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Block 8 week 2 > CNS infections 1 and 2 - Kozel > Flashcards

CNS infections 1 and 2 - Kozel Flashcards

1
Q

List some CNS infections.

A
  1. acute meningitis
  2. cerebrospinal fluid shunt infections
  3. chronic meningitis
  4. enchephalitis
  5. Focal CNS syndromes
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2
Q

What are some Focal CNS syndromes?

A
  1. brain abscess
  2. subdural empyema
  3. epidural abscess
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3
Q

What are some routine tests done on CSF samples?

A
  1. WBC count with differential - normally around 0-5 mm2
  2. glucose concentration - normally around 60% of plasma levels or about 50-80 mg/dL
  3. protein concentration - normally about 15-50 mg/dL
  4. gram stain - always order! is effective 70-80% of the time
  5. bacterial culture
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4
Q

What are some specific tests to order based on clinical suspicion?

A
  1. PCR - nucleic acid amplification - done for viruses
  2. stain and culture for acid fast bacteria
  3. VDRL test for tertiary syphillis
  4. india ink negative stain
  5. cryptococcal polysaccharide antigen
  6. fungal culture
  7. viral culture - (PCR used more)
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5
Q

Meningitis is caused by what types of different microbes?

A
  1. viral - most common
  2. bacterial - more serious
  3. tuberculous
  4. cryptococcus
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6
Q

What is increased in all types of meningitis?

A

WBC count.

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7
Q

What are the CSF findings in viral meningitis?

A
  1. WBC’s increased with mainly lymphocytes - (50-1000 mm2)
  2. glucose is normal (greater than 45 mg/dL)
  3. protein is increased (less than 200 mg/dL)
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8
Q

What are the CSF findings in bacterial meningitis?

A
  1. highly increased WBC’s - mainly neutrophils, 1000-5000 mm2
  2. glucose is decreased, less than 40 mg/dL
  3. protein is increased, about 100-500 mg/dL
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9
Q

What are the CSF findings in tuberculous meningitis?

A
  1. WBC’s are increased - 50-300 mm2, mainly lymphocytes
  2. glucose is decreased - less than 45 mg/dL
  3. protein is increased - 50-300 mg/dL
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10
Q

What are the CSF findings in cryptococcal meningitis?

A
  1. WBC’s are increased - 20-500 mm2, mainly lymphocytes
  2. glucose is decreased - 40 mg/dL
  3. protein is normal or increased - about 45 mg/dL
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11
Q

Why is the CSF WBC count increased in meningitis?

A

It is due to inflammation and immune response. If there is blood in the CSF then the WBC count must be adjusted.

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12
Q

Why is glucose generally decreased in CSF in meningitis?

A

Could be several mechanisms:

  1. increased glycolysis by leukocytes and bacteria
  2. increased metabolic rate of brain and spinal cord
  3. altered glucose transport between blood and CSF
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13
Q

Why is protein generally increased in CSF in meningitis?

A
  1. disruption of the BBB

2. must be adjusted if evidence of blood in the CSF

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14
Q

What are the contraindications for lumbar puncture?

A
  1. papilledema - increased cranial pressure

2. neurological suggestion of intracranial mass

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15
Q

What is part of the differential diagnosis when a patient presents with headache, nuchal rigidity and fever?

A

Enecephalitis, ADEM, encephalopathy, cerebral mass or abscess, meningitis.

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16
Q

What is one big difference that can help differentiate between encephalitis and meningitis?

A

Meningitis does not usually present with altered mental status early in its course and encephalitis does.

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17
Q

What is meningitis?

A

Inflammation of protective membranes (meninges) covering the brain and spinal cord.

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18
Q

What is acute meningitis?

A

Meningitis with onset of symptoms over hours or several days.

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19
Q

What is aseptic meningitis?

A

Any meningitis for which a cause is not apparent after routine stains and culture of CSF.

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20
Q

What are the symptoms of acute meningitis?

A
  1. headache and neck stiffness associated with fever
  2. confusion or altered consciousness
  3. vomiting
  4. inabilty to tolerate light - photophobia
  5. inability to tolerate loud noises - phonophobia
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21
Q

What is the initial management of acute meningitis?

A
  1. lumbar puncture with CSF analysis
  2. empiric antimicrobial therapy based on patient age
  3. adjunctive dexamethasone if appropriate - a steroid that reduces inflammation
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22
Q

What microbes are associated with viral meningitis?

A
  1. enteroviruses - 85-95% of all cases in US
  2. mumps virus
  3. herpesvirus
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23
Q

What type of microbe is the most common meningitis causing bug?

A

Viruses.

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24
Q

What microbes are associated with bacterial meningitis?

A
  1. Haemophilus influenzae - 7%
  2. Neisseria meningitidis - 16%
  3. Streptococcus pneumoniae - 61%
  4. Streptococcus agalactiae - 14%
  5. Listeria monocytogenes - 2%
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25
Q

What other types of microbes can cause meningitis?

