The clinical efficacy, patient tolerance, and pharmacokinetics-of gentamicin and the single component gentamicin C1 were studied after single and multiple doses in elderly male patients. Patient tolerance was extremely good at the dose levels used. There was some evidence of renal function impairment due to repeated intramuscular doses of gentamicin, but not gentamicin C1. The antibiotics were equally effective against the organisms present in the urine of these patients. The pharmacokinetics of the two antibiotic forms were similar, although gentamicin C appeared to have a larger distribution space.Gentamicin, a broad-spectrum antibiotic complex, has been shown to consist of three components designated C l, C la, and C2 (2). The recent availability of each component in substantially pure form has permitted their comparative evaluation with the parent complex in a variety of in vitro and in vivo studies. It was noted that gentamicin C1 (SCH 13706) required a significantly longer period of administration to produce ataxia in cats than did the gentamicin complex. Similar observations, together with reduced nephrotoxicity due to gentamicin C1, were made in the squirrel monkey. Studies in other species also demonstrated reduced eighth cranial nerve and renal toxicity with gentamicin C1 (2).In vitro bacteriological studies and in vivo mouse protection studies indicate that gentamicin C1 is slightly less active than the gentamicin complex against most strains of Enterobacteriaceae. Cross-resistance between gentamicin Cl and the parent complex is generally noted, although the former is not inactivated by bacterial acetylases (2).Since it thus appears that gentamicin C 1 may offer therapeutic advantages over gentamicin, the two antibiotics were compared in the clinical treatment of complicated urinary tract infections, with particular emphasis on efficacy, tolerance, and pharmacokinetics. by a serum creatinine < 1.5 mg/100 ml and/or a blood urea nitrogen <25 mg/100 ml. Creatinine clearances were, as expected, low, suggesting some impairment of renal function. The two patient groups were considered comparable since there were no statistically significant differences between the groups regarding age, weight, underlying pathology, incidence of indwelling catheters, or renal functions, and there were no major differences in the types of bacteria isolated from the urines in the two groups. All patients had gram-negative urinary tract infections susceptible to gentamicin as defined by the standardized disk susceptibility method (1), and all had significant bacteriuria (. 105 colonies per ml) before treatment.
MATERIALS AND MErHODSAll patients received gentamicin or gentamicin Cl by intravenous injection at a dose level of 1 mg/kg on the first day of treatment. (Gentamicin C, was supplied as the sulfate in 2-ml ampoules containing 50 mg/ml by Schering Laboratories, Bloomfield, N.J.) This was followed by 1 mg/kg every 8 h intramuscularly for 7 days. On the 8th day the patients again