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November 4 th 2009. MENINGITIS Saima Abbas M.D Fellow of Infectious Diseases. Objectives/Goals. PROMPT recognition of Meningitis Rapid Diagnostic testing to identify the etiologic pathogen and adjust therapy Rapid Initiation of appropriate Empiric Antimicrobial therapy

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November 4 th 2009

November 4th 2009

MENINGITISSaimaAbbas M.DFellow of Infectious Diseases


Objectives goals

Objectives/Goals

  • PROMPT recognition of Meningitis

  • Rapid Diagnostic testing to identify the etiologic pathogen and adjust therapy

  • Rapid Initiation of appropriate Empiric Antimicrobial therapy

  • Targeted Antimicrobial therapy

  • Do’s and Don’ts for the Boards


Meningitis

Meningitis


Bacterial meningitis

Bacterial Meningitis

  • 1805-1900’s: ~100% fatal

  • 1913: Flexner: intrathecal meningococcal antiserum. Prevented some deaths

  • 1930’s: Antibiotics. Improved survival

  • Current data:

    • Adults: 25% mortality, 21-28% neurologic sequelae

    • Bacterial meningitis remains a medical emergency!


Recognize clinical picture is often unimpressive when the patient is first seen

RECOGNIZE Clinical picture is often “unimpressive” when the patient is first seen

URIinterrupted by one of the “meningeal symptoms”: vomiting, headache, lethargy, confusion, stiff neck

aLTERED mENTAL sTATUS

FEVERHEADACHE


Cases 10 key points

Cases ~10 key points

  • 1. AGE

  • 2.SEASON

  • 3.Geography

  • 4.Predisposing factors (immunocompromised state; basilar skull fracture with CSF leak; head trauma; post neurosurgical procedures ~wound and FB)

  • 5.Onset and duration of illness (acute; subacute and chronic) ~community aquired or nosocomial


Key points

Key points

  • 6.Travel,occupational and recreational exposures( insect and animal contact)

  • 7. Vaccination history and current meds (ABX)

  • 8.Parameningeal foci or septic emboli from IE

  • 9. Imaging before Lumbar puncture

  • 10. Gram stain and Interpretation of the CSF formula


Case 1

CASE #1

  • 14-year-old male with no significant PMH is admitted to the hospital with acute onset of high fever, chills, sore throat, stiff neck, and lethargy

  • T 1040F, P 120, RR 32, BP 70/30 mmHg

  • On examination, he was oriented only to person,

  • and had evidence of nuchal rigidity

  • WBC 25,000/mm3 with 20% bands

  • CSF WBC 1,500/mm3 (98% neutrophils), glucose 20 mg/dL, and protein 200 mg/dL


Case 1 which of the following microorganisms is the most likely cause of this patient s meningitis

CASE #1Which of the following microorganisms is the most likely cause of this patient’s meningitis?

  • A Haemophilus influenzae type b

  • BNeisseria meningitidis

  • CStreptococcus pneumoniae

  • DEnterovirus 71

  • ECryptococcus neoformans


Meningococcal meningitis

Meningococcal meningitis

LOOK @ AGE/ARMY RECRUITS/COLLEGE STUDENTS/

Rash


Epidemiologic features of meningococcal meningitis

EPIDEMIOLOGIC FEATURES OFMENINGOCOCCAL MENINGITIS

  • Affects mostly children and young adults;

  • mortality 3-13% (SPORADIC 98% cases B)

  • Epidemics usually caused by serogroups A and C

  • Group Y strains associated with pneumonia

  • Serogroup C disease increasing in the US

  • Nasopharyngeal acquisition of infection

  • Predisposition in those with congenital

    deficiencies in terminal complement components (C5-C9) and properdin deficiencies


Important facts

Important facts

PEN G and AMPICILLIN are DRUGS OF CHOICE

Empiric therapy with Third Generation Cephalosporins recommended

Nasopharyngeal carrier state 10 to 15%

Infection control DROPLET precautions ~surgical mask


Case 2

CASE #2

  • 21-year-old male without significant PMH was found difficult to arouse by his roommate in his college dormitory. Patient taken via fire rescue to ER

  • On exam, he was lethargic, febrile to 1030F, tachycardic, tachypnec, and hypotensve. His neck was stiff and he had a petechial rash on the lower extremities

  • CSF revealed a neutrophilic pleocytosis, low glucose, and elevated protein. Gram’s stain showed gram-negative diplococci

  • The patient received IV penicillin G and made a full recovery. Blood and CSF grew Neisseria meningitidis


Case 21

Case # 2

  • For which of the following persons is antimicrobial chemoprophylaxis recommended?

