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Episode #31 – Truth or DAIR

31 Cover Art OPT

Summary

Drs. Jonathan Ryder and Nico Cortes-Penfield take us through the evidence and their approach to PJI (prosthetic joint infections)!

Credits

Host(s): Jonathan Ryder, Sara Dong

Guest: Nico Cortes-Penfield

Writing: Jonathan Ryder, Nico Cortes-Penfield

Producing/Editing/Cover Art: Sara Dong

Infographics: Jonathan Ryder, Sara Dong

Our Guests

Guest Consultant

Nico Cortes-Penfield, MD

Nico is an assistant professor in the division of infectious diseases at University of Nebraska Medical Center in Omaha, Nebraska. He serves as the medical director of the outpatient parenteral antibiotic therapy program and an associate medical director of antimicrobial stewardship. He did his medical school, residency, and fellowship training at Baylor College of Medicine. His clinical and research interests are in complicated bone and joint infections, as he is part of the core faculty in the orthopedic infectious diseases service line at UNMC.

Guest Co-Host

Jonathan Ryder, MD

Jonathan Ryder, MD is an infectious diseases fellow at University of Nebraska Medical Center in Omaha, NE. He completed his internal medicine residency at Indiana University. His academic interests include medical education, endocarditis, and antimicrobial stewardship. He enjoys podcasts and #IDTwitter. His hobbies include running, reading non-fiction, and NFL football.

Culture

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Consult Notes

Consult Q

Orthopedic surgery is calling about an older male patient with a red, swollen, and painful joint, please evaluate and provide antibiotic recommendations

Case Summary

54 year old male with history of diabetes mellitus type 2, rheumatoid arthritis on infliximab, and recent right total knee arthroplasty for OA who presented with right knee pain and swelling 2 months after his TKA.  He was found to have an MRSA PJI and underwent 2-stage exchange.  His course was later complicated by wound dehiscence and infection for which he underwent DAIR.

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Key Points

What are the risk factors for prosthetic joint infection (PJI)?

How do PJIs present?

  • Often presents acutely with pain, stiffness, inability to bear weight on joint over the period of days
      • Patients may or may not appear systemically ill, but they often have obvious inflammation at the joint or surgical site
  • In less common scenarios, you might see a more indolent presentation of worsening pain and instability over weeks to months (feeling like the leg will give out)
      • Patients with subacute onset often do not have fever or leukocytosis, and their physical exam findings may be more subtle
      • That said, a few items that should cause suspicion: sinus tracts (a giveaway!), delayed wound healing, ongoing drainage after surgery

Are there available PJI diagnostic criteria?

  • The standard diagnostic criteria for PJI are 2018 MSIS criteria.  As Nico discussed, these can be used clinically but can also think of these as consensus definition for research
  • Parvizi J, Tan TL, Goswami K, et al. The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria. J Arthroplasty. 2018;33(5):1309-1314.e2. doi:10.1016/j.arth.2018.02.078
  • Nico pointed out the two major criteria that confirm PJI:
      • Presence of sinus tract that communicates with hardware
      • Multiple joint cultures (either synovial fluid or tissue) growing the same organism
      • If you have either of these, case closed!
  • There are also minor criteria worth 1-3 points each, with at least 2 points indicating possible PJI and at least 6 points indicating definite PJI.  These include:
      • Elevated serum CRP, D-dimer, ESR
      • >3000 WBC or >80% PMNs in synovial fluid
      • Elevated synovial alpha-defensin, CRP, or leukocyte esterase
      • Intra-operative findings like histopathology, purulence, and a single positive culture
  • *Remember that the synovial fluid WBC that defines infection is much lower for PJI vs. native joint septic arthritis*

What is the microbiology of PJI?