A
  1. Protozoa
  2. Helminths
  3. Spirochetes such as Treponema pallidum and Borrelia burgdorferii
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26
Q

Describe the general clinical course of bacterial meningitis.

A
  1. mucosal/nasopharyngeal colonization
  2. local invasion
  3. intravascular survival
  4. meningeal invasion
  5. induction of subarachnoid space inflammation
  6. alterations of BBB
  7. cerebral edema and increased ICP
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27
Q

Are the bacteria involved with meningitis encapsulated or not encapsulated?

A

They are usually encapsulated because they need to be able to survive and spread to the meninges.

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28
Q

How many bacteria does it take to cause meningitis?

A

It only takes one single bacteria that is able to pass through the BBB and infect the meninges.

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29
Q

Age is a big determinate in what specific microbe is the most probable cause in a case of bacterial meningitis. Describe which ones are associated with which age group.

A
  1. newborns of less than one month - Group B strep (Strep aglactiae) most common but can be E. coli, Listeria or Klebsiella.
  2. 1-23 months - group B strep most common but can be E. coli, Haemophilus influenzae, Strep pneumonia and Neisseria meningitidis.
  3. 2-50 years - Strep pneumoniae is most common but can be Neisseria meningitidis.
  4. greater than 50 years of age - Strep Pneumoniae is the most common but can be Neisseria, Listeria or aerobic gram-negative bacilli.
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30
Q

What used to be a common cause of meningitis in kids 1-23 months old and why is it not anymore?

A

H. influenzae used to be the most common cause of meningitis in this age group but now it is Group B strep because we have vaccines for H. flu.

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31
Q

Most antibiotics cannot pass through a healthy BBB. Which ones can?

A

Rifampin and the fluoroquinolones.

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32
Q

What can cause increased permeability of the BBB to antibiotics?

A

Inflammation.

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33
Q

What features of antibiotics make them good at crossing BBB in the absence of meningeal inflammation?

A
  1. low molecular weight
  2. low degree of ionization at physiological pH
  3. high lipid solubility
  4. low degree of protein binding
  5. absence of active reflux system that acts on the drug
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34
Q

In newborns with meningitis caused by bacteria what is the empiric antibiotic treatment?

A
  1. ampicillin plus ceftriaxone

2. ampicillin plus an aminoglycoside

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35
Q

In the 1-23 month old age group, what is the best empiric treatment of bacterial meningitis?

A

Vancomycin plus a third-generation cephalosporin such as ceftriaxone.

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36
Q

In the 2-50 year old age group, what is the best empiric treatment of bacterial meningitis?

A

Vancomycin plus a third generation cephalosporin such as ceftriaxone.

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37
Q

In the over 50 age group, what is the best empiric treatment of bacterial meningitis?

A

Vancomycin plus ampicillin plus a third generation cephalosporin such as cetriaxone.

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38
Q

What are the recommended therapies for bacterial meningitis once gram staining or more specific tests have been done?

A
  1. Strep. pneumoniae- Vancomycin plus third generation cephalosporin
  2. Neisseria - third generation cephalosporin
  3. Listeria - ampicillin or penicillin G
  4. H. influenzae - third generation cephalosporin
  5. E. coli - third generation cephalosporin
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39
Q

What is an alternative treatment for Strep Pneumo bacterial meningitis?

A

Meropenem or fluoroquinolone.

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40
Q

What is an alternative treatment for Neisseria meningitis?

A

Penicillin G, ampicillin, fluoroquinolone.

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41
Q

What is an alternative treatment for listeria meningitis?

A

TMP-SMX or meropenem.

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42
Q

What is an alternative treatment for H. flu meningitis?

A

Cefepime, fluroquinolone.

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43
Q

What is an alternative treatment for E. coli meningitis?

A

Cefepime, meropenum, aztreonam, TMP-SMX, fluroquinolone.

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44
Q

How is chronic meningitis different from acute?

A

In chronic meningitis there is an indolent onset of greater than or equal to 4 weeks and signs of chronic inflammation in the CSF. Also, the fever will be lower , may have lethargy and disability and is often seen in immune compromised patients.

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45
Q

What are the early symptoms of chronic meningitis?

A

Headache, nausea and decreased memory and comprehension.

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46
Q

What sorts of microbes are associated with chronic meningitis?

A
  1. mycoses
  2. bacteria
  3. parasites
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47
Q

What Mycoses are associated with chronic meningitis?

A
  1. cryptococcosis
  2. coccidioidomycosis
  3. histoplasmosis
  4. candidiasis
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48
Q

What bacteria are associated with chronic meningitis?

A
  1. mycobacterium tuberculosis
  2. trepanoma pallidum
  3. borellia burgdorferii
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49
Q

What parasites are associated with chronic meningitis?

