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 were 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/I amikacin and 2, 4, 16 and 16 mg/I 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 , 0.63 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 bactericidal activity was measured at 1 and 6 h after infusion. Median serum bactericidal activities at 1 and 6 h, respectively, were 1:512 and 1:32 against 10 E. coli ; 1:1024 and 1:32 against 10 Klebsiella spp.; 1:32 and 1:4 against Ps. aeruginosa and 1:16 and 1:2 against 10 Staph. aureus . In addition this activity was ≥, 1:8 at 1 h in all sera when tested against Klebsiella spp. and Pseudomonas spp. and in 86 % of sera when tested against Staph. aureus . Thus as seen in in vitro and in vivo studies, cefotaxime and amikacin appear to provide a promising combination for infections due to those pathogens frequently causing bacteraemia in neutropenic patients.
No takes yet. Share an insight, caveat, or question.
Klášterský et al. (1980) studied this question.