Gary V Doern PhDab

aClinical Microbiology Laboratories, University of Iowa Hospital and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA b University of Iowa College of Medicine, Iowa City, IA 52242, USA

Antimicrobial agents in the macrolide family have long been considered drugs of potential utility in the management of infections caused by Streptococcus pneumoniae. However, with the emergence of macrolide resistance, the clinical value of macrolides in pneumococcal infections is threatened. In part, as a consequence of the development of macrolide resistance, recently the first agent in the ketolide antimicrobial class, telithromycin, was developed and introduced into clinical practice. The ketolides are macrolide antimicrobials whose chemistry has been modified in such a way as to avoid the effects of the most common mechanisms of macrolide resistance with S pneumoniae. The intent of this discussion is to review the current state of resistance to macrolides and ketolides with S pneumoniae in North America.

What's a macrolide or a ketolide?

Three macrolide antibiotics have been used extensively in North America, erythromycin, clarithromycin, and azithromycin. Their molecular structures are depicted in Fig. 1. Erythromycin and clarithromycin both have a 14-membered ring structure; the only difference between these two agents is a methoxy group substitution in clarithromycin for a hydroxyl group in erythromycin at the C-6 position. This substitution improves the oral bioavailability of clarithromycin and diminishes its upper gastrointestinal (GI) tract toxicity profile [1]. Azithromycin, an azalide derivative of

* Clinical Microbiology Laboratories (C606-GH), University of Iowa Hospital and Clinics, 200 Hawkins Drive Iowa City, Iowa 52242. E-mail address: [email protected]

0025-7125/06/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.mcna.2006.07.010

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