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: Teicoplanin is a glycopeptide antibiotic with a molecular structure which is related to that of vancomycin. Gram-positive bacteria such as staphylococci (including methicillin-resistant strains), streptococci, enterococci and many anaerobic Gram-positive bacteria are susceptible to teicoplanin in vitro. Teicoplanin has an exceptionally long half-life, allowing once-daily intramuscular or intravenous administration. Teicoplanin is clinically and bacteriologically effective against a wide variety of Gram-positive infections such as septicaemia, endocarditis, skin and soft tissue infections and infections associated with venous catheters. The drug is equally efficacious against methicillin-resistant and -susceptible staphylococci. Adverse effects with teicoplanin are generally limited to local effects or hypersensitivity reactions. While teicoplanin has the potential for ototoxicity and nephrotoxicity, the incidence appears to be quite low when recommended serum concentrations are maintained. Teicoplanin is a valuable alternative to vancomycin, and providing controlled comparative studies prove equivalent safety and efficacy between the 2 glycopeptides the more easily administered teicoplanin should become the preferred antibacterial agent.Drugs 10/1990; 40(3):449-86. · 4.63 Impact Factor
- Journal of Vascular Surgery - J VASC SURG. 01/1986; 3(5):732-740.
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ABSTRACT: The oxazolidinones represent a new class of antimicrobial agents which are active against multidrug-resistant staphylococci, streptococci, and enterococci. Previous studies have demonstrated that oxazolidinones inhibit bacterial translation in vitro at a step preceding elongation but after the charging of N-formylmethionine to the initiator tRNA molecule. The event that occurs between these two steps is termed initiation. Initiation of protein synthesis requires the simultaneous presence of N-formylmethionine-tRNA, the 30S ribosomal subunit, mRNA, GTP, and the initiation factors IF1, IF2, and IF3. An initiation complex assay measuring the binding of [3H]N-formylmethionyl-tRNA to ribosomes in response to mRNA binding was used in order to investigate the mechanism of oxazolidinone action. Linezolid inhibited initiation complex formation with either the 30S or the 70S ribosomal subunits from Escherichia coli. In addition, complex formation with Staphylococcus aureus 70S tight-couple ribosomes was inhibited by linezolid. Linezolid did not inhibit the independent binding of either mRNA or N-formylmethionyl-tRNA to E. coli 30S ribosomal subunits, nor did it prevent the formation of the IF2-N-formylmethionyl-tRNA binary complex. The results demonstrate that oxazolidinones inhibit the formation of the initiation complex in bacterial translation systems by preventing formation of the N-formylmethionyl-tRNA-ribosome-mRNA ternary complex.Antimicrobial Agents and Chemotherapy 01/1999; 42(12):3251-5. · 4.57 Impact Factor