  • Classic teaching about the micro of PJI defines the groups by time since surgery:
      • Both early and delayed infections are from bacteria introduced at surgery
          • Early (within 3 months of surgery): tend to be more virulent bacteria like S.aureus and Gram-negative rods
          • Delayed (3-12 mo): think more indolent and lower virulence organisms like Cutibacterium and Staph epidermidis
      • Late (>1 year out): hematogenous usually, so tend to be from bacteremia organisms like S.aureus, Gram-negatives, and Strep
  • *Nico points out that Staph was mentioned in all the categories, so you always have to think about coagulase-negative Staph and S.aureus*
  • Nico also emphasized times when you might expect something that isn’t Staph:
      • Shoulder PJI is frequently due to Cutibacterium
      • Recurrent PJI immediately following a failed course of treatment (think about difficult to treat organisms like VRE or Corynebacterium striatum)
      • When the patients has or just had an invasive bacteremic infection with another organism

What are the surgical approaches for PJI?

  • Remember that joint prostheses have both fixed metal components (that are hammed/cemented into the patient’s bone) as well as polyethylene lines that attach to the metal components to create the mobile articulating surface at the joint
  • Debridement and implant retention (DAIR) 
      • Also may hear: I&D with poly exchange, I&D with exchange of mobile components, I&D with liner exchange
      • Surgeon cuts out infected tissue/bone, removes the polyethylene liner, scrubs/irrigates, and then puts on a new liner and closes
      • Pros: Much less invasive than exchange arthroplasty (there is no removal of metal components out of patient’s bone)
      • Cons: harder to ensure that all the infected material is out, particularly for infections that have been there for a while or are due to organisms that make a lot of biofilm
      • Use for: 
          • Infections that develop within the first few weeks after surgery (or at least when we’ve caught the infection right after patient started having symptoms)
          • When there hasn’t been much time for infection to build up on the metal components
          • When no evidence of advanced infection such as hardware loosening on imaging or sinus tract
          • When you DON’T have organisms that create biofilm or are hard to treat (aka NOT S.aureus, fungi)
          • Often used in patients who might not tolerate an exchange arthroplasty due to comorbidities or overall poor health
  • Exchange arthroplasty, which can be single-stage or two-stage procedure
      • Entire prosthesis is removed along with all infected tissue
          • In single stage: surgeon immediately places a new prosthesis into same site
          • In two stage: surgeon first places a cement spacer (often mixed with antibiotics like vancomycin + tobramycin or gentamicin), then comes back a couple months later to remove the spacer and place new prosthesis
              • The idea here is that the spacer leeches antibiotics into the joint space and if there is still infection left, we’ll be able to detect and take patient back for another debridement and spacer exchange 
          • Cons: bigger surgery than DAIR; two-stage approach involves several months where patient has an antibiotic spacer, is non-weight-bearing or partial weightbearing because of space, risk of deconditioning
      • As Nico discussed, there is regional variation in how these exchange arthroplasties are used
          • In Europe, main approaches are DAIR and single-stage exchange. Two stage less common and used predominantly in high risk or difficult cases
          • In the US, two-stage exchange is the norm.

So what’s the deal with these spacers?

  • Nico delved into the history behind antibiotic spacers: 
      • Materials scientists back in the 1980s showed that you could mix antibiotics into acrylic cements, put that into a person or animal, and then have it leach out into tissues in meaningful levels.
      • Seems that orthopedic surgeons started adding antibiotics into bone cement and spacers in the 1990s, and then published how that went for their patients.  Most did well and major side effects were rare
      • So this practice become common place and “standard of care”
  • It’s hard to find any comparative studies of spacers with vs without antibiotics.  Here’s one meta-analysis that pulled data on antibiotic bone cement (not spacers!):
  • Important to note that you can get detectable serum levels of vancomycin and aminoglycosides from antibiotics spacers!  So patients can get AKI and allergic reactions up to and including anaphylaxis from antibiotics in spacers.  These are rare, but a valuable reminder that antibiotics in spacers are not totally benign.

