Related Experiment Videos
The emerging new generation of antibiotic: ketolides
1Abbott Laboratories, Abbott Park, IL 60064, USA.
Abstract:
The bacterial ribosome is a target for a variety of drug classes including macrolides. Macrolide antibiotics are primarily used for the treatment of respiratory tract infections. One of the most important features of the macrolide class is the excellent safety profile allowing the drug to be used broadly across all age groups. The emergence of macrolide resistance, especially in S. pneumoniae, threatens the long-term usefulness of macrolide antibiotics. The newly developed ketolide class, including telithromycin and ABT-773, evolved from the macrolide class and displays significant improvements over macrolides while maintaining safety profiles similar to macrolides. The key improvement in antimicrobial spectrum is the in vitro potency against macrolide resistant pathogens, especially S. pneumoniae. This review outlines the key improvements of ketolides over macrolides in terms of in vitro microbiology, as well as the pharmacokinetic and pharmacodynamic profiles and updates the current understanding of drug-ribosome interactions. The application of cutting-edge technology such as ribosome structure-based rational drug design and genetic engineering are also briefly discussed.
Insights
Ketolides offer improved efficacy against macrolide-resistant bacteria, particularly S. pneumoniae, while maintaining safety. This review details ketolide advancements over macrolides in microbiology, pharmacokinetics, and drug-ribosome interactions.
Area of Science:
- Microbiology
- Pharmacology
- Drug Discovery
Background:
- Macrolide antibiotics are crucial for respiratory infections but face resistance, especially from Streptococcus pneumoniae.
- Macrolides have a favorable safety profile, enabling broad use across age groups.
Purpose of the Study:
- To review key improvements of ketolides over macrolides.
- To update the understanding of drug-ribosome interactions.
- To discuss novel drug design strategies.
Main Methods:
- Comparative analysis of in vitro microbiology data.
- Review of pharmacokinetic and pharmacodynamic profiles.
- Discussion of ribosome structure-based drug design.
Main Results:
- Ketolides demonstrate enhanced in vitro potency against macrolide-resistant pathogens, including S. pneumoniae.
- Ketolides exhibit improved antimicrobial spectrum compared to macrolides.
- Ketolides maintain safety profiles similar to macrolides.
Conclusions:
- Ketolides represent a significant advancement over macrolides, addressing key resistance challenges.
- Further research into drug-ribosome interactions and rational drug design is ongoing.
- Ketolides offer a promising alternative for treating resistant bacterial infections.