Antibiotic Prophylaxis for Knee Replacement Surgery

Recruiting at 13 trial locations

Overseen By Jennifer Friend

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Disqualifiers: Pregnancy, Psychiatric disorder, Severe dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

1770 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug cefazolin for knee replacement surgery?

Cefazolin is commonly used worldwide as an antibiotic to prevent infections in knee replacement surgeries, and studies suggest it should be given shortly before surgery to maximize its effectiveness. Additionally, a study on hip replacements showed that cefazolin significantly reduced infection rates compared to a placebo, indicating its potential effectiveness in similar surgical procedures like knee replacements. ^{1 2 3 4 5}

Is cefazolin safe for use in knee replacement surgery?

Cefazolin is generally considered safe for use in knee replacement surgery, with studies showing no significant difference in complications compared to other antibiotics. It is commonly used to prevent infections after surgery, and no infectious complications were reported in a study comparing it to another antibiotic. ^{3 6 7 8 9}

How does antibiotic prophylaxis for knee replacement surgery differ from other treatments?

This treatment is unique because it involves the use of antibiotics specifically to prevent infections during knee replacement surgery, with a focus on combating methicillin-resistant staphylococci. It often includes a combination of antibiotics like cefazolin and vancomycin, which is different from using a single antibiotic, and can be administered regionally in the leg being operated on, which is a novel approach compared to traditional methods. ^{2 6 9 10 11}

What is the purpose of this trial?

The Antibiotic Prophylaxis in Patients Undergoing Elective Total Knee Arthroplasty (TKA): Multi-Center Trial is a study that will compare the effectiveness of various perioperative strategies for antibiotic delivery as prophylaxis for periprosthetic joint infections (PJI) and surgical site infection in elective primary TKA. The investigators hypothesize that a single dose of prophylactic antibiotic administered within 60 minutes before the incision is not an effective way to prevent PJI in elective primary total knee arthroplasty (TKA). The investigators also hypothesize that the prolonged delivery (24 hours) of antibiotic prophylaxis after surgery does not further reduce the incidence of PJI in elective primary TKA. Duke University is the only site recruiting both primary total knee arthroplasty and unilateral knee arthroplasty.

Research Team

Thorsten Seyler, MD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for adults over 18 without open wounds or active infections on the leg where knee replacement surgery will happen. It's not for those unable to consent, with severe dementia, drug abuse (except prescription cannabinoids), extreme surgical risk (ASA score of 5 & 6), emergency cases, prior septic arthritis, pregnancy, certain psychiatric conditions, or if they can't follow the study plan.

Inclusion Criteria

I am scheduled for knee replacement surgery due to arthritis or injury.

I do not have an infection in the leg or joint that needs surgery.

I have no open wounds on my leg that needs surgery.

Exclusion Criteria

I have not used antibiotic powder or beads in my surgical wound.

I have had a knee infection in the past.

I did not need extra doses of medication during surgery unless I lost a lot of blood.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Antibiotic Administration

Participants receive a single weight-based dose of prophylactic cefazolin antibiotic intravenously within less than 60 minutes prior to skin incision

1 day

1 visit (in-person)

Postoperative Antibiotic Administration

Participants in Group #2 receive two additional weight-based doses of cefazolin within 24 hours postoperatively

1 day

Follow-up

Participants are monitored for safety and effectiveness after surgery

4 weeks

Treatment Details

Interventions

• Cefazolin

Trial Overview The study tests if giving antibiotics within an hour before cutting or continuing them for a day after knee replacement surgery prevents joint and site infections better. Duke University recruits patients undergoing elective primary TKA and unilateral knee arthroplasty.

Participant Groups

Group I: Study Group 2 Experimental Treatment 1 Intervention

Patients in Group #2 will receive a single weight-based dose of prophylactic cefazolin antibiotic that is administered intravenously within less than 60 minutes prior to skin incision in elective total knee arthroplasty. In addition, two weight-based doses of cefazolin will be administered within 24 hours postoperatively. \< 120 kg - patients will receive 2 grams of cefazolin ≥ 120 kg - patient will receive 3 grams of cefazolin Patients with documented allergy/anaphylactic reaction to penicillin or cephalosporin may receive intravenous vancomycin monotherapy or dual therapy with vancomycin and gentamicin as an alternative. If allergic, patients will also receive two weight-based doses vancomycin postoperatively but not gentamicin postoperatively. In addition, the use of clindamycin as an alternative is also permitted. Vancomycin schedule: one dose preoperatively, one dose 8-12 h postoperatively, one dose 24 h postoperatively (opt.).

