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#US Neuro 2 Depression COPY ahmed > Lecture 1: Pharmacology of Neurological Infections > Flashcards

Lecture 1: Pharmacology of Neurological Infections Flashcards

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1
Q

What is the standard emperic antibiotic regimen for acute pyogenic meningitis?

A
  • [Cefotaxime or ceftriaxone] + vancomycin
  • Ampicillin added in older patients (>50 years)
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2
Q

What’s the standard treatment for infantile meningitis caused by H. influenzae type B?

A
  • Hib vaccine
  • Cefotaxime or ceftriaxone
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3
Q

What’s the empiric treatment for acute pyogenic meningitis in patients with a beta-lactam allergy?

Beta-lactam allergy in patients age >50?

A
  • Standard = Vancomycin + moxifloxacin
  • >50 y/o = Vancomycin + moxifloxacin + TMP/SMX
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4
Q

What’s the empiric treatment for acute pyogenic meningitis in immunocompromised patients?

A

Vancomycin + ampicillin + [cefepime or meropenem]

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5
Q

Which virus family and viruses in this family are the major cause of acute aseptic meningitis?

A
  • Enteroviruses
  • Coxsackievirus, echovirus
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6
Q

CSF findings (immune cells, protein, glucose, and opening pressure) seen with acute aseptic meningitis?

A
  • Lymphocytic pleocytosis
  • Moderate protein elevation
  • Normal glucose
  • Opening pressure can be normal or elevated
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7
Q

What is the standard of care if you begin antibiotics after a lumbar puncture for suspected meningits, but the bacterial cultures are negative?

A

Discontinue antibiotics

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8
Q

What are the two 3rd gen. Cephalosporins used for meningitis?

A
  • Cefotaxime
  • Ceftriaxone
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9
Q

What is the 4th gen. Cephalosporin used in the treatment of meningitis?

A

Cefepime

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10
Q

What is the Glycopeptide used in the treatment of meningitis/brain abscesses/subdural empyema?

A

Vancomycin

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11
Q

What is the Carbapenem used in the treatment of meningitis/brain abscesses/subdural empyema?

A

Meropenem

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12
Q

What is the Aminopenicillin used in the treatment of meningitis?

A

Ampicillin

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13
Q

What is the Fluoroquinolone used in the treatment of meningitis?

A

Moxifloxacin

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14
Q

What are the Benzylpyrimidine/Sulfonamide used in the treatment of meningitis?

A

Trimethoprim/Sulfamethoxazole (TMP/SMX)

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15
Q

What is the CSF content (immune cells, glucose, and protein) seen with a brain abscess?

A
  • High white cell count
  • Increased protein concentration
  • Normal glucose content
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16
Q

What are the most common pathogens that cause brain abscesses?

A
  • Viridans streptococci
  • S. aureus
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17
Q

Which group of pathogens is the most likely culprit for a brain abscess in an immunocompetent vs. immunocompromised patient?

A
  • Immunocompetent = bacteria
  • Immunocompromised = fungi (can be bacterial too)
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18
Q

What is the standard of care for a brain abscess?

A
  • Surgery + antibiotic reduces otherwise high mortality rate to 10%
  • Aspiration
  • Craniotomy to drain abscess or to totally remove it
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19
Q

What is the empiric therapy of brain abscess with unknown source?

A

Vancomycin + [ceftriaxone or cefotaxime] + metronidazole

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20
Q

Which antibiotic is used to cover aerobic and anaerobic streptococci (mouth flora) involved in a brain abscess?

A

Penicillin G

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21
Q

Which antibiotic can readily penetrate a brain abscess and is often combined with other agents during treatment of brain abscesses?

A

Metronidazole

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22
Q

Which antibiotic can be used as a substitue for Penicillin G while treating a brain abscess?

A

Ceftriaxone or Cefotaxime

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23
Q

Which organisms are covered by Ceftriaxone and Cefotaxime?