Antibiotic selection

Antibiotic duration with a 2 stage procedure?

  • Many centers typically give an initial 6-week course of antibiotic therapy, followed by a time off antibiotics (“antibiotic holiday”, anywhere from 2-6 wks)
  • Many places will trend CRP and/or ESR expecting to see inflammatory markers normalize and then not go up when off antibiotics → Nico points out that this widespread practice isn’t really based on good comparative data.
  • There is variation in what docs do after antibiotic holiday:
      • Some will do diagnostic arthrocentesis only if CRP is high or rising
      • Other groups might just take patient immediately for antibiotic spacer exchange
      • Some groups will routinely do arthrocentesis to ensure synovial fluid studies are normal before putting in new prosthesis, even when patients and CRP values are reassuring
  • At the time of second stage procedure, surgeons will send new tissue cultures to confirm the infection has been eradicated
  • Some centers may also give period of secondary antibiotic prophylaxis to prevent re-infections

What is the role of secondary prophylaxis after 2-stage exchange?

In the second portion of the episode, the patient received DAIR.  In patients who receive DAIR, we give prolonged antibiotic therapy: Typically at least 3 months and 6 months for Staph in an infected knee arthroplasty.  In non-Staph infections, some may do as little as 6 weeks after DAIR, but last year there was a large RCT called DATIPO!

DATIPO: Bernard L, Arvieux C, Brunschweiler B, et al. Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection. N Engl J Med. 2021;384(21):1991-2001. doi:10.1056/NEJMoa2020198

    • Compared 6 and 12 weeks of therapy in PJI
    • Found a large benefit in long-term cure with 12 weeks in the patients who underwent DAIR: 16% absolute risk reduction in DAIR group, which comes out to a number needed to treat of about 6
    • So prior to DATIPO, consensus and guidelines-based answer to how long to treat was at least 3 months for Staph…but now we have data to suggest most folks with PJI managed with DAIR should be treated for at least 3 months, even if they have a gram-negative or Strep or other PJI

What about rifampin?

What about chronic antibiotic suppression after DAIR?  Defined as long-term antibiotics after the initial 3-6 mo of definitive treatment.

  • Data is all retrospective. There are 3-4 comparative studies that suggest suppressive antibiotics after DAIR for PJI and other ortho hardware infections may reduce long term reinfection risk
  • Downsides: pill burden and cost, long-term risk of colonization with antibiotic-resistant bacteria, adverse events of antibiotic themselves
  • Nico points out that DATIPO trial patients did not get suppressive antibiotic therapy, and the success rate among those who had DAIR and 12 weeks of antibiotics was >85% (which is not that much worse than the 95% success rate among patients who underwent 2-stage exchange) – so likely most patients who receive DAIR wouldn’t benefit from antibiotic suppression because they’re already going to do well
  • Nico approaches suppression after DAIR with shared decision making 
  • A perspective: Cobo J, Escudero-Sanchez R. Suppressive Antibiotic Treatment in Prosthetic Joint Infections: A Perspective. Antibiotics (Basel). 2021;10(6):743. Published 2021 Jun 19. doi:10.3390/antibiotics10060743



Episode Art & Infographics

Goal

Listeners will be able to describe an approach to the diagnosis and management of prosthetic joint infection

Learning Objectives

After listening to this episode, listeners will be able to:

  • Define the common risk factors for prosthetic joint infection (PJI)
  • Identify the typical symptoms of PJI and available diagnostic criteria
  • Compare and contrast the surgical approaches for PJI
  • Recognize and briefly summarize the OVIVA and DATIPO trials

Disclosures

Our guest (Nico Cortes-Penfield) as well as Febrile podcast and hosts report no relevant financial disclosures

Citations

Cortes-Penfield, N., Ryder, J., Dong, S. “#31: Truth or DAIR”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/ff70b6f9-8443-4683-8cce-f3acc40cf2e2

Transcript

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