[Causes of quinolone resistance in gram-negative bacteria].
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.
Cullmann
W
W
Lehrstuhl für Medizinische Mikrobiologie und Immunologie, Ruhr-Universität Bochum.
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004352:Drug Resistance, Microbial / Q000502:physiology; D004755:Enterobacteriaceae / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D059005:Topoisomerase II Inhibitors
D042462:4-Quinolones; D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides; D059005:Topoisomerase II Inhibitors
Ursachen der Quinolonresistenz gramnegativer Keime.