The synergistic action of cephalosporin C and benzylpenicillin against a penicillinase-producing strain of Staphylococcus aureus.

Cephalosporin C, a hydrophilic, penicillin-like antibiotic which is insensitive to penicillinase, is much less active than benzylpenicillin against the Oxford strain of Staphylococcus aureus but much more active than benzylpenicillin against a penicillinase-producing strain of S. aureus (D3R). When used together, cephalosporin C and benzylpenicillin act synergistically against S . aureus strain D3R in Witro, presumably because cephalosporin C is a competitive inhibitor of penicillinase. When grown under certain conditions in the presence of cephalosporin C, benzylpenicillin, or bacitracin, the Oxford staphylococcus gives rise during a single culture to a resistant bacterial population consisting largely or partly of Gram-negative bacilli. In the presence of bacitracin a similar change also occurs with S. aureus strain D3R.