Antibiotics for Facial Reconstructive Surgery

Overseen By Jeffrey S Moyer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Michigan

Must not be taking: Systemic antibiotics

Disqualifiers: Antibiotic intolerance, Cutaneous malignancy, 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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

300 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used systemic antibiotics within one week before surgery.

What data supports the effectiveness of the drug cephalexin for facial reconstructive surgery?

Cephalexin is effective in treating skin and soft-tissue infections, achieving cure rates of 90% or higher, which suggests it could be beneficial in preventing infections after facial reconstructive surgery. Additionally, in a study on endoscopic skull base surgery, a regimen including cephalexin showed low rates of postoperative infections, supporting its use in surgical settings. ^{1 2 3 4 5}

Is cephalexin safe for use in humans?

Cephalexin, a type of antibiotic, is generally safe for treating skin and soft tissue infections, with common side effects being mild skin reactions and stomach issues. In studies, only about 5% of patients stopped using it due to side effects, indicating it is well-tolerated by most people. ^{6 7 8 9 10}

How does the drug used in the clinical trial for facial reconstructive surgery differ from other treatments?

The antibiotics used in the trial, such as ceftriaxone, are unique because they can be administered as a single daily dose due to their long half-life, making them more convenient and cost-effective compared to other antibiotics like cefotaxime, which require more frequent dosing. ^{1 2 3 11 12}

What is the purpose of this trial?

Antibiotics are sometimes prescribed to patients who have had reconstructive surgery of wounds on their face using skin grafts. But, it is not yet known whether antibiotics improve the healing of skin grafts and reduce the risk of infections after surgery in these patients. It is known that antibiotics, like all medications, have side-effects although these are rare. This research study is designed to show us whether antibiotics improve wound healing or not, so that we may determine if we should continue using antibiotics even if they have side-effects in some patients. Our hypothesis is that patients treated with post-operative, systemic antibiotics will demonstrate a statistically significant improvement in the survival of their facial full thickness skin grafts compared to patients who are not treated with systemic antibiotics.

Research Team

Jeffrey Y Moyer, MD

Principal Investigator

University of Michigan Otolaryngology

Eligibility Criteria

This trial is for adults needing facial reconstruction with a full-thickness skin graft, without current or recent antibiotic use, no intolerance to clindamycin and cephalexin, and no previous reconstruction at the defect site.

Inclusion Criteria

I need surgery to repair a skin or soft tissue defect on my nose or face.

Exclusion Criteria

I have had reconstruction surgery at the site of my skin or soft-tissue defect before.

I found skin cancer at the site of my recent surgery.

intolerance to both clindamycin and cephalexin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive peri-operative antibiotics and, for some, post-operative antibiotics to assess their impact on skin graft survival

1 week

1 visit (in-person) for surgery and initial treatment

Follow-up

Participants are monitored for graft survival and any post-operative complications

1 year

Regular follow-up visits as needed

Treatment Details

Interventions

• Cephalexin

Trial Overview The study tests if post-operative antibiotics (cephalexin) improve the healing of facial skin grafts compared to not using them. The goal is to see if antibiotics should be used despite potential side effects.

Participant Groups

Group I: Antibiotics Experimental Treatment 1 Intervention

All patients will receive peri-operative antibiotics per standard practice. This consists of a single dose of cefazolin or, in penicillin allergic patients, clindamycin administered at the time of anesthesia administration prior to the surgical incision. In the cohort randomized to receive post-operative antibiotics, the first choice intervention will be oral cephalexin (500 mg, three times daily or four times daily, for one week). In patients who are penicillin or cephalosporin allergic, we will prescribe clindamycin (300 mg, three times daily or four times daily, for one week).

Group II: No antibiotic treatment Active Control 1 Intervention

Withholding post-operative antibiotics following reconstructive surgery necessitating skin grafting for defects of the face or nose.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Findings from Research

In a study of 60 patients undergoing cervicofacial surgery, both cefotaxime and ceftriaxone were effective as short-term prophylactic antibiotics, with only one postoperative infection observed.

Ceftriaxone is advantageous due to its longer half-life, allowing for a single daily dose, and it is also more cost-effective compared to cefotaxime.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial prophylaxis in head and neck surgery. Panosetti, E., Lehmann, W., Smolik, JC.[2018]

Cephalexin is a highly effective antibiotic for treating streptococcal and staphylococcal skin infections, achieving cure rates of 90% or higher over 12 years of use.

It is well-absorbed and bioavailable, with a twice-daily dosage that improves patient compliance, and its mild side effects make it suitable for young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cephalexin in the treatment of skin and soft-tissue infections. Derrick, CW., Reilly, K.[2013]

In a study involving 350 patients, the use of single intravenous injections of antibiotics (Ceftriaxon, Rocifen, Lyncomycin) before surgery effectively prevented postoperative purulent complications in closed mandibular fractures and reconstructive maxillo-facial operations.

The antibiotics also significantly reduced the frequency of complications in cases of open fractures of the mandible and nasal bones, highlighting their efficacy in maxillo-facial surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevention of postoperative inflammatory complications in patients with maxillo-facial region pathology]. Basitkhanova, EI.[2012]

In a study of 132 patients undergoing endoscopic endonasal transsphenoidal surgery, a standardized antibiotic regimen of cefazolin followed by cephalexin resulted in low rates of postoperative infections, with only 4% developing sinusitis and 3% pneumonia.

