Background: Skin graft and flap coverage of burn wounds, bone, prostheses and large soft tissue defects secondary to trauma and after tumor resection is essential not only to reduce fluid, electrolyte and heat loss, but also to limit bacterial colonization and prevent infection. Unfortunately, wound infections with multi-drug resistant organisms such as methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE) spp often occur postoperatively, and the infections can cause complications such as skin graft or flap necrosis, delayed wound healing, and can be limb threatening. Purpose: To report clinical experience with linezolid in addition to wound care, debridement, and skin grafting or coverage with fasciocutaneous flap, muscle flap, or free muscle transfer, for the treatment of S aureus, (including MRSA), VRE, and mixed MRSA/VRE infections. Methods: Patients received linezolid in a dosage of 600 mg intravenously and/or orally twice daily, as part of a larger compassionate use trial. Clinical and bacteriological responses were assessed after a minimum of 7 days or 6 months following completion of therapy for a skin and soft tissue infection or osteomyelitis, respectively. Results: Forty patients enrolled in a linezolid compassionate use program, received linezolid for infections of wound coverage (n=17) such as a split thickness skin graft infection or a post-op wound infection following myocutaneous flap surgery, or received linezolid in conjunction with wound coverage techniques (n=23) for a Gram-positive infection. Of the 40 patients, 24 had a skin and soft tissue infection and 16 had osteomyelitis. Infecting pathogens were S. aureus (n=22) or VRE (n=18). The majority (86%, 19/22) of S. aureus infections were methicillin-resistant (MRSA). Patients with a S. aureus infection met inclusion criteria due to vancomycin intolerance (n=13), vancomycin treatment failure (n=4), no IV access (n=4), or a mixed MRSA/VRE infection (n=1). 17 of 18 VRE isolates were speciated and all were VRE faecium. The median patient age was 53 years old (range, 14 to 85); 55% (22/40) were female. 28% of patients (11/40) received only IV linezolid, 45% (18/40) received IV with a switch to the oral formulation, and 28% (11/40) received only the oral formulation. The clinical success and bacteriological eradication rates in the evaluable patients were 93% (14/15) and 91%(10/11), respectively for linezolid + wound coverage techniques as treatment of an infection; while the clinical success and bacteriological eradication rates in the evaluable patients were 85% (11/13) and 82% (9/11), respectively for the treatment of an infected wound coverage. Conclusions: Linezolid was an effective antibiotic for the treatment of S. aureus (including MRSA) and VRE infections, when used in conjuction with wound coverage techniques. Linezolid was also effective as treatment of S. aureus (including MRSA) and VRE post-op graft and flap infections. In addition, linezolid offers the option of treating these infections with an oral agent which is 100% bioavailable.
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