Vancomycin + Cefazolin for Surgical Site Infections

(PICS Trial)

No longer recruiting at 4 trial locations

Overseen By Dominik Mertz, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hamilton Health Sciences Corporation

Must not be taking: Antibiotics

Disqualifiers: MRSA, Beta-lactam allergy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2-3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different antibiotic methods to prevent infections after open-heart surgery. Researchers aim to determine if adding vancomycin (also known as Vancocin) to the usual cefazolin treatment can reduce surgical site infections. The trial also compares short-term and long-term antibiotic use to identify which is more effective with fewer side effects. Ideal participants are adults undergoing open-heart surgery who aren't already taking antibiotics and aren't known carriers of MRSA, a type of resistant bacteria. As an unphased trial, this study allows participants to contribute to important research that could enhance infection prevention strategies for future patients.

Do I need to stop my current medications to join the trial?

The trial requires that you are not on antibiotics at the time of surgery. If you are taking antibiotics, you would need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cefazolin is generally well-tolerated by patients. In a study of 420 patients who received cefazolin, less than 2% had lab results necessitating hospital readmission or a change in treatment. This suggests that cefazolin is a safe option for many individuals.

When vancomycin is added to cefazolin, the safety profile becomes less clear. Some studies have found that using both drugs together is not more effective than using cefazolin alone for preventing infections after surgery. Additionally, the combination increases the risk of certain side effects, such as kidney problems or allergic reactions, although these side effects are uncommon.

In summary, cefazolin alone has a strong safety record, while adding vancomycin may introduce additional risks. These factors are important to consider when evaluating participation in a trial involving these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the potential of using vancomycin and cefazolin together as treatments for surgical site infections because these combinations may offer more effective protection against a broader range of bacteria compared to standard options. Typically, cefazolin is used alone for surgical prophylaxis, but adding vancomycin could target resistant bacteria like MRSA, which cefazolin alone might miss. Additionally, the trial explores both short and long courses of these treatments, potentially offering flexibility in dosing that could minimize side effects while still providing strong infection prevention. This approach not only aims to enhance efficacy but also to provide tailored treatment protocols based on patient needs and surgical conditions.

What evidence suggests that this trial's treatments could be effective for surgical site infections?

Research has shown that cefazolin alone can greatly reduce infections at surgical sites. One study found that infection rates dropped from 15% to 3% with cefazolin. In this trial, some participants will receive cefazolin monotherapy, either as a short or long course. Others will receive a combination of cefazolin and vancomycin, also as a short or long course. When vancomycin is added to cefazolin, results are mixed. Some research found no additional benefit in preventing infections with both drugs together. However, a few studies suggest that using both drugs can reduce infections by nearly 10 times. Effectiveness can vary depending on the type of surgery and other factors. ^{1 4 6 7 8}

Who Is on the Research Team?

Dominik Mertz, MD

Principal Investigator

Hamilton Health Sciences Corporation

Are You a Good Fit for This Trial?

Adults (18+) needing open-heart surgery can join this trial. It's not for those already on antibiotics, previous participants, known MRSA carriers, people allergic to beta-lactams that prevent cefazolin use, or anyone in another interfering study.

Inclusion Criteria

I am 18 or older and will have open-heart surgery.

Exclusion Criteria

Beta-lactam allergy (IgE-mediated) precluding the use of cefazolin

I am a known carrier of MRSA.

Previous enrollment in this trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either cefazolin monotherapy or combination therapy with vancomycin, with short or long course regimens administered around the time of surgery

2-3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of surgical site infections and other outcomes

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cefazolin
• Vancomycin

Trial Overview The trial is testing if adding vancomycin to standard cefazolin before heart surgery prevents infections better and whether short-term antibiotic use is as good as long-term. It's a pilot study to see if a larger trial would work.

How Is the Trial Designed?

Group I: Combination therapy, short course Experimental Treatment 2 Interventions

One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered. In addition, one dose of vancomycin 60-90min pre-op will be administered.

Group II: Combination therapy, long course Experimental Treatment 2 Interventions

One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered followed by additional five doses every eight hours postoperatively (last dose 44 hours after the first dose). In addition, one dose of vancomycin 60-90min pre-op will be administered followed by 3 post-op doses every 12 hours (last dose 36 hours after first dose)

Group III: Cefazolin monotherapy, short course Experimental Treatment 1 Intervention

One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered

Group IV: Cefazolin monotherapy, long course Experimental Treatment 1 Intervention

One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered followed by additional five doses every eight hours postoperatively (last dose 44 hours after the first dose).

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

The Physicians' Services Incorporated Foundation

Collaborator

Trials

165

Recruited

31,700+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31681684/

Randomized controlled trial of cefazolin monotherapy ... Result: There was an overall significant reduction in the incidence of SSI (15% vs 3%; P = 0.03), endometritis (8% vs 2%; P = 0.048), and post- ...

2. academic.oup.com academic.oup.com/ofid/article/12/10/ofaf592/8263024

Evaluation of the Safety of Cefazolin Monotherapy in ... RESULTS ; Treatment complication · 55 (13.1%) ; Antimicrobial agent change, 25 (6.0%) ; Readmission, 39 (9.3%) ; Death, 2 (0.5%).

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301401

Trial of Vancomycin and Cefazolin as Surgical Prophylaxis ... The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1341321X25002302

Evaluation of Cefazolin <3 g vs. 3 g Treatment Doses ... Cefazolin 3g was associated with a higher probability of a better outcome in patients ≥120 kg with cellulitis with no difference in adverse ...

5. journals.asm.org journals.asm.org/doi/10.1128/aac.00494-24

Plasma and tissue concentrations of 2 g prophylactic cefazolin ... 2 g of prophylactic cefazolin demonstrates adequacy in maintaining coverage for a duration of at least 80 minutes of surgery below the level of the knee.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9643560/

Appropriateness of choice and duration of surgical ... Surgical site infections (SSIs) develop within 30–90 days postoperatively. Antibiotic prophylaxis helps reduce SSI incidence, with cefazolin being the most used ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1341321X25002302

Evaluation of Cefazolin <3 g vs. 3 g Treatment Doses ... Cefazolin 3g was associated with a higher probability of a better outcome in patients ≥120 kg with cellulitis with no difference in adverse ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9025420/

Cefazolin Might Be Adequate for Perioperative Antibiotic ... Cefazolin Might Be Adequate for Perioperative Antibiotic Prophylaxis in Intra-Abdominal Infections without Sepsis: A Quality Improvement Study.