Linezolid alone and in combination with rifampicin prevents experimental vascular graft infection due to methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.
ABSTRACT In this report we describe the in vivo antibacterial activity of linezolid in an experimental graft infection model in rats and compare it with teicoplanin. The objective of this study was also to determine the effects of the interaction of linezolid when it was combined with rifampicin and test this effect against strains of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.
Graft infections were established in the subcutaneous tissue of 130 Wistar rats by implantation of Dacron grafts followed by a topical inoculation with 2 x 10(7) CFU of clinical isolates of MRSA and MRSE. The study included a control group and six groups for each of the staphylococcal strains: an inoculated group that did not receive any antibiotic prophylaxis, two inoculated groups that received intraperitoneal prophylaxis with teicoplanin or linezolid alone, an inoculated group that received rifampicin-soaked grafts, and two inoculated groups that received a combination prophylaxis consisting of intraperitoneal teicoplanin or linezolid and rifampicin-soaked grafts.
There was a reduction in the quantitative bacterial graft cultures in all prophylaxis groups when compared with inoculated control groups. There was not a statistically significant difference between linezolid and teicoplanin prophylaxis groups. The best results were obtained by a combination of rifampicin-soaked grafts with linezolid or teicoplanin.
We found no evidence to suggest that linezolid differs from teicoplanin regarding effectiveness in the prevention of prosthetic vascular graft infection. Linezolid plus rifampicin and teicoplanin plus rifampicin are demonstrated to be valuable prophylactic regimens.
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ABSTRACT: Background: To evaluate in vitro and in vivo efficacies of linezolid, vancomycin, and the combination of linezolid and rifampicin against two Staphylococcus aureus strains with reduced susceptibility to beta-lactams and one of them also to glycopeptides. Methods: In vitro killing curves and a rabbit model: Meningitis was induced by intracisternal inoculation of 10(8) CFU/ml of each strain. Five hours later (0 h), rabbits were randomly assigned to control or to therapeutic groups. CSF bacterial counts, lactate and protein concentrations, and pharmacokinetic parameters were determined. Results: In vivo: linezolid and its combination with rifampicin reduced bacterial concentrations at 24 h, median cfu/mL 4.85 vs 3.87 (p < 0.05) for linezolid and 5.02 vs 4.21 (p < 0.05) for linezolid rifampicin, against the glycopeptide intermediate S. aureus (GISA) strain and improved inflammatory parameters. Conclusions: Despite the need for more experimental data, our results suggest that linezolid and its combinations could be considered as a potential alternative in difficult-to-treat CNS infections and especially in those due to GISA strains and deserve more studies.Journal of Infection and Chemotherapy 06/2014; 20(9-10). DOI:10.1016/j.jiac.2014.05.008 · 1.38 Impact Factor
Article: Infektionen von Gefäßprothesen[Show abstract] [Hide abstract]
ABSTRACT: Infektionen von Gefäßprothesen sind schwerwiegende Komplikationen von rekonstruktiven gefäßchirurgischen Eingriffen mit hoher konsekutiver Amputationsrate und Letalität. Ihre Pathogenese ist multifaktoriell, und dementsprechend existieren verschiedenste prophylaktische Ansätze. Neben den Grundsätzen der chirurgischen Asepsis werden zusätzliche Maßnahmen zur Verbesserung der hygienischen Bedingungen in der perioperativen Phase angewandt. Die perioperative Antibiotikaprophylaxe ist in diesem Zusammenhang das einzige Mittel, das einen gewissen Evidenzgrad in Bezug auf die Senkung der Rate von Protheseninfekten erreicht hat. Modifikationen von Prothesen zur Steigerung ihrer Infektresistenz z. B. durch Rifampicin- oder Silberbindung sind seit Langem in Gebrauch, die Datenlage hierfür ist allerdings nicht eindeutig und Gegenstand weiterer Untersuchungen. Ähnliches gilt für die lokale Antibiotikaapplikation z. B. in Form von Gentamicin-Kollagen-Schwämmen. Neue Technologien und antimikrobielle Substanzen werden hier in Zukunft möglicherweise einmal die komplett infektresistente Prothese schaffen.Gefässchirurgie 02/2012; 17(1). DOI:10.1007/s00772-011-0949-4 · 0.24 Impact Factor
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ABSTRACT: This study describes novel biodegradable, drug-eluting nanofiber-loaded vascular prosthetic grafts that provide local and sustained delivery of vancomycin to surrounding tissues. Biodegradable nanofibers were prepared by first dissolving poly(D,L)-lactide-co-glycolide and vancomycin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibers onto the surface of vascular prostheses. The in vitro release rates of the pharmaceutical from the nanofiber-loaded prostheses was characterized using an elution method and a high-performance liquid chromatography assay. Experimental results indicated that the drug-eluting prosthetic grafts released high concentrations of vancomycin in vitro (well above the minimum inhibitory concentration) for more than 30 days. In addition, the in vivo release behavior of the drug-eluting grafts implanted in the subcutaneous pocket of rabbits was also documented. The drug-eluting grafts developed in this work have potential applications in assisting the treatment of vascular prosthesis infection and resisting reinfection when an infected graft is to be exchanged.International Journal of Nanomedicine 01/2015; 10:885-91. DOI:10.2147/IJN.S78675 · 4.20 Impact Factor