Microbial cell-free DNA sequencing may identify periprosthetic joint infection pathogens
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Published results showed blood microbial cell-free DNA sequencing may accurately identify pathogens and be used to monitor infection clearance during the treatment period among patients with periprosthetic joint infections.
Mathias P. Bostrom, MD, Laura T. Donlin, PhD, and colleagues collected peripheral blood from 53 adults with validated hip or knee periprosthetic joint infections immediately prior to surgical treatment. Researchers sequenced and aligned microbial cell-free DNA from plasma to a genome database with more than 1,000 microbial species, and performed intraoperative tissue and synovial fluid cultures per the standard of care. Researchers considered the accuracy of organism identification with the use of blood cell-free DNA sequencing, as measured by agreement with tissue-culture results, as the primary outcome.
Results showed organisms were identified in 87% of patients by intraoperative and preoperative joint cultures. Researchers found microbial cell-free DNA sequencing identified the joint pathogen in 35 cases, including four of seven culture-negative cases and, as an adjunct to cultures, increased pathogen detection from 87% to 94%. For cases with genus-only culture results, researchers noted a median time to species identification of 3 days less than standard-of-care methods. Additional microorganisms not grown in cultures were detected by circulating cell-free DNA sequencing in 14 cases, according to results. Researchers found no detection or reduced levels of infectious pathogen with cell-free DNA sequencing at postoperative encounters.
Not only can blood microbial cell-free DNA sequencing be used as a screening and adjunct diagnostic test for potential orthopedic infections, but as a means for monitoring the clearance or persistence of an orthopedic infection during treatment, according to Donlin, co-director of the Derfner Foundation Precision Medicine Laboratory at Hospital for Special Surgery and principal investigator of the study.
“The latter can help in a variety of settings, including during treatment of a prosthetic joint infection by a two-stage surgical procedure wherein the timing of the second stage could be educated by the clearance or lack of clearance of the infection as determined by a mildly invasive blood test,” Donlin told Healio Orthopedics.
Bostrom also noted use of blood microbial cell-free DNA sequencing allows for diagnosis of periprosthetic joint infections without joint aspiration, which is painful and invasive.
“We may also be able to better diagnose infections that involve multiple organisms,” Bostrom, chief of the adult reconstruction and joint replacement service at Hospital for Special Surgery, told Healio Orthopedics. “Ultimately, this test could let us diagnose the presence of an infection before the cultures grow out of the bacteria.”
Perspective
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The article by Adriana P. Echeverria, BS, and colleagues from Hospital for Special Surgery endorses the notion that molecular techniques for isolation of infective organism will play an invaluable role in the future, in general, and in orthopedics, in particular. The promising aspect of the technology they describe is the ability to isolate the infective organism in a less invasive fashion from blood, as opposed to synovial fluid. Another positive aspect of the study is the ability to isolate infective organisms in four out of seven culture negative cases.
Future studies by the investigators and others will explore other important aspects of the technology. Inclusion of a larger cohort, a control group and longer clinical outcome would be some of those aspects. One hopes that refinements in the technology may allow it to have a better yield than culture. The infective organisms were isolated in 35 out of 46 patients, which is a lower yield than culture. The real value of molecular techniques will be their ability to isolate the infective organisms in culture negative cases. Recent studies on next-generation sequencing of joint fluid from infected cases has revealed that many of these periprosthetic joint infection cases are polymicrobial in nature. The latter is a groundbreaking finding that will change the manner in which patients are managed and is something that we had failed to recognize because of the limitations of culture. Like other fields in medicine, we need to recognize the numerous limitations of the traditional culture and stop designing studies that compare itself to culture as the gold standard. A racehorse should run faster than a donkey.
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