Approximately 750,000 total hip and knee replacement surgeries are performed each year in the United States. As a result of the aging population, these numbers are expected to increase to two and a half million by 2030. While the majority of those who undergo these procedures experience dramatic benefit, approximately three percent require re-operation, most commonly for prosthetic joint infection (PJI) or aseptic loosening of the prosthesis. Surgical and medical management of failed joint replacements depend on whether or not infection is present. However, making a microbiologic diagnosis of PJI is challenging. We have shown that native joint infection diagnostics are inaccurate for PJI. Microorganisms associated with PJI are found in biofilms on the prosthesis surface;accordingly, methods that sample the prosthesis surface should improve the diagnosis of PJI. Our research team published a manuscript in the New England Journal of Medicine, showing that a novel technique that that we have developed, which samples biofilms on the prosthesis surface, is more sensitive than conventional periprosthetic tissue for the culture-based diagnosis of PJI. Although this technique is more sensitive than conventional approaches, it is culture-based, and, accordingly has a long turnaround time. Further, despite improved sensitivity compared to periprosthetic tissue culture (i.e., 78.5 versus 60.8%, p <0.001), there remain culture negative cases. We hypothesize that a molecular microbiologic approach, targeting biofilm bacteria dislodged from explanted orthopaedic prostheses, will more sensitively, and rapidly, detect PJI compared with our culture-based approach. We further hypothesize that bacteria in biofilms, identified using molecular methods, are associated with some cases of 'aseptic'failure of prosthetic joints, the pathogenesis of which is incompletely defined. We are developing and validating closed system rapid real-time polymerase chain reaction assays, collectively targeting bacteria which cause PJI, for detection of biofilm bacteria dislodged from the surface of orthopaedic prostheses. We will prospectively evaluate these assays to confirm improved sensitivity compared to our culture- based approach, for the diagnosis of PJI. We will determine the percentage of revision hip and knee arthroplasties performed for reasons other than PJI that have previously unrecognized bacteria present at revision, as detected by molecular techniques that detect bacterial biofilms, and we will assess the outcome of such cases. Our research team has extensive translational experience in the area of PJI and has collaborated on a number of studies. Collectively, we have expertise in molecular microbiology, bacteriology, orthopaedic infection and surgery, medical biofilms, histopathology, and biostatistics. Results of this study are expected to yield a novel, rapid, and sensitive molecular diagnostic for PJI, and will assess whether microbes are associated with aseptic hip and knee arthroplasty failure, both of which will transform clinical practice.

Public Health Relevance

We propose to develop and evaluate a new test for prosthetic joint infection which will rapidly detect biofilm bacteria dislodged from the surface of orthopaedic prostheses. We will additionally determine whether some patients undergoing revision hip or knee arthroplasty might have unrecognized infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR056647-04
Application #
8241616
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Panagis, James S
Project Start
2009-07-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$258,490
Indirect Cost
$87,418
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Peel, Trisha N; Sedarski, John A; Dylla, Brenda L et al. (2017) Laboratory Workflow Analysis of Culture of Periprosthetic Tissues in Blood Culture Bottles. J Clin Microbiol 55:2817-2826
Brinkman, Cassandra L; Schmidt-Malan, Suzannah M; Mandrekar, Jayawant N et al. (2017) Rifampin-Based Combination Therapy Is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy. Antimicrob Agents Chemother 61:
Schmidt-Malan, Suzannah M; Brinkman, Cassandra L; Greenwood-Quaintance, Kerryl E et al. (2017) Activity of Electrical Current in Experimental Propionibacterium acnes Foreign-Body Osteomyelitis. Antimicrob Agents Chemother 61:
Wang, X; Greenwood-Quaintance, K E; Karau, M J et al. (2017) Ureaplasma parvum causes hyperammonemia in a pharmacologically immunocompromised murine model. Eur J Clin Microbiol Infect Dis 36:517-522
Peel, Trisha N; Spelman, Tim; Dylla, Brenda L et al. (2017) Optimal Periprosthetic Tissue Specimen Number for Diagnosis of Prosthetic Joint Infection. J Clin Microbiol 55:234-243
Norambuena, German A; Patel, Robin; Karau, Melissa et al. (2017) Antibacterial and Biocompatible Titanium-Copper Oxide Coating May Be a Potential Strategy to Reduce Periprosthetic Infection: An In Vitro Study. Clin Orthop Relat Res 475:722-732
Melendez, Dante P; Greenwood-Quaintance, Kerryl E; Berbari, Elie F et al. (2016) Evaluation of a Genus- and Group-Specific Rapid PCR Assay Panel on Synovial Fluid for Diagnosis of Prosthetic Knee Infection. J Clin Microbiol 54:120-6
Park, Kyung-Hwa; Greenwood-Quaintance, Kerryl E; Hanssen, Arlen D et al. (2016) Antimicrobial-Loaded Bone Cement Does Not Negatively Influence Sonicate Fluid Culture Positivity for Diagnosis of Prosthetic Joint Infection. J Clin Microbiol 54:1656-9
Thoendel, Matthew; Jeraldo, Patricio R; Greenwood-Quaintance, Kerryl E et al. (2016) Comparison of microbial DNA enrichment tools for metagenomic whole genome sequencing. J Microbiol Methods 127:141-5

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