A
  1. acanthamebiasis
  2. cysticercosis
  3. angiostrngylus cantonensis
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50
Q

What is encephalitis?

A

Inflammatory processes in the brain parenchyma with clinical or lab evidence of neurologic dysfunction.

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51
Q

What are the symptoms of encephalitis?

A

Fever, headache and altered mental status.

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52
Q

What are the CSF findings in encephalitis?

A
  1. lymphocytic peocytosis - magnitude varies with etiologic agent
  2. normal glucose
  3. elevated protein
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53
Q

What types of viruses are causes of encephalitis?

A
  1. HSV1 and HSV2
  2. varicella zoster
  3. CMV
  4. HHV-6
  5. arboviruses
  6. HIV
  7. eneteroviruses - primarily poliovirus
  8. rabies virus
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54
Q

What is the most common infectious agent involved in encephalitis?

A

Viruses.

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55
Q

What are some non-viral causes of meningitis?

A
  1. listeria
  2. Rickettsia spp.
  3. Ehrlichia spp.
  4. Bartonella spp.
  5. Mycoplasma pneumonia
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56
Q

What are brain abscesses?

A

Focal, intracerebral infections that begin as localized area of cerebrates and develops into collection of pus surrounded by a well-vascularized capsule.

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57
Q

What are some sources of brain abscesses?

A
  1. contiguous spread - sinusitis, otitis media or mastoiditis
  2. hematogenous
  3. trauma
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58
Q

What are the symptoms of brain abscesses?

A
  1. General - headache, nausea, vomiting, focal neurologic findings
  2. can vary with site of abscess
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59
Q

What microbes are associated with brain abscess?

A
  1. bacteria
  2. fungi
  3. protozoa and helminths
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60
Q

List some bacteria associated with brain abscess.

A
  1. Streptococcus spp. - 70%
  2. Staph aureus - 10-20%
  3. Bacterioides spp.
  4. Prevotella spp.
  5. Fusobacterium spp.
  6. Enterobacteriaceae
  7. Pseudomonas spp.
  8. Nocardia asteroides
  9. Mycobacterium spp.

Most bacterial brain abscess infections are mixed infections- not just a single bacteria involved.

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61
Q

What are some predisposing conditions for brain abscess?

A
  1. sinus infection or dental infection
  2. penetrating trauma
  3. pulmonary infection
  4. congenital heart disease
  5. HIV infection
  6. Transplantation
  7. Neutropenia
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62
Q

When sinus or dental infections cause a brain abscess, what microbes are usually involved?

A
  1. aerobic and anaerobic streptococci
  2. bacteroides spp.
  3. prevotella spp.
  4. enterobacteriaceae
  5. Staph aureus
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63
Q

When penetrating traumas are a cause of brain abscess, what microbes are usually involved?

A
  1. Staph aureus
  2. aerobic streptococci
  3. enterobacteriaceae
  4. clostridium spp.
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64
Q

When pulmonary infection is a cause of brain abscess, what microbes are usually involved?

A
  1. Fusobacterium
  2. actinomyces
  3. Bacteroides
  4. prevotella spp.
  5. nocardia spp.
  6. streptococci
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65
Q

When congenital heart disease is a cause of brain abscess, what microbes are usually involved?

A
  1. Streptococci

2. staph aureus

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66
Q

When HIV infection is a cause of brain abscess, what microbes are usually involved?

A
  1. toxoplasma gondii
  2. nocardia spp.
  3. mycobacterium spp.
  4. listeria
  5. cryptococcus neoformans
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67
Q

When transplantation is a cause of brain abscess, what microbes are usually involved?

A
  1. Aspergillus spp.
  2. candidia spp.
  3. mucorales
  4. nocardia spp.
  5. toxoplasma gondii
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68
Q

When neutropenia is a cause of brain abscess, what microbes are usually involved?

A
  1. aerobic gram negative bacilli
  2. aspergillus spp
  3. candida spp.
  4. mucorales
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69
Q

What are the general features of Neisseria meningiditis and Neisseria gonorrheae?

A
  1. gram negative cocci
  2. pathogens are fastidious - use blood agar, chocolate agar or Thayer-Martin medium
  3. produce indophenol oxiadase - used for identification
  4. resistance - easily killed by drying, sunlight, heat and chemicals
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70
Q

What is Thayer martin medium?

A

A selective medium designed to inhibit normal flora but allowing Neisseria to grow.

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71
Q

The antigenic structure of Neisseria meningitidis is classified how?

A

By group specific capsular polysaccharide. There are 12 groups. The most clinically important are:
1. Group A - classic epidemic strain but not in US, in sub-Saharan Africa
2. Group C - endemic and occasional epidemic strain
3. Groups Y and W-135 - endemic strains
4. Group B - endemic strain
Also classified by type specific outer membrane proteins and type specific lipooligosaccharide.

