Comparative in vitro activity, serum binding and binding activity interactions of the macrolides A-56268, RU-28965, erythromycin and josamycin.

The minimal inhibitory concentrations of macrolide antibiotics against staphylococci, streptococci and Haemophilus influenzae were determined in vitro. A-56268 was the most active and RU-28965 was the least active of the macrolides tested. The interaction at erythromycin binding sites in serum and at alpha 1-acid glycoprotein was studied. RU-28965 exhibited the highest binding affinity. The effect of binding on antimicrobial potencies was evaluated by measurements of the first-order generation rate constants and by determination of MICs of staphylococci in broth and in human serum. The activity of each of the macrolides was lowered by serum binding, but only that of RU-28965 was dramatically decreased.