Elsevier

The Lancet

Volume 385, Issue 9971, 7–13 March 2015, Pages 875-882
The Lancet

Articles
Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial

https://doi.org/10.1016/S0140-6736(14)61233-2Get rights and content

Summary

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.

Introduction

Pyogenic vertebral osteomyelitis generally occurs as an acute osteomyelitis infection in patients older than 55 years. The estimated incidence of vertebral osteomyelitis is four–ten per 100 000 inhabitants per year in high-income countries,1, 2 and has risen in recent years, increasing the economic burden of the disease.3, 4 The optimum duration of antibiotic treatment is unknown; however, most guidelines regard about 6–12 weeks of treatment as the standard of care,3, 4, 5, 6 although this recommendation is not evidence based.7, 8, 9 Other experts recommend antibiotic treatment for a minimum of 3 months.3, 10, 11 Long-term exposure to antibiotics increases the frequency of adverse events, health-care-related infections, costs, and antibiotic resistance.11, 12, 13 We aimed to compare treatment duration with effective antibiotics for 6 weeks and 12 weeks in patients with microbiologically confirmed pyogenic vertebral osteomyelitis.

Section snippets

Study design and patients

In this multicentre, open-label, non-inferiority, randomised, controlled trial, we enrolled patients with pyogenic vertebral osteomyelitis from 71 medical care centres (infectious diseases, rheumatology, or internal medicine departments) in France. We included patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features (with MRI or CT scan). Criteria for microbiological identification of the causative agent were isolation

Results

Between Nov 15, 2006, and March 15, 2011, 359 patients underwent randomisation: 182 patients were allocated to the 6-week antibiotic treatment regimen and 177 to the 12-week antibiotic treatment regimen. Most patients (267 [74%]) were randomly assigned on the day after giving consent (appendix). Eight patients were excluded after randomisation (six from the 6-week group and two from the 12-week group; figure).

Table 1 shows the baseline clinical characteristics of the 351 patients included in

Discussion

In this large, prospective, multicentre, randomised clinical trial, our results showed the non-inferiority of a 6-week treatment regimen versus a 12-week regimen for patients with pyogenic vertebral osteomyelitis meeting strict microbiological criteria and receiving appropriate antibiotic treatment. In our study, non-inferiority of the efficacy of 6-week treatment was not shown in some subgroups (age 75 years or older, or patients with immunodepression or diabetes, endocarditis, or neurological

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