Louis Bernard1, Aurélien Dinh2, Idir Ghout3, David Simo3, Valerie Zeller4, Bertrand Issartel5, Vincent Le Moing6, Nadia Belmatoug7, Philippe Lesprit8, Jean-Pierre Bru9, Audrey Therby10, Damien Bouhour11, Eric Dénes12, Alexa Debard13, Catherine Chirouze14, Karine Fèvre15, Michel Dupon16, Philippe Aegerter17, Denis Mulleman18. 1. Division of Infectious Diseases, University Hospital Bretonneau, Tours, France; Division of Infectious Diseases, Bretonneau University Hospital, Tours, France. Electronic address: lbernard@univ-tours.fr. 2. Division of Infectious Diseases, University Hospital Raymond Poincaré, Garches, France. 3. Clinical Research Unit, University Hospital Ambroise Paré, Boulogne, France. 4. Referral Centre for Bone and Joint Infections, Hospital Diaconesses Croix Saint-Simon, Paris, France. 5. Unité Mobile des Référents en Infectiologie, Villeurbanne, France. 6. Maladies Infectieuses et Tropicales, University Hospital, Montpellier, France. 7. Division of Internal Medicine, University Hospital, Beaujon-Clichy, France. 8. Mobile Infectious Diseases Unit, University Hospital, Créteil, France. 9. Division of Infectious Diseases, Regional Hospital, Annecy, France. 10. Division of Infectious Diseases, General Hospital of Versailles, Le Chesnay, France. 11. Division of Infectious Diseases, General Hospital, Bourg en Bresse, France. 12. Division of Infectious Diseases, Limoges University Hospital, Limoges, France. 13. Division of Infectious Diseases, University Hospital, Toulouse, France. 14. Division of Infectious Diseases University Hospital, Besançon, France. 15. Division of Infectious Diseases, Bretonneau University Hospital, Tours, France. 16. Division of Infectious Diseases, Bordeaux University Hospital, Bordeaux, France. 17. Clinical Research Unit, AP-HP, Ambroise Paré University Hospital, Boulogne, France. 18. Division of Rheumatology, University Hospitals of Tours, Tours, France.
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. FINDINGS: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%]). INTERPRETATION: 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. FUNDING: French Ministry of Health.
RCT Entities:
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. FINDINGS: 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%]). INTERPRETATION: 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. FUNDING: French Ministry of Health.
Authors: Amar Rangan; Mark Falworth; Adam C Watts; Matthew Scarborough; Michael Thomas; Rohit Kulkarni; Jonathan Rees Journal: Shoulder Elbow Date: 2018-05-16
Authors: A Vargas-Palacios; D M Meads; M Twiddy; C Czoski Murray; C Hulme; E D Mitchell; A Gregson; P Stanley; J Minton Journal: J Antimicrob Chemother Date: 2017-08-01 Impact factor: 5.790
Authors: Tamar F Barlam; Sara E Cosgrove; Lilian M Abbo; Conan MacDougall; Audrey N Schuetz; Edward J Septimus; Arjun Srinivasan; Timothy H Dellit; Yngve T Falck-Ytter; Neil O Fishman; Cindy W Hamilton; Timothy C Jenkins; Pamela A Lipsett; Preeti N Malani; Larissa S May; Gregory J Moran; Melinda M Neuhauser; Jason G Newland; Christopher A Ohl; Matthew H Samore; Susan K Seo; Kavita K Trivedi Journal: Clin Infect Dis Date: 2016-04-13 Impact factor: 9.079