A
  • Most aerobic and microaerophilic streptococci
  • Many enterobacteriaceae
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24
Q

Which antibiotics are used if a brain abscess complicates a neurosurgical procedure or cases in which the abscess culture grows P. aeruginosa?

A

Ceftazidime, cefepime, or meropenem

25
Q

What is the standard for the use of Vancomycin in the treatment of brain abscesses?

When would you stop using?

Which antibiotics will be substituted for the Vancomycin?

A
  • Included in tx regimen until culture and susceptibility results are available
  • No MRSA = NO vancomycin
  • Naficillin or oxacillin should be substituted for vancomycin
26
Q

What are the three Cephalosporin: 3rd gen. used in the treatment of brain abscesses/subdural empyema?

A
  • Cefotaxime
  • Ceftriaxone
  • Ceftazidime
27
Q

What’s a Subdural empyema?

A

Produced by bacteria (and rarely fungal) infections of the skull bones or air sinuses that spread to the subdural space

28
Q

What are the common pathogens that cause subdural empyemas?

Following neurosurgical procedures or head trauma?

A
  • Aerobic and anaerobic Streptococci,Staphylococci, Enterobacteriaceae, andanaerobic bacteria
  • Following neuro procedure/trauma: Staphylococci (MRSA) and gram-negative bacilli (P. aeruginosa)
29
Q

What is the immediate treatment for a subdural empyema?

A
  • Medical emergency!
  • Surgery to evacuate the empyema
  • Antibiotic therapy
30
Q

What is the empiric antibiotic therapy for subdural empyema that is community acquired?

A

[Cefotaxime or ceftriaxone] + vancomycin + metronidazole

31
Q

What is the empiric antibiotic therapy for subdural empyema that is hospital acquired (P. aeruginosa or MRSA)?

A

Meropenem + vancomycin

32
Q

What are 4 types of Viral Meningoencephalitis?

A

1) Parenchymal infection of the brain: associated w/ meningoencephalitis and encephalomyelitis
2) Arthropod borne viral encephalitis
3) Subacute sclerosis panencephalitis (SSPE): measles
4) Poliomyelitis

33
Q

SSPE caused by measles is characterized by?

A
  • Variable inflammation of white and grey matter
  • Neurofibrillary tangles
34
Q

What are the initial signs of Poliomyelitis?

A

Mild gastroenteritis

35
Q

Which immunoglobulins are produced with a live vaccine?

Killed vaccine?

A

Live = IgA and IgG

Killed = IgG

36
Q

Is there cell-mediated immunity produced with a live vaccine and killed vaccine?

A
  • Live vaccine = yes
  • Killed vaccine = weakly or none
37
Q

What type of vaccine is the MMR?

A

Live attenuated

38
Q

What are the 2 types of poliomyelitis vaccine and which is safer?

A

1) Inactivated poliovirus vaccine (IPV): killed virus vaccine; does NOT cause vaccine-associated paralytic poliomyelitis
2) Live attenuated oral poliovirus vaccine (OPC): can cause polio in a small % of pts

39
Q

Which fungi is a common cause of fungal meningoencephalitis?

Who is particularly at risk?

CSF finding?

A
  • Cryptococcal meningitis
  • Common opportunistic infection in setting of AIDS
  • CSF contents = likely high protein concentration
40
Q

How does fungal meningoencephalitis manifest; appearance of brain sections?

A
  • Manifests as chronic meningitis affecting the basal leptomeninges
  • Appears of “soap bubbles” on whole-brain sections
41
Q

What is the common clinical presentation for Fungal meningoencephalitis?

A
  • Stiff neck, photophobia, and vomiting
  • Lethargy and confusion
42
Q

Which infection should you hav a high suspicion of with advanced HIV patients that have a CD4 count <100 cells/uL and presenting with stiff neck, photophobia, and vomiting?

A

Cryptococcal meningitis

43
Q

Which antibiotics are used for the induction phase and then consolidation phase of therapy for funal meningoencephalitis?

