Aminoglycosides Flashcards
Name the 3 most important AGs. Which is a 4th that is less important?
- Gentamycin (gent) - Tobramycin (tobr) - Amikacin (amik) Streptomycin
Which is the most important AG?
Gentamycin
What is the general class(es) of organism(s) that gentamycin targets? What are the 3 organisms in this class that it’s most effective against? (not sire if I need to be this specific)
Gram-negative *Can also target gram-pos if another drug allows it to get into the cell - E. coli, Klebsiella pneumoniae, Proteus
How does the activity of tobramycin differ from gentamycin?
Slightly weaker gram-neg activity but more effective against pseudomonas.
What type(s) of pathogen(s) is amikacin effective against?
- Nosocomial gram-negatives (except not as good as tobr for pseudomonas) - Mycobacterial (M. tuberculosis and atypical) - Other: nocardia (rare)
What type(s) of pathogen(s) is streptomycin effective against?
- Gram-pos: enterococcus (but gentamycin is preferable) - Mycobacterial (M. tuberculosis, but less effective against atypical vs. amikacin)
What type of drugs do AG’s have synergy w/?
Cell-wall inhibitors (likely due to enhanced AG uptake)
What is unique about the distribution of AGs?
1000-fold higher conc. in urine vs. plasma (good for treating UTIs)
Differentiate b/w “traditional” (MDD) and “extended interval” (ODA) dosing.
- Traditional: multiple daily doses (q8-12 hrs) - Extended interval: once daily dosing (no less)
With conc-dependent killing, would you aim for higher or lower peak:MIC ratio?
Higher (make sure you understand why)
How is the post-antibiotic effect influenced by the peak:MIC ratio?
Bigger peak:MIC ratio = larger dose, and therefore larger PAE w/conc-dependent killing
Which is more likely to create resistance: infrequent large doses, or frequent smaller doses? (Why?) - Which leaves the bacterium more susceptible to killing?
Frequent smaller doses (bacteria more likely to survive) - 1 large dose more effective because bacteria more susceptible during drug-free time.
Which AGs are effective against gram-neg infections?
- Gentamycin - Tobramycin - Amikacin
What type of dosing is preferred when using AGs to fight gram-neg infections?
Extended interval (once daily) dosing
Which AGs are effective against gram-pos infections?
- Gentamycin - Strepamycin
What type of dosing is preferred when using AGs to fight gram-pos infections?
Traditional dosing * Counter to what has been said, but must be given in combo w/beta-lactam drug to get it into cell. Once in cell, there is synergy w/this other drug, and don’t need as high of a dose
Which AGs are effective against mycobacterial infections?
- Amikacin - Streptomycin
What type of dosing is preferred when using AGs to fight mycobacterial infections?
Extended interval dosing (3 times weekly!) - Amikamycin preferable
Explain the reasons why extended-interval dosing is preferable to traditional dosing w/r/t AGs vs. gram-neg bacteria. (6)
- Concentration-dependent bactericidal activity - Post-antibiotic effect (PAE) - Adaptive resistance - *Minimize toxicities - Cost savings - Efficacy
What are some factors that influence PAE? (4, not too important)
- Organism - Drug concentration - Duration of drug exposure - Antimicrobial combinations
What are the 2 major toxicities related to AGs?
- Nephrotoxicity - Ototoxicity
If gram-neg bacteria suspected, AGs can be used for the empiric treatment of __________, especially from a urinary source. What other conditions could they be used for?
Sepsis - Intraabdominal infections - Skin/soft tissue infections
If a pt has a h/o CF, which AG would you choose and why?
*Tobramycin (pt is more susceptible to pseudomonas)
If treating PNA with AGs, would you use a low, medium, or high dose?
High
