RENAL TOLERABILITY OF 4 DIFFERENT ONCE-DAILY DOSE REGIMEN OF NETILMICIN IN CRITICAL CARE PATIENTS

A prospective, randomized trial was conducted in a medical intensive c are unit to assess safety and tolerability of four different dose regi mens of intravenous netilmicin given once daily in the treatment of fe brile episodes in critically ill patients. Eighty patients with febril e episodes during their stay in the intensive care unit were included in the study. The patients were randomized into four groups: Group 1 r eceived a single daily dose of netilmicin based upon weight, age and r enal function according to a dosage nomogram [13] (mean dose 298 +/- 2 9 mg, median 300 mg, range 250-350 mg), group 2 received 150% of this standard dose (mean 418 +/- 45 mg, median 400 mg, range 350-500 mg), g roup 3 200% (mean 525 +/- 41 mg, median 500 mg, range 400-550 mg) and group 4 250% (mean 710 +/- 39 mg, median 650 mg, range 600-750 mg). Du ration of treatment was six days. Positive cultures were obtained in 2 9 patients. Serum creatinine and creatinine clearance, as well as neti lmicin trough levels and levels of alpha1-microglobulin showed no sign ificant difference between the groups before, during, and after therap y. Our results indicate that with once daily dosing even high doses of netilmicin are well tolerated in patients with a creatinine clearance of >70 ml/min before therapy. Necessary precautions include monitorin g of drug trough levels (<1 mg/L) and maintenance of adequate volume s tatus.