Lecture 10: Vancomycin and Friends Flashcards
MAINLY GRAM (+)
What is the Mechanism of Action for Vancomycin?
- Inhibit cell wall synthesis 2nd stage [binding to D-Ala-D-Ala] preventing the cross-linking
- Slow Bactericidal
What is the mechanism of Resistance for Vancomycin?
VRE and VRSA
- VRE: Modifications of the D-Ala-D-Ala site to D-Lac by VanA [or VanC-E]
- VISA: Thinker cell wall
What is the Spectrum of Activity for Vancomycin?
- Gram (+): Group/Viridan Strep, MSSA, MRSA [THE DOC], C. Diff
- Gram (-): Not active
What is important to know about the Pharmacology of Vancomycin?
ADME?
- PK: Vd and Cl; AUC/MIC = 400-600
- Absorption: Bad Orally so should be IV NOT IM
- Distribution: Body tissues and Fluids [even Adipose tissue] & takes 1h to move
- Elimination: Kidneys with t = 6-8h
D: Vd = 0.6-0.7; <120kg = 0.7; >120kg = 0.6
E: Half Life increases as Renal Function decreases
What are the Clinical Uses of Vancomycin?
- MRSA Infections [bacteremia, pneumonia, endocarditis…]
- Gram (+) infections when allergic to b-lactams
- PRSP
- ORAL is good for C. Diff
What are some of the Adverse Effects of Vancomycin?
- Red-Man Syndrome [Cause by high infusion rate; 1g per 1h]
- Nephrotoxicity & ototoxicity [by high doses or renal issues]
- Dermatologic [Rashs]
- Hematologic
What are the Streptogramins that are used?
- Quinupristin - Dalfopristin
What is the Mechanism of Action for Quinupristin - Dalfopristin?
- Act seperatly on 50S to inhibit bacteria synthesis
- Alone = Bacteriostatic; Together = Bactericidal
What is the Mechanism of Resistance for Quinupristin - Dalfopristin?
- Alteration of Ribosomal binding site - encoded by erm
What is the Spectrum of Active for Quinupristin - Dalfopristin?
- Gram (+): Group/Viridan Strep, PRSP, Enterococcus Faecium ONLY [VRE], MRSA, MSSA
- Gram (-): Limited activity [Neissera…]
What is important to know about the Pharmacology of Quinupristin - Dalfopristin?
- Time-dependent bactericidal Activity with PAE
- Absorption: Only Parenterally
- Distrubition: Tissues, Lungs, Bile…
- Elimination: Hepatic or Biliary Clearance; Dosage Adjustments unnecessary for Renal but Suggested with Hepatic
What are the Clinical Uses for Quinupristin - Dalfopristin?
- ONLY consider what Vancomycin, Linezolid, Daptomycin CANNOT be used
- Entercoccus Faecium [VRE]
What are some of the interactions with Quinupristin - Dalfopristin?
- Lipid-Lowering Agents [Statins increased Conc.]
- Immunosuppressive Agents [Increased Conc.
- Carbamazepine [Increased Conc.]
3A4 Inhibitor so its not going to break down as much
What are some of the Adverse Effects of Quinupristin - Dalfopristin?
- Venous Irritation, GI issues, Myalgias, Arthralgias, Rashes
What are the Oxazolidinones that are used?
- Linezolid and Tedizolid
What is the Mechanism of Action for the Oxazolidinones?
- Binds to 50s near the 30s, inhibiting the 70s; Inhibiting protein synthesis
- Bacteriostatic
What is the Mechanism of Resistance for the Oxazolidinones?
- Alteration of the target site - encoding 23s
- Cross resistance between the two
What is the Spectrum of Activity for the Oxazolidinones?
- Gram (+): Group/Viridan Strep, PRSP, Entercoccus Faecium & Faecalis [VRE], MSSA, MRSA, VISA, VRSA
- Gram (-): INACTIVE
What is important to know about the Pharmacology of the Oxazoildinones?
- Bacteriostatic; T>MIC; PAE
- Absorption: L = 100% & T = 91%
- Distribution: Into Tissues [L maybe into CSF??]
- Elimination: BOTH renal and nonrenal
NO Renal Adjustments
What are the Clinical Uses for the Oxazolidinones?
- Where Vancomycin or b-lactams cannot be used
- VRE Infections [bacteremia or UTI]
- Nosocomial Pneumonia
- MRSA
What are some of the Drug Interactions with the Oxazoildinones?
- Weak Inhibitors of Monoamine Oxidase
- Risk of Serotonin Syndrome
What are some of the Adverse Effects of Oxazoildinones?
- GI issues, CNS [Headache…], Thrombocytopenia
What is the Mechanism of Action for Daptomycin?
- Binds and inserts lipophilic tail into the cell wall; leakaging out contents and causing death
What is the Spectrum of Activity for Daptomycin?
- Gram (+): Group/Viridan Strep, PRSP, Enterococcus Faecium & Faecilis [VRE], MSSA, MRSA, VISA, VRSA, LRSA
- Gram (-): Nope
What is important to know about the Pharmacology of Daptomycin/
- Rapid Concentration Dependent Bactericidal Activity
- Distribution: Tissues [highly protein bound]
- Elimination: Kidney
DOSAGE adjustment are require in renal issues
What are some of the Clinical uses for Daptomycin?
- Where Vancomycin and/or Linezoild cannot be used
- S. Aureus Bacteremia & Endocarditis
- NOT used for Pneumonia since is inactived by pulmonary surfactant
What are some of the drug interactions with Daptomycin?
- Statins: may increase myopathy
What are some of the Adverse Effects if Daptomycin?
- GI issues, Headache, Injection Site Reactions, Rash….
What are the Lipoglycopeptides that are used?
- Telvancin, Dalcavancin, Oritavancin
What is the Mechanism of Action for the Lipoglyopeptides?
- Affect the making of D-Ala-D-Ala
- Orita & Tel have same MOA as Dapto
What is the Mechanism of Resistance for the Lipoglycopeptides?
- Alteration to peptidoglycan terminus [VanA]
- Same MOR as Vancomycin
What is the Spectrum of Activity for the Lipoglycopeptides?
- Gram (+): Group/Viridan Strep, PRSP, Enterococcus Faecium & Faecilis [VRE], MSSA, MRSA, VISA, VRSA [Ortia mostly]
- Gram (-): Nope
What is important to know about the Pharmacology of the Lipoglycopeptides?
- Concentration Dependent Bactericidal Activity
- Distribution: into tissues; NOT CSF tho
- Elimination: Tel = Kidneys; Dala = Poo/pee; Orita = ??
Half Life: T = 7.5h, D = 346h, O = 245h
What are the Clinical Effects of the Lipoglycopeptides?
- Where Vancomycin, Linezoild, AND Daptomycin cannot be used
What are some of the Drug Interaction for the Lipoglycopeptides?
- None
What are some of the Adverse Effects of the Lipoglycopeptides?
- Red Man Syndrome
- Nephrotoxocity [Have Renal issues, other nephrotoxins, >65 years]
- QTc prolongation
- Taste?
