[Clavulanic acid. Its effect on Staphylococcus aureus other than its inhibitory effect on beta-lactamases].

The influence of clavulanic acid (CA) on growth kinetics of Staph. aureus strains with MIC values (minimal inhibitory concentration) of penicillin (Pc) between 0,06 and 1 024 IU/ml was examined. Furthermore, it was tried to select mutants of the parent strains with increased resistance to CA and, in the affirmative case, to find out a relationship between Pc and CA resistance. The experiments showed that CA in subinhibitory concentrations induced a considerable increase of the latent phase of Pc sensitive strains but less of the Pc resistant ones. CA delayed also the generation time but this effect was apparently independent of Pc resistance. Successive subculturing of strains in gradually increasing CA concentrations resulted in an increase of CA resistance by a factor of 4 to 8 compared with that of the parent strains. In parallel, the Pc resistance increased by a factor of 16 to 64, however only in case of strains originally sensitive to Pc. A synergistic or additive effect of CA and Pc evaluated by the index of the fractional inhibitory concentration (IFIC) was not only shown in Pc resistant but also in Pc sensitive strains. This effect was equally demonstrable in strains with increased CA resistance. In this case, however, the MIC of Pc in the presence of CA was increased by a factor of 32 to 64 in originally Pc sensitive strains and by a factor of 2 to 4 in the originally Pc resistant ones. These results indicate a possible selection of CA resistant strains with an increased Pc resistance.