytokines

excitatory amino acids, reactiveoxygen and nitrogen species (freeoxygen radicals, nitric oxide, and

peroxynitrite) induce death of braincells

Much of the pathophysiology ofbacterial

meningitis is a direct consequence of

elevatedlevels of CSF cytokines andchemokines

TNF & IL-1 act synergistically toincrease the permeability of the blood-

brain barriervasogenic edema andthe leakage of serum proteins into the

subarachnoid space obstructs flow ofCSF through the ventricular system


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and diminishes the resorptive capacityof the arachnoid granulations in the

dural sinuses obstructive and

communicating hydrocephalus interstitial edema

Inflammatory cytokines upregulate theexpression of selectins on cerebralcapillary endothelial cells and

leukocytes leukocyte adherence to

vascular endothelial cells migrationinto the CSF.

The adherence of leukocytes tocapillary endothelial cells increases the

permeability of blood vesselsleakage of plasma proteins into the

CSF infammatory exudate.

Neutrophil degranulation release of

toxic metabolites cytotoxic edema,cell injury, and death.

During the very early stages ofmeningitis there isan increase in cerebral blood flow thendecrease in cerebral blood flow and aloss of cerebrovascular autoregulation

encroachment by the purulent exudatein the subarachnoid space andinfiltration of the arterial wall byinflammatory cells with intimal

thickening (vasculitis)narrowing ofthe large arteries at the base of the

brain ischemia and infarction,obstruction of branches of the middlecerebral artery by thrombosis,thrombosis of the major cerebralvenous sinuses, and thrombophlebitisofthe cerebral cortical veins.

The combination of interstitial,vasogenic,and cytotoxic edema leads to raised

ICP and coma.

Cerebral herniation

- effects of cerebral edema,either focal or generalized- hydrocephalus and duralsinus or cortical vein thrombosis

CLINICAL PRESENTATION

Acute fulminant illness - thatprogresses rapidly in a few hours

Subacute infection -progressively worsens over severaldays

The classic clinical triad ofmeningitis (90% of cases)

Fever

Headache

nuchal rigidity (stiffneck)

Alteration in mentalstatus (75% of cases)

Nausea, vomiting, andphotophobia

Seizures

Focal seizures

due to focal arterial ischemia orinfarction

cortical venous thrombosis withhemorrhage

focal edema

Generalized seizure activity and statusepilepticus

hyponatremia

cerebral anoxia

the toxic effects of antimicrobial

agents such as high-dose penicillin.

Obtundation and coma

raised ICP

90% will have a CSF openingpressure = 180 mmH2O

20% have opening pressures = 400mmH2O.

Signs of increased ICP

reduced level ofconsciousness

papilledema

dilated poorly reactivepupils

sixth nerve palsies

decerebrate posturing

Cushing refex(bradycardia, hypertension, andirregular respirations)


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*cerebral herniation the most disastrouscomplication

Some notable specific clinical features:

rash of meningococcemia

begins as a diffuseerythematous maculopapularrash

rapidly becomepetechial.

Petechiae are found onthe trunk and lower extremities,in the mucous membranes andconjunctiva, and occasionallyon the palms and soles


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DIAGNOSIS

Blood cultures

examination of the CSF

the need to obtainneuroimaging studies (CT orMRI) prior to LP requires clinical

judgment

Considerations:In an immunocompetent patient (-)history of recent head trauma, anormal level of consciousness, and noevidence of papilledema or focalneurologic deficits= SAFE TO PERFORM LP

If LP is delayed in order to obtainneuroimagingstudies, empirical antibiotic therapy

should be initiated after blood culturesare obtained. Antibiotic therapyinitiated a few hours prior to LPwill not significantly alter the CSFWBC count or glucoseconcentration, nor is it likely toprevent visualization of organismsby Grams stain.

Use of the CSF/serum glucoseratio corrects for hyperglycemiathat may mask a relative decreasein the CSF glucose concentration.

It takes from 30 min to severalhours for CSF glucoseconcentration to reach equilibriumwith blood glucose concentrations;

therefore, administration of 50 mLof 50% glucose (D50) prior to LP,as commonly occurs in emergencyroom settings, is unlikely to alterCSF glucose concentration

The latex agglutination (LA) test- rapid diagnosis of bacterialmeningitis, especially in patientspretreated with antibiotics and inwhom CSF Grams stain and cultureare negative.

