Oral or intravenous antibiotics for complex orthopaedic infections?

Abstract

Overview This openlabel parallel group randomised controlled noninferiority trial ( Oral versus intravenous antibiotics for bone and joint infection [OViVa]) compared oral and intravenous antibiotics for the treatment of acute or chronic bone or joint infections. participants were adults who would normally have been treated with intravenous antibiotics for 6 weeks, and the choice of antibiotic was made by local infection control specialists. patients were followed up for 1 year, and the primary outcome was treatment failure defined by at least one clinical, microbiological or histological endpoint. The sample size was based on an anticipated failure rate of 5% and a noninferiority margin of 5%. The margin was later adjusted to 7.5% after an interim analysis found that the overall failure rate was 12.5%. a total of 1054 patients were recruited from 26 uK hospitals with 1015 patients (mean age 60 years) included in the modified intentiontotreat analysis. Treatment failure occurred in 74 participants (14.6%) in the intravenous group and 67 participants (13.2%) in the oral group. The absolute difference in the risk of treatment failure between oral and intravenous therapy was −1.4% (90% CI −4.9 to 2.2; 95% CI −5.6 to 2.9), which met the authors noninferiority criteria. When the results were modelled for missing endpoint data from 39 patients by assuming that all in the oral arm and none of those in the intravenous arm had treatment failure, it still showed that oral antibiotics were noninferior. The most commonly identified organisms were Staphylococcus aureus (38%), coagulasenegative staphylococci (27%) and streptococcus species (15%). There were no significant differences between groups in the timetotreatment failure (p=0.57), incidence of Clostridium difficilerelated diarrhoea (1.7% vs 1.0%, p=0.30) or the percentage of patients reporting at least one serious adverse event (27.7% vs 26.2%, p=0.58). patients in the intravenous group were more likely to discontinue treatment early (18.9% vs 12.8%, p=0.006) and intravenous catheter complications were more common in the intravenous group (9.4% vs 1.0%, p<0.001). median hospital stay was longer for the intravenous group than for the oral group (14 days vs 11 days, p<0.001). (The study was supported by the national institute for health research [nihr], the nihr imperial college Biomedical research centre and the nihr Oxford Biomedical research centre.)