Commentary on: Intrawound vancomycin powder for prevention of surgical site infections in primary joint arthroplasty an umbrella review of systematic reviews and meta-analyses

Dear Editor, We read with great interest the recent umbrella review evaluating the prophylactic role of intrawound vancomycin powder (VP) in patients undergoing primary joint arthroplasty[1]. The results showed a significant reduction in overall infection rates, including both superficial and periprosthetic joint infections, without a statistically significant increase in wound complications. While this conclusion is promising, several nuanced aspects of the study design and interpretation warrant further discussion to refine the applicability of these results to clinical practice. First, the issue of vancomycin dosage and the lack of dose-response evaluation deserves closer attention. Although subgroup analyses indicated that both 1 and 2 g VP were effective in reducing infection rates, the review did not address whether higher doses confer a proportional benefit or merely increase the risk of adverse effects. Notably, some of the included studies, such as those by Xu et al[2], reported favorable outcomes even with 0.5 g of vancomycin, suggesting a potentially lower threshold for antimicrobial efficacy. However, without formal dose-response modeling or pharmacokinetic data, current evidence cannot support optimal dosing strategies. This is particularly relevant given concerns about delayed wound healing or local tissue toxicity at higher concentrations, which were inconsistently reported in the included studies. Second, the diagnostic heterogeneity of the included studies, although acknowledged by the authors, may have a greater impact on the observed treatment effect than is currently appreciated. Infection definitions ranged from culture-based criteria to international consensus guidelines, and some studies reported no criteria at all. These differences are not trivial: for example, culture-negative periprosthetic joint infections may be misclassified under stricter criteria, while superficial infections may be over- or underreported depending on the intensity of surveillance. Although the subgroup analysis by diagnostic method showed a consistent benefit of VP, this should be interpreted cautiously, as classification bias remains a plausible source of heterogeneity that may mask differential effects of VP in different clinical contexts. Third, the umbrella review does not adequately discuss the impact of baseline infection risk and event rarity on statistical robustness. In modern joint arthroplasty, especially with improved perioperative protocols, the absolute rate of periprosthetic joint infection is often less than 1%. In such low incidence settings, even modest misclassification or data irregularities can lead to exaggerated relative effect sizes. For example, a study with 1% infection in the control group and 0.4% in the VP group may yield a compelling odds ratio, but the absolute risk reduction is only 0.6%. Without reporting the number needed to treat or the absolute risk reduction, the clinical significance may be overestimated. In addition, some included reviews did not perform a formal sequential analysis of trials, which could help assess the risk of random error due to cumulative meta-analysis of sparse data. Fourth, translating study results into clinical practice requires standardization of VP application protocols, which is rarely addressed in the original studies. In most real-world settings, the method of vancomycin application – such as whether the powder is evenly distributed, whether it is applied before or after wound irrigation, and whether it is retained or aspirated during closure – varies widely among surgeons. These technical nuances can affect local drug concentration, tissue contact time, and ultimately efficacy. However, few studies included in the umbrella review detailed the timing, technique, or surgical field environment at the time of VP application. This lack of standardization limits reproducibility and hinders efforts to implement VP use as part of structured infection prevention bundles. In conclusion, although this review provides valuable insights into the prophylactic role of intrawound vancomycin in primary joint arthroplasty, several critical issues remain unresolved, including dosage optimization, diagnostic inconsistency, event rarity bias, and technical standardization. Future studies should integrate pharmacological modeling, report absolute risks alongside relative measures, and establish standardized VP administration protocols. Only through these refinements can the benefits of VP be fully realized in diverse clinical settings while ensuring safety, cost-effectiveness, and antimicrobial stewardship.