  • The Dean of the college

  • The ambulance driver

  • The emergency room physician

  • The triage nurse

  • The patient


Chemoprophylaxis to prevent meningococcal disease

CHEMOPROPHYLAXIS TO PREVENTMENINGOCOCCAL DISEASE

  • Household members

  • Day care center contacts

  • Persons directly exposed to patient’s oral secretions - kissing, mouth-to-mouth resuscitation

  • - endotracheal intubation or endotracheal tube management

  • Index patient if not treated with a third generation cephalosporin

  • Chemoprophylactic regimens

  • - rifampin- ceftriaxone

  • - ciprofloxacin- azithromycin


Pathogenesis

Pathogenesis


Indications for ct before lp

Indications for CT before LP

  • Immunocompromised patients

  • H/O CNS disease

  • New onset SEIZURE

  • Focal neurological signs

  • Altered consciousness

  • Papilledema

  • Delay in performing LP

  • Do Blood Cx STAT

  • Dexamethasone and empiric antimicrobials

  • CT scan

  • LP if CT negative


Typical csf findings

Typical CSF Findings


Cerebrospinal fluid findings in bacterial meningitis

CEREBROSPINAL FLUID FINDINGSIN BACTERIAL MENINGITIS

  • Gram stainPositive in 60-90%

  • CultureCSFPositive in 70-85%**

  • Blood CulturePositive in 50%

  • ** Beware of partially treated meningitis with abx for 2-3 days this may give you negative Cx although CSF remains abnormal; Shift from PMN to polys and lymphs or lymphocytic predominance

  • Do NOT assume this is NOT a bacterial infection


Meningitis saima abbas m d fellow of infectious diseases

Gram negative:

Diplococci: Meningococcus

Bacilli: E. coli

Coccobacilli: H influenzae

(small, pleomorphic)

Gram Positive:

Diplococci: Pneumococcus

Chains: Strep Group B

Clusters: Staph

Rods & cocobacilli: Listeria


Case 3

CASE #3

  • 56-year-old female with a 2-day history of fever, chills, headache, and confusion. Saw her physician 5 days earlier with complaints of earache; received ciprofloxacin

  • T 1030F, P 140, RR 32, BP 90/60 mmHg

  • Obtunded, stiff neck, purpuric rash on lower extremities

  • CSF showed opening pressure of 280 mm H2O, WBC 2,500/mm3 (99% neutrophils), glucose 15 mg/dL, protein 400 mg/dL


Case 31

Case # 3

  • Which of the following regimens should be initiated?

  • A Dexamethasone + Penicillin G

  • B Dexamethasone + Ceftriaxone

  • C Dexamethasone + Vancomycin + Ampicillin

  • D Dexamethasone + Vancomycin + Ceftriaxone

  • E Vancomycin + Ceftriaxone


Epidemiologic features of pneumococcal meningitis

EPIDEMIOLOGIC FEATURES OFPNEUMOCOCCAL MENINGITIS

  • Most common etiologic agent in US

  • Mortality of 19-26%

  • Associated with other suppurative foci of infection ~ Pneumonia (25%)

  • Otitis media or mastoiditis (3 0%)

  • Sinusitis (10-15%)

  • Endocarditis (<5%)

  • Head trauma with CSF leak (10%)


Antimicrobial therapy of choice for s pneumoniae

Antimicrobial therapy of choice for S.pneumoniae


Targeted antimicrobial therapy in bacterial meningitis

TARGETED ANTIMICROBIALTHERAPY IN BACTERIAL MENINGITIS

  • Microorganism Antimicrobial Therapy

  • S. pneumoniae Vancomycin + a third generation

  • cephalosporina,b

  • N. meningitidis Penicillin G, ampicillin, or a

  • third generation cephalosporina

  • H. influenzae type b Third generation cephalosporina

  • L. monocytogenes Ampicillin or penicillin G*

  • S. agalactiae Ampicillin or penicillin G*

  • E. coli Third generation cephalosporina

  • acefotaxime or ceftriaxone

  • baddition of rifampin may be considered, especially if dexamethasone given

  • *addition of an aminoglycoside may be considered


Adjunctive dexamethasone in bacterial meningitis

ADJUNCTIVE DEXAMETHASONEIN BACTERIAL MENINGITIS

  • Attenuates subarachnoid space inflammatory response resulting from antimicrobial-induced lysis

  • Recommended for infants and children with Haemophilus influenzae type b meningitis and considered for pneumococcal meningitis in childhood, if commenced with or before parenteral antimicrobial therapy

  • Clinical trials (predominantly in infants and children) have demonstrated reduction in neurologic and/or audiologic sequelae

  • Recommended in adults with pneumococcal meningitis

  • Administer at 0.15 mg/kg every 6 hours for 2-4 days concomitant with or just before first antimicrobial dose


Adjunctive therapy in meningitis

ADJUNCTIVE THERAPY INMENINGITIS

  • Tuberculous Meningitis

  • – Corticosteroids (extreme neurologic compromise, elevated ICP, impending herniation, impending or established spinal block;

  • CT/MR evidence of hydrocephalus or basilar meningitis)

  • Cryptococcal Meningitis

    – Reduction in intracranial pressure (frequent high- volume lumbar punctures, VP shunts)


Case 4

CASE #4

  • 60-year-old male with acute myelogenous leukemia presented with fever, headache, ataxia, and altered mental status. Recently traveled to an outdoor family picnic in rural Virginia. He is allergic to penicillin (anaphylaxis)

  • T 102oF, P 120, RR 24, BP 100/60

  • On examination, he was obtunded and had nuchal rigidity. Funduscopic exam revealed no papilledema. Babinski responses were positive bilaterally

  • WBC was 25,000/mm3 (30% bands)

  • LP revealed a WBC 1500/mm3 (50 neutrophils, 50% lymphocytes), glucose 30 mg/dL, and protein 200 mg/dL


Case 41

CASE #4

  • Which of the following antimicrobial regimens should be initiated?

  • AVancomycin administered intravenously and intrathecally

  • BVancomycin + rifampin

  • CChloramphenicol

  • DTrimethoprim-sulfamethoxazole

  • EErythromycin


Epidemiologic features of listeria meningitis

EPIDEMIOLOGIC FEATURES OFLISTERIA MENINGITIS

  • Mortality 15-29%

  • Rare cause of bacterial meningitis in US (8%)

  • Outbreaks associated with consumption of contaminatedcoleslaw, raw vegetables, milk, cheese, processed meats

  • Common in neonates (~20% of cases)

  • Disease in adults associated with:

  • ElderlyAlcoholism

  • MalignancyImmune suppression

  • Diabetes mellitusHepatic and renal disease

  • Iron overloadCollagen-vascular disorders


Case 5

Case # 5

  • CASE #2

  • 46-year-old male executive from Phoenix,Arizona presents to the ER with recent history of going on a cruise to Jamaica. One week after returning, he developed headaches, stiff neck, and vomiting.

  • He had no significant PMH and was sexually active with multiple partners.

  • Physical exam revealed low-grade fever and meningismus, but was otherwise negative.

  • CSF examination revealed a WBC count of 300/mm3 with 60% eosinophils, glucose of 45 mg/dL and protein 150 mg/dL.

  • Gram stain was negative.


Case 51

CASE #5

  • Which of the following is the most likely cause of this patient’s illness?

  • Treponema pallidum

  • Mycobacterium tuberculosis

  • Coccidioides immitis

  • Angiostrongylus cantonensis

  • Lymphoma


Features of angiostrongylus cantonensis meningitis rat lungworm

FEATURES OF ANGIOSTRONGYLUS CANTONENSIS MENINGITIS~ rat lungworm

  • Most common cause of eosinophilic meningitis

  • Reported from many countries of the world (Thailand, Malaysia, Vietnam, Indonesia, Papua New Guinea, Taiwan, Pacific Islands); recent outbreak in Jamaica

  • Rat infection rate in urban Bangkok ~40%

  • May spread as rats move freely from port to port on ships

  • Symptoms begin 6-30 days after ingestion of raw mollusks or other sources of the parasite.

  • Clinical findings are headache (90%), stiff neck (56%), paresthesias (54%), and vomiting (56%)

  • CSF reveals a moderate pleocytosis with 16-72% eosinophils; larvae are occasionally found in CSF


Treatment

Treatment

  • Usually self limited course and recover completely

  • Analgesics

  • Corticosteroids

  • Frequent but careful LPs if increased intracranial pressure


Features of coccidioidal meningitis

FEATURES OF COCCIDIOIDALMENINGITIS

  • May present acutely, although usually subacute to chronic

  • Patients generally complain of headache, low-grade fever, weight loss, and mental status changes;

  • signs of meningeal irritation are usually absent

  • Serum complement-fixing antibody titers >1:32 to 1:64 suggest disseminated disease

  • CSF examination may occasionally reveal a prominenteosinophilia; CSF protein is almost always elevated

  • Only 25-50% of patients have positive CSF cultures

  • CSF complement-fixing antibodies present in at least 70% of cases; titers parallel course of meningeal disease


Case 6

Case #6

  • 60 year old male with ESRD immigrated from Brazil to US and underwent a cadaveric renal transplant. Prior to transplant, he had recurrent epigastric pain.

