Twenty-six patients, 20 to 77 years of age, were treated with
netilmicin, mean dose 2 mg/kg every 8 h intramuscularly or in a 20-min
intravenous infusion. The mean serum half-lives in patients with
creatinine clearances of >/=90 ml/min and 60 to 90 ml/min were 3.2 and 3.4 h, respectively. In patients with serum creatinines of </=1.4 mg/100 ml and
creatinine clearances of >/=60 ml/min, mean serum levels were 9.0 and 1.2 mug/ml, respectively, 5 to 15 min and 7.5 h post-
intravenous infusion, and 7.1 and 1.7 mug/ml, respectively, 1 and 8 h post-
intramuscular injection. Twenty-five patients had acute
pyelonephritis; 7 of the 25 had
bacteremia. The infecting bacteria were Escherichia coli (15), Proteus mirabilis (5), Pseudomonas aeruginosa (2), Klebsiella pneumoniae (1), Enterobacter hafniae (1), and both Proteus rettgeri and Proteus morganii (1). All were inhibited by 6.3 mug of
netilmicin per ml, except for the P. rettgeri, which required 25 mug/ml for inhibition. Of 23 patients who could be evaluated, 19 were bacteriologically and clinically cured at follow-up. Of the remaining four, one relapsed, two became reinfected, and one was lost to follow-up. Five patients developed nephrotoxicity; two of the five had previous
renal insufficiency. Three patients, one with abnormal renal function, developed
ototoxicity detected only with audiograms. These studies suggest that
netilmicin is effective in serious gram-negative bacillary
infections, but is nephrotoxic and ototoxic in humans.