VANCOUVER, British Columbia—Erythrocyte sedimentation rate (ESR) above 22.5 mm/hr and C-reactive protein (CRP) levels above 13.5 mg/L are strong indicators of infection at the site of a total knee arthroplasty (TKA), whereas patients with lower readings on both these tests have only a 3% probability of having an infected prosthesis. Canadian researchers report the first prospective study of ESR and CRP as screening tests for the presence of infection in patients presenting for revision TKA in The Journal of Bone and Joint Surgery.¹

Lead author Nelson V. Greidanus, MD, MPH, FRCSC, concludes, "The erythrocyte sedimentation rate and the C-reactive protein level provide excellent diagnostic test information for establishing the presence or absence of infection prior to surgical intervention in patients with pain at the site of a knee arthroplasty." Dr. Greidanus is in the department of orthopaedics at the University of British Columbia, in Vancouver, Canada.

First prospective study to validate ESR and CRP as screening tests for knee infection

The cohort originally included 201 consecutive patients (207 revision knee replacements). Twenty-six patients were excluded owing to diseases or conditions, such as rheumatoid arthritis (RA), known to result in abnormal ESR or CRP levels, 19 were excluded because they already had insertion of antibiotic spacers for treatment of infection, and 11 were excluded because they were already taking empiric antibiotics. The final evaluation included 151 knees in 145 patients who had preoperative testing for ESR, CRP levels, knee aspiration and culture of the aspirate, and culture of intraoperative specimens obtained once the knee was opened surgically.

A knee was considered to be infected if at least two aspirate or tissue samples were positive on bacterial culture. The researchers found that 45 (29.8%) of the 151 knees were infected and they noted that this relatively high prevalence probably because their institution is a major referral center for an area of 4 million people.

The most common infecting organism was Staphylococcus, which was methicillin- and oxacillin-sensitive in 26 of 37 knees. Three knees were infected with more than one organism. Dr. Greidanus and colleagues used receiver-operating-characteristic curve analysis to determine the optimal positivity criterion and previously accepted criteria for establishing positivity of the tests. The resulting cut-points were 22.5 mm/hr for ESR positivity and 13.5 mg/L for CRP positivity.

Patients negative on ESR and CRP unlikely to have deep infection

The tests can be used together as a screening battery for knee infection in patients with symptoms related to TKA. Patients who are negative on both ESR and CRP have only a 3% probability of infection, whereas patients who are positive on both tests have an 84% probability of infection.

"While patients with infection at the site of a knee replacement may present with systemic symptoms and signs compatible with sepsis, many present with features that are indistinguishable from those of failure for aseptic reasons. The misdiagnosis of infection as aseptic loosening, arthrofibrosis, or unexplained pain can easily lead to a delay in appropriate treatment or to inappropriate surgery. Therefore, when evaluating pain at the site of a knee arthroplasty, and prior to embarking on revision knee arthroplasty, the surgeon must distinguish knees with infection from those without infection," the authors write.

Robert Bourne, MD, FRCSC, with the division of orthopaedic surgery at the University of Western Ontario, in Canada, told CIAOMed that he likes the approach taken by Dr. Greidanus and his colleagues. "This group performed a similar analysis to rule out infection in total hip replacements before revision. Their recommendations have proven effective and have benefited countless patients and surgeons. In total knee replacements, surgeons have used an ESR and C-reactive protein to rule out infection without rigorous scientific proof that these tests are efficacious. Dr. Greidanus and his colleagues have now provided this proof and confirmed the clinical experience of orthopaedic surgeons," he said.

Dr. Bourne advises rheumatologists to use ESR and CRP in symptomatic TKA patients to assess the possibility of deep infection. "If these tests suggest infection, the next step would be to refer the patient back to their orthopaedic surgeon who would most likely perform a knee joint aspiration with synovial joint fluid testing for cell count and aerobic/anaerobic culture and sensitivity. One note of caution is that in patients with inflammatory joint disease, the ESR and CRP might be elevated without deep infection," he said.

Javad Parvizi, MD, with the Rothman Institute of Orthopaedics at Thomas Jefferson University, in Philadelphia, Pennsylvania, agrees. "The paper is an excellent one," Dr. Parvizi told CIAOMed. "It highlights the importance of using simple and cheap tests that can, in majority of the cases, rule out infection with good sensitivity. As you know, positive tests do not necessarily imply a joint infection (low specificity). In cases of positive tests, further investigations need to be done. These tests are excellent in ordinary clinical practice."

However, Dr. Parvizi emphasizes that in patients with an underlying rheumatalogical disease, such as RA, the test results may be abnormal because of inflammatory arthritis. "These tests have little use for patients with inflammatory arthritis."

Reference

1. Greidanus NV, Masri BA, Garbuz DS, et al. Use of erythrocyte sedimentation rate and C-reactive protein level to diagnose infection before revision total knee arthroplasty. J Bone Joint Surg Am. 2007;89:1409-1416.