Interactions were studied between fusidic acid and each of several penicillins in their effect on both penicillinase-positive and penicillinase-negative strains of Estimation of the number of staphylococci that survived overnight exposure to the antibiotics, alone and in combination, showed three types of interaction.

In the commonest type, exhibited by more than half the penicillinase-positive and almost all the penicillinase-negative strains, there was two-way antagonism; more staphylococci survived overnight incubation in the presence of fusidic acid plus a penicillin than in the presence of either agent alone. Further evidence that penicillin antagonised the action of fusidic acid against these strains was provided by scanning electron microscopy, which revealed that the cell-wall collapse that followed the action of fusidic acid was inhibited by the presence of a penicillin.

In the second type of interaction there was one-way antagonism of penicillin by fusidic acid; least survivors were recovered after incubation with a penicillin alone, more from the mixture and most from fusidic acid alone.

The remaining strains showed “indifference”, in that the effect of the more bactericidal agent—which against some strains was fusidic acid—prevailed. Even when the effect of penicillin on the bulk of the bacterial population was antagonised, the presence of penicillin always prevented the emergence of fusidic acid-resistant mutants.


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