11% of the general population undergo total hip arthroplasty (THA) in their lifetime and 7% undergo total knee arthroplasty (TKA), with these rates expected to rise up to 50% by 2026. Periprosthetic joint infection (PJI) remains one of the most common complications, accounting for 30% of THA/TKA revision surgeries. Topical delivery of antibiotic powder may reduce the incidence of PJI but its potential drawbacks include wound healing complications, reduced osteoblast activity, third body wear, and antibiotic resistance. In THA and TKA, topical administration of vancomycin powder for the primary prevention of PJI has been studied in observational studies, but conclusions are limited due to the low incidence of PJI and high number of patients required to detect a significant difference. Investigators therefore propose a randomized controlled trial (RCT) investigating the impact of topical vancomycin compared to standard care on PJI rates following THA and TKA.

Aim: To determine whether topical vancomycin is a safe and effective intervention for the primary prevention of PJI after THA and TKA.

Study Design: This is a pilot multi-centre RCT to evaluate the study design and assess feasibility prior to implementation across Canada. Investigators aim to recruit 50 THA and 50 TKA patients.

Inclusion Criteria THA or TKA Patients aged 18 years or older Patients must complete 1 year follow-up Exclusion Criteria Patients undergoing surgery for inflammatory arthritis, post-traumatic arthritis, or avascular necrosis History or septic arthritis based on history or synovial aspirate Prior major operation on the affected joint Current immunosuppressive medications Vancomycin allergy or history of a vancomycin-related complication Recruitment: surgeons introduce study to the patients, research staff will conduct recruitment.

Intervention: Patients will be randomized preoperatively and remain blinded to their treatment arm. Patients allocated to the control group will have all standard care infection prophylaxis interventions. Patients allocated to the vancomycin group will undergo all the standard care measures in addition to 1g of powdered vancomycin applied to the wound.

Follow-up: Patients will complete follow-up at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year visits.

Primary outcome: PJI in the same joint. Secondary outcome: PJI in THA and TKA subgroups:

Reoperation on the same joint Superficial and non-infectious wound complications All complications

Hip and knee arthroplasty are the third and second most performed inpatient surgeries, respectively. Eleven percent of the general population undergo total hip arthroplasty (THA) in their lifetime and 7% undergo total knee arthroplasty (TKA), with these rates expected to rise up to 50% by 2026. Unfortunately, periprosthetic joint infection (PJI) remains one of the most common and devastating complications of hip and knee arthroplasty, accounting for 30% of revision surgeries.The incidence of PJI ranges from 0.2-1.6% for primary THA and 1-2% for primary TKA. Patients with PJI are subjected to repeated hospitalization and revision surgeries, which leads to increased morbidity and mortality as well as decreased functional outcomes. An estimated $1.6 billion USD is spent on treating hip and knee PJI in the United States yearly.

Topical delivery of antibiotic powder is a simple intervention which may reduce the incidence of PJI. Direct delivery of antibiotics to a target area allows for high local drug concentrations while limiting systemic side effects.Potential drawbacks of topical antibiotics include wound healing complications, reduced osteoblast activity, third body wear, and contribution to antibiotic resistance. Though systemic absorption is reduced, complications such as anaphylaxis, nephrotoxicity, and ototoxicity remain possible. Topical, intrawound administration of vancomycin powder has been well studied in spinal surgery for the prevention of surgical site infections (SSI), with good results. Based on this literature, vancomycin powder has been investigated for the prevention of SSI in multiple orthopaedic domains. In THA and TKA, topical administration of vancomycin powder for the primary prevention of PJI has been studied in a number of recent observational studies, but conclusions are limited due to the low incidence of PJI and high number of patients required to detect a significant difference.

Investigators have completed a systematic review meta-analysis of nine comparative observational studies investigating topical vancomycin for the primary prevention of PJI after hip and knee arthroplasty. Patients treated with topical vancomycin had a lower incidence of PJI compared to the control group (0.6% versus 1.8%, OR 0.40, p = 0.003). Excluding revision cases, patients undergoing primary hip or knee arthroplasty also had a lower incidence of PJI after topical vancomycin (0.6% versus 1.6%, OR 0.46, p = 0.001). After total hip arthroplasty 0.4% of patients developed a PJI in the vancomycin group compared to 1.8% of patients in the control group (OR 0.26, p = 0.003). After unicondylar or total knee arthroplasty, topical vancomycin led to a 0.8% rate of PJI compared to 1.8% in the control group. However, this difference failed to reach statistical significance (OR 0.55, p = 0.07). Topical vancomycin did not increase the rate of wound complications (4.5% versus 5.4%, OR 0.83, p = 0.40). There was no significant difference in overall complication rates between vancomycin and control groups (5.8% versus 7.0%, OR 0.87, p = 0.45).

