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New Strategies for Biofilm Related Infections (Diafilm)

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ClinicalTrials.gov Identifier: NCT03784807
Recruitment Status : Recruiting
First Posted : December 24, 2018
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Istituto Ortopedico Galeazzi

Brief Summary:
This study aims to develop new assays for synovial fluid analysis able to improve diagnosis of prosthetic joint infections. In particular, use of synovial calprotectin as marker of infection, confocal laser scanning microscopy (CLSM) analysis and methods to assess antimicrobial susceptibility will be evaluated in synovial fluids collected from patients with septic and aseptic failure of the prosthetic implant.

Condition or disease Intervention/treatment
Prosthetic Joint Infection Diagnostic Test: synovial calprotectin, confocal laser microscopy

Detailed Description:

Infection of prosthetic joints is a common complication that may occur any time after implantation. These infections require a prompt and accurate diagnosis to ensure an optimal surgical and medical management of infected patient. Despite acute infections occurring in the first weeks after surgery are easy to diagnose or when they are associated to bacteremia, diagnosis becomes challenging when infection develops for several months before diagnosis or it is caused by low virulent pathogens. Prosthetic joint infections and more widely osteo-articular infections represent the classic biofilm related infections. Biofilm is usually defined as a microbial community enveloped in a self-produced polymeric matrix. Biofilm production allows bacteria to strictly adhere to inert and biotic substrates, evade host defenses and resist to antibiotics by building a physical barrier to penetration of antimicrobials and favoring dissemination of determinants of resistance. Microbiological cultures contribute to diagnosis of infection, providing identification of the pathogen and, most importantly, definition of antibiotic susceptibility. Nonetheless, in about 15-20% of cases, culture fails to growth the pathogen. Diagnosis of prosthetic joint infection may occur either pre- or intra-operatively. In both cases analysis of synovial fluid is crucial, especially when performed before surgery when results from culture, leukocyte esterase, alpha defensin test, leukocyte count and differential may lead to define the most accurate strategy to approach patients with implant failure. However, culture of synovial fluid is characterized by a limited sensitivity in respect, for instance to culture of periprosthetic tissues or implant components. One of the causes of the lower sensitivity of synovial fluid culture might be the presence of the so called "biofilm like aggregates", agglomerates of microorganisms embedded in a matrix which has been hypothesized to act as a protective barrier. Leukocyte esterase test may give false positive results in samples strongly contaminated by blood or with metal on metal reaction, while the high costs for alpha defensin determination markedly limited its use. On the other hand, studies aiming to evaluate other synovial markers of infections like calprotectin are insufficient to support their use in routine diagnosis of prosthetic joint infection.

An alternative approach to diagnosis of these infections could be represented by use of confocal laser scanning microscopy (CLSM) which allows to detect microorganisms in synovial fluid and in tissues. This novel approach could also be used for a "real time" diagnosis during surgery while waiting for culture results.

Another issue in diagnosis of prosthetic joint infections is related to assessment of antimicrobial susceptibility. In fact, it is well known that biofilm embedded bacteria are more resistant to antibiotics than their planktonic counterpart. Since available methods for determination of antibiotic susceptibility are based on planktonic cells, it may be hypothesized that they underestimate the real antimicrobial concentration able to inhibit growth of bacteria embedded in a biofilm as occur during infection. Although several methods have been proposed to evaluate antimicrobial susceptibility pattern of biofilm microorganisms, none of them has been proposed for routinely use. However, in some cases when therapy fails to eradicate infection, evaluation of antibiotic susceptibility of biofilm embedded bacteria could provide important information to optimize antimicrobial therapy.

Therefore, diagnosis of biofilm related infections, particularly prosthetic ones is quite far from being optimized. In this sense, development of a panel able to shorten turn around time of microbiological analyses and to improve patient management could significantly ameliorate approach to patients, limiting worsening in patient's quality of life and reducing costs for health system.


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Study Type : Observational
Estimated Enrollment : 99 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: New Strategies for Diagnosis and Management of Biofilm Related Infections
Actual Study Start Date : November 2, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Infected
Patients with prosthetic joint or osteoarticular infection
Diagnostic Test: synovial calprotectin, confocal laser microscopy
Calprotectin will be determined in synovial fluid of patients with septic and aseptic failure of their prosthesis. CLSM will be used to detect presence of microorganisms in synovial fluid. Susceptibility to antimicrobials of bacterial strains isolated from patients with prosthetic joint infections will be assessed using planktonic cells and biofilm associated bacteria

Not infected
Patients with implant failure not due to infection
Diagnostic Test: synovial calprotectin, confocal laser microscopy
Calprotectin will be determined in synovial fluid of patients with septic and aseptic failure of their prosthesis. CLSM will be used to detect presence of microorganisms in synovial fluid. Susceptibility to antimicrobials of bacterial strains isolated from patients with prosthetic joint infections will be assessed using planktonic cells and biofilm associated bacteria




Primary Outcome Measures :
  1. Assessment of analytical performance of calprotectin and CLSM for diagnosis of prosthetic joint infections [ Time Frame: preoperative visit or during surgery ]
    Sensitivity, specificity, predictive values and diagnostic accuracy of calprotectin and CLSM will be calculated and compared to those of assays already used for diagnosis of prosthetic joint infections


Secondary Outcome Measures :
  1. Improvement in antibiotic therapy applying data obtained from antibiotic susceptibility testing on biofilm [ Time Frame: Afetr isolation of the pathogen, within 2 months ]
    Antimicrobial profiles obtained on biofilm bacteria will be compared with those obtained with traditional methods on planktonic cells


Biospecimen Retention:   Samples With DNA
Bacterial strains


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with osteoarticular or prosthetic joint infection
Criteria

Inclusion Criteria:

  • Diagnosis of implant failure or osteoarticular infections
  • Collection of a sufficient amount of synovial fluid
  • Informed Consent signed

Exclusion Criteria:

  • Patients not fulfilling the inclusion criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03784807


Contacts
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Contact: Elena Cittera, MSc 00390266214057 elena.cittera@grupposandonato.it
Contact: Elena De Vecchi, MSc 00390266214080 elena.devecchi@grupposandonato.it

Locations
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Italy
IRCCS Istituto Ortopedico Galeazzi Recruiting
Milano, MI, Italy, 20161
Contact: Elena Cittera, MSc    00390266214057    elena.cittera@grupposandonato.it   
Principal Investigator: Elena De Vecchi, MSc         
Sponsors and Collaborators
Istituto Ortopedico Galeazzi
Investigators
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Principal Investigator: Elena De Vecchi, MSc IRCCS Istituto Ortopedico Galeazzi

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Responsible Party: Istituto Ortopedico Galeazzi
ClinicalTrials.gov Identifier: NCT03784807     History of Changes
Other Study ID Numbers: Diafilm
First Posted: December 24, 2018    Key Record Dates
Last Update Posted: December 24, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Primary and secondary outcomes measures for all participants to the study will be made available
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data will become available within 1 year from study conclusion
Access Criteria: Requests should be sent by e-mail to the Institution

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Istituto Ortopedico Galeazzi:
synovial fluid analysis

Additional relevant MeSH terms:
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Infection
Communicable Diseases