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We used an experimental rat model to compare the therapeutic efficacy of teicoplanin, linezolid, and quinupristin/dalfopristin with that of vancomycin as standard therapy for infective endocarditis. Aortic endocarditis was induced in rats by insertion of a polyethylene catheter into the left ventricle, followed by intravenous inoculation of 10(6) colony-forming units of methicillin-resistant Staphylococcus aureus 24 hours later Forty-eight hours after bacterial challenge, intravenous antibiotic therapies were initiated. There were 6 groups of 8 rats each: un-infected control; infected, untreated control; vancomycin-treated (40 mg/kg twice daily); teicoplanin-treated (20 mg/kg twice daily after a loading dose of 40 mg/kg); linezolid-treated (75 mg/kg 3 times daily for 1 day, then 75 mg/kg twice daily); and quinupristin/dalfopristin-treated (30 mg/kg twice daily and an additional 10 mg/kg dalfopristin infusion over 6 to 12 hr daily). At the end of therapy, the aortic valve vegetations in the drug-treated rats were evaluated microbiologically. Compared with the infected, untreated group, all drug-treated groups had significantly reduced bacterial titers in the vegetations. Vancomycin, teicoplanin, and quinupristin/dalfopristin all effectively reduced the quantitative bacterial cultures of aortic valve vegetations. In addition, there was no significant difference in the comparative efficacy of teicoplanin, linezolid, and quinupristin/dalfopristin. Vancomycin significantly reduced bacterial counts in comparison with linezolid, which was nonetheless also effective. Our experimental model showed that each of the investigated antimicrobial agents was effective in the treatment of infective endocarditis. (Tex Heart Inst J 2010;37(4):400-4)

We used an experimental rat model to compare the therapeutic efficacy of teicoplanin, linezolid, and quinupristin/dalfopristin with that of vancomycin as standard therapy for infective endocarditis. Aortic endocarditis was induced in rats by insertion of a polyethylene catheter into the left ventricle, followed by intravenous inoculation of 106 colony-forming units of methicillin-resistant Staphylococcus aureus 24 hours later. Forty-eight hours after bacterial challenge, intravenous antibiotic therapies were initiated. There were 6 groups of 8 rats each: uninfected control; infected, untreated control; vancomycin-treated (40 mg/kg twice daily); teicoplanin-treated (20 mg/kg twice daily after a loading dose of 40 mg/kg); linezolid-treated (75 mg/kg 3 times daily for 1 day, then 75 mg/kg twice daily); and quinupristin/dalfopristintreated (30 mg/kg twice daily and an additional 10 mg/kg dalfopristin infusion over 6 to 12 hr daily). At the end of therapy, the aortic valve vegetations in the drug-treated rats were evaluated microbiologically. Compared with the infected, untreated group, all drug-treated groups had significantly reduced bacterial titers in the vegetations. Vancomycin, teicoplanin, and quinupristin/dalfopristin all effectively reduced the quantitative bacterial cultures of aortic valve vegetations. In addition, there was no significant difference in the comparative efficacy of teicoplanin, linezolid, and quinupristin/dalfopristin. Vancomycin significantly reduced bacterial counts in comparison with linezolid, which was nonetheless also effective. Our experimental model showed that each of the investigated antimicrobial agents was effective in the treatment of infective endocarditis. © 2010 by the Texas Heart® Institute, Houston.

We used an experimental rat model to compare the therapeutic efficacy of teicoplanin, linezolid, and quinupristin/dalfopristin with that of vancomycin as standard therapy for infective endocarditis. Aortic endocarditis was induced in rats by insertion of a polyethylene catheter into the left ventricle, followed by intravenous inoculation of 106 colony-forming units of methicillin-resistant Staphylococcus aureus 24 hours later. Forty-eight hours after bacterial challenge, intravenous antibiotic therapies were initiated. There were 6 groups of 8 rats each: uninfected control; infected, untreated control; vancomycin-treated (40 mg/kg twice daily); teicoplanin-treated (20 mg/kg twice daily after a loading dose of 40 mg/kg); linezolid-treated (75 mg/kg 3 times daily for 1 day, then 75 mg/kg twice daily); and quinupristin/dalfopristintreated (30 mg/kg twice daily and an additional 10 mg/kg dalfopristin infusion over 6 to 12 hr daily). At the end of therapy, the aortic valve vegetations in the drug-treated rats were evaluated microbiologically. Compared with the infected, untreated group, all drug-treated groups had significantly reduced bacterial titers in the vegetations. Vancomycin, teicoplanin, and quinupristin/dalfopristin all effectively reduced the quantitative bacterial cultures of aortic valve vegetations. In addition, there was no significant difference in the comparative efficacy of teicoplanin, linezolid, and quinupristin/dalfopristin. Vancomycin significantly reduced bacterial counts in comparison with linezolid, which was nonetheless also effective. Our experimental model showed that each of the investigated antimicrobial agents was effective in the treatment of infective endocarditis. © 2010 by the Texas Heart® Institute, Houston.

