[Microcalorimetric study of the kinetics of the antibacterial effect of third generation cephalosporins in an in vitro dynamic system].

The antimicrobial effect (AME) kinetics of cefotaxime and ceftizoxime was studied with respect to 4 bacterial strains (E. coli, S. aureus, K. pneumoniae and P. aeruginosa) in an in vitro dynamic model. The mean integral concentrations, i.e. the AUC values divided by the dosing interval observed in blood of humans after the drug single intravenous administration in doses of 0.25, 0.5, 1 2 and 4 g. were simulated. The simulated concentrations of cefotaxime and ceftizoxime were 6.25 and 6.75, 12.5 and 13.5, 25 and 27, 50 and 54 and 100 and 108 mg/kg, respectively accounting for the differences in their pharmacokinetics. The changes in the microbial count were recorded microcalorimetrically by the rate of heat output with the BioActivity Monitor LKB 2277-202. The AME was expressed by TE reflecting the shift of the microbial growth curve in the presence of the cephalosporins against the control growth curve (in the absence of the drugs). It was noted that in simulating the concentrations observed after the drugs administration in various doses cefotaxime was mainly superior to ceftizoxime in terms of the TE, the value of the TE correlating with the respective values of the MICs. Some discrepancies between the TE and MICs were explained by the complicated shape of the TE vs. concentration or AUC curve observed earlier in regard to cefotaxime as well as by the differences in the steady state and dynamic conditions of the experiment.