Oral versus Intravenous Antibiotics for Bone and Joint Infection

Abstract

Background The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. Methods We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. Results Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points (90% confidence interval [CI], −4.9 to 2.2; 95% CI, −5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P = 0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). Conclusions Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927.)

Interventions in the management of infection in the foot in diabetes: a systematic review

“…In most of the RCTs of antibiotic treatment of antibiotics, however, the authors prescribed parenteral antibiotics followed by a switch to oral antibiotics. One non‐inferiority RCT that was published after the inclusion dates of our systematic review, and was therefore not included in the search results, randomized subjects with a variety of severe osseous and joint infections, including approximately 20% subjects with diabetic foot osteomyelitis, to treatment with an oral versus a parenteral antibiotic regimen . There were no significant differences in treatment outcomes between the two routes of therapy for the various types of infections combined.…”

“…Saltoglu et al; Lipsky et al; Lauf et al; Grayson et al; Erstad et al; Lipsky et al; Lipsky et al; Lipsky et al; Lázaro‐Martínez et al; Ulcay et al; Tone et al, Li et al…”

Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update)

“…An ongoing large, multicenter US trial (VA INTREPID) is examining the role of rifampin in treating DFO . Several case series, and a recent large RCT, have shown that oral antibiotic therapy (usually after at least a few days of intravenous therapy) is as effective as, safer, and less expensive than intravenous therapy for complex bone and joint infection (including DFO) …”

“…We think clinicians can prescribe initial therapy by the oral route in care- shown that oral antibiotic therapy (usually after at least a few days of intravenous therapy) is as effective as, safer, and less expensive than intravenous therapy for complex bone and joint infection (including DFO). 157 The recommended duration of treatment for osteomyelitis has traditionally been 4 to 6 weeks, but this is based mostly on animal models and clinical experience. Some studies of DFO (and other types of osteomyelitis) have shown that therapy for longer than 6 weeks offers no additional benefit, 158 and based mostly on theoretical considerations, treatment for just 1 to 2 weeks (or less) should be sufficient for patients in whom all infected bone has been resected.…”

Transition to Oral versus Continued Intravenous Antibiotics for Patients with Pyogenic Liver Abscesses: A Retrospective Analysis

“…This is especially the case with orally administered β‐lactams whose bioavailability and doses are much lower than their IV counterparts . However, studies showed that PO antibiotics are as effective as IV antibiotics for other difficult to treat infections including left‐sided endocarditis and bone‐joint infections …”