Quantitative and qualitative determinations of the combined effect of tetracycline and oleandomycin. I. In vitro effect.

Growth inhibitory effect of combined treatment of tetracycline (TC) and oleandomycin (OM), at a ratio of 2:1, on certain species of pathogenic bacteria including drug-resistant ones was examined. By the crossed paper strip method, synergistic effects were demonstrated against 9 of the 16 strains of Staphylococcus aureus, and all of the 5 strains of Escherichia coli studied. Antagonism was observed with none of the strains and with 2 strains of Streptococcus pyogenes and 2 strains of Streptococcus pneumoniae tested in the present experiments. The MICs determined by the agar dilution method, also gave similar results, although synergism was not conclusively demonstrated by this method. With representative strains of S. aureus, synergism was evidenced by quantitative measurement of growth inhibition. In some strains, 1.0 mug of one drug per ml of medium inhibited the induction of resistance to the second drug. Such a small dose of one drug also inhibited the development of a mutant resistant to the second drug. These inhibitory actions were thought to be one of the important factors causing the synergistic effect of TC and OM on drug resistant bacteria.