|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
"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.
The National Institutes of Health (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. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
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.