Antimicrobials V

Question 1

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

Answer 1

Mycobacterium

Question 2

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

Answer 2

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

Question 3

What makes it difficult for antimicrobials to do their job?

Answer 3

Mycobacterial Defenses

Question 4

List 3 defenses of Mycobacterium

Answer 4

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

Question 5

Describe the thick, hydrophobic cell wall of mycobacterium

Answer 5

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

Question 6

What are efflux pumps?

Answer 6

• Located in the cell membrane

- Pump out harmful chemicals and antibiotics to increase bacterial resistance

Question 7

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

Answer 7

Mycobacterium Avium Intracellulare

Question 8

What are the two key Mycobacterium-related diseases?

Answer 8

1. Mycobacterium tuberculosis (TB)

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

Question 9

How many new cases and deaths annually are from TB?

Answer 9

9 million new cases

2 million deaths annually

Question 10

How many new cases are there worldwide of Mycobacterium Leprae?

Answer 10

2 million

Question 11

What conditions are conducive to the growth of Mycobacterium Leprae?

Answer 11

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

Question 12

In 1882 how dangerous was TB?

Answer 12

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

Question 13

How dangerous is TB today?

Answer 13

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

Question 14

What is the skin test for TB called?

Answer 14

Mantoux Tuberculin Skin Test (TST)

Question 15

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

Answer 15

Isoniazid for 9 months

Question 16

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

Answer 16

Initiate preventative treatment immediately

Question 17

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

Answer 17

“2 with 4 then 4 with 2”

Meaning:

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

Question 18

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

Answer 18

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

Question 19

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

Answer 19

1. Rifampin

2. Isoniazid

Question 20

How would you treat an intracellulare organism?

Answer 20

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

Question 21

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

Answer 21

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

Question 22

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

Answer 22

• HIV-positive
• Immunosuppressed
• Other “high risk” patients

Question 23

What is the TB rule of 5’s?

Answer 23

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

Question 24

High risk patients have a _____ risk of reactivation per ___

Answer 24

1. 5% + 5%

2. Year

Question 25

T/F TB can only reactivate in the lungs

Answer 25

FALSE, it can reactivate in a variety of locations

Question 26

What is the treatment of choice for Secondary TB?

Answer 26

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

Question 27

What does RIPES stand for?

Answer 27

``` Rifampin Isoniazid Pyrazinamide Ethambutol Streptomycin ```

Question 28

Second line drugs can be added to overcome _________ as needed

Answer 28

Drug resistance

Question 29

List the drugs that can be used to treat TB

Answer 29

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

Question 30

What is the clinical use of Isoniazid?

Answer 30

Drug of choice for prophylaxis of Mycobacterium TB *Also effective in combo against active TB

Question 31

What is the mechanism of Isoniazid?

Answer 31

Decreases Mycolic Acid synthesis

Question 32

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

Answer 32

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

Question 33

What is KatG?

Answer 33

Bacterial TB catalase oxidase enzyme

Question 34

What other effects doe KatG activation of Isoniazid have?

Answer 34

Produces free radicals like nitric oxide and can cause oxidative stress

Question 35

What are some adverse effects of Isoniazid (INH)?

Answer 35

1. Hepatotoxicity 2. Pyridoxine Deficiency 3. Disulfuram-like reaction

Question 36

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

Answer 36

With vitamin B6 to maintain heme synthesis and prevent neurotoxicity

Question 37

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

Answer 37

Because of the Disulfuram-like reaction

Question 38

T/F Pyrazinamide (PO) is another Prodrug

Answer 38

TRUE

Question 39

What are the clinical uses for Pyrazinamide?

Answer 39

-Treatment of active Mycobacterium TB infection **especially tuberculous meningitis

Question 40

Is Pyrazinamide bactericidal or bacterostatic?

Answer 40

Bacterostatic

Question 41

What is the mechanism of Pyrazinamide?

Answer 41

Inhibits Mycolic acid synthesis

Question 42

What is the net effect of the mechanism of pyrazinamide?

Answer 42

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

Question 43

What does pyrazinamide require to be activated?

Answer 43

Acidic pH

Question 44

Pyrazinamide is an essential part of the treatment of _______________

Answer 44

Tuberculous Meningitis

Question 45

What are the adverse effects of Pyrazinamide?

Answer 45

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)

Question 46

What is Ethambutal used for?

Answer 46

Treatment of Active Mycobacterium tb infefction

Question 47

What is the mechanism of Ethambutal?

Answer 47

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

Question 48

T/F Ethambutal can cross the blood brain barrier

Answer 48

TRUE

Question 49

What are the adverse effects of Ethambutal?

Answer 49

1. Ocular toxicity 2. Color Blindness 3. Ocular Neuritis: Blindness

Question 50

How often does ocular neuritis occur in patients taking Ehtambutal?

Answer 50

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

Question 51

What is the mechanism of Bedaquiline?

Answer 51

Inhibits mycobacterial ATP synthase

Question 52

In Dec 2012, bedaquiline was approved for what?

Answer 52

Use against Multi-drug resistant TB

Question 53

What are the adverse effects of Bedaquiline?

Answer 53

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

Question 54

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

Answer 54

Rifampin

Question 55

What is the drug of choice for prophylaxis of leprosy?

Answer 55

Dapsone

Question 56

What is the Mechanism of Dapsone?

Answer 56

Competes with PABA to inhibit bacterial dihydrofolate synthesis (Antimetabolite)

Question 57

What are the clinical uses of Dapsone?

Answer 57

- Prophylaxis of leprosy | - Prophylaxis of Pneumocystis jiroveci

Question 58

What are the adverse effects of Dapsone?

Answer 58

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

Question 59

What causes Travelers diarrhea/

Answer 59

- Contaminated food or water | - 80% of the time cauesd by E. Coli

Question 60

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

Answer 60

Rifaximin

Question 61

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

Answer 61

- Campylobacter Jejuni - Shigella - Salmonella

Question 62

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

Answer 62

Ciprofloxacin

Question 63

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

Answer 63

Metronidazole

Question 64

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

Answer 64

Pyrazinamide

Question 65

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

Answer 65

Isoniazid

Question 66

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

Answer 66

Ethambutol

Question 67

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

Answer 67

Streptomycin

Question 68

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

Answer 68

Azithromycin

Question 69

What antibiotics frequently cause C. Diff?

Answer 69

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

Question 70

What antibiotics cause C. Diff Infrequently?

Answer 70

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

Question 71

What antibiotics can but will rarely cause C diff?

Answer 71

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