Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections
Abstract
:1. Introduction
2. C-Reactive Protein (CRP)
3. Erythrocyte Sedimentation Rate (ESR)
4. White Blood Cell Count (WBC)
5. Percentage of Neutrophils (%N)
6. Neutrophils to Lymphocytes Ratio (NLR)
7. Platelet Count to Mean Platelet Volume Ratio (PC/mPV)
8. Fibrinogen
9. D-Dimer
10. Interleukin-6 (IL-6)
11. Procalcitonin (PCT)
12. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Serum-CRP | Infection Definition | Cut Off (mg/L) | Sensitivity | Specificity |
---|---|---|---|---|
Nilsdotter-Augustinsson et al., ActaOrtho, 2007 [10] | Positive cultures together with the clinical evaluations by orthopedic surgeons | 10 | 82% | 71% |
Bottner et al., JBJS Br, 2007 [11] | Based on findings of intraoperative culture and histology | 32 | 95% | 96% |
Ghanem et al., IntJInfDiseases, 2009 [6] | ≥1 of the following criteria: (1) an abscess or sinus tract communicating with the joint space, (2) positive preoperative aspiration culture on solid media, (3) ≥2 positive intraoperative cultures or 1 positive culture on solid media in conjunction with the presence of other indicators of infection (gross intracapsular purulence, elevated cell count and differential of the aspirate fluid) | 10 | 91% | 77% |
Piper et al., PlosOne, 2010 [12] | ≥1 of the following criteria: (1) visible pus surrounding the implant, (2) a positive histopathological examination, (3) a sinus tract communicating with the implant, or (4) positive periprosthetic tissue culture and positive sonicate fluid culture for the same microorganism | Knee 14.5 Hip 10.3 | 79% 74% | 88% 79% |
Glehr et al., CORR, 2013 [13] | MSIS 2011 | 10.25 | 91% | 72% |
Alijanipour et al., CORR, 2013 [14] | MSIS 2011 | Knee 10 | 97% | 70% |
Hip 10 | 88% | 77% | ||
Elgeidi et al., Int Orthop, 2014 [15] | ≥1 of the following criteria: visible pus surrounding prosthesis, (2) sinus tract communicating to implant, (3) growth of bacteria on culture (≥2 intraoperative cultures or growth of a virulent organism in a single specimen) | 18.0 | 100% | 86% |
Randau et al., Plos One, 2014. [16] | ≥1 of the following criteria: (1) purulent synovial fluid or ≥1700 leukocytes/µL or ≥ 65% neutrophils in the joint aspirate (TKA) (≥3600 leukocytes/µL or ≥80% neutrophils (THA)), (2) histological confirmation of PJI, (3) pathogen detection in sterile joint aspiration or in at least two intraoperative tissue specimen, or (4) definitive signs of PJI clinically or intraoperatively (e.g., sinus tract) | 9.1 | 62% | 83% |
Yuan et al., Surgical Infection, 2015 [17] | ≥1 of the following criteria: (1) ≥1 positive tissue culture, (2) pus surrounding the prosthesis, or (3) positive histopathology | 15 | 76% | 72% |
Ettinger et al., CID, 2015 [18] | MSIS 2011 | 3 | 80% | 64% |
Shahi et al., JBJS Am, 2017 [19] | MSIS 2014 | 10 | 79% | 80% |
Klim et al., Sci Rep, 2018 [20] | MSIS 2011 | 11 | 90% | 74% |
Fu et al., JoA, 2019 [21] | MSIS 2011 | 10 | 80% | 80% |
Xiong et al., JOSR, 2019 [22] | MSIS 2011 | 10 | 85% | 65% |
Yu et al., BMC Musculoskeletal Disorders, 2020 [23] | MSIS 2011 | 9.27 | 70% | 79% |
Qin et al., JoA, 2020 [24] | MSIS 2014 | 7.5 | 81% | 66% |
Klim et al., Int Orthop, 2020 [25] | MSIS 2011 | 10.3 | 90% | 67% |
Bin et al., JoA, 2020 [26] | MSIS 2011 | 4.93 | 94% | 73% |
Wu et al., JoA, 2020 [27] | MSIS 2014 | 10.8 | 73% | 95% |
Huang et al., Orthopaedic Surgery, 2021 [28] | MSIS 2014 | 10 | 74% | 91% |
Yang et al., Sci Rep, 2021 [29] | ICM 2018 | 12.51 | 91% | 83% |
