New England Journal of Medicine September 16, 2026

Short or Long Antibiotic Regimens in Orthopedics

Martin McNally, Maria Dudareva, Michelle Kümin, et al.

Bottom Line

In adults undergoing surgery for orthopedic infection with local antibiotic carrier implantation, a short course of systemic antibiotics (≤7 days) was noninferior to a standard long course (≥4 weeks) for preventing treatment failure and significantly reduced treatment-related adverse events.

Key Findings

1. Among the 475 patients assessed in the primary analysis, definite treatment failure at 12 months occurred in 11.1% (26 of 234) of the short-duration group compared with 14.1% (34 of 241) in the long-duration group.

2. The risk difference for treatment failure was -3.0 percentage points (95% CI, -9.0 to 3.0), meeting the prespecified noninferiority margin of 10 percentage points.

3. Sensitivity analyses were consistent with the primary findings, demonstrating a risk difference of -2.4 percentage points (95% CI, -8.2 to 3.5) in the included population and -2.7 percentage points (95% CI, -8.8 to 3.4) in the per-protocol population.

4. By week 6 after surgery, symptoms potentially related to antibiotic treatment were markedly less frequent in the short-duration group compared to the long-duration group (17.2% vs. 45.2%; risk difference, -28.0 percentage points; 95% CI, -36.4 to -19.6).

Study Design

Design

RCT

Open-Label

Sample

500

Patients

Duration

12 mo

Median

Setting

Multicenter

Population Adults who had undergone surgery for orthopedic infection and implantation of a local-antibiotic carrier

Intervention Postoperative systemic antibiotic therapy for a short duration (≤7 days)

Comparator Postoperative systemic antibiotic therapy for a long duration (≥4 weeks)

Outcome Definite treatment failure by 12 months

Study Limitations

• The trial utilized an open-label design, which could introduce bias into the reporting and assessment of adverse symptoms, though this was mitigated for the primary endpoint by utilizing a blinded clinical end-point committee.

• The prespecified noninferiority margin of 10 percentage points may be considered relatively wide given the low overall incidence of treatment failure (~11-14%).

• Results rely on the adequacy of surgical debridement and the efficacy of the specific local antibiotic carriers implanted, potentially limiting generalizability to cases where suboptimal local therapy is achieved.

Clinical Significance

The SOLARIO trial provides robust evidence that prolonged systemic antimicrobial therapy (≥4 weeks) is unnecessary following adequate surgical management and local antibiotic implantation for orthopedic infections. Shortening systemic therapy to 7 days or less preserves equivalent treatment efficacy while substantially reducing the burden of antibiotic-related adverse events, supporting a paradigm shift in antimicrobial stewardship for surgical bone and joint infections.

Historical Context

Orthopedic infections have historically been challenging to treat, traditionally requiring aggressive surgical debridement coupled with prolonged courses of systemic antibiotics—often lasting 4 to 6 weeks or more. This prolonged systemic therapy exposes patients to significant toxicities, extended hospitalization, and increased risks of antimicrobial resistance. The development and widespread adoption of local antibiotic carriers (e.g., antibiotic-impregnated cements and absorbable substitutes) enabled the delivery of high antimicrobial concentrations directly to the infection site without systemic toxicity. While landmark trials like OVIVA established the noninferiority of oral over intravenous therapy, the actual necessary duration of systemic coverage remained heavily debated. The SOLARIO trial addresses this critical gap, investigating whether the reliance on optimized local antibiotic delivery allows clinicians to safely truncate systemic therapy to 7 days or fewer.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

How does the presence of a bacterial biofilm in orthopedic infections explain why local antibiotic carriers might be necessary to achieve source control, allowing for a shorter course of systemic antibiotics?

Key Response

Biofilms protect bacteria from host defenses and systemic antibiotics by creating a physical barrier and maintaining a metabolically inactive state. Local antibiotic carriers provide extremely high, sustained concentrations directly at the site, penetrating biofilms better than systemic administration, which justifies reducing systemic exposure.

