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Exam 5 - Therapeutics > Central nervous system infections > Flashcards

Central nervous system infections Flashcards

1
Q

Normal WBC count in CSF

A

< 5 mm3

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2
Q

Normal differential in CSF

A

–

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3
Q

Normal protein in CSF

A

< 50 mg/dL

**Generally does not infiltrate into CSF unless inflammation

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4
Q

Normal glucose level in CSF

A

30-70 mg/dL [2/3 peripheral]

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5
Q

Barriers within the CNS

A

-BBB
-Blood-CSF barrier (BCSFB)

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6
Q

How is the BBB made?

A

Tightly joined endothelial cells
**Drugs have to pass through the BBB before they can access the CSF

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7
Q

Antibiotic characteristics that influence CSF/CNS penetration

A
  1. Lipid solubility (more lipophilic = better)
  2. Ionization (unionized = better)
  3. Protein binding (free drug = better)
  4. Molecular weight (lighter = better)
  5. Degree of meningeal inflammation (penetration enhanced when there is inflammation)
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8
Q

Abx that penetrate the CSF with or without meningeal inflammation

A

Acyclovir
TMP/SMX
Voriconazole
Fluconazole
Ganciclovir
Linezolid
Metronidazole
FQ

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9
Q

Abx that penetrate WITH meningeal inflammation

A

-PCNs
-Some cephalosporins (3rd and 4th gen)
-Aztreonam
-Meropenem
-Colistin
-Vanc

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10
Q

Abx that cannot penetrate CSF with or without inflammation

A

Macrolides
Aminoglycosides
B-lactamase inhibitor
Some cephalosporins (1st and most 2nd gen)
Clindamycin
Tetracyclines (except doxy)
Echinocandins

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11
Q

Acute bacterial meningitis

A

-Disease of very young and very old (highest risk between 1 month-4 y/o)
-Morbidity/mortality remains high

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12
Q

Acute bacterial meningitis pathogenesis

A

Hematogenous
-Once bacteria gain access to CSF, host defenses are inadequate to contain the infection
-Bacteria gain access into the CSF from the bloodstream into the subarachnoid space

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13
Q

Critical 1st step in acute bacterial meningitis pathogenesis

A

Nasopharyngeal colonization
*pathogens adhere to epithelial surface & enter bloodstream after phagocytosis
*Penetration through BBB typically by transcellular penetration/paracellular penetration
*Organisms multiple to enough that allow invasion of the BCSFB

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14
Q

Acute bacterial meningitis epidemiology

A

Direct inoculation
*RF: neurologic procedures (ventricular shunt; drains); skull fracture, trauma

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15
Q

How do bacteria gain access into the CSF via direct inoculation?

A

-Contiguous spread an infection near the CSF (untreated/uncontrolled sinusitis, otitis media, or mastoiditis)

-Direct inoculation during head trauma or neurosurgery

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16
Q

Which microorganisms are common in bacterial meningitis in neonates?

A

S. agalactiae
Listeria monocyogenes
S. pneumoniae
N. meningitidis

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17
Q

Which microorganisms are common in bacterial meningitis in infants?

A

S. agalactiae
H. influenzae
S. pneumoniae
N. meningitidis

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18
Q

Which microorganisms are common in bacterial meningitis in children & adults (2-50 y/o)?

A

S. pneumoniae
N. meningitidis

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19
Q

Which microorganisms are common in bacterial meningitis in older adults (> 50 y/o)?

A

Listeria monocyogenes
S. pneumoniae
N. meningitidis

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20
Q

Clinical s/sx of acute bacterial meningitis

A

Fever, chills
HA, back ache, nuchal rigidity, mental status change
-Photophobia
-N/V, anorexia, poor feeding habits (infants)
-Petechiae or purpura (N. meningitidis)

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21
Q

Physical signs of acute bacterial meningitis in adults

A

-Brudzinski & Kernig sign (stretching the vertebral column; very painful for the pts)
-Meningococcal rash (causes arteries & veins to bulge)

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22
Q

Physical signs of acute bacterial meningitis in neonates

A

Bulging fontanel (“soft spot”)

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23
Q

Diagnosing acute bacterial meningitis

A

-Cerebrospinal fluid should be obtained
*3 tubes via lumbar puncture
*Elevated opening pressure observed due to cerebral edema, intracranial pus, or hydrocephalus
*Head CT or MRI before lumbar puncture to rule out mass lesion

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24
Q

Empiric tx for acute bacterial meningitis is immediately administered ____ the lumbar puncture is performed

A

AFTER

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25
WBC count in bacterial infection
> 1000-5000
26
Differential in bacterial infection
> 80% neutrophils
27
Protein in bacterial infection
> 150 mg/dL (from inflammation)
28
Glucose in bacterial infection
<50 mg/dL
29
Treatment principles for acute bacterial meningitis
-Mortality occurs within 24-48H of onset (prompt diagnosis and tx) -Choice of empiric tx depends on most probable organism, abx characteristics, and pt characteristics
30
What is empiric tx
Administered while waiting for cx results
31
What is directed tx
Targeted tx against the infecting organism
32
What is duration of tx
All effective days of tx (empiric + directed)
33
Empiric abx for acute bacterial meningitis *NEONATES (< 1 month)
Ampicillin + ceftriaxone/cefepime *Ceftriaxone causes biliary sludging in neonates *Cefepime is good if we are worried about biliary sludging Ampicillin + Aminoglycoside *Gentamicin bc neonates don't have a fully formed BBB
34
Empiric abx for acute bacterial meningitis *Infants (1-23 months)
Vanc + ceftriaxone
35
Empiric abx for acute bacterial meningitis *Children & adults (2-50 y/o)
Vanc + ceftriaxone
36
Empiric abx for acute bacterial meningitis *older adults (> 50 y/o) & immunocompromised
Vanc + Ceftriaxone + Ampicillin
37
Empiric abx for acute bacterial meningitis *Head trauma/post-neurosurgery
Vanc + Cefepime, ceftazidime, or meropenem
38
Gram stain for streptococcus spp
Gram (+) diplococci
39
Tx for streptococcus meningitis sensitive to PCN
PCN G Ampicillin (based on renal function) x10-14 d
40
Tx for streptococcus meningitis with PCN resistance/intermediate
Ceftriaxone x10-14 d
41
Tx for streptococcus meningitis cephalosporin resistance
Vanc x10-14 d
42
____ develops in 30-50% of pts who survive acute bacterial meningitis
Neurologic sequelae -Seizure -Hearing loss -Hydrocephalus *infections triggers cytokine release --> weakens the BBB (steroids are used in some situations)
43
Role of steroids
Inhibit IL-1 and TNF production *Consider steroids in children > 2 months of age with suspected meningitis *administer before or with 1st dose of antibiotic and use for 2-4 days
44
Gram stain of S. aureus
Gram (+) cocci in clusters
45
Tx for S. aureus meningitis: MSSA
Nafcillin x 14-21d
46
Tx for S. aureus meningitis: MRSA
Vanc x 14-21d **Dosing based on trough level between 15-20 [do not care about AUC]
47
Gram stain of Listeria monocytogenes
Gram (+) rod; non-spore forming
48
Tx of listeria monocytogenes meningitis
Ampicillin +/- gentamicin (DOC) x 21d Alternatives: TMP/SMX; meropenem; linezolid x 21d
49
Gram stain of Neisseria meningitidis
Gram (-) intra-cellular diplococci
50
Tx of Neisseria meningitidis in PCN sensitive
PCN G continuous infusion Ampicillin x 7d
51
Tx of Neisseria meningitidis PCN resistant/intermediate
Ceftriaxone x 7d
52
Gram stain of Haemophilus influenzae
Gram (-) coccobacillus
53
Tx for Haemophilus influenzae b-lactamase negative
Ampicillin x 7d
54
Tx for Haemophilus influenzae b-lactamase positive
Ceftriaxone x 7d
55
Tx of enterobacteriaceae
Ceftriaxone Cefepime Meropenem x 21d
56
Gram stain of Haemophilus influenzae
Gram (-) coccobacillus
57
Lab values to evaluate therapeutic outcomes
CSF Blood cultures CRP WBC BMP
58
Pathogenesis of fungal meningitis
Cryptococcus neoformans (predominant) Cryptococcus gattii (mainly in northwest)
59
What is cryptococcus?
Encapsulated soil fungus -Most common acquisition is through inhalation of fungal spore into airways -Direct inoculation into skin or organ transplant
60
RF for cryptococcus
-Advanced HIV (CD4 < 200 cells/mL) -- most common -Non-HIV immunosuppression *CCS use *Organ transplant *Cirrhosis *Sarcoidosis *Lymphoma, hematologic malignancies
