The addition of sub-inhibitory concentrations of cephalothin, a competitive inhibitor of staphylococcal β-lactamase, to a culture of a penicillinase-producing containing a sub-inhibitory concentration of a hydrolysable penicillin (benzylpenicillin, phenoxymethylpenicillin, phenethicillin, propicillin, ampicillin or carbenicillin) was found to bring about an increase in the lag phase of the culture (Δ), during which there was a bactericidal effect. The extent of Δ depends upon certain enzymological parameters, of which a separate theoretical consideration has already been made (Hamilton-Miller, 1971); the observed values of Δ were found to be in line with those predicted by means of the equation derived previously. Synergism between cephalothin and penicillins was also demonstrated by MIC determinations. The system used here to analyse synergism may have applications in other circumstances where antimicrobial agents are destroyed by resistant organisms.


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