PHARM: Antibiotics

Question 1

What is the MOA of daptomycin?

CIDAL or STATIC?

Answer 1

Rapidly disrupts bacterial cell membranes (results in depolarization and loss of membrane potential and K+ efflux)–BACTERICIDAL

Question 2

What are the mechanisms of resistance to daptomycin?

Answer 2

none are identified

Question 3

What is the ROA of daptomycin?

Answer 3

IV indusion once a day after hemodialysis

NOT IM–direct muscle toxicity

Question 4

What type of metabolism does daptomycin undergo?

Answer 4

primary (bound to serum albumin)

Question 5

How is daptomycin eliminated?

Answer 5

Renal elimination (dose adjust for renal toxicity)

Question 6

What are the adverse effects of daptomycin?

Answer 6

Muscle pain and weakness

monitor for development due to serum creatinine phosphokinase elevations

Question 7

What drugs does daptomycin have DDIs with?

Answer 7

statins (if co-administered)

Question 8

What are the therapeutic uses of daptomycin?

Answer 8

• Aerobic G(+) Bacteria
• Multidrug-resistant strains of staph, strep, and enterococcus
• Complicated skin and soft tissue infections
• MSSA and MRSA bacteremia

Question 9

What type of infection is daptomycin unable to treat?

Answer 9

pneumonia (inactivated by surfactant)

Question 10

What is the MOA of linezolid?

STATIC or CIDAL?

Answer 10

Binds to the 23S RNA on 50S ribosomal subunit to inhibit protein synthesis

STATIC with staph and enterococci

CIDAL with strep

Question 11

What are the mechanisms of resistance to linezolid?

Answer 11

-Point mutation in 23S RNA

Question 12

What are the indications for linezolid?

Answer 12

• MRSA
• Resistnat staph epi
• Enterococcus faecium and faecalis
• Serious VRE infections**

Question 13

What is the ROA of linezolid?

Answer 13

Oral and Parenteral

Question 14

How does food intake alter linezolid metabolism?

Answer 14

delays absorption but not peak drug levels

Question 15

How is linezolid metabolized?

Answer 15

Non-enzymatic oxication

Question 16

How is linezolid eliminated?

Answer 16

Non-renal and renal mechanisms (no dose adjustment needed in patients with renal deficiency or mild/moderate liver failure)

Question 17

What are the AEs of linezolid?

Answer 17

• Diarrhea
• Headache
• Nausea/vomiting
• Myeosuppression (if therapy > 2 weeks)- with optic and peripheral neuropathy

Question 18

What chemical is contained within the oral suspension of linezolid?

Answer 18

aspartame

Question 19

Describe the basis for DDIs with linezolid?

Answer 19

Linezolid is a non-selective inhibitor of monoamine oxidase (caution with co-administration of drugs metabolized by MAO like PE, SSRIs, etc.)

HTN can occur from decreased breakdown of tyramine

Question 20

List 2 streptogramins.

Answer 20

Dalfopristin

Quinupristin

Question 21

How are streptogramins administred?

Answer 21

IV administration in a 70:30 combination of the two types

Question 22

What is the MOA Of streptogramins?

Answer 22

protein synthesis inhibition (bind to ribosome peptidyltransferase domain to inhibit tRNA synthetase and block AA addition to peptide chain)

Question 23

Are streptogramins bacteriostatic or bacteriocidal?

Answer 23

Synergistic bactericidal combination (but static when given alone)

Question 24

What are mechanisms of resistance to streptogramins?

Answer 24

• Changes in 23S ribosomal target site

- Constitutive expression of “erm” gene encoding MLSb phenotype

Question 25

How are streptogramins metabolized?

Answer 25

Hepatic metabolism via conjugation via CYP3A4

Question 26

How are streptogramins excreted?

Answer 26

Biliary excretion

Question 27

What are the adverse effects of streptogramins?

Answer 27

- Thrombophlebitis/pain at infusion site - Increase in conjugated bilirubin (and liver enzymes) - Joint or muscle pain (most often in people with CLD) - CYP450 inhibitor

Question 28

What are the indications for streptogramins?

