Antibiotic Injection for Non-Healing Wounds

(TAI Trial)

Overseen By Cynthia Henning

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Los Angeles

Must not be taking: Systemic corticosteroids, Biologic therapy

Disqualifiers: Uncontrolled diabetes, Dialysis, HIV, 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: 2

Duration: 1 day for TAI, ongoing for standard care

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether an antibiotic injection (CeFAZolin Injectable Solution) can aid in healing chronic wounds that resist self-healing. Participants will receive either standard wound care or a one-time antibiotic injection around the wound. Researchers aim to determine if the additional treatment improves wound healing. The trial seeks individuals with chronic wounds on their arms, legs, or trunk that haven't significantly improved after several weeks of care. Participants will attend about six study visits over six months, alongside their regular wound care. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic corticosteroids, biologic therapy, or immunosuppressants, you may need approval from the medical director to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that cefazolin, the antibiotic used in this trial, commonly treats bacterial infections in various parts of the body, such as the lungs, skin, and bones. It is also frequently used during surgery to prevent infections. Cefazolin is usually well-tolerated, with common side effects being mild, like an upset stomach or a mild rash. Serious side effects are rare but can include allergic reactions or kidney problems, especially in individuals with existing kidney issues.

Since the FDA has already approved cefazolin for other uses, extensive safety information is available. This information helps reassure about its safety when used in this new way for non-healing wounds. However, as with any medical treatment, discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CeFAZolin Injectable Solution for non-healing wounds because it introduces a new delivery method: a one-time tumescent antibiotic injection directly into the wound area. This method contrasts with the standard of care that typically involves topical or oral antibiotics, which may not effectively reach deep tissue infections. By delivering the antibiotic directly to the site of the wound, this approach has the potential to enhance healing efficiency and reduce recovery time.

What evidence suggests that this treatment might be an effective treatment for non-healing wounds?

Research has shown that using cefazolin in a cleaning solution can lower infection rates in dirty surgical wounds. This trial will test the effectiveness of a tumescent antibiotic injection with cefazolin for non-healing wounds. The treatment group will receive this injection alongside standard wound care. Early reports indicate that cefazolin penetrates wounds effectively, suggesting it can reach the areas needed to fight bacteria. While more information is needed, this supports the idea that cefazolin could help improve wound healing. ^{6 7 8 9 10}

Who Is on the Research Team?

Seth Putterman, PhD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic leg wounds that haven't healed in more than 4 weeks. Participants must be able to give informed consent, have visited a wound care center at least twice, and not seen significant healing recently. They need good blood flow to the area and agree to use contraception during the study.

Inclusion Criteria

I am willing and able to understand and sign the consent form in English.

My blood flow in the legs is confirmed to be good through specific tests.

I have a deep skin ulcer on my leg that is between 0.5 and 10 cm^2 in size.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive a one-time tumescent antibiotic injection (TAI) and continue standard wound care until the wound closes

1 day for TAI, ongoing for standard care

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits

6 months

Once weekly for 2 weeks, biweekly for 4 weeks, then at 3 and 6 months

Long-term follow-up

Participants continue to be monitored for up to 1 year to assess long-term outcomes

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• CeFAZolin Injectable Solution

Trial Overview

The study tests if injecting an antibiotic solution (CeFAZolin) around chronic wounds helps them heal better compared to standard care alone. Patients will either continue their usual treatment or receive the new intervention along with it, while being monitored for about six months.

How Is the Trial Designed?

Group I: Treatment Group (Tumescent Antibiotic Injection) Experimental Treatment 1 Intervention

The 'treatment' group will receive wound care treatment in accordance to standard of care procedures along with the study intervention, a one-time tumescent antibiotic injection (TAI).

Group II: Control Group (Standard Wound Care) Active Control 1 Intervention

The 'control' group will receive wound care treatment in accordance to standard of care procedures. The 'control' group will not receive study intervention.

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

In a study of 24 breast reduction patients, both preoperative intravenous dosing and intraoperative irrigation of cefazolin effectively maintained protective antibiotic levels in the wound, crucial for preventing surgical-site infections.

However, wound irrigation resulted in significantly higher cefazolin concentrations (up to 4185.93 microg/ml) that lasted for 24 hours, compared to intravenous dosing, which peaked at 22.49 microg/ml for only 4 to 5 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of topical and intravenous cefazolin in patients with clean surgical wounds. White, RR., Pitzer, KD., Fader, RC., et al.[2021]

In an experimental wound model, both cefazolin and cefoxitin effectively reduced bacterial concentrations and infection rates compared to a placebo, indicating their efficacy in preventing wound infections.

