The postantibiotic effect of amikacin alone and in combination with piperacillin on gram-negative bacteria

The in vitro postantibiotic effect (PAE) of amikacin was investigated using a bioluminescent assay of bacterial ATP. Two strains each of Escherichia coli, Pseudomonas aeruginosa and Serratia marcescens were exposed for one hour to different concentrations of amikacin. The aminoglycoside was removed by a 10(-3) dilution and regrowth of bacteria was followed at hourly intervals by monitoring bacterial ATP. The length of the PAE was concentration-dependent and was approximately four to six hours for the three strains at amikacin concentrations normally reached in serum during standard dosing. The PAE of amikacin in combination with 32 mg/l piperacillin on Ps. aeruginosa was also studied. These cultures were incubated with piperacillin for one hour. Thereafter different concentrations of amikacin 0.5-64 mg/l were added and the incubation then continued with the combinations for one more hour. The PAEs produced by the drugs in combination were longer than the sum of the individual effects of the drugs when they were used alone. Knowledge of synergistic PAE could have clinical implications for optimal dosing schedules during combination antimicrobial chemotherapy.