Pharmacology and Efficacy of Netilmicin

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.