Netilmicin and tobramycin. Comparison of nephrotoxicity in dogs

We compared the effects of netilmicin and tobramycin on renal function and histology in dogs. Separate groups, each containing 5 dogs, received control injections, or either netilmicin or tobramycin at doses of 25, 50, or 75 mg per kg of body weight per day for 14 days. Renal function decreased markedly only in the group receiving the 75-mg tobramycin dosage; the serum creatinine levels rose from 1.0 +/- 0.1 to 3.6 +/- 0.9 mg per 100 ml (P less than 0.05) and the endogenous creatinine clearance fell from 42.5 +/- 9.4 to 7.8 +/- 2.2 ml per min (P less than 0.05). Dogs in this group developed glycosuria, proteinuria, and polyuria, and three died before the end of the study, probably from neuromuscular toxicity. Peak drug levels were stable when renal function was normal, but increased when renal failure occurred. Light microscopic changes occurred in all groups receiving either drug, but were most severe in the high-dose tobramycin group. Ultrastructural changes were similar in all groups and identical to changes produced by gentamicin. These results show that, on a weight basis, netilmicin is less nephrotoxic than tobramycin in dogs.