Aminoglycosides etc.

Question 1

What is the structure of aminoglycosides?

Answer 1

Six-membered aminocyclitol ring

Question 2

What is the MoA for aminoglycosides?

Answer 2

Binds to outer membrane of cell, resulting in rearrangement of LPS

Once across the membrane, the drug is trapped in the bacteria

Binds to 30S and 50S subunits, decreasing protein synthesis

Question 3

How are aminoglycosides absorbed, distributed, and excreted?

Answer 3

GI tract

Distributed freely into vascular space

Concentration in lungs 25-50% of those in serum

Excreted - glomerular filtration

Question 4

What are the adverse effects of aminoglycosides?

Answer 4

Thrombophlebitis

Nephrotoxicity

Ototoxicity

Neuromuscular blockade

Question 5

What is the general use for aminoglycosides?

Answer 5

Serious gram negative infections

Question 6

What are the specific uses of streptomycin/gentamicin?

Answer 6

TB and Brucellosis

Question 7

What are oral aminoglycosides used for?

Answer 7

Suppression of intestinal bacterial flora for surgical prophylaxis

Hepatic coma

Hyperlipidemia

Intestinal amebiases; tapeworm

Question 8

What are topical aminoglycosides used for?

Answer 8

Eye, ear, and skin infections

Question 9

Why do you have to monitor aminoglycosides?

Answer 9

Narrow therapeutic index

Monitor peak and trough with 3-4th dose (Css)

Question 10

What is vancomycin?

Answer 10

Glycopeptide antibiotic derived from streptomyces orientalis

Question 11

What is the MoA of vancomycin?

Answer 11

Inhibits the biosynthesis of peptidoglycan during cell wall formation

Bactericidal

Exhibits PAE

Question 12

How is vancomycin absorbed, distribution, and excreted?

Answer 12

Absorbption: poorly through GI, IV only for systemic infections, oral for C. diff

Distribution: Distributed freely except to CSF (only with inflammation)

Excretion: renal

Question 13

What are the desired peak, trough, and dosing interval for vancomycin?

Answer 13

Peak: 20-40mcg/ml

Trough: 10-20mcg/ml

Dosing: q8hrs, 12, 24, 48

Question 14

What are the adverse effects of vancomycin?

Answer 14

Local - thrombophlebitis

Red-Man syndrome (hisatmine like reaction)

Hematologic - neutropenia, eosinophilia, thrombocytopenia

Hypersenitivity

Nephrotoxicity

Ototoxicity

Question 15

What is the spectrum of activity for vancomycin?

Answer 15

Gram positive organisms

Question 16

What are the indications for vancomycin?

Answer 16

Serious infections caused by beta-lactam resistant G+ organisms

C. diff colitis - nonresponsive or severe

Question 17

What are the prophylactic uses for vancomycin?

Answer 17

Major surgical procedures involving implantation

Surgical prophylaxis in the case of allergy to other ABX

Prophylaxis for endocarditis in high risk patients

Question 18

What is the common dosing for vancomycin?

Answer 18

1-15 gm q 12h

Oral for C. diff - 125-500mg q 6hrs

Individualization based on pharmacokinetics and nomograms

Question 19

What is the MoA for Quinupristin/Dalfopristin (Synercid)?

Answer 19

Ivversibly bind to 50s subunit

Quinupristin - inhibits chainf ormation

Dalfopristin - inhibits peptide elongation

Question 20

What is the MoA of linezolid (Zyvox)?

Answer 20

Binds to 50s subunit

Question 21

What are the indications and AE’s for linezolid?

Answer 21

MRSA, VISA, VRE, PCN-resistant strep pneumo

Myelosuppression - thrombocytopenia

Superinfection (yeasT)

Mitochondrial toxicity

Question 22

What is the drug interaction for linezolid?

Answer 22

MAO inhibitor

Watch co-administration with SSRI for serotonin storm

Question 23

What is the MoA of tedozolid (Sivextro)?

Answer 23

Binds 23s robosomal RNA of 50s subunit

Reversible MAO inhibitor

Question 24

What is the coverage of tedoxolid and AE’s?

Answer 24

Coverage: Like vanc plus VRE and most resistant G+

Thrombocytopenia, Neutropenia. paresthesias

Question 25

What is Telavancin (Vibactiv), its coverage, and its dose?

Answer 25

Semi-synthetic derivative of Vancomycin

Covers G+ organisms

Dose 10mg/kg/day

Question 26

What are the ADRs of televancin?

Answer 26

Falsely elevated INR

Nephrotoxicity

Contraindication - Concomitant IV unfractionaed heparin

Red man syndrome

QT prolongation

Pancreatitis

Question 27

What is Oritavancin?

Answer 27

Coverage: Staph, Strep and Enterococcus

Single dose regimen: 1200mg IV

Approved for skin and soft tissue infections

Red man syndrome

Question 28

What is the coverage, dose, indication, and AE for Dalbavance (Dalvance)?

Answer 28

Coverage - staph, strep, enterococcus

Dose - Single 1500mg IV, double 1000mg IV then 500mg dose

Indication: Skin/Soft tissue

AE - Ok with IV unfractionated heparin and warfarin

Question 29

What is the coverage, dose, indication, and AE for Colistin?

Answer 29

SPACE bug coverage

ADR - Nephro and Nurotoxicity

Dose - 5mg/kg/day

Indication - Pan-resistant G-, often pseudomonad and aceintobacter, resistant PEK bugs

Question 30

What is the coverage, dose, indication, and AE for Fosfomycin (Monrol)?

Answer 30

Coverage - MDR pathogens, G+ and -, MRSA/VRE, ESBL

Dose - 3g PO packet x1 dose

Indication - UTIs in mutliple antibiotic allergy patient

ADR - Mostly GI tolerance

Question 31

What is the coverage, dose, indication, and AE for Tigecycline?

Answer 31

Indication - skin infection, intra-abdominal infections, CAP

Coverage - MRSA/VRE, G-, Acinetobacter, anaerobes

Dose - 100mg first, then 50mg q12hrs

Question 32

What is the coverage, dose, indication, and AE for Daptomycin (Cubicin)?

Answer 32

Coverage - G+, MRSA and VRE

Indication - complicated skin and soft tissue infection, staph aureus and MRSA bacteremia/right sided endocarditis

Dose - 4-6mg/kg depending on infection, requires renal adjustment

ADR - Rhabdomyolysis, Eosinophilic pneumonia

Question 33

What is the coverage, dose, indication, and AE for Mupirocin (Bactroban)?

Answer 33

Indication - Topical treatment, impetigo, infected wounds, MRSA colonization eradication from Nares

Dose - 2% ointment, 0.5 grams in each nostril BIDx5 days