- specificityof 95 to 100% forS. pneumoniae and N. meningitides

- the sensitivity= 70 to 100%for detection ofS. pneumoniae and33 to 70% for detection ofN.meningitidis antigens

Limulus amebocyte lysateassay rapid diagnostic test for thedetection of gram-negativeendotoxin in CSF

- specificity of 85 to 100%and a sensitivityapproaching 100%

CSF polymerase chain reaction(PCR) tests

- not as useful in thediagnosis of bacterial

meningitis- for detecting DNA from

bacteria in CSF

NEUROIMAGING:

- MRI is preferred over CTbecause of its superiority indemonstrating areas of cerebraledema and ischemia

Petechial skin lesions, should bebiopsied.

o

The rash ofmeningococcemia results fromthe dermal seeding oforganisms with vascularendothelial damage

DIFFERENTIAL DIAGNOSIS1. Viral meningoencephalitis

o (HSV) encephalitis, can

mimic the clinical


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presentationof bacterialmeningitisi. headache, fever,altered consciousness,

focal neurologic deficits (e.g.,dysphasia, hemiparesis), and focal or

generalized seizures.

HSV Encephalitis BacterialMeningitis

CSF: alymphocyticpleocytosis with anormal glucoseconcentration

PMN pleocytosisandhypoglycorrhachia

MRI: parenchymalchanges,especially inorbitofrontal

and medialtemporal lobes

No MRIabnormalities

2. Rocky Mountain spotted fever(RMSF)o transmitted by a tick bite

o Rickettsia rickettsii.

o high fever, prostration, myalgia,

headache, ando nausea and vomiting

o characteristic rash within 96 h

of the onset of symptoms.

o Diffuse erythematous

maculopapular rash progresses to a petechial rash

to a purpuric rash ,(untreated) skin necrosis organgrene

o begins in the wrist and

ankles, and then spreadsdistally and proximally within amatter of a few hours andinvolves the palms and soles. \

o Dx: immunofluorescent

staining of skin biopsy

specimens.

3. Focal suppurative CNSinfections including subdural andepidural empyema and brainabscess,

o MRI should be performed

promptly

4. Subarachnoid hemorrhage

5. chemical meningitis - due torupture of tumor contents into theCSF (e.g., from a cystic glioma,craniopharyngioma epidermoid ordermoid cyst)

6. drug-induced hypersensitivitymeningitis

7. carcinomatous orlymphomatous meningitis

8. meningitis associated withinflammatory disorders such assarcoid, systemic lupuserythematosus (SLE), and Behchetdisease; pituitary apoplexy;

9. uveomeningitic syndromes(Vogt-Koyanagi -Harada syndrome)10. Subacutely evolving meningitiso Mycobacterium tuberculosis

o Cryptococcus neoformans

o Histoplasma capsulatum

o Coccidioides immitis

o Treponema pallidum

Empirical Antimicrobial Therapy(Table 360-2)

Goal: antibiotic therapy within 60min of a patients arrival in theemergency room

Started before the results of CSFGrams stain and culture are

known.

S. pneumoniae and N. meningitidis- most common etiologic organismsof community-acquired bacterialmeningitis

S. pneumoniae - children andadults

o third-generation

cephalosporin (e.g.,ceftriaxone or cefotaxime)and vancomycin.

Ceftriaxone or cefotaxime

o S. pneumoniaeo group B streptococci

o H. in.uenzae

o N. meningitidis.

Cefepime

o Equal to cefotaxime or

ceftriaxone against S.pneumoniae and N.meningitidis


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o greater activity against

Enterobacterspp. andPseudomonas aeruginosa.

cefepime = cefotaxime

o in the treatment of

penicillin-sensitive

pneumococcal andmeningococcal meningitis

Ampicillin should be added tothe empirical regimen - L.monocytogenes

o 3 months of age

o Age 55

o those with suspected

impaired cell-mediatedimmunity

Vancomycin + Ceftazidime

o Hospital-acquired

meningitiso meningitis following

neurosurgical procedures

o staphylococci and gram-

negative organismsincluding P. aeruginosa

o Ceftazidime should be

substituted for ceftriaxoneor cefotaxime inneurosurgical patients andin neutropenic patients.

