Aminoglycosides : Wheeless' Textbook of Orthopaedics

- Specific Agents:
- Neomycin
- Gentamicin
- Tobramycin
- Amikacin
- Netilmicin

- Discussion:
- 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;

- Cautions:
- 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;
           - references:
                 - 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.