Aminoglycosides etc. Flashcards
What is the structure of aminoglycosides?
Six-membered aminocyclitol ring
What is the MoA for aminoglycosides?
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
How are aminoglycosides absorbed, distributed, and excreted?
GI tract
Distributed freely into vascular space
Concentration in lungs 25-50% of those in serum
Excreted - glomerular filtration
What are the adverse effects of aminoglycosides?
Thrombophlebitis
Nephrotoxicity
Ototoxicity
Neuromuscular blockade
What is the general use for aminoglycosides?
Serious gram negative infections
What are the specific uses of streptomycin/gentamicin?
TB and Brucellosis
What are oral aminoglycosides used for?
Suppression of intestinal bacterial flora for surgical prophylaxis
Hepatic coma
Hyperlipidemia
Intestinal amebiases; tapeworm
What are topical aminoglycosides used for?
Eye, ear, and skin infections
Why do you have to monitor aminoglycosides?
Narrow therapeutic index
Monitor peak and trough with 3-4th dose (Css)
What is vancomycin?
Glycopeptide antibiotic derived from streptomyces orientalis
What is the MoA of vancomycin?
Inhibits the biosynthesis of peptidoglycan during cell wall formation
Bactericidal
Exhibits PAE
How is vancomycin absorbed, distribution, and excreted?
Absorbption: poorly through GI, IV only for systemic infections, oral for C. diff
Distribution: Distributed freely except to CSF (only with inflammation)
Excretion: renal
What are the desired peak, trough, and dosing interval for vancomycin?
Peak: 20-40mcg/ml
Trough: 10-20mcg/ml
Dosing: q8hrs, 12, 24, 48
What are the adverse effects of vancomycin?
Local - thrombophlebitis
Red-Man syndrome (hisatmine like reaction)
Hematologic - neutropenia, eosinophilia, thrombocytopenia
Hypersenitivity
Nephrotoxicity
Ototoxicity
What is the spectrum of activity for vancomycin?
Gram positive organisms
What are the indications for vancomycin?
Serious infections caused by beta-lactam resistant G+ organisms
C. diff colitis - nonresponsive or severe
What are the prophylactic uses for vancomycin?
Major surgical procedures involving implantation
Surgical prophylaxis in the case of allergy to other ABX
Prophylaxis for endocarditis in high risk patients
What is the common dosing for vancomycin?
1-15 gm q 12h
Oral for C. diff - 125-500mg q 6hrs
Individualization based on pharmacokinetics and nomograms
What is the MoA for Quinupristin/Dalfopristin (Synercid)?
Ivversibly bind to 50s subunit
Quinupristin - inhibits chainf ormation
Dalfopristin - inhibits peptide elongation
What is the MoA of linezolid (Zyvox)?
Binds to 50s subunit
What are the indications and AE’s for linezolid?
MRSA, VISA, VRE, PCN-resistant strep pneumo
Myelosuppression - thrombocytopenia
Superinfection (yeasT)
Mitochondrial toxicity
What is the drug interaction for linezolid?
MAO inhibitor
Watch co-administration with SSRI for serotonin storm
What is the MoA of tedozolid (Sivextro)?
Binds 23s robosomal RNA of 50s subunit
Reversible MAO inhibitor
What is the coverage of tedoxolid and AE’s?
Coverage: Like vanc plus VRE and most resistant G+
Thrombocytopenia, Neutropenia. paresthesias
What is Telavancin (Vibactiv), its coverage, and its dose?
Semi-synthetic derivative of Vancomycin
Covers G+ organisms
Dose 10mg/kg/day
What are the ADRs of televancin?
Falsely elevated INR
Nephrotoxicity
Contraindication - Concomitant IV unfractionaed heparin
Red man syndrome
QT prolongation
Pancreatitis
What is Oritavancin?
Coverage: Staph, Strep and Enterococcus
Single dose regimen: 1200mg IV
Approved for skin and soft tissue infections
Red man syndrome
What is the coverage, dose, indication, and AE for Dalbavance (Dalvance)?
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
What is the coverage, dose, indication, and AE for Colistin?
SPACE bug coverage
ADR - Nephro and Nurotoxicity
Dose - 5mg/kg/day
Indication - Pan-resistant G-, often pseudomonad and aceintobacter, resistant PEK bugs
What is the coverage, dose, indication, and AE for Fosfomycin (Monrol)?
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
What is the coverage, dose, indication, and AE for Tigecycline?
Indication - skin infection, intra-abdominal infections, CAP
Coverage - MRSA/VRE, G-, Acinetobacter, anaerobes
Dose - 100mg first, then 50mg q12hrs
What is the coverage, dose, indication, and AE for Daptomycin (Cubicin)?
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
What is the coverage, dose, indication, and AE for Mupirocin (Bactroban)?
Indication - Topical treatment, impetigo, infected wounds, MRSA colonization eradication from Nares
Dose - 2% ointment, 0.5 grams in each nostril BIDx5 days
