Serum bactericidal activity against Klebsiella pneumoniae in volunteers receiving increasing doses of tobramycin with or without cefamandole.

Ten volunteers received intravenously in a randomly allocated order and on separate days the following regimens: cefamandole (15 mg/kg); tobramycin (1.5 mg/kg); tobramycin (3 mg/kg); cefamandole (15 mg/kg) + tobramycin (1.5 mg/kg); cefamandole (15 mg/kg) + tobramycin (3 mg-kg). Tobramycin serum levels were 3.7 +/- 0.7 micrograms/ml one hour after infusion of the 1.5-mg/kg and 7.8 +/- 1.6 micrograms/ml after the higher dose. Cefamandole serum levels were 26.0 +/- 5.2 micrograms/ml at the same time. Serum bactericidal activity and killing-rate studies were performed on a collection of 18 strains of Klebsiella pneumoniae. Against cefamandole-sensitive strains, all regimens were satisfactory (median serum bactericidal activity 1:16 to 1:64). Tobramycin (3 mg/kg) and both combinations were slightly more active on cefamandole-resistant strains (1:16 to 1:32) than cefamandole (1:2) and tobramycin low dose (1:8). Except for cefamandole alone, all regimens were equivalent in killing studies.