Meropenem

o carbapenem antibiotic

that is highly active againstL. monocytogenes

o effective P. aeruginosa

meningitiso penicillin-resistant

pneumococci

Specific Antimicrobial Therapy

MENINGOCOCCAL MENINGITIS

N. meningitidis

ceftriaxone and cefotaximeprovide adequate empiricalcoverage

penicillin G - antibiotic of choicefor meningococcal meningitiscaused by susceptible strains.

A 7-day course of intravenousantibiotic therapy is adequate

for uncomplicatedmeningococcal meningitis.

chemoprophylaxis with a 2-dayregimen of rifampin (600 mgevery 12 h for 2 days in adultsand 10 mg/kg every 12 h for 2

days in children 1 year). Alternatively, adults can be

treated with one dose ofciprofloxacin (750 mg), onedose of azithromycin (500 mg),or one intramuscular dose ofceftriaxone (250 mg)

PNEUMOCOCCAL MENINGITIS

initiated with a cephalosporin(ceftriaxone, cefotaxime orcefepime) and vancomycin.

Should be tested for sensitivityto penicillin and thecephalosporins.

For S. pneumoniae meningitis,an isolate ofS. pneumoniaesusceptible to penicillin with aminimal inhibitoryconcentration (MIC) 1.0ug/mL.

For meningitis due topneumococci with cefotaxime orceftriaxone

MICs 0.5 ug/mL = treatmentwith cefotaxime or ceftriaxone isusually adequate

MIC > 1 ug/mL = vancomycin isthe antibiotic of choice.

Rifampin + vancomycin for itssynergistic effect but is inadequateas monotherapy

Patients with S. pneumoniae

meningitis = repeat LP performed24 to 36 h after the initiation ofantimicrobial therapy to documentsterilization of the CSF. Failure tosterilize the CSF after 24

to 36 h = resistance!

Patients with penicillin- andcephalosporin-


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resistant strains ofS.pneumoniae who do not respond toIV vancomycin alone may benefitfrom the addition ofintraventricular vancomycin.

A 2-week course of intravenous

antimicrobial therapy isrecommended for pneumococcalmeningitis.

L. MONOCYTOGENES MENINGITIS

Ampicillin for at least 3 weeks

Gentamicin is added (2 mg/kgloading dose, then 5.1 mg/kg perday given every 8 h and adjustedfor serum levels and renalfunction).

trimethoprim [10 to 20

(mg/kg)/d] + sulfamethoxazole [50to 100 (mg/kg)/d] given every 6 h= for penicillinallergic.

STAPHYLOCOCCAL MENINGITIS

Nafcillin - meningitis due tosusceptible strains ofS.

aureus or coagulase-negativestaphylococci

Vancomycin is the drug ofchoice for methicillin-resistantstaphylococci and for patientsallergic to penicillin.

CSF should be monitored duringtherapy. If the CSF is not sterilizedafter 48 h of intravenousvancomycin therapy, add eitherintrathecal or intraventricularvancomycin, 20 mg once daily

GRAM-NEGATIVE BACILLARYMENINGITIS

Third-generationcephalosporins: cefotaxime,ceftriaxone, and ceftazidime

EXCEPT: of meningitis due to P.aeruginosa = ceftazidime.

A 3-week course of intravenousantibiotic

Adjunctive Therapy

Dexamethasone

o inhibiting the synthesis

of IL-1 and TNF at the levelof mRNA, decreasing CSFoutflow resistance, and

stabilizing the blood-brainbarrier

o given 20 min before

antibiotic therapy inhibitingthe production of TNF bymacrophages and microgliaonly if it is administeredbefore these cells areactivated by endotoxin.o does not alter TNF

production once it has beeninduced.

o Decrease meningeal

in.ammation and neurologicsequelae such as theincidence of sensorineuralhearing loss.

o may decrease the

penetration of vancomycininto CSF, and it delays thesterilization of CSF inexperimental models ofS.

pneumoniae meningitis.

Increased Intracranial Pressure

elevation of thepatients head to 30 to 45O

intubation andhyperventilation (PaCO 25 to 30mmHg),

mannitol

Patients with 2increased ICP should be managedin an intensive care unit

PROGNOSIS

Mortality is 3 to 7% formeningitis caused by H. influenzae,N. meningitidis, or group Bstreptococci;

15% for that due to L.monocytogenes;

20% for S. pneumoniae.

risk of death from bacterialmeningitis increases with


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1. decreased level of consciousnesson admission2. onset of seizures within 24 h ofadmission3. signs of increased ICP4. young age (infancy) and age

>505. the presence of comorbidconditions including shock and/orthe need for mechanical ventilation6. delay in the initiation oftreatment.

