骨・関節感染症に対する経口 vs 静注 抗菌薬 RCT。
主要評価項目は，無作為化後 1 年以内の明らかな治療失敗。
非劣性マージンは 7.5 パーセント。
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.
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.
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%).
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.)
complex bone and joint infections are typically managed with surgery and a prolonged course of treatment with intravenous antibiotic agents. The preference for intravenous antibiotics reflects a broadly held belief that parenteral therapy is inherently superior to oral therapy a view supported by an inf luential 1970 article that suggested that “. . . osteomyelitis is rarely controlled without the combination of careful, complete surgical debridement and prolonged (four to six weeks) parenteral antibiotic therapy . . . .”
However, intravenous therapy is associated with substantial risks, inconvenience, and higher costs than oral therapy.A meta-analysis involving 180 patients with chronic osteomyelitis, 118 of whom were followed for more than 1 year, showed no advantage of intravenous therapy over oral therapy, but there was insufficient evidence to draw conclusions with potential clinical utility.
We therefore conducted a pragmatic noninferiority trial to evaluate outcomes at 1 year after intravenous therapy as compared with oral therapy administered during the initial 6 weeks of treatment for orthopedic infection.
Planned Antibiotic Therapy
The intravenous and oral antibiotic regimens that had originally been planned by the participants’ physicians were documented before randomization for 917 and 945 participants, respectively. The most frequently planned intravenous antibiotics were glycopeptides (380 of 917 participants [41.4%]) and cephalosporins (345 of 917 [37.6%]) (Table S8 in the Supplementary Appendix).
The most frequently planned oral antibiotics (excluding rifampin) were quinolones (414 of 945 participants [43.8%]) and combination oral therapy (133 of 945 [14.1%]) (Table S9 in the Supplementary Appendix). Outcomes did not vary significantly between the groups according to the intended intravenous or oral antibiotic agent (P = 0.42 and P = 0.80, respectively, for heterogeneity) (Fig. S2 in the Supplementary Appendix).
The actual antibiotics prescribed (excluding rifampin), defined by use for at least 7 days during the initial 6-week treatment period, were most commonly glycopeptides (214 of 521 participants [41.1%]) and cephalosporins (173 of 521 [33.2%]) in the intravenous group and quinolones (191 of 523 [36.5%]) and combination therapy (87 of 523 [16.6%]) in the oral group (Table S10 in the Supplementary Appendix).
The intended use of adjunctive oral rifampin was analyzed separately; it was included with planned intravenous therapy for 142 of 917 participants (15.5%) and with planned oral therapy in 487 of 945 participants (51.5%). Outcomes did not vary significantly according to intended use of rifampin (P = 0.22 for heterogeneity) (Fig. S2 in the Supplementary Appendix). The addition of adjunctive rifampin was permitted at any time after randomization; 120 of 523 participants (22.9%) in the intravenous group and 165 of 526 participants (31.4%) in the oral group received rifampin for at least 6 weeks between randomization and final follow-up (Table S11 in the Supplementary Appendix).