Novel β-Lactams, their Antibacterial and Pharmacokinetic Properties and Pre-Clinical Evaluation

Abstract

Since the introduction of the first ß-lactam antibiotics in the early part of the century a myriad of new compounds have been developed. All of these new compounds have been chosen either because of their improved pharmacokinetic properties, antibacterial activity or both. The aim of this study was firstly, to investigate the in vitro activity of five β-lactams (representative of new groups of antimicrobials) and the protecting ability of a f-lactamase inhibitor, tazobactam, on piperacillin, (a β-lactam susceptible to hydrolysis by β-lactamase): secondly, to determine the pharmacokinetics and penetration of each drug to various possible sites of infection. All of the β-lactams exhibited greater stability to hydrolysis by β-lactamases than earlier compounds such as ampicillin and cephalorodine. All inhibited a wide range of organisms with the exception of cefixime and aztreonam which had reduced or little activity against gram positive organisms. The β-lactamase inhibitor was slightly less active than clavulanic acid, however, was more stable to environmental conditions such as heat and moisture. All of the β-lactams penetrated tissues and inflammatory fluids and concentrations for the most part exceeded the minimum inhibitory concentrations of the common pathogens. Tazobactam was found in vivo in a 1:8 ratio when administered with piperacillin.