Answer 28

- G(+) bacteria except for E. faecalis - VRE infections - SSSI from MRSA or strep pyogenes - Bone infections due to VRE and MRSA

Question 29

What is the MOA of Glycylcycline/Tigecycline? STATIC or CIDAL

Answer 29

Inhibition of protein translation by binding to 30S subunit Bacteriostatic

Question 30

What are mechanisms of resistance to Glycylcycline/Tigecycline?

Answer 30

Trick question- it overcomes many of the resistance to tetracyclines by having high affinity binding at additional ribosomal sites and NOT being expelled by efflux pumps

Question 31

What is the ROA of Glycylcycline/Tigecycline?

Answer 31

IV infusion (slow)

Question 32

How is Glycylcycline/Tigecycline distributed?

Answer 32

extensively beyond plasma nad into tissues

Question 33

How is Glycylcycline/Tigecycline metabolized?

Answer 33

Very little metabolism (long half life) Need to dose adjust for impaired liver function

Question 34

How is Glycylcycline/Tigecycline excreted?

Answer 34

Biliary/fecal AND renal

Question 35

What are the adverse effects of Tigecycline?

Answer 35

- Diarrhea, N/V - Injection site RXN - Possible hepatic and pancreatic toxicity - Affects teeth and bones - Sunlight sensitivity

Question 36

What are the therapeutic uses of Tigecycline?

Answer 36

- Broad spectrum- G(+), G(-), anaerobes, MRSA - NO activity against Pseudomonas or proteus - NOT for under 18 y/o

Question 37

Other than Tb, what is rifampin used for?

Answer 37

- MRSA and Staph. Epi - Prophylactically for people exposed to meningitis caused by meningococci or H. Flu - Eradication of staphlococcus in nasal carriers - Anti-leprosy

Question 38

What is rifampin commonly given with when it is not being used to treat Tb?

Answer 38

Beta-lactam or vancomycin

Question 39

What is the MOA of clindamycin?

Answer 39

INhibition of protein synthesis (binds to 50s subunit of ribosome)

Question 40

Should clindamycin be given with erythromycin?

Answer 40

NO- binding sites are very clost and render one another ineffective

Question 41

What are the mechanisms of resistance to clindamycin?

Answer 41

- Slowly occurring | - Decreased affinity of drug for ribosome (methylation of "erm"-encoded genes)

Question 42

What are the therapeutic uses of clindamycin?

Answer 42

- Effective for G(+) and G(-) anaerobes - MRSA, G.A.S. - Bacteroides fragilis (outside CNS)

Question 43

How is clindamycin absorbed?

Answer 43

- Rapid and almost complete oral absorption - Rate inhibited by food - Acid stable

Question 44

Can clindamycin penetrate the CSF or placenta?

Answer 44

CANNOT penetrate CSF or intracellular CAN penetrate bone, abscesses, placenta, breast milk

Question 45

How is clindamycin metabolized?

Answer 45

Liver metabolized (dose adjust for liver failure)

Question 46

How is clindamycin excreted?

Answer 46

Bile and urine

Question 47

What are the AEs of clindamycin?

Answer 47

- Pseudomembranous colitis from C. diff (treat with metronidazole or vancomycin) - GI problems - Hypersensitivity rashes

Question 48

What is the MOA of mupirocin? STATIC or CIDAL

Answer 48

Binds reversible to staphylococcal isoleucyl tRNA synthetase to inhibit protein and RNA synthesis Depends on concentration

Question 49

How is mupirocin administered?

Answer 49

topically (ointment with polyethylene glycol)

Question 50

What are the indications for mupirocin?

Answer 50

- Impetigo (staph, strep, MRSA) | - Eliminate MRSA carriage by patients/health care workers

Question 51

Does mupirocin get absorbed systemically?

Answer 51

NO- quickly inactivated upon absorption

Question 52

What is the MOA of bacitracin?

Answer 52

inhibits movement of peptidoglycan building blocks of cell wall from inside to outside the cell membrane by inhibiting dephosphorylation of the isoprenyl pyrophosphate carrier protein

Question 53

What are the therapeutic indications fro bacitracin?

Answer 53

G(+) cocci and bacilli

Question 54

What is the ROA of bacitracin?

Answer 54

Topically (in ointment with neomycin and polymyxin B)

Question 55

What are the AEs of bacitracin?

Answer 55

Severe nephrotoxicity with parenteral use