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Clinical Microbiology > CNS infections > Flashcards

CNS infections Flashcards

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1
Q

Why is it concerning to find microorganisms in the CSF?

A

CSF is a sterile body fluid

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2
Q

Cerebrospinal fluid (CSF)

A

90 to 150 mL. It is an ultra-filtrate of plasma that envelopes the brain and spinal cord. Provides buoyancy, carries essential metabolites to neural tissue, and removes waste products from the CNS

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3
Q

Blood brain barrier

A

Mechanical & osmotic barrier
between blood & CSF. Hydrophobic drugs can cross, but hydrophilic drugs often cannot get into the CNS

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4
Q

Choroid plexus

A

A network of capillaries lined with specialized secretory cells
within the brain, produces CSF

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5
Q

Subarachnoid space

A

Space between the tissue layer covering the brain (i.e., pia mater) and the membrane loosely covering brain and part of the spinal cord (i.e., arachnoid)

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6
Q

Meninges

A

All membranes surrounding
the brain, including the dura

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7
Q

Arachnoid villi

A

Part of the arachnoid covering the brain that absorbs CSF and allows it to pass to blood

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8
Q

Meningitis

A

Infection within subarachnoid space. Causes: bacterial, fungal,
tuberculosis, syphilitic, viral, parasitic

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9
Q

Aseptic meningitis

A

Organisms not detected by routine culture. Symptoms similar to acute meningitis. Viral, leptospirosis, patients
receiving antimicrobials, tumor cysts, chemical

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10
Q

Encephalitis

A

Inflammation of brain parenchyma; usually viral, such as enteroviruses

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11
Q

Brain abscess

A

Circumscribed areas of tissue destruction containing organisms and inflammatory cells

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12
Q

Predisposing factors to CNS infections (4)

A
  1. Persons with decreased immune function- elderly, newborns
  2. Prosthetic devices: CNS shunts
  3. Infections adjacent to brain: upper respiratory tract,
    sinusitis, subdural abscess
  4. Surgery, trauma
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13
Q

Symptoms of CNS infections (5)

A
  1. Fever, lethargy, photophobia, skin rash, petechiae
  2. Stiff neck, headache
  3. Nausea and vomiting, poor feeding
  4. Change in mental status, irritability, restlessness
  5. Possible sequelae: learning disability, hearing loss,
    developmental delays
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14
Q

Route of CNS infections (2)

A
  1. Hematogenous: from blood, to choroid plexus, to
    subarachnoid space
  2. Respiratory tract entrance
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15
Q

Respiratory tract entrance to the CNS

A

Can enter the nasopharynx/oropharynx due to otitis media with effusion (OME), sinusitis, etc. The organism attaches to mucosal epithelium via pili. It then enters the lymphatic system and/or blood and is carried throughout body. Enters CSF- viruses can enter directly via nerve tracts or through a damaged blood brain barrier (BBB). Site lacks capillary integrity

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16
Q

Transmission of CNS infections (4)

A
  1. Kissing
  2. Sharing inanimate objects
  3. Sneezing—aerosols and droplets
  4. Environmental exposure
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17
Q

Types of meningitis (3)

A
  1. Acute
  2. Chronic
  3. Aseptic
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18
Q

Acute meningitis

A

Develops rapidly, progressive infection. Typically bacterial, purulent meningitis

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19
Q

Chronic meningitis

A

Develops over two or more weeks with slow growing organisms and can last > 4 weeks. Can be caused by multiple different organisms

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20
Q

Organisms causing chronic meningitis (5)

A
  1. Mycobacterium tuberculosis
  2. Fungi- Cryptococcus neoformans, Aspergillus, Histoplasma,
    Coccidioides, Blastomyces
  3. Spirochetes- T. pallidum, Borrelia spp., & Leptospira spp.
  4. Protozoa- Toxoplasma gondii, Taenia, Naegleria fowleri,
    Acanthamoeba
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21
Q

Causes of aseptic meningitis (5)

A
  1. Viral etiology – Arboviruses - West Nile virus, equine
    encephalitis viruses, HSV 1 & 2, Mumps, HIV
  2. Bacterial – Brucella abortus, B. melitensis, B. ovis, B.
    suis
  3. Physiological – cancer or autoimmune (lupus)
  4. Drugs – (DIAM – drug induced aseptic meningitis). Antimicrobials – SMX/TMP, isoniazid, metronidazole or radiographic agents, NSAIDs, Muromonab-CD3
  5. Head injury
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22
Q

How many meningitis cases occur in young children?

