Antibacterial activity of four cephalosporins in an experimental infection in relation to in vitro effect and pharmacokinetics.

The in vitro activity of four cephalosporins was compared with their effects in an experimental thigh infection (cefuroxime and cefamandole against Escherichia coli and cefamandole, ceftriaxone, and ceftazidime against Klebsiella pneumoniae) in granulocytopenic mice. The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate at the steepest part of a 3-h growth curve in the presence of an antibiotic. The relation between concentration and ER was described with the Hill equation. Using pharmacokinetic parameters of the plasma concentrations in vivo and those of the Hill equation the corresponding time course of ER was calculated and by integration with respect to time (0tERdt), an estimate was obtained of the effect on bacteria. For all four antibiotics this estimate was significantly correlated with the actual values of the effect in vivo (EN), defined as the difference in numbers of bacteria between controls and antibiotic-treated animals at 4 h.

Bactericidal effect of combinations of cephalosporins with tobramycin on clinical isolates of Escherichia coli, Klebsiella and Staphylococcus aureus.

The antimicrobial activities of the cephalosporins cefazolin, cefotaxime, moxalactam or ceftazidime in combination with tobramycin against clinical isolates of E. coli, of Klebsiella, of beta-lactamase-negative and beta-lactamase-producing S. aureus strains were compared in vitro by the checkerboard technique. Antibiotic dilutions differed by small arithmetic increments. Favourable interactions occurred with each bacterial species. This trend applied to third-generation cephalosporins against E. coli and Klebsiella as well as to cefazolin against S. aureus. The antibiotics with already the highest intrinsic activity generally exhibited also the most favourable interaction.