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Use of cethromycin, a new ketolide, for treatment of community-acquired respiratory infections

Hammerschlag MR, Sharma R

Expert opinion on investigational drugs, 2008

Abstract

BACKGROUND: The ketolides are a subclass of macrolides, which were designed specifically to overcome macrolide-resistant respiratory pathogens. Ketolides lack the cladinose sugar, which is replaced with a 3-ketone group. Ketolides bind to a secondary region on domain II of the 23S rRNA subunit. Telithromycin was the first ketolide to be approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and sinusitis. However, in 2006, after reports of serious hepatotoxicity, the FDA issued a public health advisory followed by a warning. In 2007 the indications for treatment of AECB and sinusitis were removed from the labeling. Cethromycin (ABT-773) is the only other ketolide currently under clinical development.

OBJECTIVE: To review currently available data on cethromycin, including chemistry, in vitro activity, pharmacokinetics, pharmacodynamics, in vivo activity and results of treatment studies in humans.

METHODS: A search was made in PubMed, pharmaceutical databases and meeting abstracts using the terms ketolides, ABT-773 and cethromycin.

RESULTS/CONCLUSIONS: Cethromycin has comparable tissue penetration, pharmacokinetics and in vitro activity compared with telithromycin to Streptococcus pneumoniae, including multidrug-resistant isolates, Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. There is only one published CAP treatment study…

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