We used an experimental rat model to compare the therapeutic efficacy of teicoplanin, linezolid, and quinupristin/dalfopristin with that of vancomycin as standard therapy for infective endocarditis.Aortic endocarditis was induced in rats by insertion of a polyethylene catheter into the left ventricle, followed by intravenous inoculation of 106 colony-forming units of methicillin-resistant Staphylococcus aureus 24 hours later. Forty-eight hours after bacterial challenge, intravenous antibiotic therapies were initiated. There were 6 groups of 8 rats each: uninfected control; infected, untreated control; vancomycin-treated (40 mg/kg twice daily); teicoplanin-treated (20 mg/kg twice daily after a loading dose of 40 mg/kg); linezolid-treated (75 mg/kg 3 times daily for 1 day, then 75 mg/kg twice daily); and quinupristin/dalfopristin-treated (30 mg/kg twice daily and an additional 10 mg/kg dalfopristin infusion over 6 to 12 hr daily). At the end of therapy, the aortic valve vegetations in the drug-treated rats were evaluated microbiologically.Compared with the infected, untreated group, all drug-treated groups had significantly reduced bacterial titers in the vegetations. Vancomycin, teicoplanin, and quinupristin/dalfopristin all effectively reduced the quantitative bacterial cultures of aortic valve vegetations. In addition, there was no significant difference in the comparative efficacy of teicoplanin, linezolid, and quinupristin/dalfopristin. Vancomycin significantly reduced bacterial counts in comparison with linezolid, which was nonetheless also effective.Our experimental model showed that each of the investigated antimicrobial agents was effective in the treatment of infective endocarditis.

Background. We aimed to investigate the therapeutic efficacy of linezolid in an experimental mediastinitis model and to compare it with vancomycin, which is commonly used. The objective of this study was also to evaluate the role of the immune system in mediastinitis. Materials and methods. Fifty adult Wistar rats were randomly divided into five groups: an uncontaminated and contaminated untreated control groups; a group that received sefazolin prophylaxis; and two groups treated with vancomycin or linezolid. Median sternotomy without access to pleural spaces was performed on all rats. All groups, except the uncontaminated one, were inoculated with 0.5 mL 10(8) colony-forming units/mL methicillin-resistant Staphylococcus aureus in the mediastinal and sternal layers. Postoperatively, vancomycin and linezolid groups were given antibiotic treatment for 7 d, starting 24 h after the end of the procedure. After 7-d treatment tissue samples from the upper ends of the sternotomy line and mediastinum. were obtained and evaluated microbiologically. Additionally, serum, heart, lung, liver, kidney, and mediastinal tissues samples were obtained to determine malondialdehyde (MDA) and myeloperoxidase (MPO). Results. The study showed that either vancomycin or linezolid successfully reduced bacterial counts in mediastinum and sternotomy line. MDA and MPO levels were found to be decreased in the treated groups, There was a positive correlation between serum and tissues MDA and MPO in all of the groups. Conclusions. Our study showed that linezolid appears to be a promising option for treating mediastinitis due to methicillin-resistant S. aureus. Additionally, it was demonstrated that a wide inflammatory process occurred after mediastinitis. (c) 2009 Elsevier Inc. All rights reserved.

