The use of ketolides in treatment of upper respiratory tract infections |
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Authors: | Zhanel George G Wierzbowski Aleksandra K Hisanaga Tamiko Hoban Daryl J |
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Institution: | (1) Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, MS673-Microbiology, Health Sciences Centre, 820 Sherbrook Street, R3A 1R9 Winnipeg, Manitoba, Canada |
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Abstract: | Recent surveillance studies suggest that the incidence of resistance to macrolide antibiotics in common communityacquired
respiratory tract pathogens, particularly Streptococcus pneumoniae and Streptococcus pyogenes, is increasing and limiting the usefulness of these drugs. The ketolides, of which telithromycin is the first to be available
for clinical use (but not yet in the United States), represent a new class of antibacterials developed specifically to combat
respiratory tract pathogens that have acquired resistance to macrolides. The ketolides possess innovative structural modifications,
a 3-keto group and a large N-substituted C11, C12-carbamate side chain. This novel structure allows ketolides, which are inhibitors
of protein synthesis, to exert a more effective interaction with domain II of the 23S rRNA, enhancing binding to bacterial
ribosomes and allowing binding to macrolide-lincosamidestreptogramin B-resistant ribosomes. This novel chemical structure
also promotes greater stability of telithromycin in acid conditions, providing the potential for greater stability in gastric
fluid and at cellular/tissue levels. Early clinical trials support the bacteriologic and clinical efficacy of telithromycin
in the treatment of upper respiratory tract infections (RTIs) such as streptococcal pharyngitis and acute sinusitis, including
infections caused by macrolide-resistant S. pneumoniae and S. pyogenes. Common adverse side effects associated with telithromycin are predominantly gastrointestinal, usually of mild to moderate
severity, and rarely involve withdrawal of the drug. Telithromycin represents an attractive option for the empiric treatment
of upper RTIs, especially as resistance to macrolides is likely to continue to increase. |
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