IO vs IV Antibiotics for Total Knee Replacement

Overseen By Thomas Sullivan

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The Methodist Hospital Research Institute

Disqualifiers: Bmi > 40, Uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day (surgical procedure)

40 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. However, if you have received or are scheduled to receive IV vancomycin or cefazolin within 7 days before the procedure, you may not be eligible to participate.

What data supports the effectiveness of the drug Intraosseous (IO) Cefazolin and Vancomycin for total knee replacement?

Research shows that intraosseous (IO) administration of antibiotics like cefazolin and vancomycin can achieve higher local tissue concentrations compared to intravenous (IV) administration, which may help in better preventing infections during knee replacement surgery. ^{1 2 3 4 5}

Is intraosseous antibiotic administration safe for total knee replacement surgery?

Studies have shown that intraosseous (IO) antibiotics, like vancomycin and cefazolin, are safe for use in total knee replacement surgery, providing higher local antibiotic concentrations with fewer side effects compared to intravenous (IV) administration. ^{1 2 3 6 7}

How is the drug Intraosseous (IO) Cefazolin and Vancomycin unique for total knee replacement?

This drug is unique because it is administered directly into the bone (intraosseous), which results in much higher local antibiotic concentrations compared to the traditional intravenous (IV) method, potentially reducing the risk of infection after knee replacement surgery. ^{1 3 8 9 10}

What is the purpose of this trial?

The goal of this clinical trial is to compare the efficacy of intravenous (IV) and intraosseous (IO) antibiotic administration techniques during primary total knee arthroplasty (TKA) in adults undergoing a TKA procedure at Houston Methodist Hospital. The main questions it aims to answer are: Does IO administration of vancomycin and cefazolin protect against perioperative exposure risks? Is there a difference in post-operative complication rates between IV and IO administration of these drugs? Participants will be randomized to receive either the standard of care IV administration of Vancomycin and Cefazolin, or the IO administration of Vancomycin and Cefazolin.

Eligibility Criteria

This trial is for adults scheduled for primary total knee replacement surgery at Houston Methodist Hospital. Participants must be eligible for the procedure and willing to receive antibiotics either through their veins (IV) or directly into the bone (IO). Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I understand the study and agree to participate.

I am scheduled for a first-time knee replacement surgery.

Exclusion Criteria

I cannot take vancomycin or cefazolin due to health reasons.

Body mass index (BMI) > 40

My diabetes is not under control (A1c > 7.5%).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either intraosseous or intravenous administration of vancomycin and cefazolin during the total knee arthroplasty procedure

1 day (surgical procedure)

1 visit (in-person)

Follow-up

Participants are monitored for postoperative infections and wound complications

90 days

2 visits (in-person) at 30 and 90 days postop

Treatment Details

Interventions

• Intraosseous (IO) Cefazolin and Vancomycin

Trial Overview The study compares two ways of giving antibiotics during knee replacement surgery: IV Vancomycin and Cefazolin versus IO Vancomycin and Cefazolin. It aims to see which method better prevents infection without increasing complications post-surgery.

Participant Groups

Group I: Intraosseous Administration of Vancomycin and Cefazolin Experimental Treatment 2 Interventions

Intraosseous vancomycin plus cefazolin is administered via an intraosseous cannulation device (Arrow EZ-IO; Teleflex, Morrisville, NC) in the OR after sterile prep of the leg and draping has occurred prior to skin incision and after the tourniquet has been inflated. The injection will take place into the tibial tubercle, which is a known safe IO injection site. The IO injection will include 500mg of vancomycin and a 1g dose of cefazolin, previously used in prior IO studies of cefazolin.

Group II: Standard IV Administration of Vancomycin and Cefazolin Active Control 2 Interventions

Patients will receive the Houston Methodist Hospital orthopedic surgery standard of care pre-operative antibiotic regimen for primary total knee arthroplasty patients. This includes IV antibiotics cefazolin will be started in the pre-operative period approximately 1 hour prior to incision. The cefazolin dose is generally 2g if patient is under 120kg, and 3g is the patient is above 120kg in line with guidelines. Vancomycin IV administration will be dosing will be weight-based at approximately 15mg/kg generally 1000-1750mg in 500mL NS.

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Findings from Research

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]

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]

References

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

Clinical outcome evaluation of intraosseous vancomycin in total knee arthroplasty. [2022]

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

Effects of renal function on the intraosseous concentration and inhibitory effect of prophylactic cefazolin in knee arthroplasty. [2018]

3. 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]

4. Germany pubmed.ncbi.nlm.nih.gov

Higher cefazolin concentrations in synovial fluid with intraosseous regional prophylaxis in knee arthroplasty: a randomized controlled trial. [2023]

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

Different microbial and resistance patterns in primary total knee arthroplasty infections - a report on 283 patients from Lithuania and Sweden. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Intraosseous Regional Administration of Prophylactic Antibiotics in Total Knee Arthroplasty. [2022]

7. 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]

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

Otto Aufranc Award: Intraosseous Vancomycin in Total Hip Arthroplasty - Superior Tissue Concentrations and Improved Efficiency. [2023]

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

Intraosseous Regional Prophylactic Antibiotics Decrease the Risk of Prosthetic Joint Infection in Primary TKA: A Multicenter Study. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Effectiveness of Prophylactic Intraosseous Antibiotic versus Intravenous Antibiotic in Knee Surgeries in Pigs: Experimental Study. [2020]