Cephalexin for Surgical Infection Prevention

Overseen by Merisa Piper, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of California, San Francisco

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Pregnant, Breastfeeding, Male, others

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is studying whether giving antibiotics after breast reconstruction surgery can prevent infections. It focuses on patients who have had a mastectomy and are getting implants. The study aims to see if antibiotics make a difference in preventing infections.

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.

What evidence supports the effectiveness of the drug cephalexin for preventing surgical infections?

Research shows that cephalexin is effective in treating bacteriuria (bacteria in the urine) in children, eradicating sensitive organisms in 97% of cases. Additionally, it has been found useful in preventing bronchopulmonary complications after surgery, indicating its potential effectiveness in surgical infection prevention. ^{1 2 3 4 5}

Is cephalexin safe for humans?

Cephalexin is generally safe for humans, with common side effects including skin rashes, itching, and mild stomach issues. In a study, only about 5% of patients stopped using it due to side effects. ^{6 7 8 9 10}

How does the drug Cephalexin differ from other treatments for preventing surgical infections?

Cephalexin is unique in its use as a single-dose oral antibiotic for preventing surgical site infections, particularly in procedures like skin lesion excisions on the lower limb. This approach is different from other antibiotics like Cefotetan, which is used for a broader range of surgical infections and has a different spectrum of activity. ^{2 6 11 12 13}

Research Team

Merisa Piper, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Cephalexin (Antibiotic)

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.

Participant Groups

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 Canada, Switzerland for the following indications:

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+

Suresh Gunasekaran

University of California, San Francisco

Chief Executive Officer since 2022

MBA from Southern Methodist University

Dr. Lukejohn Day

University of California, San Francisco

Chief Medical Officer

MD from Stanford University School of Medicine

The Plastic Surgery Foundation

Collaborator

Trials

11

Recruited

1,300+

Findings from Research

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]

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]

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 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 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 (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]

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]

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 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]

References

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

Cephalexin in the management of bacteriuria. [2017]

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. Germany pubmed.ncbi.nlm.nih.gov

Therapeutic and prophylactic effects of cephalexin and bromhexine in respiratory tract complications of abdominal surgery. [2013]

4. Australia pubmed.ncbi.nlm.nih.gov

Impact of a web-based antimicrobial approval system on broad-spectrum cephalosporin use at a teaching hospital. [2020]

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

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

6. Japan pubmed.ncbi.nlm.nih.gov

Feasibility of oral antibiotic prophylaxis in elective laparoscopic cholecystectomy during periods of limited cefazolin supply. [2022]

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

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

9. 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]

10. Canada 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. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Prevention and control of surgical infections. [2013]

12. Poland pubmed.ncbi.nlm.nih.gov

[Evaluation of the effectiveness of cefazolin++ (Kefzol) in preventing infections in patients after abdominal surgery]. [2013]

13. 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]