Optimizing infection prophylaxis in primary total knee arthroplasty: intraosseous or intravenous vancomycin?

To the Editor, Prosthetic and periprosthetic joint infections (PJI) remain a major threat to the success of primary total knee arthroplasty (TKA), often leading to complications such as reoperation, prolonged antibiotic therapy, and functional decline. Despite advances in perioperative protocols, infection rates remain a challenge, which has sparked renewed interest in optimizing local antibiotic delivery. Recent evidence suggests that intraosseous (IO) vancomycin administration could be a viable alternative to the traditional intravenous (IV) route, offering the potential for high local concentrations with limited systemic exposure. Vancomycin is primarily active against Gram-positive organisms commonly implicated in PJI, including Staphylococcus aureus (both methicillin-sensitive and methicillin-resistant strains), coagulase-negative Staphylococci, such as Staphylococcus epidermidis, and Enterococcus species. The pharmacokinetic rationale for IO delivery is well-supported. Early work demonstrated that IO regional administration achieves tissue concentrations approximately 5- to 15-fold higher than IV dosing, with significantly lower serum levels and consequently minimal renal burden1,2. IO drug administration achieves rapid perfusion of medullary bone and adjacent soft tissues, critical areas where early bacterial colonization occurs. A 2024 randomized trial comparing IO and IV vancomycin in tourniquetless primary TKA found that intraosseous vancomycin achieved comparable local tissue concentrations to intravenous delivery, while significantly reducing systemic exposure3. A retrospective review across nearly 2,000 primary TKA cases show reduced 90-day and 1-year PJI rates in IO cohorts (0.5 to 0.7%) compared to IV groups (1.6 to 1.8%)4. Moreover, a recently published meta-analysis concluded that IO vancomycin significantly reduces PJI risk and is not associated with increased complication rates5. The IO route has also been shown to be safe in routine practice. Large cohort studies did not find significantly increased rates of complications6. The accumulating evidence therefore suggests that intraosseous prophylaxis could be a feasible adjunct or replacement for systemic vancomycin in primary TKA. Nevertheless, caution has to be exercised in interpreting these findings. Much of the available evidence is from single-center studies with limited blinding and short follow-ups. Optimal dosing, timing relative to tourniquet inflation, and compatibility with other prophylactic agents need standardization. Future multicenter randomized trials should focus on infection and patient-centered endpoints rather than pharmacokinetic markers to establish definitive clinical equivalence or superiority. In conclusion, IO vancomycin delivery represents a biologically rational and evidence-supported advancement in infection prevention for primary TKA. Evidence suggests it could provide superior local bioavailability without increasing systemic toxicity and may offer particular benefit in high-risk populations. With appropriate techniques and further multicentric validation, IO vancomycin could shift the paradigm of antibiotic prophylaxis in primary knee arthroplasty. This letter adhered to the TITAN guidelines for transparent reporting of AI assistance in healthcare research7.