Cephalexin for Surgical Infection Prevention

Overseen By Laura Barnes, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Pregnant, Breastfeeding, Male, 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: 4

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how effectively the antibiotic Cephalexin prevents infections after breast surgery. Researchers aim to determine if individuals with high levels of certain bacteria, such as Staphylococcus or Pseudomonas, have a higher likelihood of developing infections post-surgery. Participants are divided into two groups: one receives Cephalexin after surgery, while the other receives it only if they show signs of infection. Suitable candidates for the trial include those scheduled for a mastectomy due to breast cancer or genetic risk, who have not recently taken antibiotics or probiotics, and who are not allergic to the trial medications. As a Phase 2 trial, this research measures Cephalexin's effectiveness in an initial, smaller group, providing valuable insights into its potential benefits.

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 have taken antibiotics or probiotics within 90 days before joining the study.

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

Research has shown that cephalexin is a commonly used antibiotic to prevent infections after surgery. In some studies, surgeons preferred cephalexin, which is usually taken four times a day for about 5 to 7 days, to stop infections caused by bacteria like Staphylococcus. One study found that using cephalexin after surgery significantly reduced symptoms of wound infections.

Regarding safety, cephalexin is generally well-tolerated. It is often chosen for its effectiveness and safety. Research indicates that it is safe to use, even for most people who are allergic to penicillin. Some side effects have been reported, but they are usually mild and uncommon. Overall, cephalexin appears to be a safe choice for preventing surgical infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this trial because it explores the potential to reduce or even eliminate the need for postoperative antibiotics in surgical infection prevention. Unlike current standard practices that involve administering antibiotics for several days after surgery, this approach could minimize antibiotic use by relying only on pre-incision and 24-hour perioperative antibiotics. This could help reduce antibiotic resistance and side effects associated with prolonged antibiotic use, making surgeries safer and more efficient for patients.

What evidence suggests that Cephalexin might be an effective treatment for preventing surgical infections?

Research has shown that cephalexin can help prevent infections after surgery. In this trial, participants in Cohort A will receive standard antibiotics, possibly including cephalexin, to evaluate its effectiveness in reducing symptoms of wound infections caused by bacteria like Staphylococcus and Pseudomonas. One study found cephalexin to be the most commonly used antibiotic for preventing infections after surgery. Evidence suggests that using cephalexin as a preventive measure can lower infection rates, making it a promising option for preventing surgical infections. ^{1 4 5 6 7}

Who Is on the Research Team?

Merisa Piper, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with breast cancer or a genetic risk for it, who are planning to have mastectomy and immediate tissue expander or implant placement. They must be able to consent and at least 4 weeks post-chemo or radiation. Excluded are those with significant health risks, recent antibiotic use, pregnancy, breastfeeding, allergy to study antibiotics, males, and recent probiotic use.

Inclusion Criteria

I have a confirmed diagnosis of breast cancer or a genetic risk for it.

It has been over 4 weeks since I finished my chemotherapy or radiation therapy.

I am scheduled for a mastectomy with immediate tissue expander or implant placement.

Exclusion Criteria

I am a male.

Patients who have a documented or reported allergic reaction to the outlined antibiotics to be used in this study

You have taken antibiotics in the last 90 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

Participants undergo mastectomy with implant-based reconstruction and receive standard pre-incision antibiotics and 24-hour perioperative antibiotics

1 week

Intra-operative visit

Post-operative Treatment

Participants in Cohort A receive postoperative antibiotics for at least 7 days; Cohort B receives no antibiotics unless infection is present

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness, including microbiome sampling and infection assessment

12 weeks

Weekly visits for the first 4 weeks, then monthly

What Are the Treatments Tested in This Trial?

Interventions

• Cephalexin

Trial Overview The trial studies the link between the abundance of Staphylococcus/Pseudomonas in breast tissue microbiome before mastectomy and the risk of infection after placing tissue expanders/implants. Cephalexin's effectiveness against these infections is being tested.

How Is the Trial Designed?

Group I: Cohort A: Standard antibiotics Experimental Treatment 1 Intervention

Receive standard pre-incision antibiotics and 24-hour perioperative antibiotics - Prescribed standard postoperative antibiotics to take for at least 7 days post-operatively

Group II: Cohort B: No antibiotics Active Control 1 Intervention

Receive standard pre-incision antibiotics and 24-hour perioperative antibiotics - No antibiotics post-operatively, unless patient develops clinical evidence of infection

Cephalexin is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in European Union as Cefalexin for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in Canada as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in Switzerland as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

The Plastic Surgery Foundation

Collaborator

Trials

11

Recruited

1,300+

Published Research Related to This Trial

A study reviewing 325 patient charts found that adjusting electronic medical record alerting rules for β-lactam antibiotics resulted in no cases of anaphylaxis (0%) among patients who received these medications after being documented as allergic to penicillins.

