1. CNS Infections Tahseen J. Siddiqui, M.D Infectious Disease Consultant Medical Director HIV/STD Care Program Jackson Park Hospital & Medical Center Chicago President The Chicago Society of Internal Medicine

3. Meningitis Mortality/Morbidity Morbidity and mortality depend on pathogen, patient's age and condition, and severity of acute illness Among bacterial pathogens, pneumococcal meningitis causes the highest rates of mortality (21%) and morbidity (15%). Mortality rate is 50-90% and morbidity even higher if severe neurologic impairment is evident at the time of presentation (or with extremely rapid onset of illness), even with immediate medical treatment. Race Blacks are at greater risk than other races, although race may not be an independent risk factor. Sex In neonates, male-to-female ratio is 3:1. No sex preference exists among adults. Age According to the Centers for Disease Control and Prevention (CDC),4 the median age is 39 years. In 1986, it was 15 months.

6. Coagulase-negative staphylococci S aureus Aerobic gram-negative bacilli Propionibacterium acnes CSF shunts S pneumoniae H influenzae Group A streptococci Basilar skull fracture Staphylococcus aureus Coagulase-negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosa Intracranial manipulation, including neurosurgery S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli Immunocompromised state S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli Age older than 50 years S pneumoniae N meningitidis H influenzae Age 18-50 years N meningitidis S pneumoniae H influenzae Age 3 months to 18 years S agalactiae E coli H influenzae S pneumoniae N meningitidis Age 4-12 weeks S agalactiae (group B streptococci) E coli K1 L monocytogenes Age 0-4 weeks Bacterial Pathogen Risk and/or Predisposing Factor

7. Slide 2. Neisseria meningitidis meningitis This cerebrospinal fluid contains a high concentration of neutrophils and many gram-negative diplococci singly and in pairs. Although Neisseria meningitidis is the most likely organism, differentiation from N. gonorrhoeae , which can also cause meningitis, is not possible with Gram stain. But with the PCR Slide 1. Streptococcus pneumoniae meningitis This cerebrospinal fluid from a child with meningitis contains many neutrophils and oval gram-positive cocci singly and in pairs. Because the number of organisms in infected cerebrospinal fluid is small, most laboratories centrifuge the specimen to increase the concentration and then use the sediment for both stains and cultures. The density of microbes per milliliter of fluid cannot be estimated from a specimen that has been centrifuged . Neisseria meningitides and Streptococcus pneumoniae account for 37% to 93% of acute bacterial meningitis

8. Slide 3. Haemophilus influenzae meningitis This cerebrospinal fluid contains many neutrophils and gram-negative coccobacilli, primarily in the cytoplasm of the white cells. Slide 4. Listeria monocytogenes meningitis This cerebrospinal fluid contains a few neutrophils and two slender gram-positive bacilli. Although Gram stains of cerebrospinal fluid are positive in specimens from about 80% of all patients with bacterial meningitis, organisms are detected in the cerebrospinal fluid of only about 40% of patients with Listeria meningitis. Even when specimens reveal bacteria, only a small number may be visible.

16. Open P . AIDS patients with crypto meningitis have increased risk of blindness, death unless open pressure maintained at <30 cm In Bact mening- Lymphocytosis with normal CSF chemistries seen in 15-25%, especially when cell counts <1000 or if partially treated. In Viral mening Up to 48 hours, significant PMN pleocytosis may be indistinguishable from early bacterial meningitis After 8-12 hours, reexamine the CSF . If initial granulocytosis changes to mononuclear predominance, CSF glucose remains normal, and patient continues to look well, the infection is most likely nonbacterial. Nontraumatic RBCs in 80% of HSV meningoencephalitis, although 10% have normal CSF results ~90% of patients with VP shunts have CSF WBC count >100 cells/mm3 are infected; CSF glucose usually normal, and organisms are less pathogenic (Staph epi, Propionibacterium acnes, and diphtheroids) and S aureus, coliforms India ink 80-90% effective for fungi; AFB stain 40% effective for TB Prior antibiotics may cause gram-positive organisms to appear gram negative and decrease culture yield on average 20%. lowest levels of CSF glucose are seen in TB, primary amebic meningoencephalitis, neurocysticercosis An aseptic profile - bacterial (eg, Mycoplasma, Listeria, Leptospira species, Borrelia burgdorferi [Lyme], spirochetes), partially treated bacterial , HSV and arboviruses TB meningitis and parasites resemble the fungal profile more closely. 5-15 cm H2 O

19. Adult doses: cefotaxime (2 g IV q4h) or ceftriaxone (2 g IV q12h) vancomycin (15-20 mg/kg IV q12h Ampicillin 50-100 mg/kg IV q6h Chloramphenicol (PCN allergic) 50-100 mg/kg/d PO/IV divided q6h AGE CAUSATIVE ORGANISM TREATMENT <1 MONTH GBS, E.COLI/GNRs, listeria Ampicillin + cefotaxime or gentamicin 1-3 months Pneumococci, meningococci, H influenzae Vancomycin IV + ceftriaxone or cefotaxime 3 months-adulthood Pneumococci, meningococci Vancomycin IV +ceftriaxone or cefotaxime >60 yrs/alcoholism/ chronic illness Pneumococci, gram – bacilli, listeria, meningococci Ampicillin + vancomycin+ cefotaxime or ceftriaxone

