Kinetics of bactericidal activity of aminoglycosides during dynamic dilution.

The time courses for viable microorganism count after addition of aminoglycosides were investigated in exponentially decreasing concentrations in in vitro using a continuous flow culture system. When aminoglycosides were added to the incubation medium containing Escherichia coli, the growth rate began to decrease after a lag phase and recovered gradually after the concentration fell below its effective level. To simulate this time course, the following equation including the retardation function was proposed; (Formula: see text) where N is the number of viables, ko is the generation rate constant, kd is the dilution rate constant, Pc is the bactericidal coefficient per unit concentration characteristic to the individual antibiotic, kr is the reciprocal of the retardation time and Co is the initial concentration of the antibiotic. Pc and kr were calculated using the nonlinear least square method and the calculated time course agreed with the observed experimental data indicating the appropriateness of this equation. Pc has a negative relationship to the minimum inhibitory concentration for six aminoglycosides studied, kanamycin, amikacin, kanamycin B, tobramycin, dibekacin and habekacin. The values of kr ranged between 3.12 X 10(-2) to 6.40 X 10(-2) min-1 and are thought to correlate with the mechanism of antibiotic actions.