An investigation of the antimicrobial effects of linezolid on bacterial biofilms utilizing an in vitro pharmacokinetic model

Abstract

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.

Linezolid Compared with Eperezolid, Vancomycin, and Gentamicin in an In Vitro Model of Antimicrobial Lock Therapy for Staphylococcus epidermidis Central Venous Catheter-Related Biofilm Infections

“…179, 2002). The study of Gander et al (13), which evaluated the activity of linezolid relative to those of other antimicrobial agents, including glycopeptides and quinuprisitin-dalfopristin, did not report effects similar to those that we have observed. However, the model used and the concentrations and the duration of exposure are not comparable to those used in our study and do not simulate antimicrobial lock therapy in the same way as our model does.…”

“…However, the model used and the concentrations and the duration of exposure are not comparable to those used in our study and do not simulate antimicrobial lock therapy in the same way as our model does. Gander et al (13) used a model consisting of a cylindrical paper sleeve encasing a compacted mesh of cellulose fibers. The biofilm is formed on the cellulose fiber.…”

Central venous catheter-related biofilm infections: An up-to-date focus on meticillin-resistant Staphylococcus aureus

“…This study highlighted that linezolid was very effective at clearing biofilm if the infected device was exposed to the antibiotic for longer time periods, whilst success with short-term exposure varied and might be dependent on the type of infected device being treated [54]. In addition, a model of ALT gave conflicting results, showing that the amount of biofilm remaining after 5 days of linezolid exposure was similar to negative controls [55].…”

Polymeric nanofiber coating with tunable combinatorial antibiotic delivery prevents biofilm-associated infection in vivo

“…Of note, Lin/Lin + Rif and Dap/ Dap + Rif coatings were more effective at preventing infection, reducing infection-associated bone changes, and promoting boneimplant contact and osseointegration than the Van/Rif coating. The particular efficacy of Lin + Rif or Dap + Rif combinations might be due to added antibiofilm activity (32,(36)(37)(38), warranting further investigation. Van acts by inhibiting cell wall synthesis, so the inferior efficacy of Van/Rif (and Van/Van + Rif) could be due to reduced Van activity against bacteria in biofilms that have increased cell wall thickness (39).…”