  • WBC 6,500 with 15% eosinophils

  • After transplant received Prednisone and Azathioprine

  • Presented 1 month later with T 39ºC, headache, meningismus and altered mental status


Case 61

Case#6

  • Lumbar puncture showed

  • WBC 2500/mm³

  • (98% neutrophils)

  • Glucose 20 mg/dl

  • Protein 450mg/dl

  • Placed on Empiric Vancomycin, Ampicillin and Ceftriaxone

  • Blood cultures and CSF Cx grew E.coli


Meningitis saima abbas m d fellow of infectious diseases

  • Which of the following diagnostic test would most likely establish the pathogenesis of E.coli meningitis in this patient?

  • A.CT scan of the head and sinuses

  • B.Bronchoscopy with transbronchial lung biopsy

  • C. Serial stool examinations

  • D.Meningeal Biopsy

  • E. Metrizimide cisternography


Epidemiologic features of meningitis caused by aerobic gram negative bacilli

EPIDEMIOLOGIC FEATURES OFMENINGITIS CAUSED BY AEROBICGRAM-NEGATIVE BACILLI

  • Klebsiellaspecies, Escherichia coli, Serratiamarcescens, Pseudomonas aeruginosa, Salmonella species

  • Isolated from CSF of patients following head trauma or neurosurgical procedures

  • Cause meningitis in neonates, the elderly,

    immunocompromised patients, and in patients with gram- negative septicemia

  • Associated with disseminated strongyloidiasis in the hyperinfection syndrome


Case 62

CASE #6

  • An 80-year-old male is brought to the hospital by his family because of personality changes and olfactory hallucinations

  • On exam, T 1010F, P 90, RR 16, BP 120/90 mmHg

  • He is confused and oriented only to person. There is no meningimus or evidence of focal neurologic deficits

  • CT of head without contrast is negative; CSF reveals aWBC of 90/mm3 (95% lymphocytes), glucose of 80mg/dL (serum 100 mg/dl), and protein of 70 mg/dL


Case 63

CASE #6

  • Which of the following is the best test for establishing the diagnosis in this patient?

  • AElectroencephalogram

  • BMRI of head with gadolinium

  • CBrain biopsy

  • DCSF polymerase chain reaction

  • ECSF antibody studies


Case 7

CASE #7

  • 50-year-old man evaluated for obtundation and fever

  • Brain MRI with gadolinium reveals swelling and enhancement of the left temporal lobe; CSF analysis reveals a WBC of 10/mm3, normal glucose and elevated protein

  • Intravenous acyclovir is initiated

  • CSF PCR for HSV 1 and HSV 2 are negative


Case 71

CASE #7

  • Which of the following is the appropriate management for this patient?

  • A.Discontinue acyclovir

  • B.Perform a brain biopsy

  • C.Begin ganciclovir + foscarnet

  • D.Send CSF for HHV6 PCR

  • E.Perform HSV PCR on a new CSF specimen


Herpes simplex encephalitis diagnosis

HERPES SIMPLEXENCEPHALITIS (DIAGNOSIS)

  • Neuroimaging

  • – MRI is procedure of choice (AFTER LP)

  • – Edema and hemorrhage in temporal lobes– Bilateral temporal lobes (pathognomonic)

  • CSF Analysis

  • – Lymphocytes, increased protein, normal glucose – Polymerase chain reaction

  • EEG

  • – Periodic lateralizing epileptiform discharges


False negatives

False Negatives

  • Published reports have found that false negatives can occur due to testing

  • Too early or too late,

  • improper sample transport,

  • or low volumes of CSF tested.

  • HSVE is frequently fatal untreated. Therefore, if MRI shows compatible temporal lobe findings and no alternative diagnosis is established, continued treatment with acyclovir should be strongly considered.

  • A second spinal tap with repeat CSF PCR or a brain biopsy may be indicated.


Case 8

Case # 8

  • 75 year old woman from Colorado presents with acute onset of altered mental status and fever

  • Neurological examination reveals bilateral tremors of theextremities and cogwheel rigidity

  • Brain MRI reveals T1 hypodense lesions in the thalamus and basal ganglia that are hyperintense on T2 images


Meningitis saima abbas m d fellow of infectious diseases

  • CSF Analysis reveals a WBC of 300/mm³ glucose of 70 and protein of 105.