72
Q

Describe the group B capsular polysaccharide of Neisseria meningitidis.

A
  1. polymer of sialic acid
  2. poorly imunogenic because is seen as self
  3. antigen expressed in neonatal tissues
73
Q

What is lipooligosaccharide (LOS)?

A

An antigen that is specific to different types of Neisseria meningitidis bacteria. It is similar to LPS which is made of lipid A, O antigens and a polysaccharide core. LOS only has the core plus Lipid A. It does not have O antigens.

74
Q

Meningococcal infections refer to which microbes?

A

Neisseria meningitidis.

75
Q

What is meningococcemia?

A

When Neisseria meningitidis bacteria infect the blood stream. Can occur with or without meningitis.

76
Q

What are the types of Meningococcal infections?

A
  1. meningococcemia
  2. meningitis
  3. petechial lesions often present
77
Q

Is meningococcal meningitis a medical emergency?

78
Q

What is the hallmark of meningococcal infections?

A

Petechial lesions.

79
Q

What is purport?

A

Hemorrhage into the skin.

80
Q

What are petechiae?

A

Small hemorrhagic spots.

81
Q

What is ecchymoses?

A

Large, irregularly formed hemorrhagic areas.

82
Q

What do petechiae correlate with when present in meningococcal infections?

A

With the degree of thrombocytopenia due to DIC.

83
Q

What are the virulence factors of the Neisseria spp?

A
  1. Capsule - is antiphagocytic
  2. LOS - extremely toxic and produces inflammation
  3. outer membrane proteins
  4. pili
84
Q

How does LOS cause so much virulence?

A

LOS is released from the bacterial surface as membrane blebs. When the bacteria are growing these blebs are released in large amounts.

85
Q

Describe the general progression of Neisseria infection.

A
  1. gains accèss to nasopharynx
  2. adheres via pili to epithelial cells
  3. remains local (carrier) or spreads via lymphatics to blood (bacteremia) and possibly to the meninges (meningitis)
  4. capsule prevents phagocytosis and complement mediated lysis
  5. tissue damage due to LOS
  6. DIC due to LOS - causes hemorrhages and shock
86
Q

Neisserial meningitis is especially associated with what condition?

A

Deficiencies with terminal components of complement - C5,C6,C7 and C8. Can also get disseminated infection with N. gonorrheae.

87
Q

What types of specimens are usually obtained in Neisserial infections?

A
  1. blood
  2. CSF
  3. nasophrynx secretions - used to identify carriers
88
Q

Describe the laboratory identification of Neisseria meningitidis.

A
  1. gram stain of CSF
  2. can culture and incubate with CO2, must do this quickly
  3. chocolate agar, blood agar are good mediums
  4. if taking a swab that may include normal flora such as a nasopharyngeal swab then Thayer-Martin medium good
89
Q

What characteristics are used to differentiate Neisseria meningitidis from other bacteria?

A
  1. gram negative dipplococci
  2. oxidase positive
  3. oxidative production of acid from sugars such as glucose and maltose
90
Q

How is Neisseria infection spread?

A

Man to man transmission.

91
Q

What groups are especially vulnerable to Neisseria infection?

A
  1. young children who lack antibody - 6-24 months (younger have antibodies from mom and older make their own)
  2. college students and military recruits due to crowding and fatigue
  3. carrier rate is 1-4 0%, few carriers develop clinical disease
  4. disease may occur sporadically or in epidemics
92
Q

How can we make antibodies to Neisseria without being exposed to it?

A

E. coli bacteria make a similar antigen as Group A Neisseria so we have antibodies to this antigen.

93
Q

Describe some characteristics of immunity to meningococci.

A
  1. antibodies made to capsule
  2. protection via complement mediated lysis and opsonization
  3. anticapsular antibody is the major factor that determines resistance vs. susceptibility
  4. lack of antibody explains risk of children between 6-24 months
  5. naturally occurring immunity due to carrier state and cross reacting bacteria such as E. coli.
94
Q

Describe the Tetravalent meningococcal polysaccharide vaccine.

A
  1. called MPSV4
  2. antibodies formed against Groups A,C, Y and W-135 polysaccharides
  3. is made from purified polysaccharide alone
  4. only vaccine licensed for persons greater than or equal to 56 years old
95
Q

Describe the Tetravalent meningococcal polysaccharide-protein conjugate vaccine.

A
  1. called MCV4 or MenACWY
  2. antibodies formed against Groups A, C, Y and W-135 polysaccharides
  3. given routinely to adolescents -11-12 years old
  4. a booster is given around 16-18 years old
96
Q

Aside from routine vaccination, what groups should receive the Meningococcal vaccine?