The study found that despite a high rate of intraoperative cerebrospinal fluid leaks (40%), there were no cases of meningitis, indicating the efficacy and safety of the 7-day antibiotic protocol in preventing serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Antibiotic Use in Endoscopic Endonasal Skull Base Surgery. Nakhla, MN., Wu, TJ., Villalpando, EG., et al.[2022]

In a study of 44 patients undergoing mandibular surgery, oral levofloxacin demonstrated a high efficacy rate of 95% for preventing postoperative infections, comparable to the 85.7% efficacy of intravenous cefazolin sodium.

Levofloxacin achieved effective concentrations in both serum and mandibular bone marrow, suggesting it is a safe and cost-effective alternative to intravenous antibiotics for this type of surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized prospective study of oral versus intravenous antibiotic prophylaxis against postoperative infection after sagittal split ramus osteotomy of the mandible. Yoda, T., Sakai, E., Harada, K., et al.[2022]

Acute rhinosinusitis is a leading cause of antibiotic prescriptions globally, raising concerns about antibiotic resistance and the safety of commonly used antibiotics like macrolides and fluoroquinolones.

A surveillance study on the new cephalosporin drug Spectracef (Cefditoren) showed promising efficacy and safety for treating acute bacterial rhinosinusitis, particularly due to its different chemical structure that may reduce the risk of cross-allergy with penicillins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A study of the efficacy and safety of new cephalosporin in the treatment of acute bacterial rhinosinusitis]. Savlevich, EL., Kozlov, VS., Zharkykh, MA.[2018]

In two randomized studies involving 343 patients, cephalexin hydrochloride was found to be as effective as cephalexin monohydrate for treating skin and soft tissue infections, with high response rates of 95.7% and 96.5% respectively.

Both formulations demonstrated a similar safety profile, with only 4.95% of patients experiencing adverse events, indicating that cephalexin hydrochloride is a safe and effective option for these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. Kumar, A., Murray, DL., Hanna, CB., et al.[2021]

In a study of over 6 million individuals, new penicillin allergies were reported more frequently after parenteral exposure (0.85%) compared to oral exposure (0.74%), indicating a higher risk of allergic reactions with injectable forms.

Anaphylaxis was rare, with only 22 cases associated with oral penicillin and 3 with parenteral penicillin, suggesting that while allergic reactions can occur, they are infrequent. Additionally, Clostridioides difficile infections were more common after parenteral antibiotic use, highlighting a potential safety concern with these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Reactions Associated with Penicillins, Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study. Liang, EH., Chen, LH., Macy, E.[2021]

Third generation cephalosporins are a safe class of antibiotics with fewer side effects and lower allergenic potential compared to other antibiotics like penicillins and aminoglycosides, making them suitable for use in various healthcare settings.

While generally safe, some third generation cephalosporins can cause specific issues such as hypoprothrombinemia and disulfiram-like reactions, and they may lead to increased diarrhea and risk of drug-resistant bacteria if not monitored properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Third generation cephalosporins: safety profiles after 10 years of clinical use. Neu, HC.[2019]

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 single intravenous dose of ceftriaxone (1 or 2 g) administered one hour before elective surgery was highly effective, achieving a therapeutic success rate of 92% in a study of 100 surgical patients.

This study supports the use of ceftriaxone as a short-term antimicrobial prophylaxis to prevent infections in surgical patients, highlighting its efficacy in a clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Short-term antibiotic prophylaxis with ceftriaxone in general surgery]. La Rosa, M., Pagano, D., Cancelliere, M., et al.[2013]

Cephalexin, a new antibiotic related to cephaloglycin, shows excellent oral absorption and minimal serum binding, which enhances its effectiveness despite lower in vitro antimicrobial activity compared to cephaloglycin.

In experimental studies with mice, cephalexin demonstrated exceptional efficacy against bacterial infections, outperforming other antibiotics like tetracycline and chloramphenicol, indicating its potential for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cephalexin, a new orally absorbed cephalosporin antibiotic. Wick, WE.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Antimicrobial prophylaxis in head and neck surgery. [2018]

2. England pubmed.ncbi.nlm.nih.gov

The role of cephalexin in the treatment of skin and soft-tissue infections. [2013]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Prevention of postoperative inflammatory complications in patients with maxillo-facial region pathology]. [2012]

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

Perioperative Antibiotic Use in Endoscopic Endonasal Skull Base Surgery. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A randomized prospective study of oral versus intravenous antibiotic prophylaxis against postoperative infection after sagittal split ramus osteotomy of the mandible. [2022]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[A study of the efficacy and safety of new cephalosporin in the treatment of acute bacterial rhinosinusitis]. [2018]

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

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. [2021]

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

Adverse Reactions Associated with Penicillins, Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Third generation cephalosporins: safety profiles after 10 years of clinical use. [2019]

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

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

11. Italy pubmed.ncbi.nlm.nih.gov

[Short-term antibiotic prophylaxis with ceftriaxone in general surgery]. [2013]

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

Cephalexin, a new orally absorbed cephalosporin antibiotic. [2021]