Single-Dose Antibiotics for Preventing Surgical Site Infections

Overseen By Mariana Phillips, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Carilion Clinic

Must not be taking: Antibiotics

Disqualifiers: Mental impairment, Pregnancy, Recent prosthetic, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

1600 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any antibiotics within 48 hours before the surgery. Other medications are not mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Cephalexin in preventing surgical site infections?

A study found that a single 2 g dose of Cephalexin given before surgery was effective in preventing surgical site infections after skin lesion excisions on the lower limb. Additionally, a retrospective study showed that using prophylactic antibiotics, including Cephalexin, significantly reduced surgical site infections and shortened hospital stays. ^{1 2 3 4 5}

Is cephalexin generally safe for humans?

Cephalexin is generally considered safe for humans, with common side effects including mild stomach issues and skin reactions. In studies, about 4.8% to 4.95% of patients experienced drug-related adverse effects, which were mostly mild. ^{3 6 7 8 9}

How does the single-dose antibiotic drug for preventing surgical site infections differ from other treatments?

The single-dose antibiotic treatment for preventing surgical site infections is unique because it involves administering a single dose of antibiotics, such as cephalexin, before surgery, which can be as effective as multiple doses. This approach reduces the risk of antibiotic resistance, lowers costs, and minimizes side effects compared to traditional multi-dose regimens. ^{1 3 10 11 12}

What is the purpose of this trial?

The purpose of the study is to assess the effectiveness of a single dose of preoperative antibiotic in reducing surgical site infections in certain dermatological procedures. Patients will undergo surgical excision or Mohs surgery as is clinically indicated and part of usual care. The study will be a double blinded, placebo-controlled clinical trial. Patients meeting inclusion criteria will be assigned to one of three participant categories: 1) patients undergoing repair with skin flap or graft on the nose, 2) patients undergoing repair with skin graft, flap, or wedge resection on the ear, or 3) patients undergoing Mohs surgery with closure or partial closure or surgical excision on the lower extremity below the knee. Within each category, participants will be randomized into one of two groups: group one will receive a preoperative placebo pill and group two will receive preoperative antibiotic prophylaxis (either a single dose of Cephalexin 2g PO or single dose of Clindamycin hydrochloride 600 mg PO if allergy to penicillin or cephalosporin). Patients will followed for 30 days +/- 7 after surgery to evaluate for any surgical site infection.

Research Team

Mariana Phillips, MD

Principal Investigator

Carilion Clinic Dermatology and Mohs Surgery

Eligibility Criteria

This trial is for adults over 18 who need certain skin surgeries at Carilion Clinic Dermatology in Roanoke, VA. It's for those getting skin flap or graft on the nose, ear repairs, or Mohs surgery below the knee. People with other conditions that could interfere are not eligible.

Inclusion Criteria

I am expected to have a one-time nose surgery involving skin repair.

I am expected to have a one-time ear surgery involving skin grafts or reshaping.

I am having or had skin surgery below the knee.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of preoperative antibiotic or placebo prior to dermatologic surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for surgical site infections for 30 days after surgery

4-5 weeks

1-2 visits (in-person or virtual)

Treatment Details

Interventions

• Cephalexin
• Placebo capsules

Trial Overview The study tests if a single dose of an antibiotic (Cephalexin or Clindamycin) before surgery can prevent infections better than a placebo. Patients are randomly given either the real drug or a fake pill without knowing which one they received.

Participant Groups

Group I: Antibiotic- nose Experimental Treatment 1 Intervention

The administration time of the oral antibiotics will be 5-15 minutes prior to surgery on the nose. 4-500 mg capsules of cephalexin will be administered to the patient. If there is concern for previous allergy to cephalexin, 4-150 mg capsules of clindamycin hydrochloride will be administered PO.

Group II: Antibiotic- leg Experimental Treatment 1 Intervention

The administration time of the oral antibiotics will be 30 minutes prior to incision in the leg group. 4-500 mg capsules of cephalexin will be administered to the patient. If there is concern for previous allergy to cephalexin, 4-150 mg capsules of clindamycin hydrochloride will be administered

Group III: Antibiotic- ear Experimental Treatment 1 Intervention

The administration time of the oral antibiotics will be 5-15 minutes prior to surgery on the ear. 4-500 mg capsules of cephalexin will be administered to the patient. If there is concern for previous allergy to cephalexin, 4-150 mg capsules of clindamycin hydrochloride will be administered PO.

Group IV: Placebo - leg Placebo Group 1 Intervention

If randomized to placebo group, 4 placebo capsules will be administered PO 30 minutes prior to incision in the leg group.

Group V: Placebo- nose Placebo Group 1 Intervention

If randomized to placebo group, 4 placebo capsules will be administered PO 5-15 minutes prior to surgery on the nose.

Group VI: Placebo- ear Placebo Group 1 Intervention

If randomized to placebo group, 4 placebo capsules will be administered PO 5-15 minutes prior to surgery on the ear.

Who Is Running the Clinical Trial?

Carilion Clinic

Lead Sponsor

Trials

85

Recruited

15,400+

Findings from Research

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]

Ceftibuten is the most effective oral cephalosporin against Enterobacteriaceae that produce plasmid-encoded broad spectrum beta-lactamases, outperforming several other antibiotics.

