VALIDATION AND NEPHROTOXICITY OF A SIMPLIFIED ONCE-DAILY AMINOGLYCOSIDE DOSING SCHEDULE AND GUIDELINES FOR MONITORING THERAPY

There is no established dosing schedule for once-daily aminoglycoside dosing regimens, and accepted guidelines for monitoring therapy are la cking, We derived a simplified schedule from the Hull and Sarubbi (J. H, Hull and F, A, Sarubbi, Ann, Intern, Med, 85:183-189, 1976) nomogra m, for which efficacy and safety in a once-daily dosing regimen were p reviously demonstrated, and prospectively followed serum aminoglycosid e levels in patients, The standard treatment was gentamicin or tobramy cin at ? mg/kg of body weight given intravenously once daily, When the renal function was decreased, the daily dose was reduced, as follows: for an estimated creatinine clearance of between 50 and 80 ml/min, th e daily dose was 3.25 mg/kg, for an estimated creatinine clearance of between 30 and 50 ml/min, the daily dose was 2.5 mg/kg, and for an est imated creatinine clearance of below 30 ml/min, the daily dose was 2 m g/kg. A total of 221 patients were studied (184 received gentamicin an d 37 received tobramycin), First trough levels above 2 mg/liter were r ecorded in 11% of the patients, and they all had a baseline creatinine clearance below 50 ml/min, or a substantial decrease in clearance bet ween enrollment and the day that the trough level was obtained, A peak level below 6 mg/liter was recorded in 6% of the patients, and half o f them received the lowest daily dose, Twenty-five of the 179 evaluabl e patients (14%; 95% confidence interval, 9 to 19%) fulfilled the crit eria for nephrotoxicity, In a multiple regression analysis, the durati on of treatment and the use of other nephrotoxic antibiotics or high-d ose furosemide, but not trough levels, were significant risk factors, Since the meaning of low peak levels is unclear and since most studies with multiple daily regimens confirm the lack of an association betwe en trough levels and toxicity, we believe that monitoring of serum dru g levels can be restricted to monitoring of trough levels in patients with a creatinine clearance below 50 ml/min or with a deteriorating re nal function.