Common sequelae:o decreased intellectual

functiono memory impairment

o seizures

o hearing loss and

dizziness

o gait disturbances.

~ MARK TURINGANACUTE VIRAL MENINGITIS

Clinical Manifestations- fever, headache, andmeningeal irritation- headache usually frontal orretroorbital with photophobiaand pain on moving the eyes

-with malaise, myalgia,

anorexia, nausea and vomiting,abdominal pain and/or diarrhea- mild degree of lethargy anddrowsiness- seizures or other focalneurologic signs or symptomsindicates of involvement ofbrain parenchyma

Epidemiology

- some viruses have seasonal

predilections: increasedincidence during summer andearly fall

Laboratory Diagnosis

(1) CSF examination- most important lab test

- lymphocytic pleocytosis (25-500 cells/L)

- normal to slightly elevatedprotein (20-80 mg/dL)

- normal glucose (may bedecreased in mumps and

LCMV)- normal to mildly elevated

opening pressure- organisms are not seen on

Grams stain or AF stainedsmears or India inkpreparations

- PMNs may predominated inthe first 48 hrs.

- As a rule, lymphocyticpleocytosis with low glucosesuggest fungal, listerial, or

TB meningitis ornoninfectious disorders

(2) PCR of viral nucleic acid- procedure of choice for HSV

meningitis- more sensitive than viral

cultures- used routinely to diagnose

CMV, EBV, VZV(3) CSF culture

- 2 mL of CSF, refrigerated

and processed ASAP- never stored in ~200C, virus

unstable at this temp.

- should be in a ~700C freezerif stored for >20 hrs.

(4) Other sources of viral isolation- throat, stool, blood, urine- enterovirus in stool is not

diagnostic(5) Serologic studies

- useful for arboviruses- less useful for HSV, VZV,

CMV, EBV- diagnosis of acute viral

infection can be made bydocumenting seroconversionbetween acute-phase andconvalescent sera or bydemonstrating the presenceof virus-specific IgMantibodies


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- IgM Abs persist for only afew months after acuteinfection except WNV IgM

- useful mainly forretrospective establishmentof a specific diagnosis

-the finding of oligoclonalbands in electrophoresismay be suggestive of certainviruses

(6) Other lab studies- CBC, liver function tests,ESR, BUN, plasma levels ofelectrolytes, glucose,creatinine, creatine kinase,aldolase, amylase, and lipase

Differential Diagnosis

(1) bacterial meningitis(2) parameningeal infections or

partially treated bacterialmeningitis

(3) nonviral infections meningitideswith culture negative (fungal,tuberculous, parasitic,syphillis)

(4) neoplastic meningitis(5) meningitis secondary to

noninfectious inflammatorydiseases

Specific Viral Etiologies

(1) Enterovirus- most common cause of viral

meningitis- typical case occurs in the

summer months, esp. inchildren < 15 y/o

- PE includes exanthemata,hand-foot-mouth disease,herpangina, pleurodynia,myopericarditis,hemorrhagic conjunctivitis

- diagnosis by PCRamplification of enteroviralRNA from CSF

(2) Arbovirus

- typically occur in thesummer

- WNV suspected when clusterof meningitis cases arepreceded by death of birdsin a certain geographic

region- history of tick exposure

sought in cases of Coloradotick fever or Powassan virusinfection

(3) HSV-2- probably the second most

common viral cause ofmeningitis

- cultures are invariablynegative

- diagnosis made by CSF PCR

-genital lesions may not bepresent

(4) VZV- suspected in the presence of

concurrent chicken pox orshingles

- 40% occur in the absence ofrash

- Can also produce cerebellarataxia

- CSF PCR used in thediagnosis

(5) EBV- may occur with or without

evidence of infectiousmononucleosis syndrome

- diagnosis suggested byatypical lymphocytes in theCSF or in the peripheralblood

- diagnose by SF PCR- patient with CNS lymphoma

may be positive in PCR in theabsence ofmeningoencephalitis

(6) HIV- presence of HIV genome by

PCR or p24 proteinestablishes the diagnosis

- cranial nerve palsiescommon

(7) Mumps


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