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?
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?
Recall: when using gentamycin (or sometimes streptomycin) to treat gram positive infections, you would normally combine it with ___________, or sometimes even ___________ for severe infections (e.g. enterococcal or staphylococcal).
- Beta-lactams (ampicillin, nafcillin) - Vancomycin (recall: lower, traditional dosing)
What part of the kidney is affected by AG nephrotoxicity?
Proximal tubule (AG uptake is saturable here)
How are AG's administered? What are the exceptions?
They are all administered IV and IM (not PO)
What are AG's mech of action? (Cidal or static?)
Irreversibly bind to 30S ribosomal subunit to inhibit ptn synth (bacteriocidal).
What are AG's mech of resistance?
Synthesis of AG-modifying enzymes (often via plasmid), altered AG uptake (efflux pump of loss of porin channel), change in ribosomal binding site/target modification
What organ eliminates AGs?
Kidneys (dose must be adjusted in kidney failure)