Progress in Macrolide and Ketolide Antibacterial

Daniel T. W. Chu Chiron Corporation, Emeryville, CA 94608

Introduction - The macolide antibiotic erythromycin was first found in the fermentation products of a strain of Streptomyces erythreus by McGuire (1). It has been used for the treatment of various bacterial infections in both out-patient and in-patient settings for more than forty years. Erythromycin derivatives such as clarithromycin and azithromycin are frequently prescribed for the treatment of both upper and lower respiratory tract infections (2,3). In addition to having better activity than their parent erythromycin A against anaerobes, streptococci, Haemophilus influenzae, Legionella spp., Branhamella spp., Chlamydia spp., Mycoplasma spp. and Pasteurella multocida, these derivatives possess improved pharmacokinetic profiles. However, MRSA and penicillin-resistant S. pneumoniae are found to become increasingly resistant to these newer macrolides. The emergence of resistant community-acquired as well as nosocomial pathogens to the clinically used antibacterial agents, including macrolides, has resulted in increased activity in macrolide research. This report summarizes the published literature in the past two years on macrolide research activities such as macrolide resistance, search for agents to overcome bacterial resistance and the identification of various non-antibacterial uses of macrolide. Historical information related to various macrolide resistance mechanisms will be included. Three reviews on recent developments in macrolide research have appeared (4-6).

N(CHj)2

Erythromycin A

Clarithromycin

Azithromycin

Erythromycin A

Clarithromycin

Azithromycin

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