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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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MENINGITIS Saima Abbas M.D Fellow of Infectious Diseases

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    1. November 4th 2009 MENINGITISSaimaAbbas M.DFellow of Infectious Diseases

    2. 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

    3. Meningitis

    4. 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!

    5. 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

    6. 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

    7. 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

    8. 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

    9. CASE #1Which of the following microorganisms is the most likely cause of this patient’s meningitis? • A Haemophilus influenzae type b • B Neisseria meningitidis • C Streptococcus pneumoniae • D Enterovirus 71 • E Cryptococcus neoformans

    10. Meningococcal meningitis LOOK @ AGE/ARMY RECRUITS/COLLEGE STUDENTS/ Rash

    11. 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

    12. 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

    13. 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

    14. 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

    15. 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

    16. Pathogenesis

    17. 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

    18. Typical CSF Findings

    19. CEREBROSPINAL FLUID FINDINGSIN BACTERIAL MENINGITIS • Gram stain Positive in 60-90% • Culture CSF Positive in 70-85%** • Blood Culture Positive 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

    20. 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

    21. 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

    22. 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

    23. 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%)

    24. Antimicrobial therapy of choice for S.pneumoniae

    25. 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

    26. 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

    27. 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)

    28. 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

    29. CASE #4 • Which of the following antimicrobial regimens should be initiated? • A Vancomycin administered intravenously and intrathecally • B Vancomycin + rifampin • C Chloramphenicol • D Trimethoprim-sulfamethoxazole • E Erythromycin

    30. 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: • Elderly Alcoholism • Malignancy Immune suppression • Diabetes mellitus Hepatic and renal disease • Iron overload Collagen-vascular disorders

    31. 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.

    32. 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

    33. 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

    34. Treatment • Usually self limited course and recover completely • Analgesics • Corticosteroids • Frequent but careful LPs if increased intracranial pressure

    35. 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

    36. 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

    37. 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

    38. 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

    39. 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

    40. 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

    41. CASE #6 • Which of the following is the best test for establishing the diagnosis in this patient? • A Electroencephalogram • B MRI of head with gadolinium • C Brain biopsy • D CSF polymerase chain reaction • E CSF antibody studies

    42. 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

    43. 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

    44. 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

    45. 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.