Cefazolin Dosing for Surgical Prophylaxis

(MorphAbxPKSurg Trial)

Overseen By June Sullivan, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Michigan

Must be taking: Cefazolin

Disqualifiers: Penicillin allergy, Pregnancy

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: 1

Duration: 1 day

104 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the optimal dosing of the antibiotic cefazolin in overweight surgical patients. Researchers aim to determine if the antibiotic achieves effective levels in blood and fat to prevent infections. They will compare two dosing methods: one based on body weight and another on body composition, including body depth and kidney function. Overweight individuals who have had a CT scan of their abdomen and are scheduled to receive cefazolin for surgery may qualify. As a Phase 4 trial, this research seeks to expand the benefits of this FDA-approved and effective treatment to 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. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for this treatment?

Research has shown that cefazolin, an antibiotic, is generally safe and well-tolerated. It is often used to prevent infections during surgery. For patients weighing 120 kg (about 265 pounds) or more, guidelines recommend a higher dose of 3 grams to ensure effectiveness. Some studies have questioned the necessity of doses over 2 grams, but no serious safety issues have been identified with these higher doses. The FDA has already approved this treatment for preventing surgical infections. Overall, cefazolin appears to be a safe choice for this purpose, especially in higher doses for heavier patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores a new method of dosing cefazolin, a common antibiotic used to prevent infections during surgery. Unlike the standard practice, which bases dosing on body weight, this trial investigates dosing based on body depth and kidney function. This approach could potentially lead to more precise dosing, reducing the risk of infection and improving patient outcomes. By tailoring the dose to individual characteristics, researchers hope to enhance the efficacy and safety of cefazolin in surgical settings.

What evidence suggests that this trial's dosing methods for cefazolin could be effective in preventing infections in overweight patients?

Research has shown that cefazolin effectively prevents infections during surgery and is a commonly used antibiotic for this purpose. In this trial, participants will follow different dosing strategies. One group will receive cefazolin doses based on standard body weight calculations, which is the standard of care. Another group will have doses adjusted based on body depth and kidney function. Studies have found that adjusting the dose based on a person's body composition, such as fat and muscle, can ensure the right amount of the drug is in the body, especially for overweight patients. This approach may lead to better drug levels in the blood and tissues, which is crucial for preventing infections. Using body shape data to adjust doses is a promising method under study to improve results. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a BMI of ≥25 kg/m^2 who are scheduled for surgery and expected to receive cefazolin. They must have had an abdominal CT scan before surgery and a creatinine clearance ≥90 mL/min, indicating good kidney function. Pregnant individuals or those with allergies to penicillin or cephalosporins cannot participate.

Inclusion Criteria

I am over 18 years old.

Body Mass Index ≥ 25 kg/m^2

Estimated creatinine clearance ≥90 mL/min

Exclusion Criteria

History of a hypersensitivity reaction to penicillin or cephalosporin

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cefazolin doses based on either body weight or morphomic measures during their scheduled surgery

1 day

1 visit (in-person, during surgery)

Follow-up

Participants are monitored for antibiotic concentrations in blood and fat tissue post-surgery

4 hours

Long-term follow-up

Participants are monitored for any surgical site infections and overall recovery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cefazolin

Trial Overview The study tests if dosing the antibiotic cefazolin based on body composition rather than just weight can better prevent infections in overweight patients during surgery. It will compare blood and fat tissue concentrations of the drug when dosed by standard care versus morphomic analysis.

How Is the Trial Designed?

Group I: Standard of Care Active Control 1 Intervention

The patients assigned to this group have cefazolin dose assignments based on body weight, which is the standard of care.

Group II: Morphomic-based Active Control 1 Intervention

The patients assigned to this group have cefazolin dose assignments based on body depth and kidney function.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Agency for Healthcare Research and Quality (AHRQ)

Collaborator

Trials

415

Recruited

6,777,000+

Published Research Related to This Trial

A quality improvement initiative successfully increased compliance with the recommended preoperative dose of cefazolin from 40% to 93% among 9086 patients, significantly reducing the risk of surgical site infections.