A
  • Induction phase: Amphotericin B + Flucytosine (5-FC)
  • Consolidation: Fluconazole
44
Q

What is Ergosterol?

A
  • Vital part of cell membranes of fungi (not found in human cell membranes)
  • Most anti-fungal agents bind ergosterol w/ a higher affinity than cholesterol
45
Q

What is the MOA of the anti-fungal, Amphotericin B?

A
  • Forms complex w/ ergosterol and disrupts the fungal cell membrane
  • Leads to cytoplasmic leakage and fungal cell death
46
Q

How is the anti-fungal, Amphotericin B administered?

Adverse effects?

A
  • Given IV and directly into the CSF (not absorbed orally)
  • Adverse effects:
  • Renal toxicity
  • Acute febrile rxn: chills and fever, common
  • Anemia

*Often nicknamed in the clinic: AWFUL-tericin or Ampho-TERRIBLE

47
Q

What is the MOA of the anti-fungal, Flucytosine (5-FC)?

Why should it not be used alone?

A
  • Antimetabolite
  • Converted to 5-fluorouracil (5-FU) inside fungal cells
  • Inhibits DNA and RNA synthesis (similar structure to uracil so can integrate itself into DNA and RNA causing cell death
  • Rapid resistance develops if used alone
48
Q

What are the possible adverse effects of the anti-fungal, Flucytosine (5-FC)?

A
  • Conversion of 5-FC to 5-FU OUTSIDE of the fungal cells
  • Bone marrow depression, nausea, vomiting, and diarrhea

*Logically, will affect the rapidly proliferating cells of your body, like within the bone marrow and GI mucosa!!!

49
Q

What is the MOA of the anti-fungals, Fluconazole, Azole, and Triazole?

How easy do they get into CSF?

A
  • Inhibit ergosterol synthesis by inhibiting fungal P450 enzymes
  • Very good CSF penetration
50
Q

What are the adverse effects of Fluconazole?

A

Limited, widest therapeutic index of all the azoles

51
Q

Which 4 antibiotic classes + one drug not belonging to a class should NOT be used to treat neuroinfections?

A

1) Cephalosporins: 1st gen –> Cefazolin
2) Aminoglycosides: (-mysin and -micin)
3) Tetracyclines: (-cyclines)
4) Macrolides: (-mysin and -micin)
5) No class: Clindamycin

52
Q

How is Metronidazole activated?

A
  • Anaerobic pathogens contain an electron transport system w/ a high negative redox potential, which donates electrons to Metronidazole
  • When electron is donated, a highly reactive nitro radical anion is formed; allows for the killing of organisms by means of radical-mediated DNA damage
53
Q

What is one major way of resisting Metronidazole?

A
  • Increasing intracellular levels of O2
  • Resistance correlates w/ impaired O2 scavenging, which leads to increased intracellular O2 levels
54
Q

Metronidazole is active against which pathogens?

A
  • Flagellated protozoa: T. vaginalis and G. lamblia
  • E. histolytica (protozoan)
  • Anaerobic cocci and Anaerobic gram-negative bacilli
  • Helicobacter and Campylobacter spp. (gram-negative)
  • Clostridium spp. (gram-positive bacilli)
55
Q

What are adverse effects that are unique to Metronidazole?

A
  • Metallic taste in pt’s mouth
  • Disulfiram-like effect: induces vomiting if alcohol consumed during or within 3 days of treatment; also flushing, abdominal discomfort, or headache
56
Q

CSF content associated with acute pyogenic meningits?

A
  • Increased neutrophils
  • Increased protein
  • Decreased glucose
57
Q

Which class does Metronidazole belong to?

A

5-nitroimidazoles

58
Q

What are the concerns with the use of live vaccines?

A
  • Attenuated viral mutants revert to virulence either during vaccine production or in the immunized person: Polio, not measles and is pathogenic in immunocompromised pts
  • Excretion of live virus to infect other: Herd immunity and Double edged sword

#US Neuro 2 Depression COPY ahmed (17 decks)

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