Each year hundreds of patients with a prosthetic joint require a revision surgery due to severe pain and swelling. These symptoms are sometimes (but not always) due to infection, but microbiological bacterial culture – the current gold standard for diagnosing such infection – often produce false or inconclusive results.

Thus, researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a unit of the National Institutes of Health, have developed a potential new test to help surgeons confirm or rule out the presence of infection-causing bacteria in prosthetic joints that require surgical revision.

Rocky Tuan, PhD, chief of NIAMS’ Cartilage Biology and Orthopaedics branch, hopes that such a test could spare patients without an infection from unnecessary treatment while ensuring that patients with infection are properly treated for it. The test is described in the March issue of the Journal of Bone and Joint Surgery.

Tuan told Medical Device Daily that 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 have to have a second surgery to remove the spacer and receive a new prosthesis.

According to Tuan, estimates of the false negative rate for joint cultures in revision surgeries range from 27% to 50%. But failure to treat an infected joint could lead to severe infection and limb amputation. That’s when the surgeon has to make a judgment call based on experience and the way things look during the operation, to decide if they should proceed with the prosthesis replacement or treat the patient for infection using a spacer.

“The physician will want to play it safe so if there is any sign of possible infection they will take out the old [prosthesis] and put in [a spacer] ... to kill whatever bacteria is around there, and let it sit there for six weeks,” Tuan said, noting that this procedure is very effective at treating infection, if that is in fact what caused the prosthesis to stop working in the first place. But, he added, “Six weeks is a long time, the patient is basically immobilized, then they have to come back in to do the second surgery.”

Not only does this mean the patient has to endure two operations and two hospital stays, but also Tuan noted that the spacer surgery alone could cost up to $40,000.

So it would be really nice, Tuan said, to find out if there really is an infection and how effective the spacer treatment may be. Also, he said, it would be nice to find out what kind of bugs are in there so the physician can use an appropriate antibiotic treatment.

To address the false-negative problem, Tuan and his colleagues first developed a way to test for joint infections using polymerase chain reaction (PCR), which detects the presence of bacterial DNA.

However, this approach picked up all bacteria — even dead or dying bacteria that cannot perpetuate infection —resulting in false-positives.

That led Tuan’s team to expand the use of the 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 said. 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 the 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 the researchers are conducting a double-blind study working with an orthopedic clinic who are performing joint revision procedures on patients who need it anyway. Tuan said his team is collecting the joint fluid specimens and storing it in a freezer. The physician will treat the patient as they normally would, but the researchers will analyze the specimens without knowing how the patient was treated.

“And, we’re mixing the patients,” Tuan said, “meaning some of the patients were found to be infected and some were deemed clean from beginning to end, and of course later on we will find out what will happen to these patients.”

The researchers hope the results from this double-blind study will validate their method of identifying or ruling out infection before a patient goes in for the joint revision surgery.

“It’s still in the verification step; we need this clinical correlation in order to really say with a great degree of certainty the results from this test can be used with confidence,” Tuan said.