title: Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia?
abstract: BACKGROUND
  Linezolid therapy has shown high rates of clinical success in patients with osteomyelitis and prosthetic joint infections caused by Gram-positive cocci. Recent studies have demonstrated that linezolid/rifampicin combination therapy prevents the emergence of rifampicin-resistant mutations in vitro. However, linezolid/rifampicin combination-related haematological and neurological toxicities have not been evaluated.
  
  
  OBJECTIVE
  To assess the tolerability of prolonged linezolid/rifampicin combination therapy compared with other linezolid-containing regimens in patients with bone and joint infections.
  
  
  METHODS
  We reviewed the medical records of 94 patients who had received linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a ≥2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 × 10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of baseline.
  
  
  RESULTS
  Anaemia was less frequent among patients on linezolid/rifampicin combination therapy than among patients on linezolid alone or in combination with other drugs (9.3%, 44% and 52%, respectively; P<0.01). In multivariate analysis, age and treatment group were independently associated with anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin combination therapy, in 48% of patients on linezolid alone and in 57.7% of patients on other linezolid-containing regimens. Age was the only variable associated with thrombocytopenia (P=0.019) in univariate analysis.
  
  
  CONCLUSIONS
  Linezolid/rifampicin combination therapy was associated with a significantly reduced incidence of anaemia among patients with bone and joint infections, but it did not have an effect on thrombocytopenia and peripheral neuropathy rates. Linezolid/rifampicin combination therapy was not associated with poor clinical outcomes.
authors.affiliation: Infectious Diseases Department, Dron Hospital of Tourcoing, Tourcoing, France. laurence.legout@free.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Legout
authors.forename: Michel
authors.initials: M
authors.lastname: Valette
authors.forename: Hervé
authors.initials: H
authors.lastname: Dezeque
authors.forename: Sophie
authors.initials: S
authors.lastname: Nguyen
authors.forename: Xavier
authors.initials: X
authors.lastname: Lemaire
authors.forename: Caroline
authors.initials: C
authors.lastname: Loïez
authors.forename: Michèle
authors.initials: M
authors.lastname: Caillaux
authors.forename: Eric
authors.initials: E
authors.lastname: Beltrand
authors.forename: Luc
authors.initials: L
authors.lastname: Dubreuil
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
authors.forename: Henri
authors.initials: H
authors.lastname: Migaud
authors.forename: Eric
authors.initials: E
authors.lastname: Senneville
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000517:prevention & control*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001170:Arthritis, Infectious / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D015994:Incidence; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000517:prevention & control; D010003:Osteoarthritis / Q000188:drug therapy*; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000009:adverse effects; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid; D012293:Rifampin