Group II: Study Group 1 Experimental Treatment 1 Intervention

Patients in Group #1 will receive a single weight-based dose of prophylactic cefazolin antibiotic that is administered intravenously within less than 60 minutes prior to skin incision in elective total knee arthroplasty. No further antibiotic administration will be given. \< 120 kg - patients will receive 2 grams of cefazolin ≥ 120 kg - patient will receive 3 grams of cefazolin Patients with documented allergy/anaphylactic reaction to penicillin or cephalosporin may receive intravenous vancomycin monotherapy or dual therapy with vancomycin and gentamicin as an alternative. In addition, the use of clindamycin as an alternative is also permitted at a minimum recommended dose.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

American Association of Hip and Knee Surgeons

Collaborator

Trials

4

Recruited

2,300+

American Association of Hip and Knee Surgeons

Collaborator

Trials

4

Recruited

2,300+

Orthopedic Research and Education Foundation

Collaborator

Trials

23

Recruited

6,200+

Findings from Research

Periprosthetic infections, particularly from Staphylococcus aureus and Staphylococcus epidermidis, occur in 0.4-2% of total knee arthroplasty patients, making effective antibiotic prophylaxis crucial.

The study suggests that administering cefazolin 10 to 30 minutes before tourniquet inflation could optimize its peak concentrations in both blood and bone, enhancing its effectiveness in preventing infections during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefazolin should be administered maximum 30 min before incision in total knee arthroplasty when tourniquet is used. Bicanic, G., Crnogaca, K., Barbaric, K., et al.[2014]

In a study of 1128 total hip and knee arthroplasties, patients receiving cefazolin had significantly lower rates of surgical site infections (SSIs) compared to those receiving clindamycin or vancomycin (0.9% vs 3.8%).

The use of cefazolin did not result in a higher frequency of interoperative hypersensitivity reactions compared to clindamycin or vancomycin, suggesting it is a safe option for patients labeled as beta-lactam allergic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefazolin vs Second-line Antibiotics for Surgical Site Infection Prevention After Total Joint Arthroplasty Among Patients With a Beta-lactam Allergy. Norvell, MR., Porter, M., Ricco, MH., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

A survey of prophylactic antibiotic use for total joint replacements in a community hospital. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Cefazolin should be administered maximum 30 min before incision in total knee arthroplasty when tourniquet is used. [2014]

3. Canada pubmed.ncbi.nlm.nih.gov

Outcome of cefazolin prophylaxis for total knee arthroplasty at an institution with high prevalence of methicillin-resistant Staphylococcus aureus infection. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Wound infection following implant removal of foot, ankle, lower leg or patella; a protocol for a multicenter randomized controlled trial investigating the (cost-)effectiveness of 2 g of prophylactic cefazolin compared to placebo (WIFI-2 trial). [2021]

5. England pubmed.ncbi.nlm.nih.gov

Prophylactic cefazolin versus placebo in total hip replacement. Report of a multicentre double-blind randomised trial. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Cefazolin vs Second-line Antibiotics for Surgical Site Infection Prevention After Total Joint Arthroplasty Among Patients With a Beta-lactam Allergy. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Surgical site infection rate is higher following hip and knee arthroplasty when cefazolin is underdosed. [2020]

8. France pubmed.ncbi.nlm.nih.gov

[Prevention of postoperative infections with cefotiam (Pansporine) in orthopedic surgery]. [2013]

9. Thailand pubmed.ncbi.nlm.nih.gov

A randomized control trial between fosfomycin and cefuroxime as the antibiotic prophylaxis in knee arthroplasty. [2013]

10. England pubmed.ncbi.nlm.nih.gov

[Antibiotic chemoprophylaxis in orthopedic prosthesis implantation]. [2014]

11. Germany pubmed.ncbi.nlm.nih.gov

Dual Antibiotic Prophylaxis in Total Knee Arthroplasty: Where Do We Stand? [2020]