Prospective Randomized Study to Compare Clinical Outcomes in Patients With Osteomyelitis Treated With Intravenous Antibiotics Versus Intravenous Antibiotics With an Early Switch to Oral Antibiotics

1.1. Background Information Osteomyelitis is a common disease associated with significant morbidity and high cost (1). The treatment of osteomyelitis can be challenging requiring prolonged administration of antibiotics and extensive surgical procedures. Even when the infection is treated, the relapse rate is as high as 20% (2). When a bone is infected, the local multiplication of bacteria produces a local inflammatory response with presence of neutrophils and macrophages with areas of microthrombi and avascular necrosis. If a significant area of avascular necrosis develops, a segment of the bone without any blood supply can become separated and form a sequestrum. Since infection of sequestrum occurs in most patients with osteomyelitis, it is considered that in addition to antibiotic treatment, the patient requires surgical intervention for removal of necrotic bone.

1.2. Scientific Rationale There is agreement regarding the minimal duration of antibiotic therapy for patients with osteomyelitis. Since an infected bone may take 3 to 4 weeks to re--- vascularize, the duration of therapy should be a minimum of 4 to 6 weeks of antibiotics. Because different organisms can cause osteomyelitis, the initial antibiotic therapy during hospitalization should include broad---spectrum antibiotics to cover the most likely organisms. As part of the initial management, a bone biopsy is regularly performed to identify the particular etiologic agent. Once the organism and its antimicrobial susceptibilities are known, the spectrum of antibiotic therapy is narrowed, and the antimicrobial therapy continues with an antibiotic that is targeted according to the susceptibility of the identified pathogen. Targeted antibiotic therapy in patients with osteomyelitis is usually performed after 3 to 5 days of broad spectrum antibiotics, since this is the time required by the microbiology department to generate antimicrobial susceptibilities after the bone biopsy is performed. In regard to the route of antibiotic administration, the standard approach is to use an intravenous antibiotic.

1.3. Potential Risks A potential risk for the use of an early switch to oral antibiotics in patients with osteomyelitis is that the blood level achieved with oral antibiotics may not be high enough to attain clinical resolution of the infection.

1.4. Potential Benefits There are several potential benefits of using oral antibiotics instead of intravenous antibiotics. First, avoiding a peripherally inserted central line eliminates the risk of line infection and line---associated deep vein thrombosis. An early switch to oral antibiotics may also facilitate early hospital discharge. A shorter hospital stay will decrease the risk of hospital---associated complications such as hospital---acquired infections. Further, the patients' quality of life may be better without a central line. Finally, the total cost of therapy will be significantly reduced with oral therapy.

2. Methods 2.1. Trial design & setting This will be a prospective, randomized, unblinded clinical trial to define if the clinical outcomes of patients with osteomyelitis treated with the experimental approach of intravenous antibiotics with an early switch to oral therapy is non---inferior to the current standard approach of intravenous antibiotics for the full duration of therapy.