A

95% of meningitis cases < 5 years old

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23
Q

Meningitis in neonates and premature infants

A

Increased mortality in this age group. Premature rupture of membranes (PROM) is a risk factor. Can be caused by E. coli, Group B streptococci, Herpes simplex viruses

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24
Q

Meningitis in newborns under 2 months

A

Group B streptococci and E. coli are still problematic in this age group. Listeria monocytogenes can also be a cause- due to unpasteurized dairy products

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25
Q

Meningitis in children under 10 years of age- causative organisms (3)

A
  1. Haemophilus influenza- covered by HIB vaccine
  2. Streptococcus pneumoniae
  3. Neisseria meningitidis
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26
Q

Sequelae of meningitis in children under 10 years (4)

A
  1. Seizures (20-30%)
  2. Cerebral edema, hydrocephalus, focal neurological change
  3. Deafness (10%)
  4. Death
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27
Q

Causative agents of meningitis in young adults

A

N. meningitidis

28
Q

Risk factors for meningitis in adults (3)

A
  1. Crowded conditions
  2. Poor nutrition
  3. Exertion
29
Q

Causative agents of meningitis in adults

A
  1. N. meningitidis
  2. S. pneumoniae
  3. Listeria monocytogenes
30
Q

S. pneumoniae meningitis

A

83 serotypes: 14, 6, 19, 18, 23, 4, 9, & 3 account for 90% of
cases of meningitis

31
Q

N. meningitidis meningitis

A

Serogroups A, B, and C make up 90% cases. Serogroup A - most common cause of epidemics. Quad-valent vaccine available and newly available B serogroup

32
Q

Causative agents of meningitis in the elderly (3)

A
  1. Streptococcus pneumoniae
  2. various GNR, e.g. K. pneumoniae
  3. Listeria monocytogenes
33
Q

Causative agents of meningitis in immunocompromised patients

A
  1. Group A streptococcus
  2. Staphylococcus epidermidis
  3. Mycobacterium tuberculosis
  4. Listeria monocytogenes
  5. Cryptococcus neoformans
34
Q

CNS shunt infection/ventriculitis

A

Shunts are placed to help correct problems with flow of CSF. Proximal end is in contact with CSF, the distal end is in the Peritoneal, pleural or vascular space

35
Q

Organisms causing CNS shunt infection (4)

A
  1. CoNS, S. aureus, Corynebacterium, Cutibacterium
    acnes
  2. aerobic Gram-negative bacilli
  3. anaerobes
  4. Meningitis related to medical procedures
36
Q

Specimen collection of CSF

A

A lumbar puncture is done- inserts a needle into the subarachnoid space. 3-5 tubes of CSF are collected- there is not a high volume of CSF in the spinal column and children will have even less than adults. Microbiology should receive the least bloody sample. If only one tube collected, microbiology should receive it FIRST. Supernatant can be used by chemistry or for antigen detection. The spinal tap is conducted by a physician, and the specimen should be labeled with patient information. It should be noted if patients are undergoing antimicrobial therapy

37
Q

Tubes collected by lumbar puncture (5)

A
  1. Tube 1: Chemistry - total protein, chemistry, immunoglobulin testing
  2. Tube 2: Microbiology - gram stain, culture, sensitivities, cryptococcal antigen testing, fungal culture
  3. Tube 3: AFB culture and stains – IF NEEDED, IF NOT THEN TO HEMA.
  4. Tube 4: Hematology - cell count, cytology, flow cytometry
  5. Tube 5: Special requests - Viral PCR, West Nile virus, Acanthamoeba, CJ disease, HSV PCR, Enterovirus PCR
38
Q

Transport of CSF samples

A

Hand deliver to laboratory immediately. Gram stains are STAT. Do not refrigerate, some microorganisms are fragile

39
Q

Processing of CSF

A

Process immediately- must use biological safety cabinet and wear gloves. If processing is delayed, store sample at 35oC or room temperature. DO NOT REFRIGERATE, exception: CSF for viral studies can be refrigerated or preferably stored at -70oC. Clear fluids should be concentrated by centrifugation or filtration. For purulent material, inoculate media directly. If there is a bloody, clotted specimen - homogenize to release trapped bacteria or to release fungal cells

40
Q

Gram stain

A

Cytocentrifuge (or centrifuge) specimen - concentration
increases the sensitivity up to 100-fold. An alternative method is acridine orange stain. Communicate /Telephone result immediately, it is ALWAYS
USED TO GUIDE THERAPY

41
Q

CNS culture media and conditions (6)

A
  1. Sheep blood agar
  2. Chocolate agar plate OR slant.
  3. Incubate plates >72 hours at 35oC in 5% CO2
  4. Thioglycollate broth - Incubate at 35oC for 7 days.
  5. Even one colony is significant!
  6. Gram stain results can guide additional plating choices
42
Q

Thioglycollate broth

A

Increases the recovery of anaerobic organisms. Traumatic injury, shunt, metal cranial plates, recovery of anaerobic Cutibacterium acnes

43
Q

How do Gram stain results guide additional plating choices?

