Aminoglycosides

GENERAL PRINCIPLES

Aminoglycosides exert their bactericidal effect by binding to the bacterial ribosome, causing misreading during translation of bacterial messenger RNA into proteins.

TREATMENT

• Traditional dosing of aminoglycosides involves daily divided dosing with the upper end of the dosing range reserved for life-threatening infections. Peak and trough concentrations should be obtained with the third or fourth dose and then every 3-4 days, along with regular serum creatinine monitoring. Increasing serum creatinine or peak/troughs out of the acceptable range requires immediate attention.

• Extended-interval dosing of aminoglycosides is an alternative method of administration in patients without significant renal impairment and is more convenient for most indications. Extended-interval doses are provided in the following specific drug sections. A drug concentration is obtained 6-14 hours after the first dose, and a nomogram (Figure 15-1) is utilized to determine the subsequent dosing interval. Drug concentrations 6-14 hours after the prior dose should be monitored at least every week; serum creatinine should be checked at least thrice weekly. In patients who are not responding to therapy, a 12-hour concentration should be checked, and if that concentration is undetectable, extended- interval dosing should be abandoned in favor of traditional dosing.

Figure 15-1 Nomograms for extended-interval aminoglycoside dosing.A, GentamicinZtobramycin. B, amikacin.

• For obese patients (actual weight >20% above ideal body weight [IBW]), an obese dosing weight (IBW + 0.4 ? [actual body weight - IBW]) should be used for determining doses for both traditional and extended-interval methods. Traditional dosing, rather than extended-interval dosing, should be used for patients with endocarditis, burns that cover more than 20% of the body, anasarca, and creatinine

clearance (CrCl) of are recommended as above. Goal serum trough levels are 14 d).