Aminoglycosides Flashcards
What is the mechanism of action of aminoglycosides?
Irreversibly bind to 30S ribosomal subunit of susceptible bacteria resulting in inhibition of protein synthesis
What are the mechanisms of resistance to aminoglycosides?
- AG modifying enzymes
- Altered AG uptake
- Change in ribosomal binding site
Gentamycin spectrum
Large spectrum of Gram negative activity.
• Gram-negative – E. coli – K. pneumoniae – Proteus – Citrobacter – Enterobacter – Morganella – Serratia – Pseudomonas
• Gram-positive – Enterococcus – S. aureus – Viridans Streptococcus – S. pyogenes
Tobramycin spectrum
Similar to gentamicin but with more activity against Pseudomonas
Amikacin spectrum
• Gram-negative
Generally,most active against nosocomial gram-negatives
-> especially Acinetobacter
(except vs tobra for Pseudomonas, most of the time)
• Mycobacterial
– M. tuberculosis
– Atypical mycobacteria
• Others
– Nocardia
Streptomycin spectrum
Gram-positive (in combination with cell wall active agent): Enterococcus
Mycobacterial: M. tuberculosis and some strains of M. kansasii, M. marinum, and M. avium.
What drugs synergies with AGs?
Cell wall agents. Likely due to increased uptake of the AGs.
What is the oral absorption of AGs like?
Poor
What is a major distribution site of AGs?
Urine
What is the main route of elimination of AGs?
99% renal elimination
AG pharmokinetics
• Concentration-dependent bactericidal
What is traditional dosing?
Multiple smaller daily doses
What is extended interval dosing?
Single daily dose of high concentration used to increase the peak levels reached
What are the reasons for the use of extended interval dosing?
- Concentration-dependent bactericidal activity
- Post-antibiotic effect (PAE)
- Minimize toxicities
What is the bactericidal effect of AGs dependent upon?
Ratio of AG Peak/MIC
