[Kinetics of the antimicrobial effect in a dynamic system: the microcalorimetric recording method and choice of parameters for characterizing kinetic curves]

Abstract

The kinetics of the in-vitro antimicrobial effect of sisomicin on E. coli, A 20363 was studied microcalorimetrically in a dynamic model simulating the pharmacokinetic profiles (intramuscular administration in a dose of 1 mg/kg) of the antibiotic obeying the one-compartmental model with first-order absorption. The microcalorimetric method was more accurate than the count of the colony forming units (CFU). Unlike the CFU method, it permits continuous recording of the process and unlike the turbidimetric method, it is more sensitive and selective. For quantitative characteristic of the curves of the antimicrobial effect kinetics it is suggested to use a new parameter, the effect duration (Td) which is determined by the difference in the moment of the antibiotic administration into the dynamic model (Tin) and the moment (Tout) when the rate of heat production or the number of the CFU or the optical density during the microbial secondary growth was the same as that at Tin. It was shown that the values of Td estimated in experiments with recording of the antimicrobial effect by different methods are similar. Evaluation of Td may be useful in predicting the optimal dosing intervals.