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Quinolone Resistance: Older Concepts and Newer Developments
Darrin J. Bast1, Joyce C. S. de Azavedo
1Department of Microbiology, Toronto Medical Laboratories, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Abstract:
New quinolone compounds have been recommended for use in the treatment of respiratory tract infections, particularly pneumonia caused by multi drug-resistant Streptococcus pneumoniae. Of concern, however, is the recent emergence of pneumococcal isolates with reduced susceptibilities to both old and new quinolone compounds. This necessitates the employment of quinolone-use strategies aimed at restricting the emergence of resistance, to extend the effectiveness of this very important class of antibacterial agents. This article provides a comprehensive review of the recent discoveries in type II topoisomerase/quinolone structure-function relationships. It also addresses new insights into the mechanisms of quinolone resistance, the predicted trends in quinolone resistance, and possible strategies for quinolone use against S. pneumoniae.
Insights
New quinolone drugs combat resistant pneumonia but face emerging resistance. Strategies are needed to preserve quinolone effectiveness against Streptococcus pneumoniae by understanding resistance mechanisms and structure-activity relationships.
Area of Science:
- Microbiology
- Pharmacology
- Drug Resistance
Background:
- Quinolones are vital for treating multi-drug resistant Streptococcus pneumoniae pneumonia.
- Emerging resistance to both old and new quinolones in pneumococcal isolates is a significant concern.
- Restricting quinolone resistance is crucial to maintain their therapeutic efficacy.
Purpose of the Study:
- To review type II topoisomerase/quinolone structure-function relationships.
- To explore new insights into quinolone resistance mechanisms.
- To discuss quinolone resistance trends and usage strategies against S. pneumoniae.
Main Methods:
- Literature review of recent discoveries.
- Analysis of structure-function relationships.
- Examination of resistance mechanisms and trends.
Main Results:
- Detailed review of type II topoisomerase/quinolone interactions.
- Insights into molecular mechanisms driving quinolone resistance.
- Projections of future resistance patterns.
Conclusions:
- Understanding quinolone-antibiotic interactions is key to combating resistance.
- Developing effective quinolone-use strategies is essential for S. pneumoniae infections.
- Continued research is needed to preserve the utility of quinolones.