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Septic arthritis after ligament reconstruction is uncommon but potentially devastating. Vancomycin graft presoaking was developed as an adjunct to standard systemic prophylaxis and sterile technique to reduce viable Gram-positive contamination before implantation and biofilm maturation. This State-of-the-Art review evaluates its biological rationale, clinical effectiveness, safety, implementation, graft-specific considerations, hypersensitivity, antimicrobial stewardship, geographic variation, cost-effectiveness, and unresolved controversies. A structured narrative search of PubMed was updated through October 11, 2026, supplemented by backward citation screening and targeted review of relevant guidance and evidence syntheses. The clinical evidence remains predominantly observational. Large comparative cohorts and pooled analyses consistently associate vancomycin graft presoaking with lower rates of septic arthritis after anterior cruciate ligament reconstruction (ACLR), with the most direct evidence applying to hamstring autografts. Limited randomized evidence is available but remains underpowered for a rare postoperative infection outcome. Absolute benefit varies with baseline infection risk. Laboratory, animal, and clinical studies have not demonstrated harm within commonly studied short-exposure protocols, although the most direct clinical safety evidence also derives from hamstring autografts. Evidence for bone-patellar tendon-bone grafts, quadriceps tendon grafts, allografts, revision procedures, and non-ACL ligament reconstructions remains substantially more limited or indirect. One uncontrolled 2026 quadriceps tendon series represents an unconfirmed graft-specific safety signal rather than evidence of a contraindication. No alternative graft-presoaking antibiotic currently has a clinical evidence base comparable to vancomycin. Based on the current evidence, vancomycin graft presoaking may be considered as an adjunct to standard systemic prophylaxis in hamstring autograft ACLR within a standardized protocol. It should not replace established infection-prevention measures, and extrapolation to other graft types or reconstruction settings should reflect the directness of the available evidence. Future research should prioritize graft-specific protocol optimization, prospective comparative evidence, antimicrobial-resistance surveillance, and long-term graft and cartilage outcomes.
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Salim et al. (2026) studied this question.
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