A
  1. college freshman living in dormitories
  2. microbiologists with potential exposure
  3. miliatary recruits
  4. travelers to endemic regions
  5. terminal complement deficiency patients
97
Q

What group of Neisseria are not protected against by the current vaccines?

A

Group B neisseria are poorly immunogenic and are not included in currently used vaccines. There was a recently approved vaccine for group B that targets Factor H binding protein.

98
Q

If N. meningitides is targeted as the infectious agent, what is the standard therapy?

A
  1. Third generation cephalosporin such as ceftriaxone or cefotaxime
    OR
  2. penicillin G, ampicillin - can work when BBB is more permeable
  3. extensive supportive care is provided
  4. chemoprophylaxis is given to contacts and in epidemics - Rifampin is given
99
Q

What Hemophilus species are clinically important?

A
  1. H. influenzae
  2. H. influenzae biogroup aegyptius - can cause Brazilian purpuric fever
  3. H. aegyptius - can cause acute conjunctivitis or pink eye
  4. H. ducreyi - causes a soft chancre mediated venereal disease that is common in subSaharan Africa
100
Q

What is the morphology of Hemophilus?

A

Very small, gram-negative rods.

101
Q

What are the nutritional requirements of Hemophilus influenzae?

A
  1. X factor (Hematin) - found in blood

2. V factor (NAD)

102
Q

What types of mediums are good for growing Hemophilus influenzae?

A
  1. chocolate agar
  2. heated blood agar - heating lyses erythrocytes to release X and V factors and inactivates an inhibitor of V factor
  3. can grow with Staph aureus because Staph aureus causes release of X factor from blood agar and secretes V factor - This is called Satelliting
103
Q

What are the nutritional requirements of H. ducreyi?

104
Q

What is the antigenic structure of H. influenzae?

A
  1. capsular polysaccharide - is antiphagocytic, types a-f

2. Nontypeable strains - lack a capsule and are very common

105
Q

What is satelliting?

A

The growing of H. influenzae with E. coli.

106
Q

What strain of H. influenzae are the cause of almost all systemic disease seen with Hemophilus?

A

Type b - is made from polyribitol phosphate.

107
Q

What strain of Hemophilus is associated with middle ear infections?

A

Nontypeable strains - because they lack a capsule and can only survive in certain environments.

108
Q

What type of infections are seen with Hemophilus influenzae?

A
  1. Epiglottitis - encapsulated strains (a medical emergency due to breathing issues)
  2. Pneumonia - primary or secondary to in fluenzae virus infection
  3. Nasopharyngitis - extending to sinuses, middle ear, blood, meninges or joints.
109
Q

What is the most common cause of Nasopharyngitis that extends to other body structures?

A

H. influenzae type b infection. Also can be caused by Strep. pneumo and Moraxella catarrhalis.

110
Q

Describe the pathogenies of H. influenzae type b (Hib) infections.

A
  1. can be an invasive disease in a healthy person if avoids killing in the blood
  2. has an antiphagocytic capsule
  3. type b capsule blocks complement mediated bacteriolysis
  4. endotoxin - induces meningeal inflammation
111
Q

How is Hib identified in the lab?

A
  1. specimens include - blood CSF and nasopharyngeal swab
  2. gram stain of CSF provides provisional diagnosis
  3. isolation requires X and V factors and must be able to separate from normal flora
112
Q

What are some identification factors for Hib?

A

Identification based on the need for X and V factors.

113
Q

Hib used to cause 20,000 cases per year of meningitis in the US but does not now. Why?

A

Because we have a vaccine. This is still a major problem worldwide.

114
Q

In Hib mediated meningitis what is the mortality rate and why?

A

The mortality rate is 5% and is primarily due to the neurological sequelae that is present in 30-50% of cases.

115
Q

What is the carrier rate for Hemophilus influenzae?

A
  1. reaches 30-50% in children
  2. most carrier strains are nontypeable and cause otitis media primarily
  3. there are few asymptomatic carriers of type b
116
Q

What age group was particularly susceptible to meningitis mediated by Hib?

A

The age group 6-36 months because they have mom’s antibodies prior to 6 months and make their own after age 36 months primarily due to exposure to cross reactive antigens on other bacteria.

117
Q

Resistance to Hib is due to what?

A

Anticapsular antibody. This antibody protects via opsoniazation and complement mediated lysis.

118
Q

There is a vaccine made in 1984 that had some issues. What were the main issues?

A
  1. The vaccine was made with polyribitol phosphate antigen or PRP - (part of capsular polysaccharide)
  2. these polysaccharides are poorly immunogenic in children younger than 18 months old
  3. these particular polysaccharide antigens are called T independent antigens because kids do not make antibodies to them
119
Q

What is the current vaccine to Hib?

