Antibiotic Elution After Two-stage Knee Revision

In Vivo Antibiotic Elution During Two-Stage Knee Revision: A Microdialysis Study

The goal of this observational study is to monitor the eluted antibiotic concentrations of gentamicin and vancomycin by a static knee cement spacer in patients being treated for periprosthetic infections of the knee. The main question aims to answer if eluted antibiotics are in a therapeutic range for treatment at sight of infection. Secondarily, local antibiotic concentrations are compared with systemic blood levels, as are systemically applied antibiotics compared to intra-articular concentrations. Intra-articular samples are collected over a 72 hour postoperative period.

Study Overview

• Status: Completed
• Conditions: Periprosthetic Knee Infection
• Intervention / Treatment: Device: Intraarticular microdialysis

Detailed Description

The present study moinitors antibiotic concentrations eluted by a static cement knee spacer as two-stage revision treatment of a knee PJI. The static cement spacer consists of COPAL G+V cement containing 2g of vancomycin and 0.5g of gentamicin. Microdialysis is used as a technique for continuous extra cellular sample collection directly from the knee joint cavity. It is implemented guided by a drainage tube during the surgery to remove the infected prosthesis and implement the spacer. Over a 72 hour period samples directly from the knee joint are generated continiously. These are analyzed for the eluded antibiotic concentrations of gentamicin and vancomycin from the knee spacer. Once every 24 hours venous blood samples were collected as well and analyzed for gentamicin and vancomycin and also systemically applied antibiotics (a.e. cefuroxim, clindamycin).

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Germany
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • University Hospital Bonn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Ten patients over 18 years with a periprosthetic knee infection after total knee arthorplasty and indication for prosthesis explanation and temporary spacer implantation.

Description

Inclusion Criteria:

• clinical indication for a two-staged revision of a knee PJI
• approval for surgery by the orthopedic and anesthesiologic departments
• being over 18 years of age
• written, informed consent after detailed patient information about the study protocol and possible study-dependent risks

Exclusion Criteria:

• known allergies to the antibiotics gentamicin and vancomycin contained in the spacer

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients presenting with an infected knee prosthesis

Device: Intraarticular microdialysis; The intervention decive is placed during the routine surgery to remove the infected knee prosthesis and implantation of the static cement spacer. A microdialysis catheter is implemented to generate continious intra-articular samples of the knee joint. To ensure complete removal and no damage of the membrane it is inserted via a regular drainage tube. The catheter membrane is placed intra-articularly next to the spacer and continious to an outlet tube for sample collection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
antibiotic concentrations in intra-articular samples	Both locally through the spacer eluted antibiotics (gentamicin and vancomycin) and systemically administered antibiotics (e.g. cefuroxim, clindamycin) are measured in intra-articular knee samples.	Concentrations are measured for 72 hours after spacer implantation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibiotic concentrations in blood samples	Antibiotic concentrations eluted by the spacer (gentamicin, vancomycin) and systemically administered antibiotics (e.g. cefuroxim, clindamycin) are measured in venous blood samples.	Antibiotic concentrations are measured once every 24 hours after spacer implantation. In total at three time points during the 72 hour observation period.

Collaborators and Investigators

• Sponsor: University Hospital, Bonn

Publications and helpful links

General Publications

• Lazic I, Scheele C, Pohlig F, von Eisenhart-Rothe R, Suren C. Treatment options in PJI - is two-stage still gold standard? J Orthop. 2021 Jan 20;23:180-184. doi: 10.1016/j.jor.2020.12.021. eCollection 2021 Jan-Feb.
• Dhanani JA, Parker SL, Lipman J, Wallis SC, Cohen J, Fraser J, Barnett A, Chew M, Roberts JA. Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions. J Pharm Anal. 2018 Dec;8(6):407-412. doi: 10.1016/j.jpha.2018.07.003. Epub 2018 Jul 6.
• Moojen DJ, Hentenaar B, Charles Vogely H, Verbout AJ, Castelein RM, Dhert WJ. In vitro release of antibiotics from commercial PMMA beads and articulating hip spacers. J Arthroplasty. 2008 Dec;23(8):1152-6. doi: 10.1016/j.arth.2007.08.020. Epub 2008 Mar 4.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2024
• Primary Completion (Actual): May 24, 2024
• Study Completion (Actual): July 20, 2024

Study Registration Dates

• First Submitted: April 17, 2025
• First Submitted That Met QC Criteria: April 17, 2025
• First Posted (Actual): April 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: infection; arthroplasty; microdialysis; PJI; two-stage exchange; bone cement; minimal inhibitory concentration; treatment monitoring
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: 2024_B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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