Sigmund et al., Int Orthop, 2021 [2] | EBJIS | 10 | 68% | 87% |
ESR | Infection Definition | Cut-Off (mm/h) | Sensitivity | Specificity |
---|---|---|---|---|
Nilsdotter-Augustinsson et al., ActaOrtho 2007 [10] | Positive cultures together with the clinical evaluations by orthopedic surgeons | 30 | 64% | 87% |
Bottner et al., JBJS Br, 2007 [11] | Based on findings of intraoperative culture and histology | 32 | 81% | 89% |
Ghanem et al., IntJInfDiseases, 2009 [6] | One of the following criteria: (1) an abscess or sinus tract communicating with the joint space, (2) positive preoperative aspiration culture on solid media, (3) ≥2 positive intraoperative cultures or 1 positive culture on solid media in conjunction with the presence of other indicators of infection (gross intracapsular purulence, elevated cell count and differential of the spirate fluid | 30 | 94% | 70% |
Piper et al., PlosOne, 2010 [12] | ≥1 of the following criteria: (1) visible pus surrounding the implant, (2) a positive histopathological examination, (3) a sinus tract communicating with the implant, or (4) positive periprosthetic tissue culture and positive sonicate fluid culture for the same microorganism | Knee 19 Hip 13 | 89% 82% | 74% 60% |
Alijanipour et al., CORR, 2013 [14] | MSIS 2011 | Knee 30 Hip 30 | 94% 95% | 68% 71% |
Elgeidi et al., Int Orthop, 2014 [15] | ≥1 of the following criteria: (1) visible pus surrounding prosthesis, (2) sinus tract communicating to implant, (3) growth of bacteria on culture (≥2 intraoperative cultures or growth of a virulent organism in a single specimen) | 45 | 82% | 83% |
Shahi et al., JBJS Am, 2017 [19] | MSIS 2014 | 30 | 73% | 78% |
Fu et al., JoA, 2019 [21] | MSIS 2011 | 30 | 33% | 100% |
Paziuk et al., JoA, 2020 [42] | MSIS (not mentioned) | 46 | 78% | 79% |
Xiong et al., JOSR, 2019 [22] | MSIS 2011 | 30 | 73% | 100% |
Yu et al., BMC Musculoskeletal Disorders, 2020 [23] | MSIS 2011 | 22 | 63% | 74% |
Qin et al., JoA, 2020 [24] | MSIS 2014 | 41 | 64% | 70% |
Bin et al., JoA, 2020 [26] | MSIS 2011 | 31 | 77% | 97% |
Wu et al., JoA, 2020 [27] | MSIS 2014 | 29 | 70% | 92% |
Huang et al., Orthopaedic Surgery, 2021 [28] | MSIS 2014 | 30 | 81% | 88% |
Yang et al., Sci Rep, 2021 [29] | ICM 2018 | 36.5 | 70% | 86% |
Infection Definition | Cut-Off (×109 Cells/L) | Sensitivity | Specificity | |
---|---|---|---|---|
Nilsdotter-Augustinsson et al. ActaOrtho 2007 [10] | Positive cultures together with the clinical evaluations by orthopedic surgeons | 10 | 92% | 60% |
Bottner et al., JBJS Br, 2007 [11] | Based on findings of intraoperative culture and histology | 6.2 | 70% | 60% |
Toossi et al., JoA, 2012 [35] | ≥1 of the following criteria: (1) positive culture, (2) Intraoperative purulence, (3) draining sinus tract. Or3 of the following 4: (a) ESR ≥ 30 mm/h, (b) CRP ≥ 10 mg/L, (c) Synovial WCC ≥ 1760 cells/µL (chronic) or ≥10,700 cells/µL, (d) percentage of neutrophils ≥ 73% (chronic) or 89% (acute). | 7.8 | 55% | 66% |
Glehr et al., CORR, 2013 [13] | MSIS 2011 | 5.48 | 91% | 34% |
Elgeidi et al., Int Orthop, 2014 [15] | ≥1 of the following criteria: (1) visible pus surrounding prosthesis, (2) sinus tract communicating to implant, (3) growth of bacteria on culture (≥2 intraoperative cultures or growth of a virulent organism in a single specimen) | 9.2 | 91% | 76% |
