title: Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.
abstract: BACKGROUND
  Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis.
  
  
  METHODS
  In this open-label, non-inferiority, randomised controlled trial, we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France. Patients were randomly assigned to either 6 weeks or 12 weeks of antibiotic treatment (physician's choice in accordance with French guidelines) by a computer-generated randomisation list of permuted blocks, stratified by centre. The primary endpoint was the proportion of patients who were classified as cured at 1 year by a masked independent validation committee, analysed by intention to treat. Non-inferiority would be declared if the proportion of cured patients assigned to 6 weeks of treatment was not less than the proportion of cured patients assigned to 12 weeks of treatment, within statistical variability, by an absolute margin of 10%. This trial is registered with EudraCT, number 2006-000951-18, and Clinical Trials.gov, number NCT00764114.
  
  
  RESULTS
  Between Nov 15, 2006, and March 15, 2011, 359 patients were randomly assigned, of whom six in the 6-week group and two in the 12-week group were excluded after randomisation. 176 patients assigned to the 6-week treatment regimen and 175 to the 12-week treatment regimen were analysed by intention to treat. 160 (90·9%) of 176 patients in the 6-week group and 159 (90·9%) of 175 of those in the 12-week group met the criteria for clinical cure. The difference between the groups (0·05%, 95% CI -6·2 to 6·3) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen. 50 patients in the 6-week group and 51 in the 12-week group had adverse events, the most common being death (14 [8%] in the 6-week group vs 12 [7%] in the 12-week group), antibiotic intolerance (12 [7%] vs 9 [5%]), cardiorespiratory failure (7 [4%] vs 12 [7%]), and neurological complications (7 [4%] vs 3 [2%]).
  
  
  CONCLUSIONS
  6 weeks of antibiotic treatment is not inferior to 12 weeks of antibiotic treatment with respect to the proportion of patients with pyogenic vertebral osteomyelitis cured at 1 year, which suggests that the standard antibiotic treatment duration for patients with this disease could be reduced to 6 weeks.
  
  
  BACKGROUND
  French Ministry of Health.
authors.affiliation: Division of Infectious Diseases, University Hospital Bretonneau, Tours, France; Division of Infectious Diseases, Bretonneau University Hospital, Tours, France. Electronic address: lbernard@univ-tours.fr.
authors.forename: Louis
authors.initials: L
authors.lastname: Bernard
authors.affiliation: Division of Infectious Diseases, University Hospital Raymond Poincaré, Garches, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Dinh
authors.affiliation: Clinical Research Unit, University Hospital Ambroise Paré, Boulogne, France.
authors.forename: Idir
authors.initials: I
authors.lastname: Ghout
authors.affiliation: Clinical Research Unit, University Hospital Ambroise Paré, Boulogne, France.
authors.forename: David
authors.initials: D
authors.lastname: Simo
authors.affiliation: Referral Centre for Bone and Joint Infections, Hospital Diaconesses Croix Saint-Simon, Paris, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Zeller
authors.affiliation: Unité Mobile des Référents en Infectiologie, Villeurbanne, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Issartel
authors.affiliation: Maladies Infectieuses et Tropicales, University Hospital, Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Le Moing
authors.affiliation: Division of Internal Medicine, University Hospital, Beaujon-Clichy, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Belmatoug
authors.affiliation: Mobile Infectious Diseases Unit, University Hospital, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesprit
authors.affiliation: Division of Infectious Diseases, Regional Hospital, Annecy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bru
authors.affiliation: Division of Infectious Diseases, General Hospital of Versailles, Le Chesnay, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Therby
authors.affiliation: Division of Infectious Diseases, General Hospital, Bourg en Bresse, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Bouhour
authors.affiliation: Division of Infectious Diseases, Limoges University Hospital, Limoges, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Dénes
authors.affiliation: Division of Infectious Diseases, University Hospital, Toulouse, France.
authors.forename: Alexa
authors.initials: A
authors.lastname: Debard
authors.affiliation: Division of Infectious Diseases University Hospital, Besançon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chirouze
authors.affiliation: Division of Infectious Diseases, Bretonneau University Hospital, Tours, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Fèvre
authors.affiliation: Division of Infectious Diseases, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Dupon
authors.affiliation: Clinical Research Unit, AP-HP, Ambroise Paré University Hospital, Boulogne, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Aegerter
authors.affiliation: Division of Rheumatology, University Hospitals of Tours, Tours, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Mulleman
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016037:Single-Blind Method; D013122:Spinal Diseases / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents