Antibiotics for Preventing Surgical Infections

Overseen By Curtis Gregoire, MD, DDS, MSc

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Abdul El-Rabbany

Must not be taking: Antibiotics, Immunosuppressants

Disqualifiers: Immunosuppression, Infections, Allergies, 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: 5

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether extra doses of antibiotics after jaw surgery prevent infections. It focuses on individuals undergoing orthognathic surgery, a procedure that corrects jaw issues and can improve speech and sleep. Participants will receive either a single dose of antibiotics before surgery or additional doses afterward. The trial seeks individuals having this type of jaw surgery who have no recent infections or allergies to the antibiotics used. The goal is to determine if post-surgery antibiotics are beneficial or if they can be safely omitted to reduce antibiotic resistance. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand its benefits for more patients.

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 used antibiotics in the two weeks before the trial, you would not be eligible to participate.

What is the safety track record for cefazolin in preventing surgical infections?

Research shows that cefazolin, the antibiotic tested in this trial, is generally safe for use during surgeries. Studies have found that cefazolin effectively lowers the risk of infections at the surgery site compared to antibiotics like clindamycin or vancomycin, helping prevent infections without increasing allergic reactions.

Cefazolin is usually well-tolerated, with mild side effects such as an upset stomach or a skin rash. Serious side effects are rare. Since this trial is in Phase 4, cefazolin is already approved for use, further supporting its safety.

There is some debate about whether extra doses after surgery are needed to further reduce infections, but no strong evidence shows harm from these additional doses in the short term. However, concerns exist about overuse leading to resistance, highlighting the importance of this study. Overall, cefazolin appears to be a safe choice for preventing infections during surgeries like those being studied. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore different dosing strategies of Cefazolin to prevent infections after orthognathic surgery. Unlike standard care that typically involves a single pre-operative dose or extended antibiotic courses, this trial investigates a 24-hour dosing regimen that includes multiple doses post-surgery, potentially offering more sustained protection. The single-dose approach aims to simplify administration while minimizing antibiotic use, which could help reduce the risk of antibiotic resistance. These strategies could lead to improved surgical outcomes and more efficient antibiotic use, which is especially crucial in the context of rising antibiotic resistance.

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

Research has shown that taking antibiotics like cefazolin before jaw surgery can greatly lower the risk of infections at the surgery site. One study found that patients who took cefazolin had a 6.2% infection rate, which was lower than those who took other antibiotics. This trial will compare two approaches: a single pre-operative dose of cefazolin and a 24-hour dosing regimen. Although some studies suggest a slight benefit to taking antibiotics after surgery, the evidence isn't strong enough to outweigh the risks, such as antibiotic resistance. Consequently, the World Health Organization advises against using antibiotics after surgery. The main focus is on taking a single dose before surgery, as this has been proven to help reduce infections. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients over the age of 16 who are healthy or have mild systemic disease (ASA 1 and 2) and are scheduled for orthognathic surgery to correct jaw deformities. It aims to determine if additional post-operative antibiotics reduce infection risk without contributing significantly to antibiotic resistance.

Inclusion Criteria

I am over 16 and considered low risk for surgery complications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Pre-operative Assessment

Informed consent is obtained and participants are randomly assigned to treatment groups

Days leading up to surgery

1 visit (in-person)

Surgery and Immediate Post-operative Care

Participants undergo orthognathic surgery and receive assigned antibiotic regimen

1 day

Inpatient stay

Follow-up

Participants are monitored for surgical site infections and adverse effects

6 weeks

3 visits (in-person) at 2, 4, and 6 weeks post-operatively

What Are the Treatments Tested in This Trial?

Interventions

• Cefazolin

Trial Overview The study compares two groups: Group A receives a single pre-operative dose of cefazolin, while Group B gets the same plus three more doses after surgery. The goal is to see if more antibiotics post-surgery prevent infections better than just one dose before surgery.

How Is the Trial Designed?

Group I: Single Dose Experimental Treatment 1 Intervention

Single pre-operative dose of 2g IV Cefazolin given prior to first incision for orthognathic surgical procedure

Group II: 24-Hour Dosing Active Control 1 Intervention

Single pre-operative dose of 2g IV Cefazolin given prior to first incision for orthognathic surgical procedure, as well as 2g IV Cefazolin q8h post-operatively for 24 hours (3 total doses)

Who Is Running the Clinical Trial?

Abdul El-Rabbany

Lead Sponsor

Trials

1

Recruited

400+

Published Research Related to This Trial

Cefazolin is associated with fewer adverse events and lower rates of surgical site infections compared to alternative antibiotics used for surgical prophylaxis, highlighting its efficacy and safety.

In a study of perioperative inpatients across 100 U.S. hospitals, patients with a documented β-lactam allergy were significantly less likely to receive cefazolin, while clindamycin was much more frequently prescribed, indicating a potential shift in antibiotic choice despite cefazolin's advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of β-Lactam Allergy Documentation and Prophylactic Antibiotic Use in Surgery: A National Cross-Sectional Study of Hospitalized Patients. Bertram, CM., Postelnick, M., Mancini, CM., et al.[2021]

In a study of 200 patients undergoing abdominal surgery, the use of cefazolin (Kefzol) significantly reduced the infection rate from 25% in the control group to 9% in the group receiving the antibiotic, demonstrating its effectiveness in preventing post-surgical infections.

Cefazolin also notably decreased wound infections, particularly after gall bladder and bile duct surgeries, and was found to be effective against 87.5% of bacterial strains tested, suggesting it can lower treatment costs by reducing infection-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the effectiveness of cefazolin++ (Kefzol) in preventing infections in patients after abdominal surgery]. Chaber, A., Wójcik, Z., Słotwiński, R., et al.[2013]

In a study of 3802 cardiac surgery patients, those who underwent preoperative penicillin allergy evaluation were significantly more likely to receive cefazolin, the first-line antibiotic, with 92% receiving it compared to only 38% of those without evaluation.

The evaluation process revealed that 97% of patients tested were not actually allergic to penicillin, highlighting the importance of allergy assessments in improving antibiotic prophylaxis and reducing surgical site infection risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative penicillin allergy testing in patients undergoing cardiac surgery. Plager, JH., Mancini, CM., Fu, X., et al.[2021]

Cefazolin is recommended for preventing surgical wound infections in bariatric surgery, based on a systematic review of seven studies, including three clinical trials and four observational studies.

However, some studies indicated that the serum and tissue levels of cefazolin after administration may be suboptimal, suggesting that further research is needed to optimize dosing and timing for effective prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic prophylaxis in obese patients submitted to bariatric surgery. A systematic review. Fischer, MI., Dias, C., Stein, A., et al.[2018]

In a retrospective evaluation, 86% of patients without a penicillin adverse drug reaction (ADR) received cefazolin for surgical antibiotic prophylaxis, compared to only 28% of patients with a penicillin ADR.

Patients with a penicillin ADR were more likely to receive broad-spectrum antibiotics, which were also associated with a higher incidence of perioperative adverse drug events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability of surgical prophylaxis in penicillin-allergic children. Butler, DF., Lee, BR., Suppes, S., et al.[2019]

In a systematic review of 6147 patients, only 0.7% had a dual allergy to cefazolin and natural penicillins, indicating that most patients with a history of penicillin allergy can safely receive cefazolin as a preoperative antibiotic.

Patients with confirmed penicillin allergies showed a higher dual allergy frequency of 3.0%, suggesting that extra caution is needed for this group when considering cefazolin administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin: A Systematic Review and Meta-analysis. Sousa-Pinto, B., Blumenthal, KG., Courtney, L., et al.[2022]

In a double-blind trial involving elective colorectal surgery, prophylactic administration of Cefazolin significantly reduced the incidence of postoperative wound infections from 32% in the control group to 10% in the treated group (P < 0.01).

