Tobramycin dosing in mechanically ventilated patients. Inaccuracy of a 'rule of thumb'

The ability of a simple rule of thumb, based on creatinine clearance, to predict tobramycin serum concentrations was evaluated in mechanically ventilated patients. They were given tobramycin intravenously over 30 min at 8 h intervals. Creatinine clearance was estimated from the formula developed by Cockcroft & Gault (1976, Nephron 16, 31-41) or was calculated after urine collection for 24 h. The loading dose was 1.5 mg/kg and then dose adjustments were performed on a daily basis. Patients were studied on day 1 and day 3. Mean values of peak and trough levels were within the therapeutic range, but individual values were outside the therapeutic range in 30% to 70% of patients on both day 1 and day 3, most of the patients having subtherapeutic serum concentrations. This was mainly related to the high volume of distribution of tobramycin calculated in these patients. These results further emphasize the need to monitor serum concentrations and to use an individual pharmacokinetic method to make dose adjustment.