Oral Antibiotics Noninferior to IV Antibiotics for Bone and Joint Infection

Senior woman holding assorted tablets.
Compared with intravenous antibiotic therapy, oral therapy was noninferior when used during the first 6 weeks for complex orthopedic infections.

Compared with intravenous (IV) antibiotic therapy, oral therapy was noninferior when used during the first 6 weeks of treatment forcomplex orthopedic infections, according to data published in The New England Journal of Medicine (OVIVA Current Controlled Trials number, ISRCTN91566927 ).

Adults being treated with joint or bone infections at 26 UK centers were randomly assigned to receive oral or IV antibiotics for the first 6 weeks of therapy, starting within 7 days post-surgery or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment.

Treatment failure within 1 year of randomization occurred in 74 of 506 patients in the IV group and 67 of 509 in the oral group. The difference in the risk for definitive failure in the oral vs IV groups was −1.4 percentage points (90% CI, −4.9 to 2.2; 95% CI, −5.6 to 2.9), according to an intention-to-treat analysis that indicated noninferiority of oral therapy. There were no significant differences in adverse events between the groups and further complete-case, per-protocol, and sensitivity analyses supported the conclusion of noninferiority.

Investigators believed that ethics concerns outweighed the limitation placed on the study by following open-label protocols, as it “would have been unethical to expose participants in the oral group to the risks associated with intravenous administration of placebo for 6 weeks.” Efforts were made to overcome this limitation by having objective end point criteria and end point committee members who were blinded to treatment group assignments. The trial also did not compare specific antibiotic agents; it was left to the expertise of the consulting infectious disease specialists to choose and adjust antibiotic regimes. These specialists were also responsible for the causal attribution of serious adverse events related to antibiotics. Therefore, potential biases in both the choice of antibiotic and assessment of adverse events are a possibility.

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The results of the trial, investigators concluded, showed that an appropriately selected oral antibiotic is noninferior to IV therapy during the first 6 weeks of treatment for bone and joint infections.


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