Cefazolin doses ordered electronically were administered correctly 94% of the time, compared to only 76% for verbal orders, highlighting the importance of electronic ordering in ensuring accurate dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A quality improvement initiative to optimize dosing of surgical antimicrobial prophylaxis. Caruso, TJ., Wang, E., Schwenk, HT., et al.[2018]

Intraoperative continuous-infusion (CI) cefazolin significantly reduced the incidence of superficial surgical site infections (SSIs) compared to intermittent (INT) dosing in patients undergoing coronary artery bypass grafting (CABG), with rates of 0.4% in the CI cohort versus 2.8% in the INT cohort.

While the overall incidence of SSIs was lower in the CI group (1.7% vs 4.6%), this difference did not reach statistical significance, indicating the need for larger studies to confirm the findings; importantly, CI cefazolin did not increase the risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Intraoperative Continuous-Infusion Versus Intermittent Dosing of Cefazolin Therapy on the Incidence of Surgical Site Infections After Coronary Artery Bypass Grafting. Shoulders, BR., Crow, JR., Davis, SL., et al.[2016]

In a study of 58 colorectal surgery patients, morphomic measurements and kidney function were found to be better predictors of cefazolin exposure than standard body weight, suggesting a need for more personalized dosing strategies in obese patients.

The research indicated that maintaining effective cefazolin levels in subcutaneous fat during surgery is challenging, particularly in patients with high creatinine clearance and significant body depth, highlighting the importance of tailored dosing based on individual body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphomics-informed population pharmacokinetic and physiologically-based pharmacokinetic modeling to optimize cefazolin surgical prophylaxis. Liu, S., Matvekas, A., Naimi, T., et al.[2023]

In a study of 24 cardiac surgery patients, administering 2 grams of cefazolin during anesthesia induction and again after starting cardiopulmonary bypass (CPB) maintained effective drug levels to combat over 90% of bacteria found on sternal skin, which were sensitive to cefazolin.

Pharmacokinetic modeling revealed that CPB significantly altered the drug's volume of distribution and clearance, indicating that patient-specific factors like albumin levels and kidney function also play a crucial role in cefazolin's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic characteristics and microbiologic appropriateness of cefazolin for perioperative antibiotic prophylaxis in elective cardiac surgery. Lanckohr, C., Horn, D., Voeller, S., et al.[2018]

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 study comparing two dosing methods of cefazolin in cardiac surgery found that continuous infusion resulted in more stable and higher drug levels in the blood and heart tissue compared to intermittent dosing.

90% of patients receiving continuous infusion met the pharmacokinetic goals for effective antibiotic levels, while only 30% of those on intermittent dosing achieved the same, highlighting the superiority of continuous administration for effective infection prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefazolin bolus and continuous administration for elective cardiac surgery: improved pharmacokinetic and pharmacodynamic parameters. Adembri, C., Ristori, R., Chelazzi, C., et al.[2014]

A successful intervention program reduced the prophylactic dose of cefazolin from 2 g to 1 g for cesarean sections, leading to a 45% decrease in the average number of vials used per surgery.

Despite the reduced dosage, the rate of surgical site infections (SSIs) decreased from 3.34% to 2.42%, demonstrating that the lower dose was both effective and safe, while also saving over $4,000 in medication costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful control program to implement the appropriate antibiotic prophylaxis for Cesarean section. Fonseca, SN., Sofia, MH., Quintana, S., et al.[2019]

The recommended dosing protocol of cefazolin for antimicrobial prophylaxis during liver surgery is generally suitable for various patient populations, including obese individuals, as it maintains effective drug concentrations in tissues.

However, if the minimum inhibitory concentration (MIC) for bacteria is set at 3 microg/ml, the standard dosing regimen may not provide adequate cefazolin levels during surgery for most patients, except those with renal insufficiency (GFR < 50 ml/min), suggesting a need for adjusted dosing in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological modeling for indirect evaluation of drug tissular pharmacokinetics under non-steady-state conditions: an example of antimicrobial prophylaxis during liver surgery. Lagneau, F., Marty, J., Beyne, P., et al.[2018]

A single intravenous dose of cefazolin administered shortly before minimally invasive gynecologic surgery effectively achieves serum concentrations above the minimum inhibitory concentrations (MIC) for susceptible pathogens, ensuring adequate antimicrobial coverage.

