Oral vs. IV Antibiotics for Bone and Joint Infections

We’ve all had that patient on the wards — the patient comes in nearly septic from a joint infection, undergoes emergent surgical washout, and recovers from surgery while on intravenous (IV) antibiotics targeting the culprit pathogen. After a few days, he or she is the most stable patient on your service. You ask yourself, “Why is this patient still in the hospital?” Then you remember that standard of care for the treatment of complex bone and joint infections is 4 to 6 weeks of IV antibiotics.

Prolonged IV antibiotic treatment is widely accepted as the best way to eradicate the initial invasive bacterial infection associated with bone and joint infections. However, it can also result in extended hospitalization, which increases risk of hospital-acquired infections and raises cost. Patients who are discharged home with central access to complete their antibiotic course are at increased risk of infection and experience the inconvenience of at-home IV antibiotic administration and central-line care.  A transition to oral antibiotics would be ideal, but the fear is that oral therapy could result in inadequate treatment and dangerous recurrent infection, requiring more antibiotics, more surgery, and an even longer and more complicated hospital course. The research to support a safe transition to appropriate oral antibiotic therapy in patients recovering from bone and joint infections is limited.

In a randomized, noninferiority trial published in NEJM, Li et al. compared the efficacy of transitioning to oral antibiotics versus staying on IV antibiotics in patients with bone and joint infections. The results suggest that the fear of increased rates of treatment failure with a transition to oral antibiotics in bone and joint infections may be unfounded.

The following NEJM Journal Watch summary explains the study and its findings.

A central tenet in infectious disease is that complicated orthopedic infections require at least 4 to 6 weeks of intravenous antibiotic therapy; however, the associated cost and complications are a source of increasing concern. Investigators in the U.K. performed a noninferiority trial to assess 1-year outcomes of oral versus intravenous antibiotic therapy in patients receiving treatment for bone or joint infection. Participants were randomized to 6 weeks of either intravenous or oral antibiotic therapy within 7 days of surgery or the start of antibiotic therapy. Selection of specific agents was at the individual physician's discretion, as was continuation of antibiotics beyond 6 weeks.

Among 1054 patients (mean age, 60), 61% had metalware-related infections. The predominant pathogens were Staphylococcus aureus (38%), coagulase-negative staphylococcus (27%), streptococcus species (15%), and pseudomonas species (5%); the primary intravenous agents were glycopeptides and cephalosporins, and the oral agents were quinolones and penicillins. Adjunctive rifampin was given to 41% of the intravenous group and 56% of the oral group, and the overall duration of antibiotic therapy was comparable for both groups. Definitive treatment failure at 1 year occurred in 15% of the intravenous group and 13% of the oral group; hence, oral therapy was found to be noninferior to intravenous therapy.

Comment: This study is limited in being unblinded, but the findings mirror those of a recent study showing that partial oral therapy was comparable to intravenous therapy for endocarditis (NEJM JW Infect Dis Oct 2018 and N Engl J Med 2018 Aug 28; [e-pub]). I believe this study may well lead to a major change in management of orthopedic infections — but I'll bet it's going to take a while before an orthopedic surgeon will accept oral antibiotic treatment for an elderly patient with a new total hip arthroplasty infection due to S. aureus.

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Angela Castellanos is a general pediatrician and editorial fellow at the NEJM.