Prosthetic Joint Infection Diagnosis Using Conventional Methods

Expires: November 5, 2021

 

 

Image of Robin Patel, M.D.Presenter

Robin Patel, M.D., is the Division Chair of Clinical Microbiology in the Department of Laboratory Medicine and Pathology in Rochester, Minnesota. She holds the academic rank of Professor of Medicine and Microbiology.

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Transcript and References

Introduction

Hi, I’m Matt Binnicker, the Director of Clinical Virology and Vice Chair of Practice in the Department of Laboratory Medicine and Pathology at Mayo Clinic. The diagnosis of prosthetic joint infection involves establishing that the joint is infected and defining the involved microorganisms through clinical evaluation and laboratory testing. In this month’s “Hot Topic,” my colleague, Dr. Robin Patel, will discuss the importance of accurate diagnosis of prosthetic joint infection and its management. She will focus on the pathogenesis, clinical presentation, and definition of arthroplasty failure, and will discuss diagnostic strategies. I hope you enjoy this month’s Hot Topic, and I want to personally thank you for allowing Mayo Clinic the opportunity to be a partner in your patient’s health care.

Thank you for the kind introduction.

Disclosures

Dr. Robin Patel has a US patent for a method and an apparatus for sonication, but has foregone her right to personally receive royalties.

Funding

  • National Institutes of Health
  • Department of Defense
  • National Science Foundation

Total Hip and Knee Replacement Procedures United States

The numbers of primary total hip and knee arthroplasties have been increasing over time, with 332,000 total hip and 719,000 total knee arthroplasties performed in 2010 in the United States.

It is estimated that 3,481,000 primary total knee and 572,000 primary total hip arthroplasties will be performed annually in the US by 2030.

Hip and knee arthroplasty are most common. Shoulder, elbow, wrist, ankle, and temporomandibular, metacarpophalangeal and interphalangeal joint replacement are less commonly performed.

Prosthetic joints improve quality of life, but may fail due to aseptic loosening, infection, dislocation, or prosthesis or bone fracture, among other reasons, necessitating revision or resection arthroplasty.

Prosthetic joint infection, although uncommon, is the most serious complication, occurring in approximately 2% of knee and 1% of hip arthroplasties.

Prosthetic Hip and Knee Infections: United States

As shown in this figure, the number of cases of prosthetic joint infection is increasing with time.

Patient-related risk factors for prosthetic joint infection include prior revision arthroplasty or prior same site prosthetic joint infection, tobacco use, obesity, rheumatoid arthritis, malignancy, immunosuppression, and diabetes mellitus.

Surgical risk factors include simultaneous bilateral arthroplasty, long operative times, and allogeneic blood transfusion.

Postoperative risk factors include wound-healing complications (such as superficial infection, hematoma, delayed healing, wound necrosis, or dehiscence), atrial fibrillation, myocardial infarction, urinary tract infection, prolonged hospital stay, and at any time postoperatively, Staphylococcus aureus bacteremia.

Surgical Management of Prosthetic Hip or Knee Infection

It is important to accurately diagnose prosthetic joint infection as its management differs from the management of other causes of arthroplasty failure.

The goal of treatment is to cure infection, prevent recurrence, and achieve a pain-free, functional joint. This can best be achieved by a multidisciplinary team, including an orthopedic surgeon, clinical microbiologist, and infectious diseases specialist. Antimicrobial agents alone, without surgical intervention, ultimately usually fail. The quality of surgical debridement is critical.

A general approach to surgical management is outlined, although different centers and surgeons may use slightly different strategies.

Chronic infections require resection arthroplasty either as a one-stage exchange (i.e., removal and reimplantation of the prosthesis during the same surgical procedure) or a two-stage exchange (i.e., removal of the prosthesis and systemic antimicrobial agents with subsequent prosthesis reimplantation).

Patients with symptoms of prosthetic joint infection of short duration, who present with early postoperative infection or hematogenous infection, and who have a well-fixed, functioning prosthesis, without sinus tracts, and with appropriate microbiology represent a select group potentially amenable to debridement and retention of the prosthesis.

When unacceptable function is anticipated following surgery or the infection has been refractory to multiple surgical attempts at cure, resection arthroplasty and creation of a pseudarthrosis for hips (the so-called Girdlestone procedure) or arthrodesis for knees, may be considered.

If the patient is not a surgical candidate, antimicrobial suppression may be considered; this approach is unlikely to cure infection, so antimicrobial agents are often continued indefinitely.

Prosthetic Join Infection Microbiology

Staphylococcus aureus, and coagulase-negative Staphylococcus species account for more than half of prosthetic hip and knee infection cases. Cutibacterium acnes are a common cause of shoulder arthroplasty infection, and Staphylococcus aureus is particularly common in patients with rheumatoid arthritis. Polymicrobial and culture-negative infections occur.

