Precision Antibiotic Dosing for Appendectomy (PANDA)

Aim 3 - Precision Coordination of Therapeutic and Prophylactic Antibiotics to Reduce Infection, Toxicity, and Emergence of Resistance Following Acute Abdominal Surgery

This research is studying a drug called cefoxitin already approved by the Food and Drug Administration (FDA) to reduce the risk of infection after surgery to remove an appendix. Researchers are studying a large group of people to continue to learn how best to dose antibiotics. This research will compare the current standard treatment which is a single dose prior to surgery to a new method that includes adding another dose of cefoxitin within 30 minutes of starting the surgery. This study will measure cefoxitin concentrations in blood, fat, and appendix tissue samples to compare the standard dosing method to our new method. This information will help us figure out the right dose of this drug to prevent infection after surgery to remove an appendix.

Study Overview

• Status: Recruiting
• Conditions: Appendicitis (Diagnosis)
• Intervention / Treatment: Drug: Cefoxitin

Detailed Description

This interventional, phase 1 study aims to improve surgical site infection (SSI) prevention in patients undergoing appendectomy for uncomplicated appendicitis. Despite standard antibiotic prophylaxis, SSI rates remain high, with a pelvic abscess risk of 9.4%. Current prophylactic antibiotic regimens may not achieve optimal tissue concentrations, especially in fat and appendix tissue.

This study will evaluate the probability of target attainment (PTA) of cefoxitin, cefuroxime, and metronidazole in plasma, subcutaneous fat, and appendix tissue. A cohort of 46 adult patients will be randomized to receive standard-of-care antibiotics with or without an additional cefoxitin dose. Antibiotic concentrations will be measured in collected blood, fat, and appendix samples.

The study's primary objective is to determine whether a supplemental cefoxitin dose improves PTA compared to standard prophylaxis. Population pharmacokinetic modeling will validate the intervention's effectiveness in optimizing antibiotic exposure and reducing SSI risk. The results may inform future precision antibiotic dosing strategies for appendectomy and other acute care surgeries.

Primary Outcome Measure:

Probability of achieving 50% time above 8 mcg/mL (cefuroxime or cefoxitin) in appendix tissue between intervention and standard care groups.

Study Design:

Randomized, interventional, phase 1 study Enrollment: 46 participants Inclusion: Adults (>18 years) undergoing appendectomy for acute appendicitis Exclusion: Pregnant individuals, prisoners, patients with perforation or abscess This study seeks to improve perioperative antibiotic management, reducing SSI rates while minimizing unnecessary antibiotic exposure and resistance development.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alexsas Matvekas, BS; Phone Number: 7346470006; Email: matvekas@umich.edu
• Study Contact Backup: Name: June Sullivan, MBA; Phone Number: 734.615-3488; Email: jusulli@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48108
      • Recruiting
      • Michigan Medicine
      • Contact: Amit Pai; Phone Number: 518-429-1476; Email: amitpai@med.umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of acute appendicitis and plan to undergo appendectomy at the University of Michigan

Exclusion Criteria:

• Prisoners
• Patients that are pregnant
• Patients with perforation or abscess on CT Scan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; The current standard of care surgical prophylaxis regimen
Experimental: Cefoxitin; Administration of Cefoxitin 2000 mg within 30 minutes of incision to the existing standard of care intervention	Drug: Cefoxitin; Cefoxitin 2000 mg Bolus Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probability of Achieving Optimal Antibiotic Concentration in Appendix Tissue	The probability of achieving 50% time above 8 mcg/mL (cefuroxime or cefoxitin) in appendix tissue in the intervention compared to the non-intervention (standard of care) arm.	4 hours

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Agency for Healthcare Research and Quality (AHRQ)
• Investigators: Principal Investigator: Manjunath Pai, PharmD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: February 28, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Appendectomy; Surgical Site Infections; Cefoxitin
• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Intestinal Diseases; Infections; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Wound Infection; Cecal Diseases; Intraabdominal Infections; Pathological Conditions, Signs and Symptoms; Disease; Surgical Wound Infection; Appendicitis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; beta-Lactams; Lactams; Cephalosporins; Thiazines; Cephamycins; Cefoxitin
• Other Study ID Numbers: HUM00263447; R01HS027788 (U.S. AHRQ Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No