- Specific Agents:
- indicated for serious Gm Neg infections caused by suseptable pseudomonas, proteus, e. coli, klebsiella, enterobacter sp., serratia, and gm neg sepsis;
- tobramycin is more active than gentamicin against pseudomonas, including gentamicin-resistant strains, and is usually indicated over gentamicin for pseudomonas infections, in combination with an antipseudomonal penicillin (AMA, 1983).
- aminoglycocides bind to the bacterial 30s ribosome and inhibit protein synthesis;
- bacterial killing occurs in a biphasic fashion;
- first bacteria are killed at an extremely rapid pace in a concentration-dependent fashion;
- second, after approximately two hours and a 3 log kill (99.99% killing), the rate of bacterial killing slows;
- adaptive resistance occurs by down regulation of aminoglycoside transport into the bacteria through energy dependent transport processes;
- extended-spectrum penicillins may inactivate aminoglycosides depending on time of exposure and the concentration of penicillin;
- may occur if both drugs are mixed together in same bottle, or in vivo in patients with renal failure in whom high concentrations of penicillin may accumulate.
- arises from nucleophilic attack of the Beta lactam ring on an amino group of aminoglycoside;
- carbenicillin causes the most inactivation;
- nephrotoxicity and oto-toxicity:
- aminoglycosides are primarily excreted unchanged in the urine
- cumulative doses and duration of therapy correlate w/ development of oto and nephrotoxicity, which may result from aminoglycoside accumulation;
- renal insufficiency increases the risk of developing aminoglycoside induced nephrotoxicity;
- when dosing aminoglycosides after hemodialysis, one should check serum levels 2 hours after dialysis to allow for redistribution;
- diuretics may increase oto and renal toxicity;
- Nephrotoxicity and ototoxicity of aztreonam versus aminoglycoside therapy in seriously ill nonneutropenic patients.
- Risk factors for nephrotoxicity in patients treated with aminoglycosides.
- Can pharmacokinetic dosing decrease nephrotoxicity associated with aminoglycoside therapy.
- A model for predicting nephrotoxicity in patients treated with aminoglycosides.
Aminoglycoside therapy. Current use and future prospects.
Aminoglycoside dosing in burn patients using first-dose pharmacokinetics.
Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration.
Studies of risk factors for aminoglycoside nephrotoxicity.
Comparative cost effectiveness of gentamicin and tobramycin.
Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia.
The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia.
Risk factors for the development of auditory toxicity in patients receiving aminoglycosides.
Wide interpatient variations in gentamicin dose requirements for geriatric patients.
Pharmacokinetic Training Packet for Pharmacists