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Format: 04/22/2014
Format: 04/22/2014


AGH Researchers Launch First Studies Exploring Role of Biofilm Infections in Failure of Joint Replacement Surgery and Bone Fracture Healing

Wednesday, October 14th, 2009

Pittsburgh, PA (October 14, 2009) - Researchers from Allegheny General Hospital’s (AGH) Department of Orthopaedic Surgery and Center for Genomic Sciences have launched dual groundbreaking studies that may help determine the cause of two common, hard-to-treat problems experienced by patients who undergo orthopedic surgery: a joint replacement that becomes infected and a bone fracture that will not heal properly.

Both clinical trials will focus on the role of biofilms - formidable, highly resistant communities of bacteria - as a root cause of these surgical complications.

AGH’s Center for Genomic Sciences is now recognized internationally as a leading center for the study of biofilms in disease management. It is led by two of the world’s foremost experts on bioflim bacteria, J. William Costerton, PhD., director of Biofilm Research, and Garth Ehrlich, Ph.D., executive director.  Dr. Costerton is also director of Microbiology Research for AGH’s Department of Orthopaedic Surgery.

Under the direction of principal investigators Dr. Costerton and Sandeep Kathju, M.D., Ph.D., director of the Center for Genomic Science’s Wound Healing Program, the AGH team is the first in the country to explore the impact of biofilm infections on the success of orthopaedic procedures.

Other key investigators in the studies include Gregory Altman, M.D., and Jeffrey Sewecke, DO, co-directors of AGH’s Division of Orthopaedic Trauma and Fractures, Nicholas Sotereanos, M.D., director of AGH’s Division of Adult Reconstructive Surgery, Stephen Conti, M.D., director of AGH’s Division of Foot and Ankle Surgery, Daniel Altman, M.D., director of Orthopaedic Spine Trauma and orthopaedic surgeons Gregory Lavigne, M.D., and Brett Smith, M.D.

“We are extremely excited to take the lead on such an innovative research project that addresses two fundamental surgical risks that healthcare professionals in our field confront on a daily basis. These complications not only cause a tremendous amount of suffering among patients, but they are also exceedingly costly to hospitals,” said Patrick DeMeo, M.D., chairman of AGH’s Department of Orthopaedic Surgery.

It is estimated that infections occur in approximately 2% of primary total joint replacements and in as many as 15% of revision total joint replacements. The costs of treating such infections range from $15,000 to $100,000 per case.

Dr. Conti, who also serves as director of Orthopaedic Research for AGH’s Allegheny Singer Research Institute, said the unique collaboration between the hospital’s Department of Orthopaedic Surgery and the Center for Genomic Sciences is a further example of AGH’s longstanding history of pioneering medical research and its commitment to enhancing the quality and safety of orthopaedic care.

AGH’s Department of Orthopaedic Surgery is one of the state’s largest and most comprehensive programs, performing more than 12,000 orthopaedic operations each year.

The first biofilm study examines how the presence of such bacteria affects the natural process of bone healing. Dr. Greg Altman said its outcome could shed light not only on whether or not biofilms are found in the setting of non-healing – or non-union – bone fractures, but if so, how physicians might one day more effectively treat the condition and improve the healing process.

“It is well established that the healing of bone fractures is delayed or incomplete when bacteria are present near the trauma site,” Dr. Costerton said. “We can use antibiotics to kill floating (planktonic) bacteria, in any infection, but it is usually necessary to surgically remove damaged tissues and biofilms when the infecting organisms have resorted to this strategy for survival and persistence.”

To conduct the non-union study, patients with open fractures of the femur (or tibia/fibula) are being recruited from AGH’s Department of Orthopaedic Surgery. Patients enrolled in the study will include those whose fractures have successfully healed without infection, patients who have healed despite the presence of a biofilm, and patients whose fractures have not healed. The presence of biofilms will be determined via a special fluorescent probe that analyzes tissues, hardware and other materials taken from the site of the fracture.

The second study at AGH is investigating the source of chronic infection in joint replacement procedures.

“Evidence is growing that chronic and difficult-to-detect infections fueled by biofilms may be the primary cause of ’aseptic’ loosening of joint replacements,” said Dr. Sotereanos. “In such cases, where failed joint replacements are not obviously infected, the optimum treatment is often unclear and frustrating for both doctors and patients.”

Dr. Sotereanos said the study at AGH takes on increasing importance as the nation’s population ages and the number of joint replacement procedures grows exponentially. Already, some 650,000 people undergo joint replacement surgery each year. That number is expected to double by 2030 as the population ages.

While joint replacement surgery is generally a highly successful procedure that dramatically improves a patient’s quality of life, infection can lead to increased morbidity and mortality, the need for additional surgeries, poor outcomes and economic loss.

“Bacteria growing in a biofilm state are increasingly linked to a number of clinical conditions, and a small but growing body of evidence points to biofilm involvement in orthopedic implant infections as well,” Dr. Costerton said.

“Our goal is to establish definitively what role biofilms play in complications associated with artificial joint implants and hopefully take an important step towards improving our ability to prevent this vexing problem in the future.”

For the study, AGH researchers will examine aspirated fluid collected from the following types of patients: those who have already undergone a joint replacement and are having problems, those who are undergoing surgery to remove a prosthesis and, as a control group, those who are having a first joint replacement surgery.

Dr. Ehrlich said fluid and tissue will be evaluated for the presence of bacteria using traditional culture methods. Because many biofilm bacteria cannot be recovered via conventional techniques, the AGH-ASRI team will also look for bacterial DNA and RNA using two of the most advanced genome sequencing technologies in the world - the investigational Ibis Universal Biosensor and the 454 LifeSciences next-generation DNA sequencer. Biofilm bacteria will be imaged in situ as well using microbiome mapping technology.

The team will collect fluid and tissue samples from up to 100 patients per implant site, including the knee, hip and elbow. They will analyze material from pre-surgical aspirates and from inter-operative samples to determine whether biofilm bacteria are present and which species of bacteria are involved.

Such information could prove to be critical for future patients by more effectively guiding antibiotic therapy before and during joint replacement surgery, Dr. Sotereanos said.


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