Tourniquet Use for Prosthetic Joint Infections

Overseen By Karen Smith, CRA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Disqualifiers: Severe allergy, Renal dysfunction, MRSA, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

50 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.

What data supports the effectiveness of the drug Ancef (Cefazolin) for preventing infections in prosthetic joint surgeries?

Research shows that Cefazolin, when given before surgery, can reduce the risk of wound infections in patients undergoing joint replacement surgeries. It is effective against common bacteria like Staphylococcus aureus, which are often responsible for infections, and achieves good concentrations in bone and soft tissue when administered properly. ^{1 2 3 4 5}

Is cefazolin (Ancef) safe for use in humans?

Cefazolin, also known as Ancef, is generally safe for most people and is commonly used in surgeries to prevent infections. It is considered safe even for patients with penicillin allergies, although rare allergic reactions can occur. ^{4 6 7 8 9}

How does the drug Ancef (Cefazolin) differ from other treatments for prosthetic joint infections?

Ancef (Cefazolin) is unique in its use as a prophylactic antibiotic for prosthetic joint infections due to its ability to achieve high concentrations in bone and soft tissue when administered shortly before surgery, particularly when a tourniquet is used. This timing ensures maximum effectiveness against common bacteria like Staphylococcus, which are responsible for most infections in these surgeries. ^{3 4 5 7 10}

What is the purpose of this trial?

Tourniquet inflation during total knee arthroplasty (TKA) is commonly used to reduce bleeding in the surgical field; thereby facilitating exposure and cementation. However, reducing circulation to the leg may also reduce antibiotic distribution to the peri-incisional tissues. Once inflated, further parenteral addition of antibiotics is not likely to achieve peak concentration. Some studies propose techniques of regional prophylaxis with a tourniquet to achieve higher cefazolin tissue concentrations. To our knowledge, the effect of tourniquet application on antibiotic tissue concentrations during total knee arthroplasty has not been explored. Furthermore, the effect of time from dose to incision, participants weight, and length of surgery on local tissue concentrations of Ancef are poorly understood. Considering that infections remain the leading source of early reoperation and revision surgery, insight and optimization of local tissue antibiotics is of paramount interest.

Research Team

Adam Hart, MD

Principal Investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Eligibility Criteria

Adults aged 18-85 needing a primary total knee replacement due to conditions like osteoarthritis, rheumatoid arthritis, or avascular necrosis can join. Those with MRSA colonization, severe allergies to the study antibiotic, or severe kidney issues (eGFR < 30 ml/min) cannot participate.

Inclusion Criteria

My gender does not limit my participation.

I have been diagnosed with osteoarthritis, rheumatoid arthritis, or avascular necrosis.

I am between 18 and 85 years old and need a knee replacement.

Exclusion Criteria

Severe allergy to antibiotic used in the study

My kidney function is severely reduced.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo total knee arthroplasty with or without tourniquet application to study the effect on local tissue concentrations of Cefazolin

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the surgical procedure

2 years

Treatment Details

Interventions

• Ancef

Trial Overview The trial is testing how using a tourniquet during knee surgery affects the concentration of Ancef (an antibiotic) in tissue around the incision. It's looking at whether less blood flow from the tourniquet means less antibiotic gets to where it's needed.

Participant Groups

Group I: Tourniquet Active Control 1 Intervention

25 participants with tourniquet application

Group II: No tourniquet Active Control 1 Intervention

25 participants without tourniquet application

Ancef is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ancef for:

• Surgical prophylaxis
• Respiratory tract infections
• Skin and skin structure infections
• Bone and joint infections
• Genitourinary tract infections
• Septicemia

Approved in European Union as Cefazolin for:

• Surgical prophylaxis
• Respiratory tract infections
• Skin and skin structure infections
• Bone and joint infections
• Genitourinary tract infections
• Septicemia

Approved in Canada as Kefzol for:

• Surgical prophylaxis
• Respiratory tract infections
• Skin and skin structure infections
• Bone and joint infections
• Genitourinary tract infections
• Septicemia

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Findings from Research

In a study of 228 surgical patients, cefazolin was found to significantly reduce the rate of major postoperative wound infections (2.56% vs. 4.50%) compared to amoxicillin + gentamycin.

Cefazolin also led to fewer minor postoperative wound infections (6.83% vs. 13.51%) and could potentially save 68.75% of the costs associated with antibiotic prophylaxis by limiting the duration of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single preoperative dose of cefazolin versus postoperative amoxicillin and gentamycin combination in prophylaxis of orthopaedic and traumatologic surgery. Perçin, S., Akbaş, L., Akbaş, A.[2017]

In a study involving 18 patients undergoing total knee arthroplasty, a 2 g dose of intravenous cefazolin resulted in significantly higher intraosseous concentrations compared to a 1 g dose, indicating a potential for improved drug delivery to the surgical site.

Despite the increased concentrations of cefazolin with the 2 g dose, there was no corresponding increase in its effectiveness against Staphylococcus aureus growth, suggesting that higher doses may not necessarily enhance antibacterial efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraosseous concentration and inhibitory effect of different intravenous cefazolin doses used in preoperative prophylaxis of total knee arthroplasty. Angthong, C., Krajubngern, P., Tiyapongpattana, W., et al.[2018]

In a study of 76 patients undergoing total hip or knee replacement, cefonicid showed no toxicity and was compared to cefazolin, with both drugs demonstrating safety in the short follow-up period of four months to one year.