A
  1. a protein conjugate vaccine
  2. the polysaccharide (PRP) is coupled to diphtheria toxoid, to nontoxic mutant diphtheria toxin, or to N. meningitides OMP depending on the vaccine
  3. this vaccine can induce antibodies in kids
  4. recommended for all childen at age 2 mos.
  5. has reduced carrier rate also
120
Q

How is Hib infection treated?

A
  1. requires prompt, vigorous treatment - DO NOT wait for culture results
  2. treat with a broad spectrum cephalosporin with good CNS penetration such as cetotaxime or ceftriaxone
  3. susceptible contacts are treated with Rifampin
121
Q

What are some other homophilus infections besides Hib?

A
  1. H. influenzae biogroup aegyptius - causes Brazilian purpuric fever
  2. H. aegyptius - causes pink eye
  3. H. ducreyi - causes venereal disease
122
Q

Describe infection by H. influenzae biogroup aegyptius.

A
  1. etiologic agent of Brazilian purpuric fever
  2. invasive H. aegyptius following conjunctivitis
  3. acute onset of fever, vomiting, and abdominal pain followed by purport, vascular collapse and death
123
Q

Describe infection by H. ducreyi.

A
  1. chancroid, formerly rare in N. America
  2. relatively common in Africa
  3. causes painful ulcers on genitalia
  4. probable co-factor in transmission of AIDS in Africa
124
Q

What is the most common cause of bacterial pneumonia and bacterial meningitis?

A

Streptococcus pneumoniae.

125
Q

What are some general features of Strep pneumo?

A
  1. gram positive and aerobic
  2. ovoid or lancet shaped and in pairs
  3. encapsulated
  4. relatively fastidious, grows on blood agar
  5. rough to smooth conversation by transformation
126
Q

What is a concern with older sample of Strep pneumo if you are trying to culture it?

A

Older cultures undergo autolysis and so gram cultures can be variable. The autolytic enzymes that are naturally within the microbe are activated by surfactants such as bile and detergents.

127
Q

What is the antigenic structure of Strep pneumo?

A

Capsular polysaccharide is the major antigen:

  1. there are over 90 different serological types
  2. essential for virulence
  3. are T-independent antigens
  4. are normally hard to see because the capsule is mostly water. If you add antigen you can see the capsule because it changes the refractive index - called the Quellung reaction
  5. Also has C polysaccharide (Teichoic acid) which is a cell wall carbohydrate that reacts with an acute phase protein - C reactive protein
128
Q

What is used to type the over 90 distinct serological strains of Strep. pneumo?

A

The Quellung reaction.

129
Q

List different types of pneumococcal infections.

A
  1. pneumonia - usually lobar -cause of about 80-90% of bacterial pneumonia
  2. sinusitis
  3. otitis media - most common cause in children older than 3 mos.
  4. meningitis - most common cause among children (not newborns) and elderly
  5. other infections and complications such as peritonitis, endocarditis and arthritis
130
Q

What are the virulence factors of Strep pneumo?

A
  1. posysaccharide capsule - essential for virulence, prevents phagocytosis
  2. Pneumolysin - a porin similar to Streptolysin O, contributes to inflammation and has multiple effects
  3. Peptidoglycan and Lipoteichoic acid - components of the cell wall that can activate the alternative pathway, can elect production of IL-1 and TNF-a and are largely responsible for inflammatory response
131
Q

Describe the pathogensis of the Strep pneumo bacteria.

A
  1. disease is characterized by abrupt onset, toxicity, fulminant course with possible DIC
  2. disease is due to inflammatory response to the bacterium and its products (it breaks down and releases some of its cell wall components)
  3. the trick for the bacterium is to produce an inflammatory response but not be killed by it
132
Q

What antigen do we make antibodies to?

A

The polysaccharide capsule. Anticapsular antibody protects by opsonization only - unlike gram negatives which can be opsonized or can removed by complement mediated lysis since they have an outer membrane..

133
Q

Why is natural resistance to Strep pneumo very high?

A

40-70% of normal individuals carry pneumococci in the nasopharynx. Some of our natural barriers are - cough and epiglottal reflex, mucus and cilia, phagocytosis by alveolar macrophages, splenic clearance from blood.

134
Q

what are some conditions that alter resistance to Strep pneumo?

A
  1. depressed action of cilia such as might be seen in viral infection (ie. like influenza which destroys cilia)
  2. depressed epiglottal reflex - caused by alcohol, morphine and anesthesia
  3. hyposplenia or asplenia - decreased clearance from blood
  4. sickle cell disease
  5. malnutrition
135
Q

Describe the clinical course of pneumococcal pneumonia.

A
  1. sudden onset (so pt often remembers) with shaking chill, fever and sharp pleural pain
  2. production of bloody, rusty sputum
  3. generally localized to lower lobes
136
Q

What specimens are typically gotten in pneumococcal infections?

A

Sputum, body fluids, blood, CSF pus.

137
Q

Describe the laboratory diagnosis.

