Resistance to polymyxins: Mechanisms, frequency and treatment options.
Polymyxins act by binding to lipid A moiety of the bacterial lipopolysaccharide and subsequently disintegrating the bacterial membranes. The most important mechanism of resistance includes modifications of the bacterial outer membrane structure, including lipopolysaccharide. Lipopolysaccharide modification is mostly mediated by PmrA/PmrB and PhoP/PhoQ two-component regulatory systems. These mechanisms exist with some differences in many gram-negative bacterial species. Resistance to polymyxins is generally less than 10%. In specific regions, such as the Mediterranean basin, Korea and Singapore, they tend to be higher. Heteroresistance to polymyxins is associated with exposure to polymyxins and especially suboptimal therapeutic dosage. Polymyxin combination regimens, tigecycline and fosfomycin may be useful options for the treatment of polymyxin-resistant gram-negative infections.
Falagas
Matthew E
ME
Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece. m.falagas@aibs.gr
Rafailidis
Petros I
PI
Matthaiou
Dimitrios K
DK
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D038622:Internationality; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D011113:Polymyxins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D011113:Polymyxins; D014157:Transcription Factors