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The in vitro and in vivo antibacterial activities of6-0-methylerythromycin A (TE-03 1 , A-56268, or clarithromycin) and 6, 1 1-di-O-methylerythromycin A (TE-032) have been compared with those of erythromycin A (EM) andjosamycin (JM). TE-03 1 and TE-032, having the same antibacterial spectra as EM,are active against aerobic Gram-positive bacteria, someGram-negative bacteria, anaerobic bacteria, L-form bacteria and Mycoplasma pneumoniae. The activity of TE-03 1 against clinical isolates is equal to or two times more potent than that of EM,whereas TE-032is 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 Haemophilusinfluenzae. The therapeutic efficacies of TE-03 1 and TE-032against systemic and subcutaneous infections provoked by Gram-positive bacteria in mice are 4-to 35-fold superior to those of EMand JM. TE-031 and TE-032 have demonstrated higher and longer-lasting plasma levels than EMwhen administered orally to mice, rats or dogs.Erythromycin A (EM) has been a clinically useful macrolide antibiotic for over three decades. EM is particularly effective against most Gram-positive bacteria; some Gram-negative bacteria, including Neisseria, Bordetella, Brucella, Campylobacter and Legionella; and Treponema, Chlamydia and Mycoplasma. 1'2) One of limitations of EMis poor absorption after po administration because of its lability at gastric pH.6-0-Methylerythromycin A (TE-03 1 , clarithromycin) and 6, 1 1 -di-O-methylerythromycin A (TE-032) are new semisynthetic macrolides prepared by the first chemical modification3) on the C-6 hydroxyl group of EM;they are more stable to acid than EM.4) In this paper we describe the antibacterial activities ofTE-031 and TE-032 which are compared with those of EM and josamycin (JM) in vitro and in vivo. Additionally, the pharmacokinetic profiles of these compounds in several species of animals are presented. Materials and Methods Bacterial StrainsClinically isolated strains (198 strains) used in this study were obtained from several Japanese hospitals. The other strains (80 strains) were from the Taisho culture collection and ATCCstrains.Antibacterial Agents TE-031 and TE-032 were prepared at Taisho Pharmaceutical Co., Ltd. EMand JM were obtained from Abbott Laboratories and YamanouchiPharmaceutical Co., Ltd., respectively. Stock solutions of the drugs were prepared for in vitro tests by dissolving lOmg of drug in 5ml of methanol. The drugs were

The in vitro and in vivo antibacterial activities of clarithromycin (CAM), a new oral macrolide antibiotic, were compared with those of erythromycin (EM), josamycin (JM) and rokitamycin (RKM). The antibacterial spectrum and in vitro activities of CAM were similar to those of EM. Therapeutic efficacies of CAM against various experimental infections in mice – including systemic infections caused by gram-positive bacteria such as Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, and subcutaneous abscess due to S. aureus, and bacterial pneumonia caused by S. pneumoniae – were superior to those of EM, JM and RKM. CAM exhibited higher serum levels than EM in mice after a single oral dose of 50mg/kg.

Antibiotics U 1200In vitro and in vivo Antibacterial Activities of the Tricyclic Ketolide TE-802 and Its Analogues. -TE-208 (Ia) and its analogues (Ib)-(Id) exhibit excellent antibacterial activity against a wide range of bacteria. -(ONO, T.; KASHIMURA*, M.; SUZUKI, K.; OYAUCHI, R.; MIYACHI, J.; IKUTA, H.; KAWAUCHI, H.; AKASHI, T.; ASAKA, T.; MORIMOTO, S.; J.