Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus

Itani, Kamal M.F.; Dryden, Matthew; Bhattacharyya, Helen; Künkel, M; Baruch, Alice; Weigelt, John A.

doi:10.1016/j.amjsurg.2009.08.045

Cited by 132 publications

(133 citation statements)

References 23 publications

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“…However, one study demonstrated that daptomycin had similar efficacy compared with vancomycin in the treatment of diabetic foot ulcers (54). Most studies have found that linezolid has equivalent or superior efficacy compared with vancomycin (55)(56)(57)(58)(59)(60) and similar efficacy as vancomycin in diabetic patients (57). Given these findings in humans, this mouse model was able to confirm the efficacy of these antibiotics against a CA-MRSA wound infection, but it was not able to recapitulate the potentially increased efficacy of linezolid or daptomycin compared with vancomycin in nondiabetic mice.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice

Guo

Ramos

Cho

et al. 2013

Antimicrob Agents Chemother

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c Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents. C ommunity-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs), such as impetigo, folliculitis, cellulitis, and infected wounds and ulcers, have been increasing for more than a decade and are creating a serious public health concern (1, 2). In particular, outpatient and emergency room visits for SSTIs have been estimated to result in 11.6 to 14.2 million ambulatory care visits per year in the United States (3, 4). In 2004 and 2008, CA-MRSA was identified as the most common cause (59%) of all SSTIs presenting to emergency rooms across the United States (5, 6). In these and other studies, the USA300 clone has been isolated in up to 90% of all CA-MRSA SSTIs in the United States (5-8). USA300 causes severe and necrotic SSTIs and often causes infections in otherwise healthy individuals without any known risk factors for infection (1, 2, 9).Uncomplicated CA-MRSA SSTIs, such as impetigo, infected abrasions, and folliculitis/furunculosis can be managed in an outpatient setting with oral antibiotics and/or incision and drainage (10-12). Typical oral antibiotic regimens used for CA-MRSA infections include trimethoprim-sulfamethoxazole (TMP/SMX), a tetracycline...

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Section: Discussionmentioning

confidence: 99%

In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice

Guo

Ramos

Cho

et al. 2013

Antimicrob Agents Chemother

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“…A large, international, open-label, phase IV trial compared linezolid with vancomycin (15 mg/kg i.v. q12 h, adjusted to trough levels) in patients with MRSA-confirmed cSSSI (n = 1052) [37]. This was a non-inferiority study with a nested superiority test.…”

Section: Linezolidmentioning

confidence: 99%

New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance

Gould

David

Esposito³

et al. 2012

International Journal of Antimicrobial Agents

262

181

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Meticillin-resistant Staphylococcus aureus (MRSA) remains one of the principal multiply resistant bacterial pathogens causing serious healthcare-associated and community-onset infections. This paper reviews recent studies that have elucidated the virulence strategies employed by MRSA, key clinical trials of agents used to treat serious MRSA infections, and accumulating data regarding the implications of antibacterial resistance in MRSA for clinical success during therapy. Recent pre-clinical data support a species-specific role for Panton-Valentine leukocidin in the development of acute severe S. aureus infections and have elucidated other virulence mechanisms, including novel modes of internalisation, varying post-invasion strategies (featuring both upregulation and downregulation of virulence factors) and phenotypic switching. Recent double-blind, randomised, phase III/IV clinical trials have demonstrated the efficacy of linezolid and telavancin in hospital-acquired pneumonia (HAP) and complicated skin and skin-structure infections (cSSSIs) caused by MRSA. Tigecycline was non-inferior to imipenem/cilastatin in non-ventilator-associated HAP but was inferior in ventilator-associated pneumonia and has shown a higher rate of death than comparators on meta-analysis. Ceftaroline was clinically and microbiologically non-inferior to vancomycin/aztreonam in the treatment of MRSA cSSSI. Key resistance issues include a rise in vancomycin minimum inhibitory concentrations in MRSA, reports of clonal isolates with linezolid resistance mediated by acquisition of the chloramphenicol/florfenicol resistance gene, and case reports of daptomycin resistance resulting in clinical failure. Novel antimicrobial targets must be identified with some regularity or we will face the risk of untreatable S. aureus infections.

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“…Current treatment can include administration of broad-spectrum antibiotics; however, in the case of known or suspected MRSA targeted antibiotics are administered over 7-14 days [12][13][14] . Vancomycin, linezolid, and daptomycin are among the most common antibiotics used in the treatment of ABSSSI, but there is limited evidence on their comparative effectiveness 15,16 . Recently approved antibiotics for the treatment of ABSSSI, such as oritavancin 17 , dalbavancin 18 , and tedizolid 19 , further highlight the need for comparative effectiveness research.…”

Section: Introductionmentioning

confidence: 99%

Comparative efficacy of antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSI): a systematic review and network meta-analysis

Thom

Thompson²,

Scott³

et al. 2015

Current Medical Research and Opinion

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Objective:The objective was to conduct a systematic review and network meta-analysis (NMA) of existing treatments for ABSSSI focusing on the novel lipoglycopeptide oritavancin. Methods:EMBASE, MEDLINE, MEDLINE in Process, CENTRAL (Cochrane), and select conferences were searched for randomized controlled trials investigating antimicrobial agents for the treatment of ABSSSI. NMA was used to estimate the odds ratios of the Test-Of-Cure (TOC) and Early Clinical Response (ECR) outcomes for treatments relative to vancomycin in the ITT populations. Sub-group analyses in MRSA and MSSA populations were conducted for TOC; sensitivity analyses investigated the use of the clinically evaluable (CE) populations and the restriction to trials following the recent FDA guidelines for clinical trials. Results:The systematic review identified 52 trials. The most commonly investigated treatments were vancomycin and linezolid; most trials reported TOC, but not ECR. The posterior mean and 95% credible intervals for odds ratios of TOC for antimicrobial agents relative to vancomycin were: linezolid (1.55; 0.91-2.57), daptomycin (2.18; 0.90-5.42), and oritavancin 1200 mg (1.06; 0.80-1.43). The odds ratio of ECR for oritavancin 1200 mg was 1.02 (0.23-4.33). In the MRSA sub-group the odds ratios relative to vancomycin for TOC were: linezolid (1.55; 0.96-2.46), daptomycin (0.74; 0.13-3.66), and oritavancin 1200 mg (0.94; 0.44-2.02). In the MSSA sub-group they were linezolid (1.36; 0.15-13.34) and oritavancin 1200 mg (0.82; 0.08-7.83). These results were robust to the sensitivity analyses. Conclusions:This NMA provides a unified framework for the comparison of all available antimicrobial agents used in the treatment of ABSSSI and is the first to assess the ECR end-point. The results suggest equivalence of clinical efficacy between vancomycin, daptomycin, linezolid, and novel antimicrobial agents including oritavancin for the treatment of ABSSSI at TOC. The wide uncertainty margins indicate the heterogeneity of the available evidence and the need for further research.

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Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus

Cited by 132 publications

References 23 publications

In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice

In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice

New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance

Comparative efficacy of antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSI): a systematic review and network meta-analysis

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