Knee Prosthetic Joint Infection Antibiotic Elution

Antibiotic Elution Profile and Outcomes in the Treatment of Prosthetic Joint Infections of the Knee

Patients presenting with prosthetic joint infections of a total knee replacement who are treated with an antibiotic spacer will be observed prospectively for their response to treatment and antibiotic elution profiles will be measured post-operatively utilizing mass spectrometry from synovial fluid acquired as part of standard of care in the management of prosthetic joint infection. Secondary outcomes including post-operative complications, re-operation rates, and re-admission rates will also be compared.

Study Overview

• Status: Withdrawn
• Conditions: Arthroplasty Complications; Prosthetic-joint Infection
• Intervention / Treatment: Procedure: Treatment of Chronic TKA PJI

Detailed Description

The current study aims to assess the surgical and patient-reported outcomes and in vivo antibiotic elution profile of the management of total knee arthroplasty (TKA) prosthetic joint infection (PJI). Within the standard of care, TKA PJI is treated via a resection arthroplasty and antibiotic cement spacer placement. Patients will be enrolled if they are undergoing surgical management for a chronic TKA PJI and will receive surgical treatment according to the standard of care. In the post-operative period, patients will be monitored for surgical and patient-reported outcomes including re-operation rate, pain scores, complication rates, and re-infection rates. Synovial fluid obtained from intra-articular postoperative drains and at postoperative knee aspirations during reimplantation evaluations will also be utilized for antibiotic concentration quantification via mass spectrometry, if sufficient specimen is available. Patient who undergo surgical management for their chronic TKA PJI will then have their measured antibiotic elution concentrations compared. The study hypothesizes that patients undergoing treatment of a PJI with antibiotic spacer + antibiotic cement spacer will have better surgical and patient-related outcomes with higher antibiotic elution concentrations. These improved outcomes would include lower re-operation rates, lower pain scores, lower wound healing complications, and higher rates of second stage re-implantation observed in patients with higher antibiotic elution concentrations.

Specific aims:

1. To evaluate the antibiotic elution profile and post-operative intra-synovial concentrations in the treatment of chronic PJI after TKA.
2. To evaluate surgical and patient-related outcomes in chronic TKA PJI patients following implant resection and knee spacer placement, including amount of post-operative drain output, wound healing complications, 30- and 90-day risk of re-operation, pain scores, and rate of second stage re-implantation.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will comprise of patients who have had a previous total knee arthroplasty (TKA), presenting with clinical and laboratory findings concerning for a chronic TKA prosthetic joint infection (PJI) undergoing staged surgical management consisting of resection arthroplasty followed by mobile antibiotic spacer placement. Patients who have had prior surgical treatment of a PJI and are less than 18 years of age will not be included in the study population.

Description

Inclusion Criteria:

• Patients planned for treatment of a total knee arthroplasty prosthetic joint infection
• Patients greater than 18 years of age
• Patients able to provide informed consent

Exclusion Criteria:

• Prior history of ipsilateral or contralateral prosthetic joint infection warranting operative management
• Patients less than 18 years of age
• Patients unable to provide informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chronic TKA PJI Group; Patients presenting for surgical management of a chronic total knee arthroplasty (TKA) prosthetic joint infection (PJI). Patients will be excluded if they are less than 18 years of age, have a prior history of ipsilateral or contralateral PJI warranting operative management, or are unable to provide informed consent.	Procedure: Treatment of Chronic TKA PJI; Patients will all undergo standard of care treatment for a chronic total knee arthroplasty prosthetic joint infection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-articular Antibiotic Elution Profile	Antibiotic concentration will be quantified utilizing mass spectrometry from intra-articular synovial fluid obtained from post-operative drain and knee aspirations performed for re-implantation evaluation.	Post-operative day 2 and during 2nd stage re-implantation evaluation (around 10 weeks according to standard of care)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drain Output	Measured volume of output from post-operative drain will be quantified every 12 hours	Each 12 hours period until removal of the drain up to 5 days postoperatively based on drain output less than 30cc in 12 hours.
Wound Healing Complications	Any issues with wound healing including closure, occurrence of infection, high drainage, or hematoma formation will be among wound healing complications which are measured.	up to 6 months following surgery
Re-operation Rates	Rates of return to operating room will be quantified over course of 30 days and 90 days.	30 days and 90 days post-operatively.
Re-admission Rates	Rates of re-admission will be quantified over course of 30 days and 90 days.	30 days and 90 days post-operatively.
Pain Scores	Pain scores utilizing visual analog scale from 0 to 10 will be quantified during post-operative course.	Daily on postop day 0 until postop day 5, 3 weeks, 6 weeks and 10 weeks, 6 months postoperatively.
Second Stage Re-implantation Rates	Rates of successful second stage re-implantation will be quantified during the post-operative course.	Through study completion up to 1 year
Knee aspiration cell count	Knee aspiration with number of white cells less than 1300	3 weeks, 6 weeks and 10 weeks - 6 months postoperatively.
Knee aspiration culture	Knee aspiration without evidence of bacteria on bacterial culture	3 weeks, 6 weeks and 10 weeks - 6 months postoperatively.
C-reactive protein assessment	C-reactive protein normalization (less than 1mg/dl)	baseline, 10 weeks to 6 months posteroperatively
ESR assessment	Erythrocyte sedimentation rate normalization (less than 20 mm/hr)	baseline, 10 weeks to 6 months posteroperatively

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Johannes F Plate, MD, PhD, University of Pittsburgh Medical Center

Publications and helpful links

General Publications

• Anagnostakos K, Wilmes P, Schmitt E, Kelm J. Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo. Acta Orthop. 2009 Apr;80(2):193-7. doi: 10.3109/17453670902884700.
• Chen AF, Parvizi J. Antibiotic-loaded bone cement and periprosthetic joint infection. J Long Term Eff Med Implants. 2014;24(2-3):89-97. doi: 10.1615/jlongtermeffmedimplants.2013010238.
• Slane J, Gietman B, Squire M. Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin. J Orthop Res. 2018 Apr;36(4):1078-1085. doi: 10.1002/jor.23722. Epub 2017 Sep 20.

Study record dates

Study Major Dates

• Study Start (Estimated): January 5, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: August 14, 2023
• First Submitted That Met QC Criteria: August 31, 2023
• First Posted (Actual): September 5, 2023

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Prosthetic Joint Infection; Revision Total Knee Arthroplasty; Antibiotic Elution Profile
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathologic Processes; Disease Attributes; Arthritis; Joint Diseases; Infections; Communicable Diseases; Arthritis, Infectious
• Other Study ID Numbers: STUDY22070087

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: There are no plans at present to make individual participant data (IPD) available to other researchers, however we may share de-identified data with other researchers in the future.

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