infectious diseases
Aminoglycosides
Dosing Considerations for Aminoglycosides
Because toxicity depends more on duration of therapeutic levels than on peak levels and because efficacy is Time vs concentration of a single dose of a theoretical antibiotic rather than time-dependent, frequent doses are avoided. Once/day IV dosing is preferred over traditional intermittent dosing for most indications. Once/day dosing may not be preferred when used for gram-positive synergy (eg, enterococcal endocarditis) or in patients who are pregnant, have significant burns (> 20% of body surface area), or have renal failure (creatinine clearance < 40 mL/minute). IV aminoglycosides are typically infused over 30 to 60 minutes. If a patient is below their ideal body weight (IBW), their total body weight (TBW) should be used to calculate doses. If TBW is greater than IBW but less than 120% of IBW, dosing should be based on IBW. If TBW is greater than 120% of IBW, adjusted body weight (ABW) should be used to calculate doses: IBW in kg (males): 50 + (2.3 × inches above 60 inches) IBW in kg (females): 45.5 + (2.3 × inches above 60 inches) ABW in kg: IBW + [0.4 × (TBW – IBW)] In patients with normal renal function, once/day dosing is Gentamicinortobramycin: 5 mg/kg (7 mg/kg if patients are critically ill) every 24 hours Amikacin: 15 mg/kg every 24 hours If patients respond to the 7-mg/kg dose ofgentamicinortobramycinclinically and renal function continues to be normal, the once/day dose can be reduced to 5 mg/kg after the first few days of treatment. In critically ill patients, peak serum levels should be determined after the first dose. In all patients, peak and trough levels are measured after the 2nd or 3rd dose (when the daily dose is divided) or when therapy lasts>3 days, as well as after the dose is changed. Serum creatinine is measured every 2 to 3 days, and if it is stable, serum aminoglycoside levels do not need to be measured again. Peak concentration is the level 60 minutes after an IM injection or 30 minutes after the end of a 30-minute IV infusion. Trough levels are measured during the 30 minutes before the next dose. With once/day dosing, peak levels in serum of at least 10 times the minimum inhibitory concentration (MIC) are desirable. This desired peak level is typically 15 to 20 mcg/mL forgentamicin(31.35 to 41.80 micromol/L) andtobramycin(32.08 to 42.78 micromol/L). Dosing is adjusted to ensure a therapeutic peak serum level (to facilitate concentration-dependent activity) and nontoxic trough levels. In critically ill patients, who are likely to have expanded volumes of distribution and who are given higher initial doses, target peak serum levels are 16 to 24 mcg/mL forgentamicin(33.44 to 50.16 micromol/L) andtobramycin(34.22 to 51.34 micromol/L) and 56 to 64 mcg/mL (95.65 to 109.31 micromol/L) foramikacin. Forgentamicinandtobramycin, trough levels should be<1 mcg/mL (< 2.09 micromol/L forgentamicinand < 2.14 micromol/L fortobramycin) at 18 to 24 hours after the first dose with once/day dosing and between 1 and 2 mcg/mL (between 2.09 and 4.18 micromol/L forgentamicinand between 2.14 and 4.28 micromol/L fortobramycin) with traditional intermittent dosing. For patients with renal insufficiency on traditional intermittent dosing, the loading dose is the same as that for patients with normal renal function; usually, the dosing interval is increased rather than the dose decreased. Guidelines for maintenance doses based on serum creatinine or creatinine clearance values are available (see table Dosing for Aminoglycosides in Adults ), but they are not precise, and measurement of blood levels is preferred. If patients are taking a high dose of a beta-lactam and an aminoglycoside, the high serum levels of the beta-lactam can inactivate the aminoglycosidein vitroin serum specimens obtained to determine drug levels unless the specimen is assayed immediately or frozen. If patients with renal failure are concurrently taking an aminoglycoside and a high-dose beta-lactam, the serum aminoglycoside level may be lower because interaction in vivo is prolonged. 