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Bacterial resistance to fluoroquinolones
1Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York.
Reviews of Infectious Diseases
|January 1, 1988
Summary
Fluoroquinolone antibiotics target bacterial DNA gyrase. While resistance can develop, high-level resistance often involves permeability changes alongside DNA gyrase alterations, though it remains uncommon in many settings.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Fluoroquinolones are synthetic antibiotics that inhibit bacterial DNA gyrase, essential for DNA replication.
- Resistance to older quinolones like nalidixic acid is linked to gyrA gene mutations.
- Newer fluoroquinolones exhibit low-frequency single-step resistance mutations, resulting in lower resistance levels compared to older agents.
Purpose of the Study:
- To investigate the mechanisms and clinical relevance of bacterial resistance to fluoroquinolones.
- To compare resistance patterns between older and newer fluoroquinolone agents.
- To identify specific bacterial pathogens and clinical settings associated with fluoroquinolone resistance.
Main Methods:
- Analysis of spontaneous mutation frequencies leading to fluoroquinolone resistance.
- Characterization of genetic alterations (e.g., DNA gyrase mutations) in resistant strains.
- Assessment of bacterial permeability changes and outer membrane protein expression in resistant isolates.
- Review of clinical data on fluoroquinolone resistance in various infection types and patient populations.
Main Results:
- High-level fluoroquinolone resistance can emerge through serial exposure, involving DNA gyrase alterations and decreased permeability (loss of outer-membrane proteins).
- Cross-resistance to multiple fluoroquinolones is common with high-level resistance.
- Clinical resistance is infrequent, primarily observed in respiratory pathogens like Pseudomonas aeruginosa (especially in cystic fibrosis) and occasionally in Serratia marcescens and Staphylococcus aureus from wound infections.
- Urinary and diarrheal isolates show rare resistance.
Conclusions:
- While spontaneous single-step resistance to fluoroquinolones is rare, high-level resistance can develop via specific mechanisms.
- Fluoroquinolone resistance is not yet a widespread problem but requires monitoring in specific clinical contexts.
- Understanding resistance mechanisms is crucial for effective antibiotic stewardship and managing treatment failures.