SLR - April 2019 - Zinnia M. Rocha

Oral Versus Intravenous Antibiotics for Bone and Joint Infection

Reference: Li H-K, Rombach I, Zambellas R, et al. Oral versus intravenous antibiotics for bone and joint infection. N Engl J Med 2019;380:425–436.

Scientific Literature Review

Reviewed By: Zinnia M. Rocha, DPM
Residency Program: MedStar Washington Hospital Center, Washington, DC

Podiatric Relevance: Management of lower-extremity osteomyelitis typically involves a long course of intravenous antibiotic therapy, both in inpatient and outpatient settings. This method thus requires the use of a peripherally inserted central catheter, which inherently carries the risk of insertion site infection, venous thrombosis, pulmonary emboli and line malfunction. Additionally, the parenteral antibiotics themselves can introduce patients to an increased risk of developing adverse reactions, such as nephrotoxicity and muscular toxicity, as with vancomycin and daptomycin, respectively.  Evaluating the efficacy of an oral-only regimen for treating osteomyelitis is of special utility in managing lower-extremity infections.

Methods: Across 26 U.K. centers, adults with native osteomyelitis of the extra-axial or vertebral skeleton, native joint infection requiring excision, prosthetic joint infection or orthopaedic hardware infection were randomized to receive either parenteral or oral antibiotics for six weeks. Additional oral therapy beyond six weeks was permitted in both groups. The primary endpoint was treatment failure within one year, defined as the presence of at least one clinical, microbiologic or histologic sign. The study team also evaluated early termination, IV complications, Clostridium difficile infection, serious adverse events, resource use, quality of life, hip/knee function and compliance.

Results: A total of 1,015 subjects were included in the intent-to-treat analysis. Treatment failure at one year occurred in 14.6 percent of participants in the IV group and 13.2 percent of those in the oral group. The difference in risk of treatment failure at one year was -1.4 percentage points [90 percent confidence interval (CI), -4.9 to 2.2; 95 percent CI, -5.6 to 2.9], meeting the noninferiority criteria. Early termination was more common in the IV group than in the oral group. There was no significant difference in the incidence of C. difficile infection nor the incidence of serious adverse events. Median hospital stay was significantly longer in the IV group at 14 days versus 11 days. Patient-reported outcome measures did not differ significantly. The most frequently utilized IV antibiotics included glycopeptides (41.1 percent) and cephalosporins (33.2 percent), while the most common oral agents were quinolones (36.5 percent) and combination therapy (16.6 percent). Oral rifampin adjunct was allowed in both groups and was utilized in 15.5 percent of IV group regimens and 51.5 percent in oral group regimens. Total treatment duration did not differ between groups.

Conclusions: Overall, this study demonstrates that treatment with oral antibiotics is noninferior to parenteral therapy when used for the first six weeks of treatment for bone and joint infections and with shorter hospital stays and fewer complications. Although subjects were nonblinded, the risk of introducing a placebo via catheter to the oral group was rightly avoided. An analysis of the patient population, including comorbidities, would prove useful as well as a discussion on antibiotic use in perfused versus necrotic bone. While this study was quite inclusive, future studies with narrower study criteria are warranted in application to lower-extremity osteomyelitis.

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