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Monday, March 3, 2008
New Test for Joint Infection Could Spare Some Patients an Unnecessary Procedure
A potential diagnostic test that could help surgeons confirm or rule out the presence of infection-causing bacteria in prosthetic joints that require surgical revision has been developed by researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH). Such a test could spare a subgroup of people who need the surgery a time-consuming and costly treatment for infection, while helping to ensure that people who need the procedure get it. The test is described in the March issue of the Journal of Bone and Joint Surgery.
Each year, hundreds of thousands of joint replacement surgeries are performed in this country. And each year, thousands of them must be revised (the prosthetic joint must be removed and replaced) due to severe pain and swelling. These symptoms are often due to infection, says Rocky S. Tuan, Ph.D., chief of NIAMS' Cartilage Biology and Orthopaedics Branch.
The standard treatment for suspected infection is to remove the joint prosthesis and replace it with a spacer that has been impregnated with antibiotics. After about six weeks, patients must undergo another surgery to remove the spacer. Only then can the surgeon implant the new prosthesis.
The problem with this approach is that confirming the presence of infection-causing bacteria is an inexact science. Currently, doctors check for infection by culturing a sample of the joint fluid. A positive culture confirms live bacteria, making spacer surgery a certainty. A negative culture, however, does not necessarily mean there is no infection. In fact, Tuan says that estimates of the false negative rate for joint cultures in revision surgeries range from 27 percent to 50 percent. But because failure to treat an infected joint could lead to severe infection and limb amputation, spacer surgery is sometimes performed for safety's sake even when infection test results are inconclusive.
To get around the false-negative problem, Tuan and his colleagues developed a way to test for joint infections using polymerase chain reaction (PCR), which detects the presence of bacterial DNA. However, this approach proved to have pitfalls, too. It picked up all bacteria — even dead or dying bacteria that cannot perpetuate infection — thereby giving false positives.
Tuan says this new problem led them to expand their PCR approach by testing for bacterial messenger ribonucleic acid (mRNA). "When bacteria are dying, their mRNA is one of the first things to go," he says. As a result, the researchers hypothesized that a good mRNA test would not only detect bacteria, but would likely tell them if any bacteria they detected were still viable. Unlike DNA, mRNA is not directly quantifiable by known techniques, so the mRNA test that Tuan's group developed employs a process called reverse transcription PCR (RT-PCR) to convert the mRNA into DNA for measurement.
Tuan's group tested the validity of their new method by introducing bacteria into infection-free joint fluid to simulate infection. To ensure that the bacteria were indeed present, they used the PCR test, which accurately showed the amount of bacterial DNA. The researchers then treated the joint fluid cultures with potent antibiotics designed to kill off the bacteria. As expected, the PCR-DNA test still showed that the fluid contained plenty of bacteria, but when the group analyzed the cultures with the RT-PCR test for mRNA, they found that the viable bacteria population was declining.
Now Tuan's team is recruiting 50 people who need joint revision for a clinical trial that will involve testing patients' joint fluid for bacteria and then following them for 6 months to a year after surgery. They hope that the results from this study will validate the protocol to identify or rule out infections before a person begins a surgical revision.
Tuan would like to be able to tell patients who need infection treatment, "There is a really bad infection and we know what to do."
"But we also want to tell the person without infection that it's O.K. to put in a revision joint. That saves the spacer, the additional surgery and its associated risk, and 6 weeks of being laid up," Tuan says.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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Birmingham P et al. Simulated joint infection assessment by rapid detection of live bacteria with real-time reverse transcription polymerase chain reaction. J Bone Joint Surg Am 2008;90:602-08.