Unusual Causes of Prosthetic Joint Infection

An ever-expanding list of bacteria and fungi are rare causes of prosthetic joint infection.

The pathogenesis of prosthetic joint infection involves the formation of microbial biofilms.  Bacteria, typically inoculated at the time of implantation, adhere to the implant and enter into a phenotypically unique, biofilm state in which they are relatively protected from conventional antimicrobial agents and the host immune system.

Alternatively, microorganisms may seed the implant hematogenously, or via compromised local tissues.

Virulent organisms such as Staphylococcus aureus inoculated at implantation typically present acutely (or, with hematogenous seeding of the implant, at any time) following surgery, whereas less virulent organisms, such as coagulase negative staphylococci more often manifest several months or even years postoperatively as chronic infection.

Prosthetic Joint Infection Clinical Presentation

The most frequent symptom of prosthetic joint infection is pain.

In infection caused by virulent bacteria, patients typically present with local and systemic signs and symptoms.

In contrast, chronic infection is generally characterized by subtle signs and symptoms, often not suggestive of infection, such as persistent pain alone, accompanied by loosening of the prosthesis, and sometimes by sinus tract formation with discharge.

Infections due to hematogenous seeding of the implant occur at any time postoperatively, typically presenting with sudden onset of joint pain.

Criteria for Diagnosis of Prosthetic Joint Infection

Although there is no universally accepted definition of prosthetic joint infection, criteria listed have been are described in the referenced publications.

C-Reactive Protein Erythrocyte Sedimentation Rate

In the absence of underlying inflammatory conditions, C-reactive protein is the most useful preoperative blood test.

Although C-reactive protein and erythrocyte sedimentation rate are elevated after uncomplicated arthroplasty surgery, C-reactive protein returns to preoperative levels earlier than does erythrocyte sedimentation rate.

We examined preoperative C-reactive protein and erythrocyte sedimentation rate in 582 patients with knee, hip or shoulder implant failure. Both were statistically significantly higher in the groups with prosthetic knee or hip infection compared to those with aseptic implant failure. However, in the shoulder implant group, the erythrocyte sedimentation rate was not significantly different in the groups with prosthetic shoulder infection versus aseptic shoulder implant failure, and C-reactive protein was minimally elevated in the former compared to the latter group.

Here we looked at the data separated by erythrocyte sedimentation rate and C-reactive protein based on standard cutoffs of >30 mm/h and >10 mg/L, respectively. C-reactive protein performed better than erythrocyte sedimentation rate for detection of prosthetic hip implant infection, and neither test performed well for detection of prosthetic shoulder implant infection. Overall, therefore, C-reactive protein is preferred to erythrocyte sedimentation rate, but neither test performs well for diagnosis of prosthetic shoulder infection.

Plain radiographs are inaccurate for diagnosis; periprosthetic radiolucency, osteolysis, and/or migration may be present in either prosthetic joint infection or aseptic loosening.

Computed tomography and magnetic resonance imaging are hampered by artifacts produced by prostheses, although non-ferromagnetic (i.e., titanium or tantalum) implants are associated with minimal artifacts and provide good magnetic resonance imaging resolution for soft-tissue abnormalities.

Bone scans, including those performed as three-phase studies, are sensitive for detecting failed implants but cannot be used to determine the cause of failure, and may remain abnormal for more than a year after implantation.

Combined bone and gallium scans offer improvement over bone scan alone, however, labeled leukocyte imaging combined with bone scans has better accuracy.

Newer imaging strategies, such as antigranulocyte scintigraphy with monoclonal antibodies and hybrid imaging, such as positron emission tomography/computed tomography, which is shown here, perform even better.

In this patient (whose images were also shown on the prior slide), Staphylococcus epidermidis and Finegoldia magna were isolated from peri-prosthetic tissue.

Synovial Fluid Leukocyte/Differential Prosthetic Knee

The most useful pre-operative diagnostic test is joint aspiration for total and differential cell count and aerobic and anaerobic culture.

A synovial fluid leukocyte count of more than 1.7x103/μl or a neutrophil percentage of more than 65% is consistent with prosthetic knee infection.

Hip aspiration may require imaging guidance.

Higher synovial fluid leukocyte count and neutrophil percentage cutoffs are applied for prosthetic hip infection diagnosis.

The cutoffs used are lower than those used to diagnose native joint infection.

Synovial fluid culture has a sensitivity of 56-75% and specificity of 95-100%, and to achieve ideal sensitivity and specificity should be performed by inoculation into blood culture bottles.

If an organism of questionable clinical significance is isolated, repeat synovial fluid aspiration for culture should be considered. Prior antimicrobial treatment reduces sensitivity of culture.

