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Routine Diagnostic Tests for Periprosthetic Joint Infection Demonstrate a High False-Negative Rate and Are Influenced
Michael M Kheir1, Timothy L Tan1, Noam Shohat2
1The Rothman Institute at Thomas Jefferson University, Philadelphia, Pennsylvania.
Background:
Current guidelines recommend serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as the first-line testing for evaluation of suspected periprosthetic joint infection, in addition to synovial white blood-cell (WBC) count and polymorphonuclear percentage. However, the sensitivity and other diagnostic measures of these tests using a standardized definition of periprosthetic joint infection and the influence of organisms on these inflammatory markers remain inadequately investigated.
Methods:
A retrospective review of an institutional database of 549 periprosthetic joint infection cases and 653 aseptic total joint arthroplasty revisions was performed. Periprosthetic joint infection was defined using major criteria from the International Consensus Meeting (ICM) on Periprosthetic Joint Infection. The mean inflammatory marker levels were compared among organisms with Student t tests and the proportions of elevated laboratory levels were compared among organisms with chi-square analyses. Receiver operating characteristic curve analyses were performed to calculate new cutoffs, sensitivities, and specificities for each organism and overall for serum CRP and ESR and synovial WBC and polymorphonuclear percentage.
Results:
The sensitivity of these markers for diagnosing chronic periprosthetic joint infection was 0.85 for ESR, 0.88 for CRP, 0.83 for WBC count, and 0.78 for polymorphonuclear percentage. For ESR, antibiotic-resistant organisms had higher mean values (84.3 mm/hr) than culture-negative cases (57.4 mm/hr), coagulase-negative Staphylococcus (68.3 mm/hr), and Streptococcus species (66.1 mm/hr); Staphylococcus aureus (81.0 mm/hr) was higher than culture-negative cases (57.4 mm/hr). For CRP, culture-negative cases had lower mean values (41.0 mg/L) than gram-negative organisms (87.4 mg/L), antibiotic-resistant organisms (86.0 mg/L), S. aureus (112.2 mg/L), and Streptococcus species (114.6 mg/L); S. aureus (112.2 mg/L) was higher than coagulase-negative Staphylococcus (66.0 mg/L). For WBC count, culture-negative cases had lower mean values (27,984.5 cells/mL) than S. aureus (116,250.0 cells/mL) and Streptococcus species (77,933.7 cells/mL). For polymorphonuclear percentage, there were no significant differences in mean values among all organisms.
Conclusions:
It appears that serological markers, namely ESR and CRP, have a higher false-negative rate than previously reported. Synovial markers similarly exhibit high false-negative rates. Furthermore, the sensitivity of these tests appears to be related to organism type. Surgeons should be aware of the high rate of false-negatives associated with low-virulence organisms and culture-negative cases.
Level Of Evidence:
Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.
Insights
Serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests show higher false-negative rates for diagnosing periprosthetic joint infection than previously thought. Test sensitivity varies by organism type, necessitating awareness of limitations in clinical practice.
Area of Science:
- Orthopedic surgery
- Infectious disease diagnostics
- Biomarker research
Background:
- Current guidelines recommend serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), alongside synovial white blood-cell (WBC) count and polymorphonuclear percentage, for diagnosing periprosthetic joint infection (PJI).
- The diagnostic accuracy, particularly sensitivity, of these markers and the impact of specific organisms on their levels require further investigation.
Purpose of the Study:
- To evaluate the sensitivity and diagnostic performance of serum ESR, CRP, and synovial WBC count and polymorphonuclear percentage for periprosthetic joint infection (PJI).
- To assess the influence of different microorganisms on the levels of these inflammatory markers in PJI cases.
Main Methods:
- Retrospective review of 549 PJI cases and 653 aseptic revisions using International Consensus Meeting (ICM) criteria.
- Comparison of inflammatory marker levels and proportions of elevated levels among different organisms using statistical analyses.
- Receiver operating characteristic (ROC) curve analyses to determine sensitivities, specificities, and optimal cutoffs for each marker.
Main Results:
- Sensitivities for diagnosing PJI were 0.85 for ESR, 0.88 for CRP, 0.83 for WBC count, and 0.78 for polymorphonuclear percentage.
- Elevated ESR and CRP levels were observed with specific organisms like Staphylococcus aureus and gram-negative organisms, while culture-negative cases showed lower levels.
- Significant differences in mean WBC counts were noted between S. aureus/Streptococcus species and culture-negative cases, but not for polymorphonuclear percentage.
Conclusions:
- Serum markers (ESR, CRP) and synovial markers (WBC, polymorphonuclear percentage) exhibit higher false-negative rates than previously reported for PJI diagnosis.
- The sensitivity of these diagnostic tests is influenced by the type of causative organism.
- Clinicians must be aware of the potential for false-negatives, especially with low-virulence organisms and in culture-negative PJI cases.
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