The new alerting rules, which only flagged similar side chain antibiotics, effectively reduced unnecessary alerts for prescribers while maintaining patient safety, although some patients did experience non-anaphylactic delayed reactions like rashes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-lactam exposure outcome among patients with a documented allergy to penicillins post-implementation of a new electronic medical record system and alerting rules. Buffone, B., Lin, YC., Grant, J.[2022]

Cefotetan is effective in reducing the occurrence of surgical wound infections and postoperative infections in the genitourinary system, making it a valuable antibiotic for surgical prophylaxis and treatment.

The use of Cefotetan is associated with a very low incidence of side effects, highlighting its safety profile in the context of preventing nosocomial infections during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and control of surgical infections. Bertelli, A., Germiniani, R.[2013]

The implementation of a web-based antimicrobial approval system at the Royal Melbourne Hospital led to a significant reduction in the use of cefotaxime and ceftriaxone, decreasing from 38.3 to 21.2 defined daily doses per 1000 bed days over 15 months.

Concordance with national antibiotic guidelines improved from 25% to 51% within 5 months post-intervention, indicating that the system effectively promoted appropriate antibiotic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of a web-based antimicrobial approval system on broad-spectrum cephalosporin use at a teaching hospital. Richards, MJ., Robertson, MB., Dartnell, JG., et al.[2020]

In a study involving 60 patients undergoing elective laparoscopic cholecystectomy, oral cephalexin (CEX) was found to be as effective as intravenous cefazolin (CEZ) in preventing surgical site infections and other complications, indicating it can serve as a suitable alternative during CEZ shortages.

While both antibiotics showed similar efficacy, the oral group experienced significantly higher rates of postoperative nausea and vomiting, but had lower C-reactive protein levels on the first day after surgery, suggesting a potential benefit in inflammation control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of oral antibiotic prophylaxis in elective laparoscopic cholecystectomy during periods of limited cefazolin supply. Tsunematsu, M., Nakashima, S., Ishiyama, S.[2022]

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]

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]

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]

Cephalexin was highly effective in treating bacteriuria in 93 children, successfully eradicating sensitive bacteria in 97% of cases, regardless of factors like recurrence or renal function.

However, some patients, particularly those with major anatomical abnormalities, experienced recurrences with new, resistant organisms during a six-week follow-up, although the incidence of drug reactions was low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cephalexin in the management of bacteriuria. Fennell, RS., Walker, RD., Garin, EH., et al.[2017]

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 involving 100 patients at risk for bronchopulmonary complications after abdominal surgery, the combination of cephalexin and bromhexine demonstrated very good effectiveness and excellent tolerance.

This treatment is considered highly beneficial for both preventing and treating bronchopulmonary complications in post-surgical patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic and prophylactic effects of cephalexin and bromhexine in respiratory tract complications of abdominal surgery. Palmieri, B., Monni, S., Misella, A., et al.[2013]

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]

Cefotetan is as effective as cefoxitin for surgical prophylaxis and treating mild-to-moderate polymicrobial infections, making it a reliable alternative.

Cefotetan's longer serum elimination half-life allows for less frequent dosing compared to other antibiotics, which could improve patient compliance and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefotetan: a perspective for the surgical patient. Fry, DE.[2019]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36471429/

Effectiveness of postoperative oral administration ... We aimed at evaluating the effectiveness of postoperative oral administration of cephalexin and metronidazole on SSI among obese women undergoing CS.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4160501/

What are the Patterns of Prophylactic Postoperative Oral ... Cephalexin 500 mg four times a day was the most frequently used first-line prophylactic postoperative oral antibiotic. Trimethoprim/sulfamethoxazole was not an ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2352587824000172

Efficacy of 24 hours versus 5 days of prophylactic ... 204 patients met the inclusion criteria: 104 in the 5-day group and 100 in the 24-hour prophylaxis group. The overall infection rate was 3.4%: 3% in the 24-hour ...

4. aricjournal.biomedcentral.com aricjournal.biomedcentral.com/articles/10.1186/s13756-022-01191-y

Effectiveness of postoperative oral administration of ... Our results showed that postoperative administration of cephalexin and metronidazole significantly reduced wound infection symptoms, including ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S240585722200119X

Review Article Prophylactic antibiotics and Postoperative ... This meta-analysis evaluated the effect of AP on the risk of SSIs and adverse events (AE) of AP in clean and clean/contaminated cutaneous surgical procedures.

6. ashp.org ashp.org/surgical-guidelines

Clinical Practice Guidelines for Antimicrobial Prophylaxis in ... Prophylaxis refers to the prevention of an infection and can be characterized as primary prophylaxis, secondary prophylaxis, or eradication.

7. med.stanford.edu med.stanford.edu/content/dam/sm/bugsanddrugs/documents/clinicalpathways/SHC-Surgical-Prophylaxis-ABX-Guideline.pdf

SHC Surgical Antimicrobial Prophylaxis Guideline Cefazolin is the drug of choice for MOST procedures and is safe to use for most patients with allergies (including anaphylaxis) to penicillin, ...