Authors: Rao N, Regalla D
Title: A prospective evaluation of linezolid for the treatment of gram-positive orthopedic infections.
Addresses: UPMC Presbyterian Shadyside, School of Nursing Bldg, 2nd Floor
5230 Centre Avenue, Pittsburgh, PA
Purpose: To evaluate the efficacy and safety of linezolid for treatment of gram-positive orthopedic infections
Methods: Fifty one adult patients with complicated gram-positive orthopedic infections were prospectively enrolled from July 2000 to January 2005 for treatment with oral linezold 600mg/day. All had clinical evidence of infection confirmed by intra-operative bone and/or tissue cultures. Tests for diagnosis and monitoring included: erythrocyte sedimentation rate; C-reactive protein; blood count with differential throughout the course of therapy. Treatment with linezolid was stopped with development of thrombocytopenia (platelet count < 100 X 103/mm3), anemia (hemoglobin < 9 g/dL) and other adverse effects. Follow-up during therapy and every three months included: side effects; compliance; evidence of success or failure. Success was defined as no clinical evidence of recurrence, and failure as evidence of clinical recurrence and recovery of the same organism after cessation of therapy. Appropriate surgical intervention was carried out and followed by orthopedic surgeons. Infections with mixed pathogens not covered by linezolid had additional appropriate antibiotic coverage.
Results and Discussion: There were 51 patients, 26 (51%) females and 25 (51%) males, with total of 53 infections (mean age 54 years; range 17-83). Types of infections: prosthetic joints 23 (43%), chronic osteomyelitis 19 (36%), diabetic osteomyelitis 6 (11%), complicated skin and soft tissue 3 (6%) and septic arthritis 2 (4%). 33 infections involved orthopedic hardware of which 19 were removed. Pathogens include: methicillin-resistant staphylococcus aureus 18 (34%); coagulase-negative staphylococcus 17 (32%); methicillin-sensitive staphylococcus aureus 4 (8%); vancomycin resistant enterococcus 4 (8%); vancomycin sensitive enterococcus 3 (5%); group G streptococcus 1 (2%) and multiple mixed organisms 6 (11%). Duration of treatment: 2-106 weeks (mean 8.8 weeks). Follow-up: 1-53 months (mean 25 months). 37 patients with 39 infections achieved clinical cure; 10 had clinical improvement but required suppressive antibiotic therapy, one failed and three were excluded from evaluation due to premature discontinuation of treatment. Adverse effects: thrombocytopenia 9 (17%); anemia 3 (6%); nausea 2 (4%); decreased appetite 2 (4%); leucopenia 1 (2%); neuropathy 1 (2%), blurred vision 1 (2%) and bad taste in mouth 1 (2%). Therapy was stopped prematurely in 3 (anemia 1 (2%); thrombocytopenia 2 (4%)) which resolved within 10 days after discontinuation of linezolid.
Conclusion: Linezolid continues to hold promise for the treatment of gram-positive orthopedic infections. The hematologic side effects need to be monitored with weekly blood counts during the course of therapy.