Studies of Intrasurgical Frozen-Section Histopathologic Findings of Acute Inflammation in Prosthetic Joint Infection Diagnosis

In cases where the diagnosis of prosthetic joint infection has not been established preoperatively, assessment for acute inflammation on intraoperative frozen section provides rapid intraoperative assessment for prosthetic joint infection, with sensitivities of 43-100% and specificities of 77-100% (using cutoffs varying from >5 to ³10 polymorphonuclear cells per high power field), and inter-observer reproducibility of 86%.

Prospective Vortexing/Sonication Clinic Study Hip or Knee Implants

Defining the pathogen or pathogens is critical to directing the antimicrobial regimen. If this has not been done preoperatively, it is important that appropriate specimens for microbiologic study be collected at the time of surgery.

Antimicrobial therapy should be discontinued at least two weeks prior to collection of specimens for culture, and, at surgery, antimicrobial agents should be withheld until culture specimens have been collected.

Cultures of sinus tract exudates are often positive due to microbial skin colonization, correlate poorly with surgically obtained specimens and should be avoided.

Due to poor sensitivity, neither intraoperative swab cultures, nor periprosthetic tissue Gram stain are recommended.

Collection of multiple periprosthetic tissue specimens for aerobic and anaerobic bacterial culture is imperative because of the poor sensitivity of a single tissue culture, and to distinguish contaminants from pathogens.

We recommend four tissues if using conventional plate and broth cultures and three if culturing tissues in blood culture bottles. The latter is a recommended practice.

In addition to prior systemic antimicrobial therapy, cultures may be falsely negative because of leaching of antimicrobial agents from antimicrobial impregnated cement, biofilm growth on the prosthesis surface, a low number of organisms in tissue, inappropriate culture media or inadequate culture incubation time, or prolonged transport to the laboratory.

Fungal and/or mycobacterial cultures may be considered on a case-by-case basis, but are not routinely recommended.

Since microorganisms associated with prosthetic joint infection attach to the prosthesis and persist as biofilm microorganisms, obtaining a sample from the prosthesis surface is useful for microbiologic diagnosis if the implant is being removed and the microbiology of the infection has not been defined.

Vortexing combined with sonication of the implant is a simple technique that can be performed in most microbiology laboratories and has good sensitivity and specificity, provided that an appropriate cutoff for significant results is applied.

Sonication in bags is not recommended due to contamination.

This slide shows an outline of the procedure that we use for implant sonication.  The implant is collected in a sterilized polypropylene (Nalgene) jar and transported to the laboratory.

400 milliliters of Ringer’s solution is added to each container.

The container is vortexed for 30 seconds and then subjected to bath sonication for 5 minutes, followed by additional vortexing for 30 seconds.

In our original studies, we directly plated 0.5 ml of sonicate fluid to aerobic and anaerobic sheep blood agar plates, but we now concentrate the sonicate fluid 100-fold by centrifugation and plate 0.1 ml of concentrated sonicate fluid, as shown.

Staphylococcus epidermidis Biofilm on Polycarbonate Coupons Scanning Electron Microscopy

Sonication removes bacterial biofilms from surfaces as shown in this figure illustrating Staphylococcus epidermidis biofilm on polycarbonate coupons treated with soaking alone, scraping with a wooden stick or sonication, as described on the previous slide.

This slide shows periprosthetic tissue and sonicate fluid culture from the same patient.

Note that there are much greater numbers of colonies growing from the sonicate fluid compared to the periprosthetic tissue specimen.

Prospective Vortexing/Sonication Clinical Study Hip or Knee Implants

We initially validated the vortexing and sonication technique by performing a prospective clinical trial of patients undergoing total knee or hip revision or resection for aseptic failure or presumed infection at our institution from August 2003 through December 2005.

Those patients whose components were contaminated in the operating room or did not fit in the container, or in whom fewer than two tissues were cultured or who underwent partial revision were excluded from the study.

Definition of Prosthetic Hip and Knee Infection

Prosthetic hip and knee infection was defined as shown, excluding microbiologic criteria.

Number of Microorganisms Detected by Sonicate Fluid Culture

252 subjects with aseptic implant failure and 79 with prosthetic joint infection were enrolled.

Sonicate fluid was not concentrated; 0.5 ml was plated on an aerobic and anaerobic sheep blood agar plate and incubated aerobically and anaerobically, respectively.

This slide shows the quantity (and type) of microorganisms detected by sonicate fluid culture.

Most of the prosthetic joint infection specimens yielded more than 100 colony forming units per plate, whereas most of the aseptic failure specimens yielded no growth or a small number of colonies.

A cutoff of five colony forming units of the same organism was determined to most accurately differentiate aseptic failure from infection.

