Thirty-one patients with severe
gram-negative bacterial infections were treated successfully with a combination of
cefamandole nafate plus
gentamicin or
tobramycin. The patients were divided into two treatment groups: group 1 received low-dose
therapy (80--100 mg of
cefamandole nafate/kg per 24 hr plus 3 mg of either
gentamicin or
tobramycin/kg per 24 hr), and group 2 patients, who had suspected
bacteremia, received high-dose
therapy (170 mg of
cefamandole nafate/kg per 24 hr plus 5 mg of either
gentamicin or
tobramycin/kg per 24 hr). All of the patients were clinically and bacteriologically cured of their primary
infections. All four episodes of
bacteremia were cleared within 24 hr after
therapy was initiated. There was a uniform decrease in the rate of
creatinine clearance which was slightly greater in group 2 patients; however, all
creatinine clearance values were within the normal range and actually improved during
therapy. There was no difference between the clearance values of the
tobramycin-treated patients and
gentamicin-treated patients. A few transient abnormalities in results of liver function tests occurred during the study. In one patient whose serum was positive for
hepatitis-associated
antigen, the
alkaline phosphatase,
aspartate aminotransferase, and
bilirubin values were elevated on admisssion of the patient to the hospital, increased fivefold during
therapy, and decreased to the base-line admission values six days after
therapy; however, it is difficult to establish that this reaction was
antibiotic-induced hepatic toxicity.