An investigation of the antimicrobial effects of linezolid on bacterial biofilms utilizing an in vitro pharmacokinetic model.
Biofilms of methicillin-susceptible and -resistant Staphylococcus aureus, a strain of coagulase-negative staphylococcus and glycopeptide-intermediate strains of S. aureus (GISA) were exposed to the oxazolidinone linezolid, and four comparator antibiotics (quinupristin/ dalfopristin, vancomycin, teicoplanin and ciprofloxacin) using a Sorbarod model. The effects of these antibiotics were assessed by monitoring the reduction in the number of cells eluted from the biofilms. The biofilms were exposed to the antibiotics by two methods. The first was an exponentially decreasing drug concentration method, where the rate of dilution was matched to the half-lives of the antibiotics and the initial concentration matched peak serum levels. The second was a constant drug concentration method, in which biofilms were exposed to antibiotics for 2 h, with the concentration of the antibiotic equalling the total amount of drug used in the exponentially decreasing method. The results indicate that linezolid produces a greater reduction in the number of cells eluted with the exponentially decreasing method compared with the constant concentration exposure against all strains tested except for one of the GISA strains, Mu 50. Overall, ciprofloxacin produced the greatest effects in the exponentially decreasing concentration experiments, but only against non-resistant strains. In the constant concentration exposure no one drug was responsible for the largest reductions in cell numbers observed. Linezolid and quinupristin/dalfopristin produced a reduction in the number of cells eluted from the biofilms of all of the strains tested in both methods of exposure and should be considered for further clinical studies of the treatment of staphylococcal biofilm-associated infections.
Gander
Sarah
S
Division of Microbiology and Infectious Diseases, Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham NG5 1PB, UK.
Hayward
Katy
K
Finch
Roger
R
D000081:Acetamides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000706:statistics & numerical data; D024901:Drug Resistance, Multiple, Bacterial / Q000502:physiology; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D023303:Oxazolidinones / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid