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The in vitro and in vivo antibacterial activities of 6-O-methylerythromycin A (TE-031, A-56268, or clarithromycin) and 6,11-di-O-methylerythromycin A (TE-032) have been compared with those of erythromycin A (EM) and josamycin (JM). TE-031 and TE-032, having the same antibacterial spectra as EM, are active against aerobic Gram-positive bacteria, some Gram-negative bacteria, anaerobic bacteria, L-form bacteria and Mycoplasma pneumoniae. The activity of TE-031 against clinical isolates is equal to or two times more potent than that of EM, whereas TE-032 is slightly less active than EM. The activities of TE-031 and TE-032 are pH dependent (more active at pH 8 than at 5) and are increased by adding serum to medium. TE-031 and TE-032 show dose-related bactericidal activities against Haemophilus influenzae. The therapeutic efficacies of TE-031 and TE-032 against systemic and subcutaneous infections provoked by Gram-positive bacteria in mice are 4- to 35-fold superior to those of EM and JM. TE-031 and TE-032 have demonstrated higher and longer-lasting plasma levels than EM when administered orally to mice, rats or dogs.

journal of antibiotics

Chemical modification of erythromycins. III. In vitro and in vivo antibacterial activities of new semisynthetic 6-O-methylerythromycins A, TE-031 (clarithromycin) and TE-032.