Disruptors of the plasma membrane

Question 1

Drug groups that act as disruptors of the plasma membrane

Answer 1

Polymyxins
Cyclic lipopeptides

Question 2

Types of polymyxin available

Answer 2

Polymyxin B and E

Question 3

Colistin is also called

Answer 3

Polymixin E

Question 4

ADME polymyxin B

Answer 4

Topical, ophthalmic, and IV administration

Question 5

Polymyxin is often combined with

Answer 5

Carbapenems
Tetracyclines
Aminoglycosides

Question 6

Polymyxins MOA

Answer 6

Cationic agents that disrupt bacterial cell membranes by binding to lipopolysaccharides (LPS) and phospholipids, increasing membrane permeability

Question 7

Polymyxins B bind to ——- portion of —– and inactivate it

Answer 7

Lipid A
Endotoxin

Question 8

Disruptor of the membrane Administered as colistimethate sodium (CMS) IV/IM or inhaled

Answer 8

Colistin (Polymyxin E)

Question 9

The inhaled form of polymyxin E is used for

Answer 9

Cystic-fibrosis infections

Question 10

Colistimethate vs Colistin

Answer 10

IV - Topical use

Question 11

Polymyxins only act against

Answer 11

Gram-negative bacteria, primarily anaerobes

Question 12

Susceptible microorganisms to polymyxins

Answer 12

Pseudomonas
Acinetobacter
Enterobacterales

Question 13

When are polymyxins used for bacteremia, pneumonia or meningitis?

Answer 13

ONLY when pathogens are resistant to other treatments

Question 14

What infections can polymyxins treat?

Answer 14

Bacteremia
Pneumonia (including ventilator-associated pneumonia, VAP)
Bone & joint infections
Burn wound infections
Cellulitis & skin infections
Cystic fibrosis-related lung infections
Endocarditis
Gynecologic infections
Meningitis & ventriculitis (only for resistant bacteria)

Question 15

Polymyxin used for systemic infections and corneal ulcers due to P. aeruginosa

Answer 15

Polymyxin B

Question 16

Colimethate (IV polymyxin E) is used for

Answer 16

treatment of UTIs

Question 17

Colistin (topical polymyxin E) is used for

Answer 17

Infections of the skin, mucous membranes, eye and ear

Question 18

External otitis due to Pseudomonas is treated with

Answer 18

Colistin (polymyxin E)

Question 19

Polymyxin B adverse effects

Answer 19

• Nephrotoxicity (limits systemic use)
• Neurotoxicity (paresthesia, dizziness, confusion)
• Respiratory muscle paralysis (rare, but can occur with high doses)
• Local irritation (topical use)

Question 20

Colistin E adverse effects

Answer 20

• Nephrotoxicity
• Neurotoxicity (dizziness, confusion, paresthesia, neuromuscular blockade)
• Bronchospasm (inhaled form)
• Respiratory failure (rare, but serious)

Question 21

Colistin contraindication

Answer 21

Classified as pregnancy category C

Question 22

Polymyxins contraindication

Answer 22

Concomitant Use of Nephrotoxic or Neurotoxic Drugs:
- Increased toxicity risk when used with aminoglycosides, vancomycin, NSAIDs, diuretics (e.g., furosemide), or muscle relaxants

Question 23

Polymyxins resistant moos

Answer 23

• Proteus and Serratia spp.
• Stenotrophomonas
• Burkholderia

Question 24

Fosfomycin drugs and food interactions

Answer 24

Best taken on an empty stomach
Food may reduce absorption and urinary concentration

Question 25

Polymyxins emergent resistant moos

Answer 25

Acinetobacter Klebsiella

Question 26

Daptomycin is classified as a --------- disruptor of the plasma membrane

Answer 26

Cyclic lipopeptide

Question 27

Administration of daptomycin

Answer 27

IV

Question 28

Daptomycin MOA

Answer 28

Binds to bacterial membrane (calcium-dependent insertion) → Depolarization & potassium efflux → Cell death (bactericidal)

Question 29

Daptomycin therapeutic uses

Answer 29

Serious gram-positive infections that cause: Complicated skin and soft tissue infections Bacteremia and endocarditis due to MRSA or VRE Osteomyelitis

Question 30

Myopathy and rhabdomyolysis is the most serious adverse effect of

Answer 30

Daptomycin

Question 31

Not the most serious adverse effects of daptomycin

Answer 31

Eosinophilic pneumonia Peripheral neuropathy GI symptoms

Question 32

T or F: daptomycin can be used for pneumonia

Answer 32

F; inactivation by lung surfactant

Question 33

Daptomycin should not be taken with -------- as they increase the risk of myopathy

Answer 33

Statins

Question 34

Although rare, VRE and MRSA can develop resistance to daptomycin via...

Answer 34

Cell membrane modifications

Question 35

------------------------ alter membrane charge, reducing daptomycin binding

Answer 35

Mutations in mprF genes