Preoperative Daptomycin Prophylaxis in Two-Stage Exchange Arthroplasty: A Prospective, Randomized, Double-Blinded Trial

Preoperative Daptomycin Prophylaxis for Preventing Gram-Positive or Methicillin-Resistant Staphylococcus Aureus Infection in Two-Stage Exchange Arthroplasty: A Prospective, Randomized, Double-Blinded Trial

The gold standard for treating prosthetic joint infection (PJI) is two-stage exchange arthroplasty. This includes the first stage of debridement and removal of the artificial joint, and the second stage of reimplantation of the artificial joint. Methicillin-resistant staphylococcus aureus (MRSA) infection is one of the factors leading to the failure of artificial joint infection treatment. Before the second stage of the joint surgery, the surgeon will prescribe prophylactic antibiotics based on previous bacterial cultures. The usual preoperative antibiotic is a first-generation cephalosporin antibiotic. If it is MRSA, vancomycin will be given. Increasingly, literature reports link prosthetic joint infections to MRSA, but no changes have been made to the routine recommendation for MRSA prophylactic antibiotic use.

Daptomycin is a cyclic lipopeptide antibiotic that can rapidly penetrate biofilms and bones, and its safety and tolerability have been confirmed. Therefore, it can effectively combat Gram-positive organisms, including MRSA. Daptomycin has many characteristics of an ideal prophylactic: short infusion time, low adverse events during administration, and a range limited to Gram-positive organisms. We aim to assess whether adding antibiotics that cover MRSA would reduce prosthetic joint infections and increase surgical success rates, in addition to the standard recommended prophylactic antibiotics. Thus, this prospective randomized trial is designed to assess, besides using the first-generation cephalosporin antibiotic, the effects of adding an antibiotic with MRSA coverage (Daptomycin vs. Vancomycin).

Study Overview

• Status: Not yet recruiting
• Conditions: Periprosthetic Joint Infection
• Intervention / Treatment: Drug: Cefazolin with Daptomycin; Drug: Cefazolin with vancomycin

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Feng-Chih Kuo, MD; Phone Number: 886-7-7317123; Email: fongchikuo@cgmh.org.tw

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 833
    • Kaohsiung Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients aged 18 or older with an infection that meets the 2018 International Consensus Meeting (ICM) criteria7 at the time of the first-stage resection arthroplasty with a gram-positive organism, especially MRSA.
2. Will undergo a second stage of reimplantation.

Exclusion Criteria:

1. Patients with a fungal infection or culture-negative infections
2. Known allergies to Cefazolin, Daptomycin, or Vancomycin.
3. Currently receiving surgical treatment for acute postoperative or acute hematogenous PJI.
4. Chronic kidney disease (Creatinine Clearance Rate [CCR] < 30 ml/min/1.73m2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative Daptomycin Prophylaxis in Two-Stage Exchange Arthroplasty	Drug: Cefazolin with Daptomycin; For patients randomized to receive daptomycin (8 mg/kg), the drug will be administered in a 50 cc bag, accompanied by a 500 cc bag of normal saline within 60 minutes before surgical incision and discontinued after 24 hours postoperatively.
Experimental: Preoperative Vancomycin Prophylaxis in Two-Stage Exchange Arthroplasty	Drug: Cefazolin with vancomycin; Then vancomycin (15 mg/kg) will concurrently be given and completed within 60 minutes before surgical incision and discontinued after 24 hours postoperatively9. Patients in the vancomycin arm will receive this drug in a 50 cc bag accompanied by a 500 cc bag of normal saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection	Infection that meets the 2018 ICM criteria after second stage reimplantation.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Kidney Injury	efined by the Kidney Disease Improving Global Outcomes (KDIGO)11, which includes a rise in serum creatinine by ≥0.3 mg/dl within 48 hours; or an increase in serum creatine ≥1.5 times the patient's preoperative baseline within 7 days; or urine volume <0.5 ml/kg/h for 6 hours.	48 hours

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: December 19, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Cefazolin; Daptomycin
• Other Study ID Numbers: 202301864A3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No