In a pharmacodynamic model, ceftibuten demonstrated bactericidal activity against Haemophilus influenzae and Streptococcus pneumoniae at concentrations similar to those achieved in human serum after a 200 mg oral dose taken twice daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftibuten and bactericidal kinetics. Comparative in vitro activity against Enterobacteriaceae producing extended spectrum beta-lactamases. Bauernfeind, A.[2019]

In a study of 52 patients undergoing lower limb skin lesion excision, a single 2 g dose of cephalexin given before surgery showed a reduction in surgical site infections (SSI) from 35.7% in the placebo group to 12.5% in the cephalexin group, indicating a potential benefit of the antibiotic.

Although the results suggested a 65% relative reduction in infection rates, the study was underpowered to definitively confirm this effect, highlighting the need for further research to establish the efficacy of cephalexin in preventing SSIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of surgical site infection in lower limb skin lesion excisions with single dose oral antibiotic prophylaxis: a prospective randomised placebo-controlled double-blind trial. Smith, SC., Heal, CF., Buttner, PG.[2022]

The study found that administering prophylactic antibiotics before surgery significantly reduced the occurrence of surgical site infections (SSIs), with only one infection in the group that received antibiotics compared to three infections in the group that did not.

Patients who received preoperative antibiotics had a shorter average hospital stay (38.5 hours) compared to those who did not receive antibiotics (57.3 hours), indicating both safety and efficacy of the antibiotic prophylaxis in surgical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Antibiotics for the Prevention of Surgical Site Infections in Two Government Hospitals in Taif, Saudi Arabia: A Retrospective Study. Alsaeed, OM., Bukhari, AA., Alshehri, AA., et al.[2022]

In a study involving 221 patients undergoing elective colorectal surgery, amoxycillin-clavulanic acid and cefotetan were found to have similar efficacy in preventing postoperative infections, with failure rates of 10% and 13% respectively.

The trial demonstrated that both antibiotics are effective prophylactic options, as there was no significant difference in infection rates between the two groups (P = 0.63), indicating that either can be safely used for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose amoxycillin-clavulanic acid vs. cefotetan for prophylaxis in elective colorectal surgery: a multicentre, prospective, randomized study. The PRODIGE Group. Arnaud, JP., Bellissant, E., Boissel, P., 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 401 patients with acute localized skin or soft tissue infections, both ofloxacin and cephalexin demonstrated similar high rates of microbiologic cure, with 93.4% for ofloxacin and 94.0% for cephalexin.

Ofloxacin was found to be as effective as cephalexin in clinical outcomes, with 85.2% of patients showing clinical cure or improvement, while also being well tolerated, although it had a slightly higher rate of drug-related adverse effects (7.9% vs. 4.8% for cephalexin).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ofloxacin versus cephalexin for treating skin and soft tissue infections. Lipsky, BA., Yarbrough, DR., Walker, FB., et al.[2019]

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]

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 838 adult patients undergoing cardiac surgery, a single dose of cefazolin was found to be less effective than a 24-hour regimen in preventing surgical site infections, with infection rates of 8.3% versus 3.6%, respectively.

Despite the higher infection rate with single-dose cefazolin, there were no significant differences in mortality or hospitalization duration between the two groups, indicating that while single-dose may be less effective, it does not impact overall patient outcomes in terms of survival or length of stay.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of single-dose and 24-hour multiple-dose antibiotic prophylaxis for cardiac surgery. Tamayo, E., Gualis, J., Flórez, S., et al.[2013]

In a study using Swiss-Webster mice, both single and multiple doses of cefazolin significantly reduced wound bacterial concentrations and infection rates compared to a control group, indicating its effectiveness in preventing wound infections.

Cefonicid, despite its extended half-life, did not show superior efficacy over a single dose of cefazolin, suggesting that cefazolin is a cost-effective option for surgical prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of antibiotic prophylaxis. An experimental study. Scher, KS., Wroczynski, AF., Jones, CW.[2019]

A single 1g dose of cefotaxime was found to be more effective than multiple-dose regimens in preventing surgical wound infections, particularly in clean and clean-contaminated surgeries, with fewer infections reported (p < 0.05) when excluding colorectal procedures.

Patients receiving single-dose cefotaxime experienced significantly fewer adverse reactions (p < 0.001) and lower costs compared to traditional multiple-dose regimens, confirming its safety, efficacy, and economic advantage for surgical prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefotaxime single-dose surgical prophylaxis in a prepaid group practice. Comparisons with other cephalosporins and ticarcillin/clavulanic acid. Jones, RN., Slepack, JM., Wojeski, WV.[2018]

References

1. Italy pubmed.ncbi.nlm.nih.gov

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

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

Ceftibuten and bactericidal kinetics. Comparative in vitro activity against Enterobacteriaceae producing extended spectrum beta-lactamases. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Prevention of surgical site infection in lower limb skin lesion excisions with single dose oral antibiotic prophylaxis: a prospective randomised placebo-controlled double-blind trial. [2022]

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

The Use of Antibiotics for the Prevention of Surgical Site Infections in Two Government Hospitals in Taif, Saudi Arabia: A Retrospective Study. [2022]

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

Single-dose amoxycillin-clavulanic acid vs. cefotetan for prophylaxis in elective colorectal surgery: a multicentre, prospective, randomized study. The PRODIGE Group. [2019]

6. United States 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Ofloxacin versus cephalexin for treating skin and soft tissue infections. [2019]

8. 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]

9. United States 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. [2021]

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

Comparative study of single-dose and 24-hour multiple-dose antibiotic prophylaxis for cardiac surgery. [2013]

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

Duration of antibiotic prophylaxis. An experimental study. [2019]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Cefotaxime single-dose surgical prophylaxis in a prepaid group practice. Comparisons with other cephalosporins and ticarcillin/clavulanic acid. [2018]