Cefotaxime and amikacin: results of in vitro and in vivo studies against Gram-negative bacteria and Staphylococcus aureus EORTC International Antimicrobial Therapy Project Group

The activities of cefotaxime and amikacin alone and in combination were evaluated in in vitro checkerboard studies, in a neutropenic mouse model and in human volunteers. In vitro checkerboard studies weTe performed using a microtitre technique for 26 strains of Escherichia coli, 39 Klebsiella spp., 39 Pseudomonas aeruginosa and 50 Staphylococcus aureus. Over 90 % of these strains were inhibited by 4, 2, 16 and 4 mg/1 amikacin and 2, 4, 16 and 16mg/l cefotaxime, respectively. FIC indices were calculated as a measure of antibiotic synergy when the 2 antibiotics were used together. For cefotaxime and amikacin the median FIC index was 0-5 for E. coli, 063 for Klebsiella spp., 0-75 for Ps. aeruginosa and 1-0 for Staph. aureus. Neutropenic mice infected with E. coli sensitive to both drugs received either cefotaxime 1-0 to 1-5 mg/kg, amikacin 0-75 mg/kg or the 2 drugs together at the same doses. Survival was 1/20, 1/20 and 7/20 respectively. Six human volunteers each received cefotaxime 15 mg/kg, amikacin 15 mg/kg and the combination on separate days in a randomly determined order. Serum bacteri-cidal activity was measured at 1 and 6 h after infusion. Median serum bactericida