  • Which of the following tests is most likely to confirm the diagnosis in this patient?

  • A.Serum Ig M antibody

  • B.Serum Ig G antibody

  • C.CSF IgM antibody

  • D.CSF PCR

  • E.Brain Biopsy


West nile virus

WEST NILE VIRUS

  • First US cases reported in 1999 in New York City

  • Birds are main reservoirs

  • Transmission

    • -mosquito vector

    • -transfusion

    • -transplantation

    • -Breast feeding


Meningitis saima abbas m d fellow of infectious diseases

Clinical features of WNV

  • Age >50 years~ increased incidence

  • 1/150 develop neuroinvasive disease

  • Tremors and Myoclonus

  • Parkinsonism

  • Poliomyelitis like flaccid paralysis

  • Serum IgM and IgG capture ELISA (cross reactivity with other flaviviruses)

  • CSF IgM antibodies (diagnostic of neuroinvasive disease)

  • CSF PCR (positive in <60%)


Etiologies of viral encephalitis

Etiologies of Viral encephalitis

Echo virus

Coxsakie and Enteroviruses

Herpes Simplex

West Nile virus

Un identified etiology

32- 75%

Herpes Encephalitis is

“NOT SEASONAL”

sporadic

**Clues !!!

epidemiological factors

  • THERAPY FOR ENCEPHALITIS

  • EtiologyTherapy

  • HSVAcyclovir

  • VZVAcyclovir

  • CMVGanciclovir + foscarnet

  • HHV-6Ganciclovir or foscarnet

  • HIVHAART

  • JC virusHAART


Case 9

Case # 9

  • 56 year old man s/p Kidney transplant in 2006 s/p Left mastectomy for a painful mass on Sept 1st 2009 discharged POD # 3

  • re-admitted a week later with urinary retention and rectal bleeding.

  • Unclear cause of urinary retention relieved after foley catheter insertion

  • Rectal bleeding attributed to constipation and a bowel regimen ordered by general surgery


Meningitis saima abbas m d fellow of infectious diseases

  • Day 4 of admission patient began to have some hallucinations and beginning confusion.

  • Agitation increased gradually over the next few days.

  • CT Brain No acute abnormality MRI ( X AICD )

  • Day 7 after admission; after a bowel movement patient is turned back to supine position turns gray codes and is intubated ( ?Aspiration)

  • Day 14 ID is consulted for a persistent fever on Vancomycin and Cefepime with a RLL Pneumonia


Meningitis saima abbas m d fellow of infectious diseases

  • Patient was on Haldol round the clock for severe agitation attributed to ICU delirium..initially sleep deprivation

  • WHAT ARE WE MISSING?

  • Fever, altered mental status

    in an Immuno-compromised host ???????

    CONFOUNDERS pneumonia with Achromobacter Xylosoxidans I to cefepime


Meningitis saima abbas m d fellow of infectious diseases

  • Noninvasive testing was ordered and so was and LP

  • Serum Cryptococcal Antigen was 1:1024!!!!

  • CSF CrAG was 1:2084

  • Protein was 594

  • Glucose was 37

  • CSF wbc

  • Neutrophils

  • Lymphocytes


Meningitis saima abbas m d fellow of infectious diseases

  • Patient was initiated on High dose Fluconazole and 5 Flucytosine without reversal of neurological status.

  • He underwent trach and peg and died 2 weeks after initiation of therapy.


Laboratory and cerebrospinal fluid findings in cryptococcal meningitis

LABORATORY ANDCEREBROSPINAL FLUID FINDINGSIN CRYPTOCOCCAL MENINGITIS


D d of meningitis syndrome

d/d of Meningitis SYNDROME

  • Septic Emboli with Infective Endocarditis

  • Brain Abscess

  • Secondary Syphilis

  • Parameningeal focus

  • Rocky mountain Spotted fever ~ Doxycycline

  • Aspetic Meningitis like picture

    • Leptospirosis~ water rodent exposure Hepatitis/ meningitis

    • LYME disease

    • Lymphocytic choriomeningitis ~grip like illness Influenza like

    • 2000-3000 lymphocytes / winter peak

    • Mumps~ peaks in winter with orchitis and parotitis

    • Brucellosis

  • Midline tumors craniopharyngiomas

  • MEDS NSAIDs ( afebrile)


Suggested reading

Suggested reading

  • Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:11267-84.

  • Spanos A, Harrell FE Jr, Durack DT. Differential diagnosis of acute meningitis: an analysis of the predictive value of initial observations. JAMA 1989;262:2700-7.


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