A
  1. gram stain, DNA probe
  2. isolate on blood agar
  3. need to differentiate from Strep Viridans
  4. serologic tests - test for free antigen in body fluids - looking for pneumococcal C polysaccharide
  5. interpretation of tests depends on source of specimen and clinical picture - ie. is more concerning if you find it in sputum or CSF but not so much if in throat swab because it is normal flora then, it depends on the clinical picture
138
Q

How can you differentiate between Strep Viridans and Strep pneumo?

A
  1. they are both alpha hemolytic
  2. Strep pneumo is optochin sensitive
  3. Step pneumo is bile soluble
139
Q

Most Strep pneumo infections are endogenous in origin. Where do they enter and exit from?

A

The upper respiratory tract.

140
Q

Incidence of Strep pneumo infection is associated with what?

A

Predisposing factors. Most healthy adults lack anti capsular antibody.

141
Q

How can Strep pneumo infection be controlled/prevented?

A
  1. prevent primary damage
  2. immunization as needed
  3. isolation to prevent transmission to patients at risk
142
Q

Describe a Strep pneumo vaccine.

A
  1. called Pneumovax, Pnu-immune or PPSV23
  2. made from purified capsular polysaccharide - is a T independent antigen so not effective for those younger than 2 years
  3. polyvalent (23 serotypes) - covers 94% of bacteremic cases
  4. induces opsonic antibody
  5. 60-80% efficacy
  6. titers persist for at least 5 years
  7. recommended for all adults age 65 or older (with PCV13) and anyone aged 6-18 years with specific risk factors
143
Q

Describe another Strep pneumo vaccine.

A
  1. called PCV13
  2. made with a polysaccharide- protein conjugate -a T dependent antigen
  3. polyvalent - 13 serotypes so covers more than 80% of bacteremic disease and 65% of acute otitis media among children younger than 6 years
  4. recommended for all children aged 2-59 months
  5. recommended for those equal to or greater than 65 years old in series with PPSV23
  6. recommended for at risk children aged 6-18 years
  7. reduces carriage and produces herd immunity
144
Q

How is Strep pneumo infection treated?

A
  1. penicillin or ceftriaxone - drug of choice if susceptible - there is increasing need for sensitivity testing
  2. resistance - via acquisition of penicillin binding protein with reduced affinity for antibiotic (usual because normally the primary mechanism of resistance is production of beta lactamase)
  3. alternatives include vancomycin, macrolides, doxycycline or quinolone
145
Q

What is the treatment for pneumococcal meningitis?

A
  1. empiric treatment with ceftriaxone/penicillin with vancomycin
  2. meningitis causes inflammation so there is increase in permeability to BBB - means you can use penicillin if no resistance
  3. can reduce inflammation with use of corticosteroids
146
Q

What is a caveat to using penicillin to treat pneumococcal meningitis?

A

Penicillin kills bacteria and causes release of peptidoglycan and teichoic acids. These are virulence factors so they will cause even more inflammation which contributes to increased ICP and possibly to irreversible brain damage.

147
Q

Penicillin does not normally cross the BBB. What can help it cross?

A

The presence of inflammation - causes the BBB to be more permeable.

148
Q

What cephalosporin does cross the BBB fairly well?

A

Ceftriaxone.

149
Q

What med is given if there is resistance to Beta lactams?

A

Vancomycin.

150
Q

What is another name for Streptococcus agalactiae?

A

Group B strep because it has Group B lance field antigen in its cell wall.

151
Q

Strep agalactiae is part of the normal flora where?

A
  1. GI tract

2. female genital tract - 10-30% of women

152
Q

Group B strep is the leading cause of what?

A

Neonatal sepsis and meningitis - has an extremely high mortality rate.

153
Q

What other groups are particularly vulnerable to Group B strep?

A

Causes systemic disease in adults compromised by diabetes, cancer or HIV infection.

154
Q

What is the key virulence factor of Group B strep?

A

The antiphagocytic capsular polysaccharide. Antibody to this is protective (via opsonization) - also is protective for the newborn.

155
Q

Describe the infections of Group B strep in neonates.

A
  1. Early onset - presents in first week of life, acquired in utero or during birth, causes bacteremia most commonly but also pneumonia and/or meningitis
  2. Late onset - presents from 1 week to 3 months of age, acquired from mother or another infant, causes bacteremia and meningitis
156
Q

Describe infections of Group B strep in adults.

A
  1. not a primary invader unless there is an underlying condition
  2. patients generally older and have debilitating underlying conditions such as diabetes mellitus, liver disease, malignancy
  3. Can present as bacteremia, pneumonia, bone/joint infection, skin and soft tissue infection
157
Q

What are some risk factors for early onset streptococcal infection in newborns?

A
  1. exposure to bacterium
  2. absence of anti capsular antibody - either in mom or if baby is born before maternal antibodies are passed (less than 37 weeks gestation)
158
Q

How are neonates exposed to Group B strep?