The study involved 21 women and demonstrated that the timing of cefazolin administration did not significantly affect serum levels, indicating that cefazolin is a reliable prophylactic agent for preventing infections in these surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefazolin prophylaxis in minimally invasive gynecologic surgery - are dosage and timing appropriate? Prospective study using resampling simulation. Lavie, M., Lavie, I., Cohen, A., et al.[2021]

In a study of 20 obese patients undergoing cesarean delivery, a 4-g dose of cefazolin resulted in significantly higher tissue and plasma concentrations compared to the traditional 2-g dose, indicating better potential for effective antibacterial prophylaxis.

All tissue samples from both dosage groups exceeded the target concentration of 4 mcg/g, and no adverse effects or infections were reported, suggesting that the higher dose is safe but its impact on infection prevention remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma and tissue cefazolin concentrations in obese patients undergoing cesarean delivery and receiving differing pre-operative doses of drug. Stitely, M., Sweet, M., Slain, D., et al.[2013]

Cefazolin is an effective choice for surgical antimicrobial prophylaxis in small animal surgeries, as it maintains effective concentrations in surgical wounds for over 12 hours after administration.

A bolus dose of 20 mg/kg given intravenously at the start of surgery, followed by subcutaneous doses, ensures that cefazolin concentrations remain above the effective level needed to inhibit common pathogens like staphylococci and E. coli.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefazolin antibacterial activity and concentrations in serum and the surgical wound in dogs. Rosin, E., Uphoff, TS., Schultz-Darken, NJ., et al.[2013]

Intraoperative continuous infusions of cefazolin provide better drug exposure and higher probabilities of target attainment compared to intermittent bolus dosing, even at lower doses, which is crucial for preventing infections during major surgery.

The study highlights the importance of considering patient factors like body weight and renal function when determining cefazolin dosing regimens, as these factors significantly influence drug clearance and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative total and unbound pharmacokinetics of cefazolin administered by bolus versus continuous infusion in patients undergoing major surgery: a randomized controlled trial. Naik, BI., Roger, C., Ikeda, K., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-4-surgical-prophylaxis-2-2023-eed8d

Cefazolin Dosing for Surgical Prophylaxis A quality improvement initiative successfully increased compliance with the recommended preoperative dose of cefazolin from 40% to 93% among 9086 patients, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37728152/

Morphomics-informed population pharmacokinetic ... - PubMed This prospective study measured cefazolin plasma, fat, and colon tissue concentrations in colorectal surgery patients in order to develop a morphomics-informed ...

3. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2878

Morphomics‐informed population pharmacokinetic and ... Algorithms exist to repurpose radiologic data into body composition (morphomics) and inform dosing decisions in obesity.

4. researchgate.net researchgate.net/publication/374075784_Morphomics-Informed_Population_Pharmacokinetic_and_Physiologically-Based_Pharmacokinetic_Modeling_to_Optimize_Cefazolin_Surgical_Prophylaxis

Morphomics‐Informed Population Pharmacokinetic and ... Methods This prospective study measured cefazolin plasma, fat, and colon tissue concentrations in colorectal surgery patients in order to ...

5. mdpi.com mdpi.com/2079-6382/12/12/1738

Effective Antimicrobial Prophylaxis in Surgery Appropriate surgical antimicrobial prophylaxis (SAP) is an important measure in preventing surgical site infections (SSIs).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6320352/

Prophylactic Cefazolin Dosing and Surgical Site Infections To date, no outcome study has shown the superiority of using a dose of prophylactic cefazolin exceeding 2- g in obese surgical patients.

7. academic.oup.com academic.oup.com/ofid/article/10/Supplement_2/ofad500.1302/7446587

versus Three-Gram Cefazolin Dosing for Surgical Prophylaxis ... International guidelines recommend an elevated dose of cefazolin 3 grams for surgical prophylaxis in patients weighing ≥ 120 kg.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0007091224007797

Evaluation of the need for dosing adaptations in obese ... The need for more than 2 g doses of cefazolin in obese patients for perioperative antibiotic prophylaxis has been studied and debated with differing results. We ...

9. fda.gov fda.gov/media/182329/download

OFFICE OF CLINICAL PHARMACOLOGY REVIEW Proposed Dosage: Add a new dosing regimen of 3 g/150 ml for the indication of perioperative prophylaxis in adult.

10. 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.