Michael Barbella, Managing Editor09.02.22
DNA can spot the pathogens responsible for joint infections better than conventional methods, according to recent study data.
Results published in the Journal of Bone and Joint Surgery show that next-generation sequencing (NGS) reliably detected "opportunistic" pathogens in approximately two-thirds of culture-negative patients who met ICM PJI infection criteria. The study compared two infection detection technologies head-to-head: standard culture and NGS. The study is the largest of its kind, with more than 300 infected participants across top orthopedic institutions that included the Rothman Institute of Orthopedics, Cleveland Clinic, and Rush University Medical Center.
From June 2016 to August 2020, samples were taken from patients meeting ICM PJI infection criteria, and the samples were tested using both culture and NGS. The traditional method of diagnosing a suspected periprosthetic joint infection (PJI) combines culture with immune response biomarkers. However, the study indicated that culture had a “no growth” failure rate of more than 28% for patients with PJI, providing no useful guidance to physicians. The study then evaluated NGS results from the culture-negative 28%. NGS found one or more pathogens in 56 of the 81 culture-negative cases, with 91% returning polymicrobial results (at least two different species detected).
Periprosthetic joint infection is a dangerous infection. With a higher mortality rate than prostate cancer, melanoma, or breast cancer, PJI presents a significant health risk to those with knee or hip replacements. With more than 1 million total hip and total knee replacement procedures performed annually in the United States, an infection rate of 1.5% leaves thousands of patients at risk of death or amputation when revision surgeries fail.
“This study, the result of four years of extensive collaborative research between numerous high-caliber institutions in the US, has revealed that next-generation sequencing is indeed a very promising technology for identification of infective pathogens in joint infections. This is a major step forward for the medical community in taking care of patients with a very challenging condition,” said Javad Parvizi, M.D., PRCS, the James Edwards chair of Orthopedics at Sidney Kimmel Medical School, Philadelphia.
This study demonstrated the newer molecular technique of next-generation DNA sequencing overcame the challenge of organisms failing to grow in culture by using sample DNA to identify bacteria and fungi that may be causing infection. NGS provided a more comprehensive picture of the microbial profile of infection that is often missed by traditional culture, and demonstrated that a majority of infections are in fact polymicrobial. This multi-center study paves the way for additional studies to compare patient outcomes when NGS or culture are used for PJI diagnosis and treatment.
Participating institutions in the study included: Rothman Institute at Thomas Jefferson, Philadelphia; Cleveland Clinic, Dept of Orthopaedic Surgery, Cleveland; Rush University Medical Center, Dept of Orthopaedic Surgery, Chicago; Penn Presbyterian Medical Center, University of Pennsylvania, Philadelphia; University of Utah, Dept of Orthopaedics, Salt Lake City; University of Louisville, Adult Reconstruction Program, Louisville, Ky.; University of California San Francisco, San Francisco; University of Pittsburgh Medical Center, Dept of Orthopaedic Surgery, Pittsburgh; New England Baptist Hospital, Chestnut Hill, Mass.; University of South Florida, Dept of Orthopaedic, Surgery, Clearwater, Fla.; Northside Hospital, Atlanta; GA Anderson Orthopaedic Research Institute, Alexandria, Va.; Hospital for Special Surgery, New York, N.Y.; University of Florida, Dept of Orthopaedics and Rehabilitation, Gainesville, Fla.; Colorado Joint Replacement, Denver; and Texas Tech University, Dept of Biological Sciences, Lubbock, Texas.
Results published in the Journal of Bone and Joint Surgery show that next-generation sequencing (NGS) reliably detected "opportunistic" pathogens in approximately two-thirds of culture-negative patients who met ICM PJI infection criteria. The study compared two infection detection technologies head-to-head: standard culture and NGS. The study is the largest of its kind, with more than 300 infected participants across top orthopedic institutions that included the Rothman Institute of Orthopedics, Cleveland Clinic, and Rush University Medical Center.
From June 2016 to August 2020, samples were taken from patients meeting ICM PJI infection criteria, and the samples were tested using both culture and NGS. The traditional method of diagnosing a suspected periprosthetic joint infection (PJI) combines culture with immune response biomarkers. However, the study indicated that culture had a “no growth” failure rate of more than 28% for patients with PJI, providing no useful guidance to physicians. The study then evaluated NGS results from the culture-negative 28%. NGS found one or more pathogens in 56 of the 81 culture-negative cases, with 91% returning polymicrobial results (at least two different species detected).
Periprosthetic joint infection is a dangerous infection. With a higher mortality rate than prostate cancer, melanoma, or breast cancer, PJI presents a significant health risk to those with knee or hip replacements. With more than 1 million total hip and total knee replacement procedures performed annually in the United States, an infection rate of 1.5% leaves thousands of patients at risk of death or amputation when revision surgeries fail.
“This study, the result of four years of extensive collaborative research between numerous high-caliber institutions in the US, has revealed that next-generation sequencing is indeed a very promising technology for identification of infective pathogens in joint infections. This is a major step forward for the medical community in taking care of patients with a very challenging condition,” said Javad Parvizi, M.D., PRCS, the James Edwards chair of Orthopedics at Sidney Kimmel Medical School, Philadelphia.
This study demonstrated the newer molecular technique of next-generation DNA sequencing overcame the challenge of organisms failing to grow in culture by using sample DNA to identify bacteria and fungi that may be causing infection. NGS provided a more comprehensive picture of the microbial profile of infection that is often missed by traditional culture, and demonstrated that a majority of infections are in fact polymicrobial. This multi-center study paves the way for additional studies to compare patient outcomes when NGS or culture are used for PJI diagnosis and treatment.
Participating institutions in the study included: Rothman Institute at Thomas Jefferson, Philadelphia; Cleveland Clinic, Dept of Orthopaedic Surgery, Cleveland; Rush University Medical Center, Dept of Orthopaedic Surgery, Chicago; Penn Presbyterian Medical Center, University of Pennsylvania, Philadelphia; University of Utah, Dept of Orthopaedics, Salt Lake City; University of Louisville, Adult Reconstruction Program, Louisville, Ky.; University of California San Francisco, San Francisco; University of Pittsburgh Medical Center, Dept of Orthopaedic Surgery, Pittsburgh; New England Baptist Hospital, Chestnut Hill, Mass.; University of South Florida, Dept of Orthopaedic, Surgery, Clearwater, Fla.; Northside Hospital, Atlanta; GA Anderson Orthopaedic Research Institute, Alexandria, Va.; Hospital for Special Surgery, New York, N.Y.; University of Florida, Dept of Orthopaedics and Rehabilitation, Gainesville, Fla.; Colorado Joint Replacement, Denver; and Texas Tech University, Dept of Biological Sciences, Lubbock, Texas.