Optimizing Infection Risk in Primary Total Knee Arthroplasty: A Narrative Review of Current Concepts, Controversies,...

Periprosthetic joint infection (PJI) remains one of the most serious complications following primary total knee arthroplasty (TKA), despite its relatively low incidence. Prevention requires addressing multiple interacting factors related to patient characteristics, microbial burden, antimicrobial prophylaxis, operative technique, and postoperative wound management. The objective of this review is to synthesize contemporary evidence on strategies for reducing infection risk in primary TKA, with particular emphasis on clinically actionable interventions, areas of controversy, and current evidence gaps. This narrative review integrated evidence from the source manuscript and its supporting evidence base, prioritizing TKA-specific systematic reviews, meta-analyses, randomized controlled trials, registry studies, large observational cohorts, clinical guidelines, and implementation studies. Evidence was evaluated according to study design, TKA relevance, consistency of findings, susceptibility to confounding, and applicability to current clinical practice. No de novo systematic search, formal risk-of-bias assessment, or meta-analysis was performed. Current evidence supports structured preoperative risk assessment and optimization, Staphylococcus aureus screening and decolonization, avoidance of intra-articular injections within three months before TKA when feasible, timely cefazolin-based systemic prophylaxis in patients without true contraindications, and stewardship-conscious antibiotic duration. Standardized antiseptic skin preparation and irrigation, efficient operative workflow, meticulous wound management, and early surveillance are also supported as components of a comprehensive prevention strategy. However, several controversies remain. Body mass index, glycemic control, nutritional status, anemia, and smoking are established risk markers, but evidence is insufficient to define universal thresholds for postponing surgery. Cefazolin remains the preferred prophylactic agent, although the optimal regimen for patients with true beta-lactam allergy or resistant-organism risk remains uncertain. Extended oral antibiotic prophylaxis may benefit selected high-risk patients but lacks sufficient evidence for routine use. Evidence regarding antibiotic-loaded bone cement and intraosseous antibiotic prophylaxis remains heterogeneous. Recent randomized evidence does not support routine intrawound vancomycin powder in primary TKA because it did not reduce infection and was associated with more minor wound complications. Persistent wound drainage also remains incompletely standardized in terms of escalation and surgical intervention. Infection prevention in primary TKA should be approached as a risk-stratified perioperative pathway rather than as a single intervention or universal checklist. Current evidence favors systematic host optimization, microbial-burden reduction, appropriate systemic prophylaxis, standardized antisepsis, efficient high-quality surgery, and structured wound surveillance, while selective use of controversial adjuncts should be guided by patient risk and local protocols. Future research should prioritize registry-nested randomized trials, standardized definitions of high-risk patients, procedure-specific outcomes, antimicrobial-stewardship measures, cost-effectiveness, and implementation studies evaluating complete perioperative prevention bundles.