Patients receiving Cefazolin also experienced a significant reduction in hospital stay by about 3 days (P < 0.05), indicating both safety and efficacy of the antibiotic in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antibiotic prophylaxis in colon surgery with Cefazolin]. Dürig, M., Neff, U., Rittmann, WW., et al.[2013]

In a study of 201 patients undergoing cholecystectomy, those who received a single preoperative dose of cephazolin had a significantly lower rate of wound sepsis (3.2%) compared to the control group (16.9%) who did not receive the antibiotic.

Patients who received both a preoperative dose and a five-day postoperative course of cephazolin had a wound sepsis rate of 5.5%, indicating that while additional postoperative antibiotics may provide some benefit, the single preoperative dose was the most effective in reducing infection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic use of cephazolin against wound sepsis after cholecystectomy. Strachan, CJ., Black, J., Powis, SJ., et al.[2019]

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]

In a study of 57 patients undergoing elective surgery, 26% did not comply with national guidelines for cefazolin administration, which is used to prevent surgical-site infections (SSI).

Among those who did not follow the guidelines, 67% had low cefazolin levels at the end of the procedure, indicating a significant risk for inadequate infection prevention, while compliance with guidelines resulted in better outcomes, though it did not guarantee sufficient antibiotic levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

End-of-procedure cefazolin concentrations after administration for prevention of surgical-site infection. Koopman, E., Nix, DE., Erstad, BL., et al.[2019]

A single dose of 1 g of cephazolin significantly reduced the rate of postoperative infections in patients undergoing clean lumbar spine surgeries, with 9 infections in the cephazolin group compared to 21 in the placebo group (p < 0.05).

While cephazolin was effective in reducing infections, it was associated with a higher isolation rate of cephazolin-resistant pathogens, indicating a potential risk for developing antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative prophylactic cephazolin in spinal surgery. A double-blind placebo-controlled trial. Rubinstein, E., Findler, G., Amit, P., et al.[2022]

In a study of 118 women undergoing breast cancer surgery, prophylactic cefazolin did not significantly reduce the overall incidence of postoperative wound infections compared to a placebo, with only three infections in the cefazolin group versus five in the placebo group.

However, cefazolin did delay the onset of infection, with an average of 17.7 days for the cefazolin group compared to 9.6 days for the placebo group, suggesting it may provide some benefit in prolonging the time before infection occurs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy. Wagman, LD., Tegtmeier, B., Beatty, JD., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26917207/

Prevalence of Surgical Site Infections Following ... The prevalence of infection was significantly lower in the cefazolin group (6.2%) compared with the penicillin (14.3%; P < .0001) and clindamycin (10.4%; P < .

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05852158?term=CEFAZOLIN%20INJECTION&rank=7

Study Details | NCT05852158 | Antibiotics for Prevention of ... The primary outcome of this study is the rate of development of surgical site infection following the described antibiotic protocols. Secondary outcomes are ...

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. academic.oup.com academic.oup.com/ofid/article/10/6/ofad224/7137405

Cefazolin vs Second-line Antibiotics for Surgical Site Infection ... Patients allergic to beta-lactams receiving cefazolin had fewer surgical site infections after total joint arthroplasties compared clindamycin and/or vanco.

5. ajog.org ajog.org/article/S0002-9378(24)00507-6/fulltext

Metronidazole and cefazolin vs cefazolin alone for surgical ... The addition of metronidazole to cefazolin before gynecologic surgery decreased the surgical site infection rate by half, even after accounting ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10289809/

Cefazolin vs Second-line Antibiotics for Surgical Site ... Overall, cefazolin was shown to have a significantly lower frequency of SSI compared with clindamycin and/or vancomycin without an increased risk of HSR.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27789268/

A Double-Blind, Randomized Controlled Trial on a 3-Day ... Three days of postoperative cefazolin and cephalexin markedly decreases SSI rates compared with 1 day. However, the number needed to treat of 10 suggests ...

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2667070

Effect of Antibiotic Prophylaxis on Surgical Site Infections ... A single preoperative dose of intravenous cefazolin did not reduce the risk of surgical site infection within 30 days following removal of orthopedic implants.