Effect of increasing doses of amikacin with or without piperacillin in the serum bactericidal test

To determine whether high doses of amikacin would prevent the development of resistance in clinical isolates, the serum bactericidal activity and killing rate of conventional and high doses of amikacin and piperacillin alone and in combination were measured in volunteer sera against a series of ten strains each of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Amikacin serum levels were 24.9 +/- 6.0 mg/l 1 h after infusion of the 7.5 mg/kg dose and 44.8 +/- 5.0 mg/l after the two-fold dose. Median serum bactericidal titers for low dose piperacillin + amikacin were 1:8-1:64 and for high-dose piperacillin + amikacin 1:16-1:128. Both were satisfactory, except against piperacillin-resistant Pseudomonas aeruginosa (median bactericidal titers less than or equal to 1:2), and both combinations had equivalent killing rates.