Resident

When transitioning a patient to this new 7-day systemic antibiotic protocol after implanting a local carrier for osteomyelitis, what specific antibiotic-related adverse events are you monitoring for, and how does this short course change your post-operative follow-up plan compared to the traditional 4-6 week IV regimen?

Key Response

Prolonged antibiotics risk PICC line infections, C. difficile colitis, AKI, and bone marrow suppression. A short course dramatically reduces these risks, shifting post-op care from intensive PICC and lab monitoring to focusing primarily on surgical site healing and local carrier complications.

Fellow

This study evaluated patients with orthopedic infections who received local antibiotic carriers. How do the pharmacokinetics and elution profiles of different carriers impact your confidence in shortening systemic therapy for a complex periprosthetic joint infection versus a fracture-related infection?

Key Response

PMMA has a rapid burst followed by a long tail of sub-therapeutic elution, risking resistance, whereas calcium sulfate completely elutes and resorbs but can cause sterile drainage. Understanding these profiles is critical when deciding if local therapy is robust enough to substitute for systemic therapy in high-risk cases.

Attending

Historically, the dogma for orthopedic bone and joint infections has been a mandatory 4-6 weeks of systemic therapy. How do you plan to navigate the cultural shift and potential pushback from infectious disease colleagues or traditional surgical partners when implementing this 7-day regimen in your practice?

Key Response

Practice-changing evidence often meets resistance due to ingrained dogma. Attendings must synthesize the noninferiority and safety data to champion multidisciplinary consensus, emphasizing that adequate surgical debridement and local antibiotic delivery are the true cornerstones of cure.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

In evaluating a noninferiority trial design for antibiotic duration, how might the choice of the noninferiority margin and the handling of loss to follow-up bias the results toward the null, potentially making the short course appear falsely noninferior?

Key Response

In noninferiority trials, poor adherence, crossover, or high loss to follow-up in both arms dilutes the treatment effect, making the groups look more similar and increasing the risk of a false-positive conclusion of noninferiority. Analyzing the robustness of the per-protocol and intention-to-treat analyses is critical.

Journal Editor

As a reviewer, what specific subgroups would you demand the authors stratify in their primary outcome analysis to ensure the overall noninferiority claim does not mask unacceptable failure rates in certain high-risk phenotypes?

Key Response

A broad inclusion criteria might lump easily treatable cases with extremely difficult ones like retained hardware or Pseudomonas. An editor must ensure the short course is genuinely noninferior across these critical, distinct clinical scenarios before endorsing the paper.

Guideline Committee

Current IDSA and MSIS guidelines typically recommend 4-6 weeks of targeted systemic therapy for osteomyelitis and PJI. Does this single RCT provide sufficient evidence to downgrade the strength of those recommendations in favor of a 7-day course when local carriers are used?

Key Response

Guideline committees must weigh this new RCT against prior data. This may introduce a conditional recommendation for short courses specifically in patients receiving local carriers and adequate debridement, highlighting a shift towards personalized, surgery-dependent durations.

Clinical Landscape

Noteworthy Related Trials

2015

Tone DFO Trial

n = 40 · Diabetes Care

Tested

6 weeks of antibiotic therapy

Population

Patients with nonsurgically treated diabetic foot osteomyelitis

Comparator

12 weeks of antibiotic therapy

Endpoint

Clinical remission at 1 year

Key result: There was no significant difference in clinical remission rates between the 6-week and 12-week antibiotic regimens despite the smaller sample size.

2019

OVIVA Trial

n = 1,054 · NEJM

Tested

Oral antibiotic therapy

Population

Adults being treated for a bone or joint infection

Comparator

Intravenous antibiotic therapy

Endpoint

Definitive treatment failure at 1 year

Key result: Oral antibiotic therapy was found to be noninferior to intravenous therapy for the treatment of bone and joint infections.

2021

DATIPO Trial

n = 410 · NEJM

Tested

6 weeks of antibiotic therapy

Population

Patients with prosthetic joint infections

Comparator

12 weeks of antibiotic therapy

Endpoint

Treatment failure within 2 years

Key result: A 6-week course of antibiotics was not shown to be noninferior to a 12-week course and resulted in a higher rate of treatment failure.

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