Source: Anti-Cancer Drugs  |  Posted 4 years ago

By Chris Berrie

MUNICH, GERMANY -- April 9, 2007 -- The combination of linezolid and rifampicin (LRC) appears to be effective in the treatment of patients with chronic osteomyelitis, including those with orthopaedic devices, although this therapy can result in reversible anaemia and/or prolonged peripheral neuropathy.

Co-investigator Xavier Lemaire, MD, clinician in infectious diseases, infectious diseases department, Dron Hospital of Tourcoing, CHRU of Lille, Lille, France, presented this finding here at the joint 17[^]th[] European Congress of Clinical Microbiology and Infectious Diseases and 25[^]th[] International Congress on Chemotherapy (ECCMID-ICC).

High clinical success rates and satisfactory tolerance have been reported for linezolid in the treatment of patients with chronic osteomyelitis and prosthetic joint infections due to Gram-positive cocci. Similarly, in vitro studies have recently shown that combination of linezolid with rifampicin prevents emergence of rifampicin-resistant mutantations.

Dr. Lemaire and colleagues conducted their study to evaluate the efficacy and tolerance of the combination of linezolid and rifampicin in bone and joint infections, particularly as there is little data regarding longer-term linezolid treatment, he explained in a presentation on April 1[^]st[].

Patients were selected from a computerised database of patients with chronic osteomyelitis who were treated with prolonged LRC therapy and for whom post-treatment follow up of more than 1 year was available. The researchers selected those patients with bacteriologically documented osteomyelitis based on intraoperative samples and/or joint aspiration cultures.

Chronic infection defined as symptoms of lasting more than 30 days. The diagnosis of chronic osteomyelitis was assessed according to fever greater than 38 ?C, inflammation or purulent discharge in the area of the osteosynthesis device, or biological inflammatory syndrome (erythrocyte sedimentation rate, >50 mm/hour; C-reactive protein, >10 mg/L), radiological evidence of loose osteosynthesis device or prosthesis (luxation or pseudarthritis), evidence of chronic osteomyelitis on plain radiography, presence of leukocytes on direct examination of intraoperative samples, and/or positive Gram-stained smear.

Clinical outcome measure was absence of clinical, biological and radiological evidence of infection during all post-treatment follow up, for a minimum of 12 months.

During the study period of June 1999 to March 2004, 134 patients had received linezolid, 59.7% had chronic osteomyelitis, 29 of whom (36.3%) had received LRC therapy for more than 28 days and had follow up for at least 12 months from end of treatment.

Demographic and clinical characteristics included the following: mean age of 55 years; male, 48.3%; prosthetic joints, 37.9% (knee, 24.1%; hip, 13.8%); osteosynthesis, 24.1%; chronic osteomyelitis, 37.9%; fistula, 44.8%; steroid therapy, 10.4%; diabetes mellitus, 31.1%.

Microbiological data analysis showed pathogen isolation of mainly methicillin-resistant Staphylococcus aureus (MRSA; 30.3%) and methicillin-resistant coagulase negative Staphylococcus (MRCNS) (27.3%), with Gram-negative bacilli (GNB) (mixed infection; 18.1%), Enterococcus spp. (15.1%), methicillin-susceptible S. aureus (MSSA) (12.1%) and Streptococcus spp. (6.0%).

Mean duration of therapy was 17.2 weeks (range, 6-36 weeks). At end of treatment, 89.6% of these patients were cured; 1 patient relapsed during follow up, resulting in a final overall success rate of 86.2%. Surgical intervention was performed in 79.3% of patients.

In the safety analysis, drug-related adverse effects included reversible anaemia (17.2%) that required transfusion, and peripheral neuropathy (10.3%), with drug discontinuation in 20.7%. Of note, the 3 patients who displayed peripheral neuropathy remained symptomatic to 24 months after end of treatment despite pyridoxine supplementation.

Despite the high overall success rate, Dr. Lemaire indicated that clinicians should be aware of this potential for prolonged peripheral neuropathy when prescribing linezolid.

Despite this, this combination treatment was effective in patients with chronic osteomyelitis, including those with orthopaedic devices, as Dr. Lemaire said.

"When you have a problem with vancomycin because of renal insufficiency, and when you have less than 1 month of treatment, it is a good combination," he said.

It can be considered in particular for patients with chronic osteomyelitis associated with Gram-positive cocci who are intolerant to other anti-staphylococcal agents and/or who have pathogens resistant to these agents, he said.

[Presentation title: Efficacy and Tolerance of Linezolid-Rifampicin Combination (LRC) Prolonged Oral Therapy for Bone and Joint Infections. Abstract P853]