Few phrases in diabetic foot care sound more reassuring than a “clean margin.” The words suggest a bright line: infected bone on one side, healthy bone on the other, with antibiotic duration determined accordingly. It is an elegant idea. It is also much less certain in practice than the label implies.
In a new Clinical Infectious Diseases Viewpoint, Christopher V. Radcliffe, Marjorie Golden, and Rupak Datta examine the growing use of resection margins to guide antibiotic therapy after surgery for diabetic foot osteomyelitis (DFO). Their central message is both timely and appropriately cautious: margin-directed treatment is conceptually attractive, but the construct itself remains inconsistently defined, inconsistently measured, and insufficiently validated.
Why the margin now matters
The 2023 IWGDF/IDSA guideline on diabetes-related foot infections moved practice toward more individualized antibiotic duration. It advises considering up to three weeks of antibiotics after a minor amputation when a bone-margin culture is positive, compared with six weeks when DFO is treated without bone resection or amputation. The recommendation is conditional and supported by low-certainty evidence.
That distinction makes intuitive sense. If all infected bone has been removed, prolonged antimicrobial exposure may offer little additional benefit while increasing the risks of adverse effects, drug interactions, Clostridioides difficile infection, selection for resistance, and treatment burden. If infected bone remains, stopping too early may invite persistence or relapse. This is exactly where antimicrobial stewardship and limb preservation should meet.
But a treatment algorithm is only as reliable as the measurement beneath it. What, exactly, makes a margin “clean”?
Three views of the same margin
The surgeon assesses the operative field: bone quality, bleeding, color, texture, anatomic extent, and whether the remaining tissue appears viable. The pathologist evaluates sampled tissue for inflammatory and structural changes. The microbiology laboratory asks whether organisms grow from the specimen. Each discipline is observing something real, but they are not observing the same thing.
This is the practical force of the paper’s elephant perspective. Surgical assessment, histopathology, and microbiology may each touch a different part of the problem. A margin can look healthy to the surgeon yet yield a positive culture. Histology may suggest residual osteomyelitis when cultures are negative, perhaps because antibiotics suppressed growth or sampling missed the relevant organisms. A positive culture may represent residual infection, contamination, or colonization introduced during specimen handling. Even the location, number, size, and orientation of specimens can change the answer.
Calling these results simply “positive” or “negative” compresses a complex biological and procedural question into a binary label. Worse, it can create false precision: two centers may both report a “clean margin” while using different sampling protocols, histological criteria, culture methods, or combinations of tests. The recommended physical dimensions of the margin are themselves unclear, and histopathological interpretation can vary between observers.
The evidence beneath the current treatment distinction also deserves perspective. The authors note that a prospective randomized pilot trial of 93 patients found similar outcomes with three versus six weeks of antibiotics after surgical debridement, but the ascertainment of residual infection was not clearly grounded in standardized microbiological and histopathological criteria. This is useful evidence, but not yet a universal operating definition of a clean margin.
What this means at the bedside
A margin result should inform care, not dictate it in isolation. The most defensible interpretation is multidisciplinary and patient-specific. Surgeons, infectious diseases clinicians, pathologists, microbiologists, wound-care specialists, and vascular colleagues should reconcile the operative impression with specimen quality, histopathology, culture results, vascular supply, soft-tissue infection, wound trajectory, offloading, and the feasibility of close follow-up.
Discordance should prompt a conversation rather than an automatic extension or discontinuation of antibiotics. Was the specimen truly taken from newly exposed proximal bone with clean instruments? Does the histology represent active infection or chronic remodeling? Is the cultured organism plausible and concordant with other samples? Was the patient already receiving antibiotics? Is there residual necrotic bone, ischemia, or an unaddressed biomechanical driver that makes recurrence more likely?
There are promising ways to make that conversation more reproducible. At the authors’ center, a templated operative note asks surgeons to record strong suspicion of cure, strong suspicion of residual infection, or uncertainty pending pathology and culture. Preliminary experience across 131 patient-surgeries showed 88% agreement between an intraoperative assessment of cure and pathology without acute inflammation. That is encouraging, but it also reinforces the need to define, test, and follow these judgments prospectively.
This approach is not indecision. It is disciplined interpretation. Stewardship is not merely about using fewer antibiotics; it is about using the right therapy for the right indication, for the right duration, with the best available understanding of source control.
The next step: standardize before we simplify
The authors’ call for prospective standardization deserves attention. Future studies should define how margin specimens are obtained, how contamination is minimized, what histopathological features constitute residual osteomyelitis, how microbiological results are interpreted, and which patient-centered outcomes are measured. They should also test whether margin-directed strategies actually improve remission, healing, adverse-event, antimicrobial-use, and limb outcomes across diverse clinical settings.
Until then, the “clean margin” is best understood not as a single verdict, but as a composite clinical judgment with important uncertainty. The concept can help us tailor therapy—but only if we resist asking one imperfect measurement to carry more certainty than it can support.
The practical takeaway: treat the margin as evidence, not an oracle. When the surgical, pathological, and microbiological stories disagree, the safest answer is not to choose one discipline reflexively. It is to put the whole team—and the whole patient—back into the picture.
References
- Radcliffe CV, Golden M, Datta R. The Clean Margin in Diabetic Foot Osteomyelitis: Conceptual Appeal, Practical Uncertainty. Clinical Infectious Diseases. Published online July 31, 2026. doi:10.1093/cid/ciag467.
- Senneville É, et al. IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-Related Foot Infections. Clinical Infectious Diseases. 2023;ciad527. doi:10.1093/cid/ciad527.

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