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Questions and Answers
What is the mechanism of action for oxazolidinones like linezolid?
What is the mechanism of action for oxazolidinones like linezolid?
- Inhibition of DNA synthesis
- Interference with protein translation at the ribosome (correct)
- Inhibition of RNA polymerase activity
- Disruption of cell wall integrity
Which of the following bacterial strains are oxazolidinones effective against?
Which of the following bacterial strains are oxazolidinones effective against?
- Clostridium difficile
- Staphylococcus aureus (both MSSA and MRSA) (correct)
- Escherichia coli
- Pseudomonas aeruginosa
What should be monitored weekly while on therapy with certain antibacterial agents?
What should be monitored weekly while on therapy with certain antibacterial agents?
- Liver enzymes
- Serum creatinine
- Serum CPK (correct)
- Complete blood count (CBC)
Why are certain antibiotics not suitable for treating pneumonia?
Why are certain antibiotics not suitable for treating pneumonia?
What is the primary reason for the unique dosing parameters in treatment for Staphylococcus aureus in obese patients?
What is the primary reason for the unique dosing parameters in treatment for Staphylococcus aureus in obese patients?
What is the mechanism of action of dapto?
What is the mechanism of action of dapto?
What is a significant adverse effect associated with linezolid?
What is a significant adverse effect associated with linezolid?
What distinguishes telavancin from vancomycin?
What distinguishes telavancin from vancomycin?
For what condition would ceftaroline be primarily indicated?
For what condition would ceftaroline be primarily indicated?
Which pharmacokinetic characteristic is NOT true for linezolid?
Which pharmacokinetic characteristic is NOT true for linezolid?
Which of the following organisms is NOT susceptible to ceftaroline?
Which of the following organisms is NOT susceptible to ceftaroline?
What is true about the protein binding of telavancin?
What is true about the protein binding of telavancin?
What renal adjustment is necessary when using telavancin?
What renal adjustment is necessary when using telavancin?
Which condition is a common indication for linezolid?
Which condition is a common indication for linezolid?
What is the most important side effect to monitor when using linezolid?
What is the most important side effect to monitor when using linezolid?
What is the primary method of elimination for vancomycin?
What is the primary method of elimination for vancomycin?
What is the recommended serum trough concentration of vancomycin for serious infections?
What is the recommended serum trough concentration of vancomycin for serious infections?
What type of organisms is vancomycin effective against?
What type of organisms is vancomycin effective against?
What mechanism makes vancomycin-resistant Staphylococcus (VRSA) rare?
What mechanism makes vancomycin-resistant Staphylococcus (VRSA) rare?
What is a significant adverse effect of daptomycin?
What is a significant adverse effect of daptomycin?
Daptomycin is primarily indicated for treating which type of infections?
Daptomycin is primarily indicated for treating which type of infections?
What is the mechanism of action (MOA) of daptomycin?
What is the mechanism of action (MOA) of daptomycin?
Which of the following is a contraindication for daptomycin use?
Which of the following is a contraindication for daptomycin use?
What is the half-life (T1/2) of vancomycin?
What is the half-life (T1/2) of vancomycin?
Which condition significantly increases the risk of nephrotoxicity when using vancomycin?
Which condition significantly increases the risk of nephrotoxicity when using vancomycin?
What percentage of daptomycin is bound to serum proteins?
What percentage of daptomycin is bound to serum proteins?
What is a notable characteristic of VISA?
What is a notable characteristic of VISA?
How is daptomycin primarily excreted from the body?
How is daptomycin primarily excreted from the body?
Which of the following bacteria can be treated with daptomycin?
Which of the following bacteria can be treated with daptomycin?
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Study Notes
Vancomycin
- Elimination: Primarily renal; 90% via glomerular filtration; altered renal function requires dose adjustments.
- Pharmacokinetics: Half-life (T1/2) of 4-6 hours; constant monitoring needed for renal insufficiency.
- Administration Routes: IV for systemic infections; oral administration limited to gut-targeting (C. difficile).
- Nephrotoxicity: Historically linked to impure products; current understanding: exposure mitigates risk; ideal serum trough concentrations are 15-20 mcg/ml for serious infections.
- Spectrum of Activity: Effective against gram-positive cocci and bacilli, including MRSA; ineffective against gram-negative organisms.
Resistance and Susceptibility
- Staphylococcal Resistance: Extremely rare; enterococcal resistance more common.
- Susceptibility Guidelines:
- Susceptible: ≤ 2 mcg/ml
- Intermediate: 4-8 mcg/ml
- Resistant: ≥ 16 mcg/ml (VISA and VRSA present)
- VISA Mechanism: Thickened cell wall limits drug effectiveness; presents false binding sites.
- VRSA Mechanism: Involves VanA gene from vancomycin-resistant Enterococcus; co-infections are common.
Daptomycin
- Classification: Semisynthetic cyclic lipopolypeptide derived from Streptomyces roseosporus.
- Mechanism of Action: Disrupts cell membrane via calcium-mediated insertion.
- Pharmacokinetics: Administered IV; T1/2 of 8-9 hours; highly protein-bound (90%); excreted renally.
- Microbiology: Active against aerobic gram-positive organisms, including MRSA and vancomycin-resistant strains; ineffective against gram-negative bacteria.
Indications and Concerns for Daptomycin
- Indications: Complicated skin infections, bacteremia due to MSSA or MRSA, right-sided endocarditis.
- Caveat: Inferior to ceftriaxone for pneumonia; inactivated by human lung surfactant.
- Adverse Drug Events (ADEs): Injection reactions, gastrointestinal disturbances, central nervous system effects, and potential rhabdomyolysis.
Oxazolidinones (Linezolid, Tedizolid)
- Spectrum of Activity: Effective against aerobic gram-positive organisms, including resistant strains of enterococci and staphylococci.
- Mechanism of Action: Inhibits protein synthesis by binding to the 50S ribosomal subunit.
- Administration: Available IV and orally; oral bioavailability (BA) is 100%.
- ADEs: Include thrombocytopenia, anemia, leukopenia; risk of serotonin syndrome, particularly when taken with serotonergic agents.
Telavancin
- Classification: Semisynthetic cyclic lipoglycopeptide, modified from vancomycin for improved efficacy.
- Mechanism of Action: Similar to vancomycin, with enhanced cell wall disruption due to hydrophobic tail.
- Approval and Pharmacology: Administered IV with a half-life of 8 hours; renal excretion with no routine therapeutic monitoring.
- Signal of Mortality: Black box warning due to increased mortality noted in specific patient populations.
Ceftaroline
- Classification: Advanced generation cephalosporin sometimes referred to as 5th generation.
- Activity: Active against MRSA through binding to low-affinity PBP 2a; limited effectiveness against gram-negative organisms.
- Indication: Administered IV; T1/2 of 2.6 hours; renally eliminated and expensive.
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