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[Causes of quinolone resistance in gram-negative bacteria]
1Lehrstuhl für Medizinische Mikrobiologie und Immunologie, Ruhr-Universität Bochum.
Abstract:
Some years ago the 6 alpha-fluoroquinolones were introduced into therapy; within the recent years the frequency of quinolone-resistant enterobacteria remained unchanged at a very low level. The frequency of resistant Staphylococcus aureus isolates in clinical specimens increased slowly and there was a markedly increase in quinolone-resistant Pseudomonas aeruginosa isolates. So far, resistance to quinolones among gram-positive organisms can be attributed to alterations of the subunit A of the DNA-gyrase, whereas in gram-negative rods both alterations of the subunits A and B of the DNA-gyrase as well as alterations of the composition of the outer membrane can be made responsible for phenotypic resistance. With respect to the resistance mechanisms there are no striking discrepancies between enterobacteria and Pseudomonas aeruginosa. Alterations of the outer membrane composition responsible for quinolone resistance cannot be attributed only to changes of the protein profile, but also to alterations of the lipopolysaccharide. Thus, it can be explained that cross-resistance with chemically unrelated classes such as beta-lactams, chloramphenicol, tetracyclines and gentamicin may occur, whereas hypersusceptibility to these agents will occur in other quinolone-resistant clones. The rapid emergence of quinolone resistance in Pseudomonas aeruginosa is not a feature characteristic for quinolones, but rather for the species Pseudomonas aeruginosa. At present, the benefit of a combination therapy with quinolones and beta-lactams to avoid emergence of resistant Pseudomonas aeruginosa clones cannot be decided.
Insights
Quinolone resistance in bacteria is increasing, particularly in Pseudomonas aeruginosa, due to DNA gyrase alterations and outer membrane changes. Understanding these mechanisms is crucial for effective antibiotic strategies.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- 6 alpha-fluoroquinolones introduced years ago.
- Quinolone resistance in enterobacteria remains low.
- Increasing quinolone resistance observed in Staphylococcus aureus and Pseudomonas aeruginosa.
Purpose of the Study:
- To investigate quinolone resistance mechanisms in bacteria.
- To analyze the emergence of quinolone resistance in Pseudomonas aeruginosa.
- To evaluate potential cross-resistance patterns.
Main Methods:
- Analysis of quinolone resistance mechanisms in gram-positive and gram-negative bacteria.
- Investigation of DNA gyrase subunit alterations (A and B).
- Examination of outer membrane composition changes, including lipopolysaccharide and protein profiles.
Main Results:
- Quinolone resistance in gram-positive bacteria linked to DNA gyrase subunit A alterations.
- Resistance in gram-negative bacteria involves DNA gyrase subunits A and B, and outer membrane changes.
- Outer membrane alterations contribute to cross-resistance with unrelated antibiotic classes.
- Rapid quinolone resistance emergence in Pseudomonas aeruginosa is species-specific.
Conclusions:
- Quinolone resistance mechanisms vary between bacterial types.
- Outer membrane modifications play a significant role in quinolone resistance and cross-resistance.
- The rapid rise in Pseudomonas aeruginosa resistance is a species characteristic.
- The efficacy of combination therapy to prevent resistance requires further investigation.