61
Clinical presentation of cryptococcus
Usually presents as subacute (chronic) meningitis with symptoms present for weeks--> months: -Constitutional: fevers; malaise -Pulmonary: SOB, cough, chest pain -CNS: cognitive abnormalities, HA, neck stiffness, seizures, cranial nerve abnormalities, altered mentation, memory loss -Skin: papular lesions, vascular lesions, cellulitis -Other: Virtually any organ can be involved
62
WBC in CSF fungal infection
10-500 mm3
63
Differential in CSF fungal infection
>50% lymphs
64
Protein in CSF in fungal infection
40-150 mg/dL
65
Glucose in CSF in fungal infection
<30-70 mg/dL
66
Other supportive tests in fungal infections
High opening pressure India ink stain + culture Cryptococcus antigen (CrAg) BioFire PCR
67
Tx for cryptococcus **INDUCTION**
Ampho B or liposomal ampho + Flucytosine x 2 weeks
68
Tx for cryptococcus **CONSOLIDATION**
Fluconazole x 8 weeks
69
Tx for cryptococcus **MAINTENANCE PHASE** -Non-HIV infected pt
Fluconazole x 6-12 months
70
Tx for cryptococcus **MAINTENANCE PHASE** -HIV infected pt
Fluconazole x at least 12 months AND CD4 > 200 AND suppression of viral load on ART
71
Managing immunosuppression in HIV/AIDS
ART should be initiated, but not until 5 weeks after initiation of tx for cryptococcal meningitis *Particularly for pts whose CSF < 5 WBC/mm3 *IRIS-paradoxical inflammatory response
72
Management of immunosuppression in transplant populations
-Immunosuppression should gradually be reduced to the extent feasible *Too rapid of reduction can lead to IRIS
73
Follow up for cryptococcus
-Repeat LP at the end of the induction phase is not necessary unless persistent sx exist -Serum cryptococcal antigen (CrAg) is not helpful in follow-up
74
Viral encephalitis
Inflammatory process of the brain parenchyma in association with clinical and lab evidence of neurologic dysfunction
75
Which age group has the highest viral encephalitis incidence?
Infants, then elderly
76
Viremia pathogens of viral encephalitis
Enterovirus (poliovirus) Arbovirus (West Nile virus, Colorado tick fever)
77
Pathogens in reactivation of latent virus in encephalitis
HSV VZV CMV HHV-6 (B-herpes virus family)
78
Etiology of encephalitis
Time of year (summer/fall) Pt hx -Travel/outside exposure (camping, hiking) -Insect bites; animal exposure -Sick family member; daycare attendee -Sexual hx (HSV, recent outbreak); recent rash
79
Transmission of enterovirus
Fecal-oral and pharyngeal spread (close contact) *Most common cause of aseptic meningitis
80
Transmission of arbovirus
Via mosquitos and birds -Peaks in late summer/early fall; outdoor exposure
81
Transmission of herpes virus
-HSV-1 (adults) and HSV-2 (newborns) -Sexually active adults may develop HSV encephalitis during or after outbreak of genital/rectal herpes
82
Clinical features of viral infections
-Shares some clinical features with meningitis -Most often characterized by fever, HA, ALTERED MENTAL STATUS (extreme confusion) -Focal neurologic signs (ataxia, aphasia, cranial nerve palsies)
83
WBC count in viral infection
5-300 mm3
84
Differential in viral infection
50% lymphs (bc lymphocytes deal with viruses)
85
Protein in viral infection
30-150 mg/dL
86
Glucose in viral infection
<40-70 mg/dL
87
Other supportive tests for viral infections
PCR on respiratory secretions, skin vesicles, brain tissue
88
Tx of encephalitis
Most of the cases are benign and self-limiting with full recovery in 7-10d -Supportive care, fluid, analgesics, antipyretics
89
Tx of HSV encephalitis
Acyclovir x 14-21 days
90
Tx of VZV encephalitis
Acyclovir x 10-14d *Alternative: ganciclovir
91
Tx of CMV encephalitis
-Ganciclovir x 14-21d *Can combine with foscarnet **Always combine in persons living with HIV

Exam 5 - Therapeutics (11 decks)

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