Linezolid versus teicoplanin in the treatment of Gram-positive infections in the critically ill: a randomized, double-blind, multicentre study

Cepeda, Jorge

doi:10.1093/jac/dkh048

Cited by 98 publications

(68 citation statements)

References 40 publications

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“…The TEC dose used in the present study was comparable to the doses used in previous studies of experimental rabbit models of MRSA infection (32,33). The TBG and TCS implants were found to be more effective in curing infection at 6 weeks postimplantation than intravenous injection of TEC.…”

Section: Discussionsupporting

confidence: 72%

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

Jia

Huang

et al. 2015

Antimicrob Agents Chemother

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There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. Bacterial infection resulting from orthopedic surgery is a serious complication. The pathogenic organisms responsible for such infections are often resistant to multiple drugs. Methicillinresistant Staphylococcus aureus (MRSA) has become the most common osteomyelitis-inducing microorganism clinically (1, 2). Currently, the main treatment for chronic osteomyelitis includes surgical debridement and prolonged systemic antibiotic therapy over a course of several weeks. As an antibiotic, teicoplanin (TEC) has a long serum half-life and broad-spectrum antibacterial activity against most Gram-positive aerobic and anaerobic organisms such as MRSA and methicillin-resistant coagulase-negative S. aureus (3). Compared to vancomycin (a more widely used antibiotic), the use of TEC also results in less ototoxicity, nephrotoxicity, and gastrointestinal side effects. Because of its favorable pharmacokinetics, TEC is commonly used in Europe to treat osteomyelitis (4).Even after thorough debridement, residual infection often remains in the bone. The surgical procedure also creates a bone defect that usually requires subsequent reconstruction (5). Furthermore, nidus formation considerably limits the efficacy of systemic antibiotic therapy because of the compromised vascular perfusion at the infected site. High concentrations of antibiotics in the blood resulting from long-t...

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Section: Discussionsupporting

confidence: 72%

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

Jia

Huang

et al. 2015

Antimicrob Agents Chemother

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“…One study (Cepeda et al 25 ) supplied requested data regarding unpublished pneumonia outcomes. No additional data from unpublished abstracts were identifi ed.…”

Section: Resultsmentioning

confidence: 99%

Linezolid vs Glycopeptide Antibiotics for the Treatment of Suspected Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia

Walkey

O’Donnell

Wiener

2011

Chest

111

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“…fluoroquinolone and rifampicin for MSSA or linezolid for MRSA) have been proposed. 2,3 The use of older antimicrobial agents such as minocycline or trimethoprim/sulfamethoxazole, combined with rifampicin or fusidic acid, may represent particularly interesting treatment alternatives for both communityand healthcare-associated MRSA infections. 1,4,5 The only anti-MRSA antibiotic agent that has undergone in-depth clinical evaluation in its oral formulation is linezolid.…”

Section: Introductionmentioning

confidence: 99%

Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection

Harbarth

Dach

Pagani

et al. 2014

Journal of Antimicrobial Chemotherapy

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Objectives: The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the noninferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection. Methods:We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/ sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1: 1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854).Results: Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI 29.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI 26.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/ sulfamethoxazole and rifampicin group.Conclusions: Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infection.

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Linezolid versus teicoplanin in the treatment of Gram-positive infections in the critically ill: a randomized, double-blind, multicentre study

Abstract: Linezolid has similar safety and efficacy to teicoplanin in treating Gram-positive infections in the critically ill. Short-term MRSA clearance achieved with linezolid suggests better skin and mucosal penetration.

Cited by 98 publications

References 40 publications

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

Linezolid vs Glycopeptide Antibiotics for the Treatment of Suspected Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia

Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection

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