20. 21 Ceftazidime plus an aminoglycoside ... P aeruginosa 21 Ceftriaxone or cefotaxime plus an aminoglycoside ... Enterobacteriaceae 14-21 Penicillin G plus an aminoglycoside, if warranted ... S agalactiae 14-21 Ampicillin or penicillin G plus an aminoglycoside ... Listeria monocytogene 7 Penicillin G or ampicillin ... N meningitidis Ceftriaxone or cefotaxime Beta-lactamase-positive 7 Ampicillin Beta-lactamase-negative H influenzae Ceftriaxone or cefotaxime plus vancomycin or rifampin Ceftriaxone MIC >0.5 mg/L Ceftriaxone or cefotaxime MIC >2 mg/L Ceftriaxone or cefotaxime MIC 0.1-1 mg/L 10-14 Penicillin G Penicillin MIC <0.1 mg/L S pneumoniae Duratiin Days Antibiotic(s) Susceptibility Bacteria

26. Differentiating Lyme meningitis from enteroviral meningitis (Aseptic meningitis) The duration of symptoms before evaluation was longer for patients with Lyme meningitis (12 days) than with enteroviral meningitis (1 day). Cranial neuropathy , erythema migrans rash or papilledema occurred mostly in patients with Lyme meningitis; no patients with enteroviral meningitis Lyme meningitis was unlikely when cerebrospinal fluid neutrophils exceeded 10%

27. Meningitis: Complications 􀂃 Death 􀂃 Hearing loss 􀂃 Seizures 􀂃 Learning disorders

36. Cryptococcus neoformans & HIV Cryptococcal meningitis is the most common opportunistic infection of the CNS, affecting 5-7% of patients with AIDS . The second most common type of meningitis is aseptic meningitis, which may be caused by HIV-1 itself. HIV-associated meningitis develops within days to weeks after HIV infection. It appears as a mononucleosis-like illness and is rarely associated with encephalitis. Tx with HAART

44. Cumulative Total Entire Country: 547 West Nile Virus Cumulative 2010 Data as of 3 am, Sep 28, 2010 1 Kentucky 6 Kansas 3 Iowa 5 Indiana 18 Illinois 1 Idaho 10 Georgia 7 Florida 7 Connecticut 38 Colorado 50 California 3 Arkansas 101 Arizona 3 Alabama 2 Ohio 8 North Dakota 89 New York 11 New Mexico 17 New Jersey 2 Nevada 36 Nebraska 4 Missouri 5 Mississippi 3 Minnesota 16 Michigan 3 Massachusetts 9 Maryland 18 Louisiana 4 Wyoming 1 Wisconsin 2 Virginia 31 Texas 1 Tennessee 20 South Dakota 12 Pennsylvania

47. Laboratory criteria for diagnosis Four-fold or greater virus-specific serum antibody titer , OR Isolation of virus from or demonstration of specific viral antigen or genomic sequences in tissue, blood, cerebrospinal fluid (CSF), or other body fluid, OR Elevated virus-specific immunoglobulin (IgG) antibodies in the acute or convalescent serum specimen as measured by VN or HI, or IgG enzyme immunoassay (EIA), OR Virus-specific immunoglobulin M (IgM) antibodies demonstrated in serum by IgM antibody-capture enzyme immunoassay (EIA) Case classification A case must meet one or more of the above clinical criteria and one or more of the above laboratory criteria. Confirmed case : Four-fold or greater change in virus-specific serum antibody titer, OR Isolation of virus from or demonstration of specific viral antigen or genomic sequences in tissue, blood, CSF, or other body fluid, OR Virus-specific immunoglobulin M (IgM ) antibodies demonstrated in CSF by antibody capture enzyme immunoassay (EIA), OR Virus-specific IgM antibodies demonstrated in serum by antibody-capture EIA and confirmed by demonstration of virus-specific serum immunoglobulin G (IgG) antibodies in the same or a later specimen by another serologic assay (e.g., neutralization or hemagglutination inhibition) Probable case : Stable (less than or equal to a two-fold change) but elevated titer of virus-specific serum antibodies , OR Virus-specific serum IgM antibodies detected by antibody-capture EIA but with no available results of a confirmatory test for virus-specific serum IgG antibodies in the same or a later specimen West Nile Virus

56. RABIES Patients with rabies could present atypically with aseptic meningitis , and rabies should be suspected in a patient with a history of animal bite (eg, skunk, raccoon, dog, fox, bat).

57. Rabies: Major Vector Species in the U.S.

62. Prions