Serum Bactericidal Titres After Cefoperazone With and Without Sulbactam

Abstract

11 healthy volunteers were enrolled in a crossover ex vivo study comparing cefoperazone (2g) with the combination of cefoperazone (2g) + sulbactam (1g). The antibiotics were given by intravenous infusion over 30 minutes. Blood samples were obtained 30 minutes and 12 hours after the end of infusion for the measurement of serum concentrations, bactericidal titres and killing rates. Two parameters were derived from the killing curves: the initial rate of killing and the relative bioactivity (area under the time-kill curve as a percentage of the growth control curve). 60 test organisms were studied including oxacillin-susceptible and -resistant Staphylococcus aureus, Escherichia coli, Enterobacter cloacae, Serratia marcescens, Bacteroides fragilis and Acinetobacter baumanii. Mean serum concentrations of cefoperazone were 131.6 and < 2 mg/L at 30 minutes and 12 hours, respectively, after the end of infusion. Synergy between cefoperazone and sulbactam was observed in two-thirds of the strains by the checkerboard method, including oxacillin-resistant S. aureus. Using the serum bactericidal titres, synergy occurred mainly against A. baumanii and B. fragilis, but restricted to the senjm obtained at 30 minutes. Using the killing curve method in serum, synergy on both the relative bioactivity and killing rate was observed on the serum obtained at 30 minutes, but not at 12 hours.