Cefazolin was found to be as effective as cefoxitin in preventing infections from common contaminants like Staph. aureus and E. coli, suggesting that anaerobic coverage provided by cefoxitin is not necessary for effective prophylaxis in contaminated wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anaerobic coverage for wound prophylaxis. Comparison of cefazolin and cefoxitin. Sarap, MD., Scher, KS., Jones, CW.[2019]

A single 2-g intravenous dose of cefazolin given before bariatric surgery effectively achieves protective levels in adipose tissue against methicillin-sensitive S. aureus (MSSA) for approximately 4.8 hours, which is sufficient for the duration of the surgery.

Cefazolin penetrates adipose tissue at only 6-8% of serum levels, but still exceeds the minimum inhibitory concentration (MIC) for MSSA, indicating that higher doses (like 3 or 4 g) are unnecessary and that redosing during surgery is not required.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Cefazolin Prophylactic Dosing for Bariatric Surgery: No Need for Higher Doses or Intraoperative Redosing. Chen, X., Brathwaite, CE., Barkan, A., et al.[2018]

In a study involving 12 guinea pigs with experimental crush wounds contaminated with bacteria, irrigation with different concentrations of cefazolin and penicillin did not significantly reduce bacterial counts compared to the control group.

The high-dose irrigation group showed no clinical signs of infection, while lower doses and the control group had varying rates of infection, suggesting that while the high dose may prevent infection, it did not significantly lower bacterial counts in the tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacterial counts in experimental, contaminated crush wounds irrigated with various concentrations of cefazolin and penicillin. Lammers, R., Henry, C., Howell, J.[2013]

In a study of 1030 patients undergoing Mohs micrographic surgery, intraincisional clindamycin significantly reduced the risk of postoperative wound infections compared to a control group, with only 6 infections in the clindamycin group versus 23 in the control group.

Clindamycin offers a safe and effective alternative to nafcillin for patients with penicillin allergies, demonstrating its potential as a convenient preoperative antibiotic treatment in dermatologic surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clindamycin for intraincisional antibiotic prophylaxis in dermatologic surgery. Huether, MJ., Griego, RD., Brodland, DG., et al.[2022]

Cefazolin shows variable penetration into interstitial fluid (ISF) in patients with complicated skin and soft tissue infections, with a 1 g every 8 hours (q8h) regimen achieving high probabilities of maintaining effective drug levels against most methicillin-susceptible Staphylococcus aureus (MSSA).

For infections caused by Enterobacteriaceae, a higher dose of 2 g q8h is necessary to ensure adequate drug exposure, particularly to meet pharmacodynamic targets at the current breakpoint for these bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Cefazolin in Serum and Tissue for Patients with Complicated Skin and Soft Tissue Infections (cSSTI). So, W., Kuti, JL., Nicolau, DP.[2020]

In mouse studies, adding cefazolin to saline irrigation of contaminated surgical wounds significantly reduced infection rates, highlighting its efficacy in wound care.

Topical application of cefazolin powder was found to be as effective as systemic administration in preventing wound sepsis, while povidone-iodine irrigation did not show improved effectiveness and could pose toxicity risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of wound infection: the comparative effectiveness of topical and systemic cefazolin and povidone-iodine. Scher, KS.[2017]

A quality improvement initiative successfully increased compliance with the recommended preoperative dose of cefazolin from 40% to 93% among 9086 patients, significantly reducing the risk of surgical site infections.

Cefazolin doses ordered electronically were administered correctly 94% of the time, compared to only 76% for verbal orders, highlighting the importance of electronic ordering in ensuring accurate dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A quality improvement initiative to optimize dosing of surgical antimicrobial prophylaxis. Caruso, TJ., Wang, E., Schwenk, HT., et al.[2018]

Subcutaneous administration of cefazolin in a porcine model achieved maximum serum concentrations at about 42.6 minutes post-injection, with a relative bioavailability of 95%, indicating effective absorption.

This method resulted in lower maximum serum concentrations compared to intravenous injection, suggesting that subcutaneous delivery could provide higher local concentrations of antibiotics at the surgical site, potentially improving the prevention of surgical site infections (SSIs).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous cefazolin to reduce surgical site infections in a porcine model. Dubrovsky, G., Huynh, N., Rouch, JD., et al.[2019]

In a study involving 12 adult female Beagles, negative pressure wound therapy (NPWT) did not significantly affect the tissue concentrations of cefazolin compared to nonadherent dressings, indicating similar antibiotic delivery in both treatment methods.

