Antimicrobials V Flashcards

1
Q

What type of a microorganism has a nearly impermeable cell wall made up of mycolic acid?

A

Mycobacterium

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2
Q

What aspect of the mycobacterium cell wall shields and prevents many drugs from accessing the membrane or getting inside the cytosol?

A

> 60% of the cell wall is lipid, mainly mycolic acid

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3
Q

What makes it difficult for antimicrobials to do their job?

A

Mycobacterial Defenses

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4
Q

List 3 defenses of Mycobacterium

A
  1. Very thick, hydrophobic cell wall
  2. Efflux pumps
  3. Some species can hide inside patients cells
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5
Q

Describe the thick, hydrophobic cell wall of mycobacterium

A
  1. Rich in Mycolic acid
  2. Liparabinomannan
  3. “Waxy” Coat
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6
Q

What are efflux pumps?

A
  • Located in the cell membrane

- Pump out harmful chemicals and antibiotics to increase bacterial resistance

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7
Q

Give an example of a species of Mycobacterium that can hide inside patients cells

A

Mycobacterium Avium Intracellulare

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8
Q

What are the two key Mycobacterium-related diseases?

A
  1. Mycobacterium tuberculosis (TB)

2. Mycobacterium leprae (Hansen’s disease or leprosy)

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9
Q

How many new cases and deaths annually are from TB?

A

9 million new cases

2 million deaths annually

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10
Q

How many new cases are there worldwide of Mycobacterium Leprae?

A

2 million

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11
Q

What conditions are conducive to the growth of Mycobacterium Leprae?

A

They grow better in areas with cooler body temperatures closer to skin surface (i.e., extremities)

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12
Q

In 1882 how dangerous was TB?

A

It killed 1 out of every 7 people living in the United States and Europe

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13
Q

How dangerous is TB today?

A

Among infectious diseases, TB remains the 2nd leading killer of adults in the world, with 2 million TB-related deaths annually

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14
Q

What is the skin test for TB called?

A

Mantoux Tuberculin Skin Test (TST)

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15
Q

What is the prophylactic treatment of choice for Latent or Asymptomatic infectdions?

A

Isoniazid for 9 months

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16
Q

What should you do if you detect latent or asymptomatic TB in a patient?

A

Initiate preventative treatment immediately

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17
Q

What is the treatment of choice for an active infection of TB?

A

“2 with 4 then 4 with 2”

Meaning:

  • 2 Months treatment with 4 drugs
  • 4 months treatment with 2 drugs
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18
Q

What are the 4 drugs used for the first 2 months of TB treatment?

A
Combination of:
1. Rifampin
2. Isoniazid
3. Pyrazinamide
4. Ethambutol
(RIPE)
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19
Q

What are the 2 drugs used for the 4 months treatment of TB?

A
  1. Rifampin

2. Isoniazid

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20
Q

How would you treat an intracellulare organism?

A

Treat with RIPE for 12 months in conjucntion with Azithromycin (macrolide)

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21
Q

What treating intracellulare organisms, what is important to note about Pyrazinamide?

A

Its use should be restricted to only the 1st 2 months because it is hepatotoxic

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22
Q

Reactivated (Or resistant) TB is a greater risk in who?

A
  • HIV-positive
  • Immunosuppressed
  • Other “high risk” patients
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23
Q

What is the TB rule of 5’s?

A

Otherwise healthy patients infected with Mycobacterium tuberculosis have a 5% risk of reactivation in the first 2 years and then a 5% lifetime risk of reactivation

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24
Q

High risk patients have a _____ risk of reactivation per ___

A
  1. 5% + 5%

2. Year

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25
Q

T/F TB can only reactivate in the lungs

A

FALSE, it can reactivate in a variety of locations

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26
Q

What is the treatment of choice for Secondary TB?

A
  1. 2 months of treatment with RIPES combination
  2. Followed by 4 months treatment with isoniazid and rifampin

**2 with 5, then 4 with 2

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27
Q

What does RIPES stand for?

A
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin
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28
Q

Second line drugs can be added to overcome _________ as needed

A

Drug resistance

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29
Q

List the drugs that can be used to treat TB

A
  1. Streptomycin
  2. Azithromycin
  3. Rifampipn
  4. Isoniazid
  5. Ethambutol
  6. Bedaquiline
30
Q

What is the clinical use of Isoniazid?

A

Drug of choice for prophylaxis of Mycobacterium TB

*Also effective in combo against active TB

31
Q

What is the mechanism of Isoniazid?

A

Decreases Mycolic Acid synthesis

32
Q

T/F Isoniazid is a Prodrug that must be activated by the host enzyme, KatG

A

FALSE, it is a prodrug but the enzyme is a bacterial one

33
Q

What is KatG?

A

Bacterial TB catalase oxidase enzyme

34
Q

What other effects doe KatG activation of Isoniazid have?

A

Produces free radicals like nitric oxide and can cause oxidative stress

35
Q

What are some adverse effects of Isoniazid (INH)?

A
  1. Hepatotoxicity
  2. Pyridoxine Deficiency
  3. Disulfuram-like reaction
36
Q

Because INH can cause a pyridoxine deficiency you should always administer it how?

A

With vitamin B6 to maintain heme synthesis and prevent neurotoxicity

37
Q

Why should you tell patients to avoid alcohol 72 hours before and after INH?

A

Because of the Disulfuram-like reaction

38
Q

T/F Pyrazinamide (PO) is another Prodrug

A

TRUE

39
Q

What are the clinical uses for Pyrazinamide?

A

-Treatment of active Mycobacterium TB infection

**especially tuberculous meningitis

40
Q

Is Pyrazinamide bactericidal or bacterostatic?

A

Bacterostatic

41
Q

What is the mechanism of Pyrazinamide?

A

Inhibits Mycolic acid synthesis

42
Q

What is the net effect of the mechanism of pyrazinamide?

A

More pyrazinoic acid accumulates inside granulomas (more absorbed at a high pH than at a neutral pH)

43
Q

What does pyrazinamide require to be activated?

A

Acidic pH

44
Q

Pyrazinamide is an essential part of the treatment of _______________

A

Tuberculous Meningitis

45
Q

What are the adverse effects of Pyrazinamide?

A
  1. Hepatotoxicity (if used for longer than 2 months)
  2. Increases uric acid (which can cause gout or make it worse)
  3. Rash
  4. Contraindicated in pregnancy (can cause fetal harm)
46
Q

What is Ethambutal used for?

A

Treatment of Active Mycobacterium tb infefction

47
Q

What is the mechanism of Ethambutal?

A

Obstructs mycobacterial cell wall formation by decreasing carbohydrate polymerization which it does by inhibiting arbinosal transferase

48
Q

T/F Ethambutal can cross the blood brain barrier

A

TRUE

49
Q

What are the adverse effects of Ethambutal?

A
  1. Ocular toxicity
  2. Color Blindness
  3. Ocular Neuritis: Blindness
50
Q

How often does ocular neuritis occur in patients taking Ehtambutal?

A

In up to 6% of patients within the first 3 months of use

51
Q

What is the mechanism of Bedaquiline?

A

Inhibits mycobacterial ATP synthase

52
Q

In Dec 2012, bedaquiline was approved for what?

A

Use against Multi-drug resistant TB

53
Q

What are the adverse effects of Bedaquiline?

A
  1. Common side effects include:
    • Nausea
    • Vomiting
    • Arthralgias
    • Headache
  2. Black-box warning for patients with arrhythmias
    • May induce prolonged QT syndrome
54
Q

What is the drug of choice for treatment for TB and leprosy?

A

Rifampin

55
Q

What is the drug of choice for prophylaxis of leprosy?

A

Dapsone

56
Q

What is the Mechanism of Dapsone?

A

Competes with PABA to inhibit bacterial dihydrofolate synthesis (Antimetabolite)

57
Q

What are the clinical uses of Dapsone?

A
  • Prophylaxis of leprosy

- Prophylaxis of Pneumocystis jiroveci

58
Q

What are the adverse effects of Dapsone?

A
  1. Hepatotoxicity
  2. Hemolysis
  3. Cross-sensitivity if allergy to sulfoanimes
59
Q

What causes Travelers diarrhea/

A
  • Contaminated food or water

- 80% of the time cauesd by E. Coli

60
Q

What is the drug of choice for Treatment of traveler’s diarrhea due to E. coli?

A

Rifaximin

61
Q

What are other bacteria that can cause traveler’s diarrhea?

A
  • Campylobacter Jejuni
  • Shigella
  • Salmonella
62
Q

What is the drug of choice to treat traveler’s diarrhea due to bacteria other than E. Coli?

A

Ciprofloxacin

63
Q

What is the drug of choice to treat C. Diff?

A

Metronidazole

64
Q

What drug should you avoid during pregnancy and always limit its use to 2 months max because of its hepatotoxicity?

A

Pyrazinamide

65
Q

What drug should you always give with Vit B6 to prevent neuropathy?

A

Isoniazid

66
Q

What drug will cause Ocular toxicity or optic neuritis, leading to blindness?

A

Ethambutol

67
Q

What drug is ototoxic, nephrotoxic, and should be avoided during pregnancy?

A

Streptomycin

68
Q

What drug should be added in cases of Mycobacterium Avium Intracellulare?

A

Azithromycin

69
Q

What antibiotics frequently cause C. Diff?

A
  1. Ampicillin
  2. Amoxicillin
  3. Cephalosporins
  4. Clindamycin
  5. Other Penicillins
  6. Aztreonam
70
Q

What antibiotics cause C. Diff Infrequently?

A
  1. Tetracyclines
  2. Sulfonamides
  3. Macrolides
  4. Chloramphenicol
  5. Trimethoprim
  6. Quinolones
71
Q

What antibiotics can but will rarely cause C diff?

A
  1. Parenteral Aminoglycosides
  2. Metronidazole
  3. Bacitracin
  4. Vancomycin