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Mayo Researchers Test FilmArray Blood Culture ID for Prosthetic Joint Infections

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NEW YORK (GenomeWeb) – A new study has taken the first steps in assessing whether commercially available multiplex panels can be used to deduce the cause of prosthetic joint infection, or PJI.

Published last month in the Journal of Clinical Microbiology, the study evaluated the performance of the FilmArray Blood Culture ID panel from BioMérieux subsidiary BioFire Diagnostics.

The BCID panel, which was cleared by the US Food and Drug Administration in 2013, detects 24 pathogens and 3 antibiotic resistance genes associated with bloodstream infections.

"We had previously shown that a panel of PCR assays targeting the organisms that cause PJI was a sensitive and specific way to diagnose" infection, Robin Patel, corresponding author on the independent study and chair of the division of clinical microbiology at the Mayo Clinic, told GenomeWeb in an email.

In the new study the group chose to evaluate the BCID panel "because it is easy to use and fast," Patel said.

As many as two percent of prosthetic joint implants each year in the US will become infected. If this happens, the prosthesis is usually removed, but antimicrobial therapy and potential revision of the implant require accurate diagnosis of the infectious agent. Determining PJI had previously been a trickier endeavor, since the particular bacterial culprits often form biofilms on the surfaces of medical implants or devices.

Patel, who is also a professor of microbiology and medicine at Mayo, is part of a team pioneering the use of vortexing and sonication to shake the films loose and separate the clumps, thus improving yield of bacteria.

The technique can be used for sonicate culture, and, according to a 2013 study it showed improvement compared to culturing homogenates of tissue removed from adjacent to the prosthesis, but still produced an unsatisfactory number of culture-negative cases.

In the JCM evaluation, the team looked at 216 frozen samples of sonicate fluids from an archive, 98 of which were known PJI cases and 118 were aseptic joint failures. The overall sensitivity of BCID to detect the cases was 53 percent, compared to 69 percent for culture. The panel specificity, meanwhile, was 99 percent. 

Patel and her team had previously tested the PCR-ESI/MS diagnostic platform from Abbott Molecular. In that evaluation, they found that PCR-ESI/MS and culture had sensitivities for detecting PJI of about 78 percent and 70 percent, respectively, and specificities of around 94 percent and 99 percent.  

So, in the JCM study, they also compared pathogen-specific performance of BCID to PCR-ESI/MS, as well as to a 16S rRNA gene PCR and a ten-target PCR panel. The PCR-ESI/MS had a longer turnaround time, Patel noted, but like culture and 16s rRNA PCR, it detected a number of pathogens not represented on the BCID panel.

The study reported that BCID missed two Enterococcus and one Pseudomonas aeruginosa infection, but detected two additional Staphylococcus aureus infections. It was notably poor at detecting coagulase-negative staphylococci, with a 54 percent sensitivity attributed to the fact that the panel is optimized for blood culture and its performance for this family of targets is known to vary by species.

However, the method was able to detect a pathogen in six culture-negative samples.

The authors concluded that "a BCID-like approach would possibly be a useful adjunct to PJI diagnosis," provided the sensitivity for coagulase negative bacteria were increased, and additional PJI-related pathogens, as well as perhaps a universal 16S rRNA target, were added.

The method might pick up more culture-negative cases, the study said, and knowing the exact name of the infection that caused the joint implant to fail can improve a patient's satisfaction.

Importantly, the study also suggested that the two minutes of hands-on time and one-hour turnaround could perhaps allow the method to inform surgical decisions, which differ between infected and non-infected cases.

"If this works, it could potentially be applied to synovial fluid, which could be aspirated in the office and quickly tested in a nearby laboratory, even while the patient waits," Patel said. 

There are several companies developing PJI panels, she said, and she expects they will be commercially available in the future.

There were more than one million knee and hip replacements in the US in 2010, according to the US Centers for Disease Control and Prevention. The demand for joint replacements is likely to increase, and the cost of infections was projected in one study to exceed $1.6 billion by 2020.