The conclusions of this meta-analysis are limited by the retrospective nature of the included studies. Most studies use a consecutive series of patients without vancomycin administration followed sequentially by a series implementing topical vancomycin, or a single surgeon using vancomycin compared to a different surgeon as a control.

Additionally, results are limited by the relatively short minimum follow-up period, as many studies reported only three-month results, along with varied definitions of PJI and reporting of complications.

PJI after hip and knee arthroplasty remains a devastating and difficult to treat complication following hip and knee arthroplasty. Low level evidence suggests that topical vancomycin may be effective prophylaxis against PJI. However, given the substantial limitations of prior studies and potential for harm, higher quality studies are required before topical vancomycin can be routinely recommended. Investigators therefore propose a randomized controlled trial investigating the impact of topical vancomycin compared to standard care on PJI rates following THA and TKA.

Research Question: The overarching aim of this study is to determine whether topical vancomycin is a safe and effective intervention for the primary prevention of PJI after THA and TKA. Understanding its impact on PJI and other complication rates with high quality evidence can help make recommendations for or against its routine use and reduce risks to patients.

Study Design: The proposed research project is a pilot study which will precede a multi-centre randomized controlled trial to evaluate complication rates in THA and TKA following vancomycin administration compared to standard care. This pilot study will allow us to evaluate the study design and assess feasibility prior to implementation across Canada. Surgery will take place at one of the four major academic adult orthopedic hospitals: Peter Lougheed Center, Foothills Medical Centre, Rockyview General Hospital, and South Health Campus either Peter Lougheed Centre or Rockyview General Hospital with plans to expand to hospitals across Calgary and Canada in the future study. Investigators aim to recruit 50 patients undergoing THA and 50 patients undergoing TKA and will follow patients for one year postoperatively.

Recruitment: Initial introduction to the study will be done by the surgeons, followed by screening and recruitment, which will be completed by the research coordinator. Patients will have an opportunity to read the consent form and ask questions prior to signing the consent form. Baseline demographics including age, sex, gender, BMI, ethnicity, comorbidities, and smoking status will be recorded.

Intervention: Once enrolled, patients will be randomized preoperatively on the day of surgery Randomization will be done using R software (version 4.0.2), randomize R package. Block Randomization with randomly mixed block sizes to assign equal sample numbers to control and treatment groups (the allocator will hide the block size from the executer). This will be done via 'blockrand' Function in R. with an online randomizer (e.g. studyrandomizer.com). Patients will be blinded to their treatment arm.

Patients allocated to the control group will have all standard care infection prophylaxis interventions such as pre- and post-operative intravenous antibiotic administration, sterile surgical helmet systems, saline pulse lavage irrigation, and antimicrobial drapes. No povidone-iodine lavage will be used. Antibiotic impregnated cement may be used according to the individual surgeons' routine practices but will not differ for an individual surgeon between treatment arms.

Patients allocated to the vancomycin group will undergo all the standard care measures in addition to 1g of powdered vancomycin applied to the wound, in the intra-articular space and along wound edges after irrigation and prior to fascial closure.

Follow-up: Patients will complete follow-up at their regularly scheduled clinical follow-ups. At two weeks, six weeks, three months, six months, and one year visits patients will be assessed for the outcomes noted below.

Inclusion Criteria:

• Adult patients aged 18 years or older, who are undergoing elective primary THA or TKA for osteoarthritis
• Patients must be able and willing to complete one year of follow-up postoperatively

Exclusion Criteria:

• Patients undergoing surgery for inflammatory arthritis, post-traumatic arthritis, or avascular necrosis
• History or septic arthritis based on history or synovial aspirate
• Prior major operation on the affected joint including osteotomy, open reduction internal fixation, or major open ligamentous repair, but excluding arthroscopic procedures such as ACL reconstruction or meniscus or labral debridement/repair
• Current immunosuppressive medications
• Vancomycin allergy or history of a vancomycin-related complication such as ototoxicity or nephrotoxicity