Ketolides: the future of the macrolides?

Area of Science:

• Microbiology and Infectious Diseases
• Pharmacology and Drug Development

Background:

• Increasing antibiotic resistance in bacterial pathogens causing community-acquired respiratory tract infections (cARTIs).
• Limitations of existing macrolide antibiotics against resistant strains, particularly Streptococcus pneumoniae and Streptococcus pyogenes.

Purpose of the Study:

• To evaluate the efficacy of novel ketolide antibiotics against key respiratory pathogens.
• To assess the potential of ketolides to overcome common macrolide resistance mechanisms.

Main Methods:

• Development and preclinical evaluation of semi-synthetic ketolides derived from erythromycin.
• Assessment of antibacterial spectrum, potency, and post-antibiotic effects.
• Investigation of mechanisms to overcome macrolide resistance in Streptococcus species.

Main Results:

• Ketolides demonstrate effectiveness against macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes.
• Improved potency and extended post-antibiotic effects compared to traditional macrolides.
• Maintenance of the broad antibacterial spectrum characteristic of the macrolide class.

Conclusions:

• Novel ketolides, cethromycin (ABT-773) and telithromycin, possess promising antibacterial properties.
• These agents are potential candidates for treating cARTIs, addressing significant resistance challenges.
• Clinical development and regulatory review are underway for these new antibiotic candidates.