[Linezolid in the treatment of antibiotic-resistant gram-positive infections of the musculoskeletal system].
PURPOSE OF THE STUDY: The growing incidence of resistant microorganisms has been responsible for complications associated with treatment of osteomyelitis, infections following joint arthroplasty, as well as septic arthritis. Their therapy often requires a long-term administration of antibiotics to which the bacterial strain is sensitive. Oxazolidinons present a novel group of antibiotics recently adopted in clinical medicine. However, the only member of this group so far approved for clinical use is linezolid. It is effective for Gram-positive bacteria including antibiotic-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), resistant coagulase-negative staphylococci and penicillin-resistant pneumococci. Linezolid is well absorbed in the intestinal system. Oral administration results in serum levels comparable with those following intravenous injection of the same dose. MATERIAL, METHODS AND RESULTS: In the 1st Orthopedic Department of the 1st Faculty of Medicine at Charles University, linezolid was used for treating infections of the musculoskeletal system caused by MRSA and methicillin-resistant Staphylococcus epidermidis (MRSE). Fourteen patients, eight women and six men, were treated in the period from 1999 to 2005. The average age at the time of therapy was 65 years (range, 24-80). The treatment involved infection of 10 joints following arthroplasty (six total hip and four total knee replacements), one osteomyelitis, one septic arthritis, one abscess in the gluteal region and one infected amputation stump. With the exception of one patient, antibiotic therapy was always combined with an appropriate surgical intervention. The average antibiotic course was 27 days, with intravenous administration of linezolid at the beginning (average, 11.4 days; range, 9-14) and oral administration later (average, 15.9 days; range, 14-18). Antibiotic therapy was well tolerated by the patients, and no adverse side-effects were recorded. The success rate of therapy was 93 %. The only failure was in the patient in whom the infection of total knee replacement was treated with mere antibiotics, without any surgical intervention. DISCUSSION: Linezolid is a treatment option for joint infections following arthroplasty that are caused by resistant bacterial strains, such as MRSA, MRSE or VRE. The therapeutic efficiency varies in relation to whether the patients have undergone conservative or surgical treatment and, in the latter case, on the surgical technique used. On the basis of our results we suggest that a radical surgery is necessary, but in agreement with other recent reports we prefer a surgical approach combined with antibiotic therapy. The costs of linezolid treatment are high, but the possibility of its oral administration, with maintenance of the required tissue levels, markedly reduces hospital stay costs and increases patients' comfort during treatment. In our group, the patients received linezolid doses orally for up to 16 days, which means a hospital stay shorter by more than two weeks. The antibiotic course varies and, in relation to the kind of infection, may range from 5 days to 2 months; however, linezolid administration for 4 to 8 weeks is most frequent. The period of 28 days recommended by the manufacturer is thus usually extended. CONCLUSIONS: Infections caused by Gram-positive bacteria resistant to common antibiotics present serous epidemiological, therapeutic and economic problems, which will soon be in the focus of attention in the majority of Czech hospitals. In the patients who, due to allergic reactions, intolerance or bacterial resistance, cannot be treated with vancomycin or other antibiotics, linezolid may be a useful option for treatment of musculoskeletal system infections. The possibility of linezolid administration in oral doses markedly reduces hospital stay costs and increases patients' comfort during treatment.