BACKGROUND: We aimed to investigate the therapeutic efficacy of linezolid in an experimental mediastinitis model and to compare it with vancomycin, which is commonly used. The objective of this study was also to evaluate the role of the immune system in mediastinitis. MATERIALS AND METHODS: Fifty adult Wistar rats were randomly divided into five groups: an uncontaminated and contaminated untreated control groups; a group that received sefazolin prophylaxis; and two groups treated with vancomycin or linezolid. Median sternotomy without access to pleural spaces was performed on all rats. All groups, except the uncontaminated one, were inoculated with 0.5 mL 10(8) colony-forming units/mL methicillin-resistant Staphylococcus aureus in the mediastinal and sternal layers. Postoperatively, vancomycin and linezolid groups were given antibiotic treatment for 7 d, starting 24 h after the end of the procedure. After 7-d treatment tissue samples from the upper ends of the sternotomy line and mediastinum were obtained and evaluated microbiologically. Additionally, serum, heart, lung, liver, kidney, and mediastinal tissues samples were obtained to determine malondialdehyde (MDA) and myeloperoxidase (MPO). RESULTS: The study showed that either vancomycin or linezolid successfully reduced bacterial counts in mediastinum and sternotomy line. MDA and MPO levels were found to be decreased in the treated groups. There was a positive correlation between serum and tissues MDA and MPO in all of the groups. CONCLUSIONS: Our study showed that linezolid appears to be a promising option for treating mediastinitis due to methicillin-resistant S. aureus. Additionally, it was demonstrated that a wide inflammatory process occurred after mediastinitis.

INTRODUCTION: The treatment of postoperative mediastinitis is very important because of its high morbidity, mortality, and increased hospital stay and hospital costs. The aims of our research were to investigate whether linezolid alone can be an effective treatment agent for methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis, and to determine whether linezolid can provide synergistic activity when given in combination with rifampin. METHODS: A partial upper median sternotomy was performed on 70 rats. The animals were divided into seven groups: an uncontaminated control group; an untreated contaminated group; three contaminated groups that received antibiotic therapy with either 25 or 50 mg/kg linezolid twice a day, or rifampin 5 mg/kg twice a day; and two contaminated groups that received a combination therapy consisting of 25 or 50 mg/kg linezolid and rifampin 5 mg/kg twice a day. The antibiotic treatment lasted 7 days. Tissue samples from the upper ends of the sternum and swab specimens of the upper mediastinum were obtained and evaluated microbiologically. RESULTS: The 25-mg/kg dose of linezolid, either alone or combined with rifampin, was not effective in reducing the bacterial counts in mediastinum and sternum. Quantitative bacterial cultures of mediastinum and sternum were significantly lower in the groups receiving 50 mg/kg linezolid alone or in combination with rifampin compared with the control. Adding of rifampin to linezolid therapy did not result in a significant change in bacterial counts versus linezolid alone. CONCLUSION: A high dose of linezolid should be considered as a possible therapeutic agent for the treatment of post-sternotomy infection caused by MRSA.

Background: Graft infections are severe complications of vascular surgery that may result in amputation or mortality. Staphylococci are the most frequent cause of vascular graft infections. Objective: In this study we assessed the prophylactic efficacy of linezolid in comparison with vancomycin in preventing prosthetic vascular graft infection due to methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). Methods: This randomized, controlled, experimental study using healthy adult (aged > 5 months) male Wistar rats was conducted in the research laboratory of the Pamukkale University, Denizli, Turkey. The study consisted of an uncontaminated control group and 3 groups for both staphylococcal strains: a contaminated group that did not receive any antibiotic prophylaxis; a contaminated group that received preoperative intraperitoneal (IP) prophylaxis with vancomycin; and a contaminated group that received preoperative IP prophylaxis with linezolid. All rats received a vascular Dacron graft placed inside a subcutaneous pocket created on the right side of the median line. Sterile saline solution (1 mL), to which MRSA or MRSE at a concentration of 2 x 10(7) colony-forming units per milliliter had been added, was inoculated onto the graft surface using a tuberculin syringe to fill the pocket. The grafts were explanted 7 days after implantation and assessed by quantitative culture. Results: Seventy rats (mean [SD] weight, 323.7 [17.9] g; mean [SD] age, 5.98 [0.64] months) were evenly divided between the 7 groups. Statistical analysis of the quantitative graft culture suggested that both vancomycin and linezolid were effective in significantly inhibiting bacterial growth when compared with the untreated contaminated groups (all, P < 0.001). However, a statistically significant difference was not observed between the bacteria count in the vancomycin and linezolid prophylaxis groups. When a comparison was made between the bacterial growth in the contaminated control groups, MRSA had significantly greater affinity to the Dacron prostheses than MRSE (all, P < 0.001). Conclusion: Our study found that linezolid was as effective as vancomycin in suppressing colony counts in MRSA- or MRSE-infected vascular Dacron grafts in rats.

Background. 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. Materials and methods. 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. Results. 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. Conclusions. 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. (C) 2007 Elsevier Inc. All rights reserved.