1969 Volume 22 Issue 4 Pages 144-150
A mixture of ampicillin (aminobenzyl penicillin, AB-PC) and cloxacillin (methylchlorophenylisoxazolyl penicillin, MCI-PC) showed an excellent bactericidal activity even at low concentrations in which either of the penicillins alone did not have any activity against a clinically isolated strain of Escherichia coli, resistant to both of these penicillins. In this case, the microbial degradation of AB-PC, caused by penicillinase (PC-ase), was strongly inhibited in the presence of MCI-PC. The enzymatic hydrolysis of AB-PC by extracellular and cell-bound PC-ase, obtained from an AB-PC resistant strain of Staphylococcus aureus, was also inhibited in the presence of MCI-PC. Against that, under comparable conditions, penicillin G (PC-G) was almost completely destroyed by cell-bound PC-ase from this organism. An in vivo synergism was observed when mixtures of AB-PC and MCI-PC were applied for the treatment of mice challenged with a clinically isolated strain of E. coli resistant to both of these penicillins. Similar results were obtained in the treatment of mice experimentally infected with a strain of Staphylococcus aureus, which is highly resistant to AB-PC, but sensitive to MCI-PC.