Results Prosthetic Hip or Knee Infection

The sensitivity of sonicate fluid culture (78.5%) was superior to that of tissue culture (60.8%). The sensitivity of synovial fluid culture was 56.3%.

The specificities of sonicate fluid, tissue, and synovial fluid culture were 98.8%, 99.2%, and 98.1%, respectively.

Prospective Clinical Study Shoulder Implants

We then published a prospective clinical trial of patients undergoing shoulder arthroplasty revision or resection for aseptic failure or presumed infection at our institution from August 2004-November 2008.

Those patients in whom fewer than two tissues were cultured, who underwent partial revision or whose sonicate fluid was not archived were excluded from the study. Vortexing and sonication were performed as described in our hip and knee implant study except that after December 14, 2005, we introduced sonicate fluid concentration, as previously described.

Definition of Definite Prosthetic Shoulder Infection

Patients were classified as having definite prosthetic shoulder infection if at least one of the following was present: (i) visible purulence surrounding the prosthesis, (ii) acute inflammation on histopathologic examination of permanent tissue sections, or (iii) a sinus tract communicating with the prosthesis.

Patients were classified as having probable prosthetic shoulder infection if they did not meet these criteria but the same organism was isolated from at least two periprosthetic tissues and in significant quantity (³5 cfu/plate for sonicate fluids processed without concentration and ³20 cfu/plate for sonicate fluids processed with concentration).

Aseptic failure was defined as a failure that did not meet these criteria.

Prospective Clinical Study Shoulder Implants

136 patients undergoing arthroplasty revision or resection were studied; 33 had definite prosthetic shoulder infections and 101 had aseptic implant failure.

Sonicate fluid culture was more sensitive than periprosthetic tissue culture for the detection of definite prosthetic shoulder infection (66.7 and 54.5%, respectively).

The specificities were similar.

Acknowledgments

In conclusion, the diagnosis of prosthetic joint infection involves first establishing whether the joint is infected and then, if it is, defining the involved microorganism or microorganisms. This is done with clinical evaluation of the patient, as well as, if needed, preoperative testing with C-reactive protein, and synovial fluid aspiration for cell count, differential and aerobic and anaerobic culture (preferably in blood culture bottles), and/or intraoperative testing with histopathology, and culture of multiple peri-implant tissues and/or the implant itself (using vortexing and sonication).

I would like to thank the team of researchers listed above and acknowledged the National Institutes of Health for their generous support.

References

  1. Kurtz S, Ong K, Lau E, et al: Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. Apr 2007;89:780–5.
  2. Kurtz S, Lau E, Watson H, et al: Economic burden of periprosthetic joint infection in the United States. J Arthroplasty. Sept 2002;8:61-653.
  3. Del Pozo J, Patel Robin: Infection associated with prosthetic joints. N Engl J Med. Aug 2009;361:787-794.
  4. Tande A, Patel R: Prosthetic joint infection. Clin Microbiol Rev. Apr 2014;27(2):302-345.
  5. Marculescu C, Berbari EF, Cockerill III FR, et al: Unusual aerobic and anaerobic bacteria associated with prosthetic join infections. Clin Orthop Relat Res 2006;451:55-72.
  6. Parvizi J, Zmistowski B, Berbari EF, et al: New definition of periprosthetic joint infection: from the workgroup of the Musculoskeletal Infection Society.  Clin Orthop Relat Res. Nov 2011;469(11):2992-2994.
  7. Osmon D, Berbari EF, Berendt AR, et al: Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases. Jan 2013;56(1):e1-e25.
  8. Parvizi J, Gehrke T, Chen AF: Proceedings of the international consensus on periprosthetic joint injection. Bone Joint J. 2013;95-B:1450-1452.
  9. Piper K, Fernandez-Sampedro M, Steckelberg K, et al: C-reactive protein, erythrocyte sedimentation rate and orthopedic implant infection. PLoS One. Feb 2010;5(2):e9358.
  10. Ye W, Shang W, Yang Y: Staphylococcus infection associated with arthroplasty, recent advances in artoplasty, Dr. Samo Fokter (Ed.), ISBN: 978-953-307-990-5, InTech, Available from: http://www.intechopen.com/books/recent-advances-in-arthroplasty/staphylococcus-infection-associated-with-arthroplasty.
  11. Trampuz A, Hanssen AD, Osmon D, et al: Synovial fluid leukocyte count and differential for the diagnosis of prosthetic knee infection. Am J Med. Oct 2004;117(8):556-562.
  12. Trampuz A, Piper K, Jacobson M, et al: Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. Aug 2007;357:654-663.
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Robin Patel, M.D.

Robin Patel, M.D., is the Division Chair of Clinical Microbiology in the Department of Laboratory Medicine and Pathology in Rochester, Minnesota. She holds the academic rank of Professor of Medicine and Microbiology.