Cefazolin was administered intravenously and monitored through tissue biopsies and plasma samples, showing that both NPWT and nonadherent dressings maintained comparable cefazolin levels in wound tissue over the 3-day treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefazolin concentration in surgically created wounds treated with negative pressure wound therapy compared to surgically created wounds treated with nonadherent wound dressings. Coutin, JV., Lanz, OI., Magnin-Bissel, GC., et al.[2018]

In a study of 72 patients treated in an urban emergency department, 18% of parenteral antibiotics prescribed for wound care did not align with established literature guidelines, indicating a notable discrepancy in treatment practices.

The most commonly prescribed antibiotics were cefazolin and ceftriaxone, with discrepancies primarily involving these medications, leading to an excess cost of $380 during the study period, highlighting potential areas for improvement in adherence to treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overuse of parenteral antibiotics for wound care in an urban emergency department. Waldrop, RD., Prejean, C., Singleton, R.[2019]

In a study of 73 patients with non-invasive wound infections, adjuvant systemic antibiotic therapy showed a significant improvement in microbiological cure rates compared to placebo, particularly in eliminating susceptible bacteria.

While the clinical cleanliness of wounds did not show a statistically significant difference, the antibiotics effectively penetrated the wound exudate, promoting bacterial clearance and potentially enhancing wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of adjuvant systemic antibiotic therapy in localised wound infections among hospital patients: a comparative study. Huizinga, WK., Kritzinger, NA., Bhamjee, A.[2019]

The GelMA-based hydrogel drug delivery system (GelMA-DDS) effectively encapsulates the antibiotic cefazolin with up to 99% efficiency, allowing for precise local delivery to prevent and treat surgical site infections (SSIs).

Cefazolin released from the GelMA-DDS demonstrated dose-dependent antibacterial efficacy against S. aureus, indicating that this system can provide effective localized treatment while minimizing systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin. Vigata, M., O'Connell, CD., Cometta, S., et al.[2021]

Citations

1.

withpower.com

withpower.com/trial/phase-2-wounds-and-injuries-2-2024-88430

Antibiotic Injection for Non-Healing Wounds (TAI Trial)

Research suggests that cefazolin, when added to an irrigating solution, can help reduce infection rates in contaminated surgical wounds, indicating its ...

2.

clinicaltrials.ucbraid.org

clinicaltrials.ucbraid.org/trial/NCT06327113

Antibiotic Tumescent For Chronic Wounds

This Non-healing Wound study at University of California Health is now recruiting people ages 18 years and up.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5286546/

Wound Penetration of Cefazolin, Ciprofloxacin, Piperacillin ...

This initial report suggests that (1) vancomycin, ciprofloxacin, and piperacillin/tazobactam effectively penetrate wounds during NPWT and (2) cefazolin as well ...

4.

science.org

science.org/doi/10.1126/sciadv.ade7007

Breakthrough treatments for accelerated wound healing

In chronic wounds, advanced bandages target the dysregulated inflammatory phase, replace skin tissue, and protect against infection. In diabetic ...

5.

go.drugbank.com

go.drugbank.com/drugs/DB01327/clinical_trials?conditions=DBCOND0061499%2CDBCOND0015509&phase=2&purpose=treatment&status=recruiting

Cefazolin Recruiting Phase 2 Trials for Non Healing ...

Cefazolin Recruiting Phase 2 Trials for Non Healing Wounds / Wound Treatment ; NCT06327113. Antibiotic Tumescent For Chronic Wounds. Cefazolin (DB01327) ...

6.

mayoclinic.org

mayoclinic.org/drugs-supplements/cefazolin-injection-route/description/drg-20073267

Cefazolin (injection route) - Side effects & uses

Cefazolin injection is used to treat bacterial infections in many different parts of the body (eg, lungs, bladder, skin, bone and joints, and more).

7.

medlineplus.gov

medlineplus.gov/druginfo/meds/a682731.html

Cefazolin Injection: MedlinePlus Drug Information

Cefazolin injection is used to treat certain infections caused by bacteria. Cefazolin injection also may be used around the time of surgery.

8.

reference.medscape.com

reference.medscape.com/drug/ancef-kefzol-cefazolin-342492

Ancef, Kefzol (cefazolin) dosing, indications, interactions, ...

Medscape - Indication-specific dosing for Ancef, Kefzol (cefazolin), frequency-based adverse effects, comprehensive interactions, contraindications, ...

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/207131s009lbl.pdf

cefazolin injection - accessdata.fda.gov

The safety and effectiveness of Cefazolin Injection for perioperative prophylaxis have not been established in pediatric patients younger than 10 years old.

10.

drugs.com

drugs.com/mtm/cefazolin-injection.html

Cefazolin injection Uses, Side Effects & Warnings

Cefazolin is an antibiotic that is used in adults and children at least 1 month old to treat bacterial infections of the lungs, bone and joints, urinary tract, ...