A
  1. genital/GI carriage of bacteria in mom
  2. prolonged membrane rupture
  3. intrapartum fever
159
Q

Describe the laboratory diagnosis of Group B strep infection.

A
  1. gram stain CSF
  2. is beta hemolytic - but is less beta hemolytic than Group A strep
  3. can do the agglutination test for Lancefield group B antigen
160
Q

How can you prevent Group B strep infection in neonates?

A
  1. universal screening of all pregnant women at 35-37 weeks gestation for vaginal and rectal colonization
  2. look for additional/alternative risk factors
  3. intrapartum antibiotic prophylaxis - at time of labor or rupture of membranes fro all pregnant women who test positive or have risk factors - give penicillin G or ampicillin
  4. there is no approved vaccine
161
Q

What is the treatment for neonatal Group B strep infection?

A
  1. empiric treatment - ampicillin plus amino glycoside

2. specific treatment - penicillin G

162
Q

When is prophylaxis indicated for possible intrapartum Group B strep?

A
  1. if the mom has a previous infant with invasive GBS disease
  2. GBS bacteriuria during pregnancy
  3. positive GBS screening during current pregnancy
  4. if GBS status in unknown plus any of the following are present - delivery at less than 37 weeks, if amniotic membranes are ruptures for greater than or equal to 18 hours, if intrapartum temperature of baby is greater than or equal to 100.4 degrees celcius
163
Q

When is intrapartum prophylaxis for GBS not indicated?

A
  1. when previous pregnancy was positive with GBS but current pregnancy is not
  2. GBS bateriuria during previous pregnancy and not currently positive
  3. negative vaginal and rectal GBS culture in late gestation during current pregnancy regardless of risk factors
  4. planned cesarean delivery performed in the absence of labor or membrane rupture regardless of culture status
164
Q

What are the general features of cryptococcus?

A
  1. encapsulated yeast
  2. opportunistic infector
  3. four serotypes of capsular polysaccharide (called CrAg) - A, B, C and D
  4. There are two species
  5. globally, the most serious and life-threatening of the pathogenic fungi
165
Q

What are the two species of cryptococcus?

A
  1. C. neoformans - serotypes A and D

2. C. gattii - serotypes B and C

166
Q

What is the basis of cryptococcus diagnosis?

A

Assay for the CrAg.

167
Q

Where is cryptococcus found and how is it transferred?

A

Has a worldwide distribution and is transferred via the environment - no man to man transmission. It is a ubiquitous saprophyte so it likely infects all individuals sub- clinically.

168
Q

What are the environmental sources associated with cryptococcus?

A
  1. pigeon droppings

2. C. gattii is associated with eucalyptus trees and other plant hosts

169
Q

What is the association between HIV and cryptococcus infections?

A
  1. latent infection is activated with loss of T cell function
  2. causes a million cases a year with more than half ending in death
  3. most infections seen in sub-Saharan Africa
  4. generally well controlled in developed countries due to HAART
170
Q

Most infections are due to Cryptococcus neoformans but Cryptococcus gattii has also caused infection. What was unusual about the outbreaks seen?

A

There were outbreaks seen in the Pacific Northwest where C. gattii was the infectious agent and the patients had no obvious immune deficiencies.

171
Q

List the clinical syndromes associated with cryptococcal infection?

A
  1. pulmonary cryptococcosis - thought that most infections begin this way, variable in presentation, common with C. gattii infection
  2. Cryptococcal meningitis - most common clinical form of Cryptococcal infection - highly neutropenic and fatal if untreated
  3. can have skin lesions, ocular infection and prostatic involvement
  4. opportunistic infection - occurs with immune suppression such as in HIV or organ transplant. Opportunistic C. gattii patients are usually not immune compromised
172
Q

What is a possible asymptomatic reservoir for cryptococcus in men?

A

The prostate gland.

173
Q

Describe the diagnosis of cryptococcosis.

A
  1. specimens obtained from blood and CSF
  2. can use india ink negative stain of CSF to look for the encapsulated yeast
  3. can culture
  4. can look for antigen (CrAg) in serum, plasma or CSF via latex agglutination, enzyme immunoassay or lateral flow immunoassay
174
Q

What is the treatment for cryptococcosis?

A
  1. Antifungal agents used alone or in combo - Amphotericin B (IV), Flucytosine, Fluconazole
  2. treatment strategy depends on patient risk group - ie. HIV-infected, organ transplant patient etc.
175
Q

What are the phases of treatment for cryptococcosis?

A
  1. induction
  2. consolidation
  3. maintenance
176
Q

What is immune reconstitution inflammatory syndrome (IRIS)?

A
  1. occurs at the initiation of HAART

2. overwhelming inflammatory response

Block 8 week 2 (4 decks)

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