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 290 ml/min and 60 to 90 ml/min were 3.2 and 3.4 h, respectively. In patients with serum creatinines of 51.4 mg/100 ml and creatinine clearances of 260 ml/min, mean serum levels were 9.0 and 1.2 ,ug/ml, respectively, 5 to 15 min and 7.5 h post-intravenous infusion, and 7.1 and 1.7 ,ig/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 ,ug of netilmicin per ml, except for the P. rettgeri, which required 25 ,ug/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.The aminoglycosides gentamicin, tobramycin, and amikacin have all proved to be useful agents in therapy of serious infections caused by gramnegative bacilli. These antibiotics are nephrotoxic and ototoxic. Netilmicin, a new aminoglycoside with broad-spectrum activity against gram-negative bacilli, has been shown to be less nephrotoxic and ototoxic than gentamicin in experimental animals (3,15,18).The purpose of this study was to investigate the pharmacology and efficacy of netilmicin in patients with suspected bacteremia caused by gram-negative bacilli.
