Microbial kinetics of β‐lactam antibiotics against Escherichia coli

Microbial kinetics of Escherichia coli NIHJ JC‐2 and E. coli B/r were investigated in the presence of β‐lactam antibiotics. To maintain a constant drug concentration during the experiment, a novel technique, using a dialysis membrane tube containing the drug solution, was successfully employed. The drug‐affected generation curves of E. coli exhibited common features. After the addition of drug, an apparent lag period was noted, followed by a first‐order decrease of the sensitive organisms and, 6 h later, by a regrowth of resistant organisms, depending on the antibiotic concentration used. The relationship between the apparent generation rate constant, k_app, and the antibiotic concentration was found to be nonlinear. This phenomenon is consistent with a saturable receptor site model for the drug action. A good linear free energy relationship was observed between the microbial kinetic parameter, k_max, and the alkaline degradation rate constants, k_OH, of the cephalosporins studied.