Linezolid in the treatment of orthopaedic bone and joint infections—a systematic literature review

Introduction In the past years, several studies have reported about the use of linezolid in the treatment of orthopaedic bone and joint infections, especially those caused by multiresistant bacteria. However, inhomogeneities in the patients’ collectives, primary surgical indication, causative pathogenic organisms, length of therapy and length of follow-up make a sufficient comparison of these studies difficult. The aim of this systematic review was to discuss linezolid in the treatment of orthopaedic bone and joint infections. Materials and methods A systematic literature search was conducted through PubMed until 2012. Search terms included ‘linezolid’ in combination with ‘bone (infection)’, ‘joint (infection)’ and ‘osteomyelitis’. Results A total of 47 studies with 881 patients could be identified. A great majority of the studies reported on linezolid treatment against various multiresistant bacteria such as methicillin-resistant Staphylococcus aureus, methicillinresistant Staphylococcus epidermidis, methicillin-resistant coagulasenegative staphylococci and vancomycin-resistant enterococci. Linezolid was administered either intravenously, orally or intravenously followed by an oral phase. In 30 of 47 studies, the total length of linezolid therapy exceeded the accredited period of 28 days. A total of 24 different adverse reactions were reported. Among these adverse reactions, haematological disorders (anaemia, thrombocytopenia, neutropenia), gastrointestinal complaints and peripheral neuropathy were the most frequent ones. The infection eradication rate varied between 55% and 100 % depending on the infection cause. Conclusion The present data indicate that linezolid can be a promising alternative in the treatment of bone and joint infections. Future studies are required for further investigation of the possible adverse reactions and the eradicating effect of the infection. Introduction Despite numerous prophylactic measures, bone and joint infections still remain a hazardous complication in orthopaedic surgery. The majority of these infections are caused by gram-positive bacteria, especially staphylococci1,2. Depending on the infection size and localization, presence of hardware, the pathogen organism, its virulence and antibiotic resistance profile and the patient’s comorbidities, several treatment options are available including conservative and operative options. In the past years, an increasing number of multiresistant bacteria have been reported at the site of orthopaedic bone and joint infections1,2. Among these, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin-resistant enterococci (VRE) are most frequently isolated1,2. Since these bacteria cannot be successfully treated by most antibiotic groups, new drugs have been developed such as linezolid, daptomycin or tigecycline. Linezolid is a new antimicrobial agent that belongs to the group of oxazolidinones. Linezolid is characterized by a broad spectrum of activity against gram-positive organisms. It inhibits the bacterial protein synthesis by blocking the formation of the 70S initiation complex and is an alternative treatment option to vancomycin in skin and soft-tissue infections caused by MRSA3. Linezolid has been shown to penetrate rapidly infected4 and uninfected5 bones and tissue in patients after total hip and knee arthroplasty. Resistance to linezolid is extremely rare6. Linezolid also has excellent oral bioavailability. Several studies have reported on the successful use of linezolid in orthopaedic bone and joint infections. This application is an off-label use since linezolid is approved only for the treatment of ambulatory and nosocomial pneumonia as well as severe skin and soft-tissue infections. However, inhomogeneities in the patients’ collectives, primary surgical indication, causative pathogenic organisms, length of therapy and length of follow-up make a sufficient comparison of these studies difficult. The aim of the present work was to systematically review the current literature about the use of linezolid in the treatment of orthopaedic bone and joint infections. Materials and methods A literature search was made through PubMed until 2012. Search terms included ‘linezolid’ in combination with ‘bone (infection)’, ‘joint (infection)’ * Corresponding author Email: [email protected] Klinik für Orthopädie und orthopädische Chirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany