Role of efflux mechanisms on fluoroquinolone resistance in Streptococcus pneumoniae and Pseudomonas aeruginosa.
Prokaryotic efflux mechanisms can effectively increase the intrinsic resistance of bacteria by actively transporting antibiotics out of cells, thus reducing the effective concentration of these agents. The fluoroquinolones, similar to most other antimicrobial classes, are susceptible to efflux mechanisms, particularly in Gram-negative organisms, such as Pseudomonas aeruginosa. Resistant P. aeruginosa clones isolated after fluoroquinolone therapy frequently over express at least one of the multiple efflux pump mechanisms found in this organism. Gram-positive bacteria, such as Streptococcus pneumoniae, also possess efflux mechanisms, though their effect on fluoroquinolone resistance seems to be more limited and selective. In the future, efflux pump inhibitors may offer effective adjunctive therapy to antibiotics for the treatment of difficult infections by efflux mutants. In the meantime, appropriate antibiotic selection and optimal dosing strategies should aim to eradicate the causative pathogen before a resistant efflux mutant can emerge.
Zhanel
George G
GG
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Manitoba, Canada. ggzhanel@pcs.mb.ca
Hoban
Daryl J
DJ
Schurek
Kristen
K
Karlowsky
James A
JA
D001692:Biological Transport; D024901:Drug Resistance, Multiple, Bacterial / Q000502:physiology*; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D024841:Fluoroquinolones; D026901:Membrane Transport Proteins