Increased Risk of Periprosthetic Joint Infection Following Aseptic Revision Hip and Knee Arthroplasty With the Use of Non-Cefazolin Alternative Antibiotics.

BACKGROUND: Although perioperative cefazolin antibiotic prophylaxis is associated with a reduced risk of periprosthetic joint infection (PJI) in primary total joint arthroplasty (TJA) compared to non-cefazolin alternatives, its relative efficacy in the aseptic revision setting is less defined. Furthermore, the roles of postoperative oral antibiotic prophylaxis and the management of unexpected positive cultures (UPC) remain controversial. Therefore, we examined PJI in aseptic revision TJA based on (1) perioperative antibiotic prophylaxis, (2) postoperative oral antibiotic regimen, and (3) UPC status. METHODS: We evaluated all patients undergoing aseptic revision total knee arthroplasty (TKA) and total hip arthroplasty (THA) at a single academic institution between January 2000 and March 2024, yielding 5,993 revision arthroplasties (n = 3,429 THA, n = 2,564 TKA). Cases were analyzed based on perioperative antibiotic type (cefazolin versus non-cefazolin), postoperative oral antibiotic regimen, and intraoperative culture results. Cox proportional hazards regressions were used to determine survivorship free from PJI. RESULTS: Among this cohort, 94% received cefazolin perioperative prophylaxis. In total, 234 cases (4%) subsequently developed PJI. Cefazolin perioperative prophylaxis was associated with significantly higher survivorship free from PJI compared to non-cefazolin alternatives (hazard ratio (HR): 0.5; P = 0.006). In patients receiving perioperative cefazolin, the addition of oral antibiotics with either cefadroxil or cephalexin did not significantly reduce PJI risk compared to no oral antibiotics. The incidence of UPCs was 4%, most commonly coagulase-negative Staphylococcus (44%), and was not significantly associated with subsequent PJI (HR: 1.5; P = 0.21). CONCLUSION: Perioperative cefazolin prophylaxis is a critical modifiable risk factor, providing a substantial protective effect against PJI in aseptic revision TJA. In contrast, extended oral antibiotic prophylaxis provided no additional benefit for culture-negative patients. While UPCs occurred in 4% of cases, only one case subsequently developed PJI with a concordant microorganism. These findings reinforce the importance of standardized cefazolin prophylaxis over alternative agents in aseptic revision TJA.