A

If anaerobes suggested, add anaerobic blood agar plate. If GNR seen, inoculate MacConkey plate. If yeast or mycobacteria are suspected, inoculate appropriate media. For fungus, inoculate two tubes. Incubate at 30oC and 35oC. For mycobacteria, inoculate on a Lowenstein-Jensen slant. If no organisms seen, it may suggest viral etiology

44
Q

Other visual detection methods (4)

A
  1. Wet mount or direct trichrome stain for amoebas
  2. AFB stain
  3. India ink
  4. Quellung reaction
45
Q

AFB stain

A

Only done if patient history of TB exposure, positive PPD or immunocompromised. PCR on CSF is recommended to replace culture (.5 mL for PCR, more than 10 mL is best for culture)

46
Q

India ink

A

Done to visualize capsule of Cryptococcus neoformans. Only about 50% sensitivity, should perform antigen testing

47
Q

Quellung reaction

A

Rapid identification of S. pneumoniae directly from patient specimen (CSF and blood). Perform on lancet-shaped gram positive cocci only. Poly valent antisera against 84 serotypes. Methylene blue. Positive - swelling of capsule producing a sharply marked halo

48
Q

Non-culture detection methods (3)

A
  1. Molecular methodology
  2. Direct antigen testing
  3. Serology
49
Q

Molecular methodology for organism detection

A
  1. PCR methods - BioFire or Verigene assays
  2. MALDI-TOF - direct testing on processed samples (non-FDA approved)
  3. TMA - AccuProbe by GenProbe - S. pneumoniae, Haemophilus, TB
    Used to detect viruses - West Nile, HSV, Enterovirus
50
Q

Direct antigen testing

A

ONLY FOR Cryptococcal antigen (CRAG) is diagnostic at ~98% sensitivity from CSF. If the test is positive, sample must be tested for rheumatoid factor. If rheumatoid factor is positive, cryptococcal antigen test is uninterpretable. Prozone phenomenon can cause false-negative result

51
Q

Serology

A
  1. Neurosyphilis - general CSF lab tests: 100-750 lymphs, 50-250 mg/dL protein, normal glucose. VDRL (Venereal disease research laboratory) antibodies Treponema pallidum in CSF.
  2. Coccidioides immitis - ~100% sensitivity
  3. Cryptococcus neoformans, Histoplasma capsulatum
52
Q

Neisseria meningitidis vaccines (3)

A
  1. Meningococcal polysaccharide vaccine (Menomune®)
  2. Meningococcal conjugate vaccine (Menactra® and Menveo®)
  3. Group B vaccination, target bacterial proteins – Bexsero ® -Novartis
53
Q

Neisseria meningitidis complications

A

10%-14% of cases are fatal, of those that recover 11%-19% have permanent hearing loss, mental retardation, loss of limbs, or other serious sequelae

54
Q

Streptococcus pneumoniae complications

A

14% death rate in hospitalized adults with invasive disease.
Neurologic sequelae and/or learning disabilities can occur in meningitis patients

55
Q

Streptococcus pneumoniae vaccines (2)

A
  1. 7-valent pneumococcal conjugate vaccine (PCV7)- part of the routine infant immunization schedule, recommended for all children <5 years of
    age.
  2. 23-valent pneumococcal polysaccharide vaccine (PPSV23). Recommended for ages 19-64 with underlying medical conditions and for all adults aged ≥65 years
56
Q

Haemophilus influenzae type B complications

A

3%-6% of cases are fatal; up to 20% of surviving patients
have permanent hearing loss or other long-term sequelae

57
Q

Haemophilus influenzae type B vaccines

A

4 different Hib conjugate vaccines currently available, either mono-valent or multi-
valent combination. Multiple immunization schedule, starting at 2 months, recommended for all children <5 years of age. If >5 years of age, vaccination is not needed.

58
Q

Sources of brain abscesses (4)

A
  1. Sinus or ear infections
  2. Hematogenous spread
  3. Skull trauma - Staphylococcus aureus
  4. Predisposing factors: diabetes mellitus, corticosteroid
    therapy, AIDS, malignancy
59
Q

Common organisms causing brain abscesses (6)

A
  1. Aerobic and anaerobic streptococci
  2. Bacteroides spp.
  3. Gram-negative aerobes
  4. Staphylococci
  5. Citrobacter koseri
  6. Fungi
60
Q

Citrobacter koseri

A

Source of infection is unknown, possible vertical transmission from mother or horizontal from hospital staff. Rarely ever reported after neonatal period

61
Q

Fungal organisms causing brain abscesses (3)

A
  1. Aspergillus spp.
  2. Zygomyces
  3. Dimorphic fungi
62
Q

Diagnosis of brain abscesses (3 methods)

A
  1. Tissue biopsy—submit under anaerobic conditions
  2. Homogenize tissue
  3. Media - aerobic and anaerobic media required
63
Q

Normal CSF characteristics (4)

A

Leukocytes: 0-5
Predominant cell type: none
Protein: 15-50
Glucose: 45-100

64
Q

CSF characteristics- viral infection

A

Leukocytes: 2-2,000, 80 is the average
Predominant cell type: mononuclear
Protein: slightly elevated (50-100) or normal
Glucose: normal (45-100)

65
Q

CSF characteristics- bacterial infection

A

Leukocytes: 5-20,000
Predominant cell type: PMN (left shift)
Protein: elevated- greater than 100
Glucose: low, less than 45- but may be normal early in the course of disease

Clinical Microbiology (19 decks)

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