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| |  Linezolid Shows Efficacy for Complicated Skin and Soft-Tissue Infections: Presented at ECCMID By Chris Berrie BARCELONA, Spain -- April 25, 2008 -- Linezolid is as effective as vancomycin for treatment of complicated skin and soft-tissue infections (cSSTIs) proven to be due to methicillin-resistant Staphylococcus aureus (MRSA), according to a multicentre, open-label study. Principal investigator Kamal M. F. Itani, MD, Professor, Department of Surgery, Philadelphia VA Medical Center, Philadelphia, Pennsylvania, presented the randomised, comparator-controlled, phase 4 study here at the 18th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Linezolid is an oxazolidinone antibiotic used to treat infections caused by Gram-positive pathogens. The study evaluated patients hospitalised for complicated skin and soft-tissue infections, including MRSA infection. For enrolment, patients were required to have 2 specific symptoms of infection involving subcutaneous tissue, fascia, or skeletal muscle (purulent drainage, erythema, swelling/induration, tenderness to palpitation or pain, and local warmth), plus elevated body temperature, hypotension (systolic blood pressure <90 mm Hg), elevated total peripheral white blood cell (WBC) count (WBC >10,000/mm3), or >15% immature neutrophils regardless of total peripheral WBC count. The study excluded patients with infected devices that were not removed, or with known or suspected necrotising fasciitis, gas gangrene, gangrene, septic arthritis, or osteomyelitis, Dr. Itani said during his presentation on April 19. A total of 1,077 patients were randomised to 7 to 14 days of treatment with either linezolid 600 mg IV or PO every 12 hours or vancomycin 15 mg/kg body-weight IV every 12 hours (adjusted for creatine clearance). For Gram-negative pathogens, patients were permitted to receive treatment with aztreonam or another antibiotic. The treatment groups were well balanced according to age, sex, weight, skin injury and severity scores. At baseline, 329 patients in the linezolid group and 325 in the vancomycin group had confirmed MRSA and formed the modified intention-to-treat (mITT) population. The per protocol (PP) population consisted of patients who completed all steps of the protocol up to the end of the study (EOS) as in each arm (234 vs 217, respectively), Dr. Itani also noted. The secondary endpoints included clinical and microbiological efficacy at end of treatment (EOT; as PP and mITT), and EOS microbial efficacy, safety, hospital length of stay (LOS)/duration of IV therapy, and resource use. For the clinical success in the PP at EOS assessment, there was no significant difference between the treatments, although there was a trend in favour of linezolid compared with vancomycin (84.4% vs 79.5%, respectively; P = .179). The same was the case in the PP at EOT assessment (91.8% vs 87.7%; P = .134). There was, however, a more pronounced difference in favour of linezolid in the mITT population at EOT (89.7% vs 84.7%; P = .071), with statistical significance at EOS (81.1% vs 73.5%; P = .032). Linezolid showed a numerical advantage in the treatment of abscesses (89% vs 80%), diabetic ulcer (78% vs 69%), and skin ulcer (90% vs 85%), but these differences were not significant, Dr. Itani said. MRSA eradication or presumed eradication in the PP at EOT showed significant benefit for linezolid over vancomycin (86% vs 69%; P < .001), with a numerical advantage at EOS (75% vs 68%; P = .121). Significant benefits for linezolid over vancomycin were also seen for hospital LOS (8.9 vs 7.5 days; P = .014) and duration of IV therapy (10.4 vs 5.5 days; P < .001). The most frequent treatment-related adverse events were nausea and diarrhoea with linezolid, and pruritis, infusion site inflammation, and red man syndrome (pruritis and erythematous rash on the face, neck, and upper torso) with vancomycin. Ten patients showed treatment-related serious adverse events (11.9%): linezolid, 2 patients (anaemia); vancomycin, 8 patients (red man syndrome [5 patients], rash, drug hypersensitivity, urticaria). Dr. Itani concluded, "Overall, linezolid has an acceptable safety and tolerability profile for the treatment of complicated skin and soft-tissue infections, and no unexpected adverse events were seen." Funding for this study was provided by Pfizer Inc.
[Presentation title: Linezolid in the Treatment of Subjects With Complicated Skin and Soft Tissue Infections Proven to Be Due to Methicillin-Resistant Staphylococcus Aureus. Abstract O80]
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