Robin Patel discusses her work on prosthetic joint infections and how metagenomics is changing infectious disease diagnostic procedures.
Julie’s Biggest Takeaways:
The term antimicrobial resistance can mean many things. Although acquisition of genetic elements can lead to drug resistance, so can different growth lifestyles of bacteria; the same bacteria growing in liquid culture may be more susceptible to a drug than those bacteria growing on a biofilm. Lifestyle and genetics can intertwine, however, when bacteria growing as a biofilm exchange resistance genes through horizontal gene transfer.
How do bacteria reach an implanted surface, such as on a prosthetic joint, to cause infection? It may rarely occur during surgery, if even a single bacterium reaches the joint surface despite the sterile conditions; alternatively, it could occur through hematogenous spread (through the blood) after the surgery is over. Most infections are believed to be seeded at the time of implantation.
While scientists don’t perform teeny, tiny implants in animal models of infection, the materials are placed in animal bone to mimic as similar an immune response as possible.
Targeted metagenomics and shotgun metagenomics are both being developed clinically. Targeted metagenomics looks at one specific gene found in a number of species, such as the 16S ribosomal RNA gene. Shotgun metagenomic looks at all DNA present, and requires a lot more cleaning up to eliminate human genomic material, which is the major sequence of any human-derived sample.
“Antimicrobial resistance is a global challenge. It’s also a national challenge; it affects all of us. It’s a problem that’s really compromising human medicine today but it really touches on everybody. (Antimicrobial resistance) touches on us as patients but it also involves the use of antibiotics, which is something that happens in many sectors, not just in medicine: in agriculture, in animal husbandry, in the raising of crops, in management of wastewaters. So many areas that ASM members have expertise in.”
“Most of the organisms that cause PJI are organisms that microbiologists would easily recognize. Many of them would be easily recognizable as skin flora; Staphylococci are particualrly common, but not just Staphylococcus aureus, also the coagulase-negative Staphylococci, especially Staphylococci epidermidis. Streptococci, such as viridans group Streptococci, Enterococci, gram-negative bacilli including members of the Enterobacteriaceae as well as nonfermenting members such as Pseudomonas aeruginosa can cause these infections, and interestingly anaerobic bacteria can cause these infections as well. Cutibacterium acnes, which used to be called Proprionibacterium acnes, is not an infrequent cause, especially when we look at shoulder implants.”
“I hope over time that by better understanding how prosthetic joint infections are happening, we can come up with ways to better prevent them, because we’ve learned in infectious diseases in general that prevention is the best strategy.”
“[Successful implementation of sequencing data] is contingent on having high enough quality data to put the whole puzzle together. Imagine if you’re doing a 1000-piece puzzle and you end up with only 50 pieces, you may be able to figure out what the puzzle is of, but you still don’t have all the pieces there. If you have most of the puzzle put together, then you know where those pieces are, and if you know where it is that you’re looking, you can know whether you have that piece.”
“I come at [using metagenomics] from the perspective of a clinical microbiologist, and when I’m applying these tools I really want to get to clinical grade performance, which mean a high frequency of being right.”
“We can do the most amazing thing in the laboratory, but what comes out and gets delivered to healthcare providers and patients is our report. If the report is not clear or wrong, then it’s just the same as not having done a good job in the laboratory or having made a mistake. Clarity in reporting is key, and clarity in reporting of metagenomic data is a complicated task.”
“With metagenomics, it gets metacomplicated!”
Links for This Episode:
- Robin Patel Mayo Clinic website
- Mayo Clinic Medical Laboratories: www.MayoMedicalLaboratories.com
- News Release on AMR Challenge from Center for Disease Control and Prevention & partners
- Infection and Immunity paper looking at S. aureus intracellular survival.
- Journal of Clinical Microbiology and Clinical Infectious Diseases reports on shotgun metagenomics for prosthetic joint infection diagnostics
- Robin Patel on This Week in Microbiology
- Molecular Microbiology: Diagnostic Principles and Practice, 3rd Ed.
- HOM Tidbit: History of Streptococcal Research
- MTM Listener Survey
History of Microbiology tidbit
Prosthetic joint infections couldn’t occur if we didn't’ have the methodology to implant them, so in today’s history of microbiology tidbit, I want to visit the history of surgery. There are so many surgeons who have contributed to infection control and detection, but I want to head back to the 1800s, as bacteria were first recognized as the cause of various infections. Theodor Billroth was an Austrian surgeon who contributed many advances to surgery; for example, he was the first surgeon to remove a patient’s larynx, the first to remove sections of an esophagus, and first to excise a rectal cancer. His name lives on in a procedure called a Billroth I which joins part of the stomach to the duodenum, but his influence lives on in bacterial nomenclature as well.
In addition to treating patients by performing their surgeries, Billroth also treated the fever that often followed surgery; let’s face it, sterile technique in the 1800s wasn’t what we enjoy today. In microscopic investigations of patient pus exudates, he discovered what he described as “small organisms (Kettenkokken) as found in either isolated or arranged in pairs, sometimes in chains of 4 to 20 or more links.” He called these Kettenkokken: ketten for chain and kokken, or in English we say cocci, which is Greek for berries. Chain-berries, if you will. What Billroth observed of course is what we know today as Streptococcus, a common cause of post-surgical infection and, as Robin explained earlier in our episode, one of the frequent causes of prosthetic joint infection.