Aminoglycosides: 9/10/15 Flashcards
What is the mechanism of action of aminoglycosides (AG)?
They inhibit protein synthesis by binding to the ribosome 30 s subunit
Gentamycin targets which type of bacteria?
gram negative
- enterobacteriaceae
- slightly anti-pseudomonas*
gram positive: most effective of aminoglycosides
- S. aureus
- S. pyogenes
- enterococci (-cidal)
- virdans streptococci
THINK: “Gentleman get to treat all the ladies except pseudo” = both gram +/-
Aminoglycosides are typically used with aminopenicillin and vancomycin to achieve ____________.
synergistic effects: maybe due to increased uptake of cell wall inhibitor abx
remeber, AGs are concentration dependent
Describe the pharmacodynamics for aminoglycosides
- IV or IM only
- distribution: no CSF or sputum
- elimanation: renal
Which two abx are commonly used to create an synergistic effect with aminoglycosides?
aminopenicillin
vancomycin
What types of clinical presentations would benefit from treatment with aminoglycosides?
- In combination with beta-lactams to treat resistant and/or serious infections: enterococcal or staphylococcal endocarditis
- Urinary sepsis [enterobacteriae]
- Mycobacterial infections [MAC, TB, atypical TB]
- Pneumonia [high dose required bc only 40% of AG to pleural space]
- Bloodstream, intra-abdominal, skin/soft tissue infections
Name the two main adverse affects with giving aminoglycosides and whether they are reversible or irreversible
Nephrotoxicity: reversible
- gentamicin = most reported
Ototoxcity: irreversible
- affects both vestibular and cochlear ducts
Describe traditional dosing using aminoglycosides
Low doses, given multiple times per day
- maintains a low baseline level of drug in the body
- allows for greater risk of bacteria to become resistant and prolonged exposure leading to adverse effects
- associated with elevated trough levels
Describe extended interval dosing using aminoglycosides
One large dose given, following dose given after drug becomes undetectable in the body
- allows for periods of time there is no drug inside of the body = less risk of resistance and toxic effects
- PAE present: so still see effects when drug is gone
How does dosing change when treating gram positive vs gram negative vs mycobacteria with aminoglycosides?
gram positive
- extended interval prefered
gram negative
- traditional and extended interval are both okay
- no advantageous effects with higher peak level
mycobacteria
- large doses are required
How do penicillin and aminoglycosides vary in terms of PAE and time/concentration dependent killing and mechanism of action?
MOA
- PCN = binds to cell wall PBP
- AGs = bind to bacterial ribosome
killing type
- PCN = time depend.
- AGs = concen depend.
PAE
- PCN = no PAE
- AGs = PAE
List two ways that bacteria may exhibit resistance against AG
- efflux/secretory pump activity: pump AGs out of the body
- loss of porins: prevents uptake of AGs
Tobramycin targets which type of bacteria?
Best for: pseudomonas
Gram positive:
- none
Gram negative:
- enterobacteria
Amikacin targets which type of bacteria?
Best for: Mycobacteria: TB or atypical mycobacteria
Gram positive:
- norcardia
Gram negative:
- enterobacteria: broad spectrum
In general, the AGs have best coverage for which type of bacteria?
Gram negative bacteria
Do AGs use time or concentration dependent killing?
- Concentration dependent killing
- We care about how tall the peak is above the MIC, NOT the time above the MIC
- PAE present