No significant difference in efficacy was found between cefonicid and cefazolin in preventing infections, indicating that larger studies with longer follow-up are needed to assess the potential benefits of cefonicid over the established drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind study comparing cefonicid with cefazolin as prophylaxis in patients undergoing total hip or knee replacement. DeBenedictis, KJ., Rowan, NM., Boyer, BL.[2019]

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 24 patients undergoing total knee arthroplasty, a five-minute interval between cefazolin administration and tourniquet inflation resulted in significantly better penetration of the antibiotic into soft tissue compared to one-minute intervals, achieving a median penetration of 14.5%.

The five-minute group also had a higher percentage of patients reaching the desired cefazolin concentration for effective infection prophylaxis, indicating that this timing may optimize antibiotic efficacy during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic prophylaxis and tourniquet inflation in total knee arthroplasty. Friedman, RJ., Friedrich, LV., White, RL., et al.[2013]

A study involving 27,467 surgeries showed that using cefazolin as surgical prophylaxis in patients with penicillin allergies, including those with anaphylaxis histories, did not result in increased allergic reactions or adverse events compared to other antibiotics.

After implementing a policy change to routinely use cefazolin, there were no documented cases of anaphylaxis in penicillin-allergic patients, indicating that cefazolin is a safe option for surgical prophylaxis in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of administering cefazolin versus other antibiotics in penicillin-allergic patients for surgical prophylaxis at a major Canadian teaching hospital. Grant, JM., Song, WHC., Shajari, S., et al.[2021]

Parenteral prophylactic antibiotics, particularly first-generation cephalosporins like Cefazolin, are effective in reducing infection rates in clean orthopedic procedures, supported by numerous animal and clinical studies.

Administering the antibiotic at the start of anesthesia or at least 10 minutes before tourniquet inflation is crucial, and 24 hours of postoperative coverage is generally sufficient for effective infection prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of parenteral prophylactic antibiotics in clean orthopaedic surgery. A review of the literature. Oishi, CS., Carrion, WV., Hoaglund, FT.[2022]

Cefazolin (Ancef) is a first-generation cephalosporin antibiotic commonly used in surgeries to prevent bacterial infections, and it is generally considered safe for most patients.

Despite concerns about cross-reactivity with penicillin allergies, the article aims to investigate the safety of cefazolin for patients with such allergies, suggesting that it may be a viable option rather than using less effective alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are Cephalosporins Safe for Surgical Prophylaxis in Patients with Penicillin Allergy? Abraham-Aggarwal, K., Kacker, A.[2023]

A study involving 2289 surgeries across three trauma centers found that administering cephalosporins to pediatric patients with a reported penicillin allergy did not lead to a higher rate of allergic reactions compared to those without such allergies.

Only one patient experienced an anaphylactic reaction to cefazolin, indicating that cephalosporins can be safely used in pediatric orthopedic patients labeled as penicillin-allergic, thus supporting their use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical prophylaxis in pediatric orthopedic patients with penicillin allergy: a multicentered retrospective prognostic study. Khokhar, AS., Batko, BD., Hanna, G., et al.[2023]

Staphylococcus epidermidis is a major cause of postoperative infections in orthopedic surgeries, leading to the use of antibiotics like cefazolin and cefuroxime for prevention, but increasing methicillin-resistant strains have necessitated the use of glycopeptide antibiotics like vancomycin and teicoplanin.

Regional prophylaxis with teicoplanin during total knee replacement surgery has been shown to be safe and effective, providing higher antibiotic concentrations at the surgical site and achieving similar infection rates compared to traditional systemic prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic prophylaxis in orthopedic prosthetic surgery. de Lalla, F.[2022]

References

1. Poland pubmed.ncbi.nlm.nih.gov

A single preoperative dose of cefazolin versus postoperative amoxicillin and gentamycin combination in prophylaxis of orthopaedic and traumatologic surgery. [2017]

2. Italy pubmed.ncbi.nlm.nih.gov

Intraosseous concentration and inhibitory effect of different intravenous cefazolin doses used in preoperative prophylaxis of total knee arthroplasty. [2018]

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

A double-blind study comparing cefonicid with cefazolin as prophylaxis in patients undergoing total hip or knee replacement. [2019]

4. 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]

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

Antibiotic prophylaxis and tourniquet inflation in total knee arthroplasty. [2013]

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

Safety of administering cefazolin versus other antibiotics in penicillin-allergic patients for surgical prophylaxis at a major Canadian teaching hospital. [2021]

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

Use of parenteral prophylactic antibiotics in clean orthopaedic surgery. A review of the literature. [2022]

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

Are Cephalosporins Safe for Surgical Prophylaxis in Patients with Penicillin Allergy? [2023]

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

Surgical prophylaxis in pediatric orthopedic patients with penicillin allergy: a multicentered retrospective prognostic study. [2023]

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

Antibiotic prophylaxis in orthopedic prosthetic surgery. [2022]