Mechanisms of quinolone resistance.

摘要: Two mechanisms of resistance to fluoroquinolones are known: (i) alteration the molecular target quinolone action — DNA gyrase, and (ii) reduction accumulation. Mutations altering N-terminus gyrase A subunit, especially those around residues Ser83 Asp87, significantly reduce susceptibilities towards all quinolones, while alterations B subunit rarely found minor importance. Reduced drug accumulation is associated with outer membrane protein profile in gram-negative bacteria. Such mutations include marA locus inEscherichia coli result low level quinolones unrelated drugs. Increased activity naturally existing efflux systems, such as transmembrane NorA staphylococci, may also lead reduced gram-positive Clinical fluoroquinolone intrinsically highly susceptible organisms asEnterobacteriaceae involves a combination at least two mutations. In contrast, species moderate intrinsic susceptibility asCampylobacter jejuni, Pseudomonas aeruginosa, andStaphylococcus aureus require only one mutation become clinically resistant. As consequence development during therapy from acquisition already resistant strains case species, selection mutants less species.