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Reference: N Engl J Med 2019 Jan 31;380(5);425 (level 2 [mid-level] evidence)
Prolonged antibiotic therapy for joint infections and osteomyelitis has substantial costs in terms of dollars, time, and the potential development of antibiotic resistance. Standard duration of intravenous antibiotic therapy is 6 weeks for osteomyelitis; 2-6 weeks for septic arthritis. Recently, a randomized, unblinded non-inferiority trial was conducted in the United Kingdom (UK) comparing intravenous to oral antibiotic therapy for bone and joint infections, most often following surgical debridement. More than 1,000 patients were recruited from multiple surgical centers in the UK with clinically suspected osteomyelitis, vertebral diskitis, or septic arthritis of a native or prosthetic joint, most with symptoms of pain, redness, and drainage from a previous surgical site or wound. Patients were on average 60 years old. Comorbidities included diabetes in 20%, renal disease in 2%, and peripheral vascular disease in 6%. Sites most commonly affected were the hip (25%), knee (29%), and foot (20.5%). Sixty percent of infections involved a prosthetic joint or hardware. Infectious disease specialists and surgeons determined initial preoperative antibiotic therapy and selected operative procedure if one was needed. Over 90% of patients had surgical debridement of the area, followed by implant removal, one-step replacement, or retention. Participants were randomized within 7 days of surgery or at the start of antibiotic therapy if managed conservatively to either oral or intravenous antibiotics for a minimum of 6 weeks. Specialists determined antibiotic selection, including need for oral rifampin.
The primary outcome evaluated in this trial was definitive treatment failure within 1 year, defined as clinical infection at the site, microbiological isolation of organisms from biopsy, or histological growth of organisms at time of another intervention. A failure rate of 5% was expected based on a pilot study, and the initial non-inferiority margin was set at 5 percentage points. When it was clear that the failure rate was nearing double digits, the non-inferiority margin was increased to 7.5 percentage points. Clinician- and patient-reported outcomes were collected at 3 time points during the 1 year of follow-up. In the per-protocol analysis, the primary outcome of definitive treatment failure occurred in 15.6% of patients receiving intravenous antibiotics and 13.1% of patients receiving oral antibiotics. The lower end of the 95% confidence interval for the difference was 2.1% and so non-inferiority was met using either the 7.5 or 5 percentage point marks. Early discontinuation of therapy and catheter-related infections were more common in patients receiving intravenous antibiotics. Rates of antibiotic therapy beyond 6 weeks were similar in both groups. The estimated total non-surgical cost was higher by nearly 3,000 US dollars (2,740 Euros) in the intravenous group compared to the oral group, but there was no difference in quality-adjusted life years between the two groups.
In this unblinded trial, which included a wide variety and severity of bone and joint infections, oral antibiotics appear to have similar efficacy compared to intravenous antibiotics, with fewer adverse events and reduced cost. It should be noted however, that after 3 months, 50% of patients were still on antibiotics, and this is likely due to the majority of patients having infected prosthetic joints. Oral therapy may not be appropriate for a variety of patient specific factors, but this trial suggests it may be a reasonable option for some patients.
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DynaMed Plus EBM Focus Editorial Team
This EBM Focus was written by Carina Brown, MD, Faculty Development and Information Mastery Fellow and Clinical Instructor at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed Plus and Associate Professor in Family Medicine at the University of Massachusetts Medical School and Katharine DeGeorge, MD, MS, Assistant Professor in Family Medicine at the University of Virginia and Clinical Editor at DynaMed Plus.