The Effect of Oral Antibiotics on Synovial Fluid and Differential for the Diagnosis of Infection

The Effect of Oral Antibiotics on Synovial Fluid Leukocyte Count and Differential for the Diagnosis of Periprosthetic Hip and Knee Infection

Periprosthetic joint infection following total hip or knee arthroplasty is a rare but potentially devastating complication. Accurate diagnosis of these infections remains one of the most challenging undertakings in orthopaedics. Multiple studies have shown the high diagnostic accuracy of synovial fluid white blood cell count (WBC) and neutrophil percentage (%PMNs) in detecting PJI. This study's goal is to evaluate how antibiotics affect those two important diagnostic measures.

Study Overview

• Status: Withdrawn
• Conditions: Infection
• Intervention / Treatment: Drug: Antibiotic; Drug: No antibiotics

Detailed Description

Periprosthetic joint infection (PJI) following total hip or knee arthroplasty is a rare but potentially devastating complication. Accurate diagnosis of these infections remains one of the most challenging undertakings in orthopaedics. Clinical presentation of PJI may be subtle and distinguishing between infection versus aseptic issues can be difficult. Currently no diagnostic approach has been developed that accurately and unequivocally diagnoses PJI.

Multiple studies have shown the high diagnostic accuracy of synovial fluid white blood cell count (WBC) and neutrophil percentage (%PMNs) in detecting PJI. This has led to incorporation of these two parameters into criteria for the diagnosis of PJI. WBC and %PMN cutoffs have been published for prosthetic hips and knees in both the acute and chronic setting. Meanwhile, synovial fluid cell counts are believed to be of particular value when patients present on systemic antibiotics, which have been shown to compromise intraarticular cultures by causing false negative results.

However, the effect of antibiotics on synovial fluid cell count and differential has not been well delineated. One prospective study by Trampuz et al. of 133 synovial fluid specimens prior to total knee revisions noted that patients receiving antimicrobial agents had lower leukocyte counts than did those who were not receiving antimicrobial agents. To the contrary, a recent animal study examined intra-articular administration of the antibiotic amikacin in horses and reported a statistically significant increase in the synovial nucleated cell count. The effect of antibiotics on synovial fluid WBC and %PMN thus remains unclear.

Furthermore, to reduce false-negative culture results, it is recommended that patients be off of antibiotics for a minimum of two weeks prior to obtaining samples for culture. Investigators have shown reduced false-negative culture rates in patients not taking antibiotics prior to surgery compared to those taking antibiotics at the time of surgery. However, the two-week time interval is relatively arbitrary and adequate supporting data do not exist.

The primary aim of this study is to evaluate how antibiotics affect synovial fluid leukocyte and differential counts. A secondary aim is to assess how long patients need to be off of antibiotic therapy to generate accurate synovial fluid cultures. Further examination of the effects of systemic antibiotics on synovial fluid composition will provide valuable information for clinicians caring for patients with possible PJI.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient>18 years old.
2. Patient with a prosthetic hip or knee in place.
3. Patient with PJI of the hip or knee based on MSIS criteria3(Table 1).
4. Patient off of antibiotics for a minimum of two weeks prior to preoperative joint aspiration.
5. Patient with a culture-positive preoperative joint aspiration

Exclusion Criteria:

1. Inadequate preoperative or intraoperative synovial fluid sample to perform synovial fluid WBC, %PMN and aerobic/anaerobic cultures.
2. Pregnant women.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral antibiotic therapy group; This group will receive preoperative oral antibiotic therapy tailored to the infecting organism (if identified) for two weeks before the time of revision surgery	Drug: Antibiotic; The intervention involves giving an infected patient antibiotics.
Active Comparator: No antibiotic therapy group; This group will not receive preoperative oral antibiotic therapy.	Drug: No antibiotics; The intervention involves not giving an infected patient antibiotics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A change in synovial fluid white blood cell count with antibiotic treatment	White blood cell count will be measured from synovial fluid. This fluid will be sent to our in-house laboratory testing facility. WBC is measured as the total number per mL of fluid.	pre-operative to intraoperative
A change in synovial fluid neutrophil percentage with antibiotic treatment	Neutrophil percentage will be measured from synovial fluid. This fluid will be sent to our in-house laboratory testing facility. %PMN is a percentage out of total white blood cell count.	pre-operative to intraoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A change in culture results with antibiotic treatment	Synovial fluid will be sent to our in-house lab and they will try and grow cultures from this fluid to see if they can identify the organism causing the infection.	pre-operative to intraoperative

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Investigators: Principal Investigator: Craig Della Valle, MD, Professor of Orthopaedic Surgery

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): November 5, 2019
• Study Completion (Actual): November 5, 2019

Study Registration Dates

• First Submitted: October 26, 2017
• First Submitted That Met QC Criteria: June 7, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 16071701

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