Randau et al., Plos One, 2014 [16] | ≥1 of the following criteria: (1) purulent synovial fluid or ≥1700 leukocytes/µL or ≥65% neutrophils in the joint aspirate (TKA) (≥3600 leukocytes/µL or ≥80% neutrophils (THA)), (2) histological confirmation of PJI, (3) pathogen detection in sterile joint aspiration or in at least two intraoperative tissue specimen, or (4) definitive signs of PJI clinically or intraoperatively (e.g., sinus tract) | 10.3 | 21% | 94% |
Yuan et al., Surgical Infection, 2015 [17] | ≥1 of the following criteria: (1) ≥1 positive tissue culture, (2) pus surrounding the prosthesis, or (3) positive histopathology | 10.5 | 64% | 54% |
Klim et al., Sci Rep, 2018 [20] | MSIS 2011 | 5.68 | 90% | 39% |
Yu et al., BMC Musculoskeletal Disorders, 2020 [23] | MSIS 2011 | 8.91 | 35% | 94% |
Klim et al., Int Orthop, 2020 [25] | MSIS 2011 | 8.17 | 42% | 92% |
Yang et al., Sci Rep, 2021 [29] | ICM 2018 | 7.4 | 79% | 49% |
Sigmund et al., Int Orthop, 2021 [2] | EBJIS | 10 | 36% | 89% |
%N | Cut-Off | |||
Toossi et al., JoA, 2012 [35] | ≥1 of the following criteria: (1) positive culture, (2) Intraoperative purulence, (3) draining sinus tract. Or3 of the following 4: (a) ESR ≥ 30 mm/h, (b) CRP ≥ 10 mg/L, (c) Synovial WCC ≥ 1760 cells/µL (chronic) or ≥10,700 cells/µL, (d) percentage of neutrophils ≥ 73% (chronic) or 89% (acute). | 68% | 52% | 75% |
Sigmund et al., Int Orthop, 2021 [2] | EBJIS | 69% | 66% | 67% |
NLR | Cut-Off | |||
Yu et al., BMC Musculoskeletal Disorders, 2020 [23] | MSIS 2011 | 2.13 | 85% | 68% |
Sigmund et al., Int Orthop, 2021 [2] | EBJIS | 3.82 | 63% | 73% |
PC/mPV | Cut-Off | |||
Paziuk et al., JoA, 2020 [42] | MSIS (year not mentioned) | 31.7 | 48% | 81% |
Huang et al., Orthopaedic Surgery, 2021 [28] | MSIS 2014 | 31.7 | 55% | 81% |
Sigmund et al., Int Orthop, 2021 [2] | EBJIS | 29.4 | 43% | 81% |
Fibrinogen | Infection Definition | Cut-Off (mg/dL) | Sensitivity | Specificity |
---|---|---|---|---|
Klim et al., Sci Rep, 2018 [20] | MSIS 2011 | 519 | 90% | 66% |
574 | 81% | 75% | ||
Klim et al., Int Orthop, 2020 [25] | MSIS 2011 | 515 | 94% | 73% |
Bin et al., JoA, 2020 [26] | MSIS 2011 | 360 | 79% | 95% |
Wu et al., JoA, 2020 [27] | MSIS 2014 | 361 | 76% | 86% |
Sigmund et al., Int Orthop, 2021 [2] | EBJIS | 457 | 69% | 89% |
Huang et al., Orthopaedic Surgery, 2021 [28] | MSIS 2014 | 401 | 78% | 88% |
Yang et al., Sci Rep, 2021 [29] | ICM 2018 | 420 | 86% | 90% |
D-Dimer | Infection Definition | Cut Off (ng/mL) | Sensitivity | Specificity | Serum/Plasma |
---|---|---|---|---|---|
Shahi et al., JBJS Am, 2017 [19] | MSIS 2014 | 850 | 89% | 93% | not mentioned |
Fu et al., JoA, 2019 [21] | MSIS 2011 | 850 | 67% | 60% | Plasma |
Xiong et al., JOSR, 2019 [22] | MSIS 2011 | 756 | 81% | 80% | Serum |
Pannu et al., JoA, 2020 [77] | ICM 2013 | 850 | 96% | 32% | Serum |
Qin et al., JoA, 2020 [24] | MSIS 2014 | 1170 | 93% | 75% | Serum |
Wu et al., JoA, 2020 [27] | MSIS 2014 | 410 | 76% | 67% | Plasma |
Huang et al., Orthopaedic Surgery, 2021 [28] | MSIS 2014 | 1170 | 60% | 85% | Plasma |
Il-6 | Infection Definition | Cut-Off (pg/mL) | Sensitivity | Specificity |
---|---|---|---|---|
Bottner et al., JBJS Br, 2007 [11] | Based on findings of intraoperative culture and histology | 12 | 95% | 87% |
Glehr et al., CORR, 2013 [13] | MSIS 2011 | 2.55 | 94% | 53% |
Gollwitzer et al., JBJS Am, 2013 [80] | ≥1 of the following criteria: (1) sinus tract, (2) 2 positive major criteria (positive intraoperative microbiological culture and positive histopathological analysis), or (3) 1 positive major criterion and 1 positive minor criterion (CRP > 1.0 mg/dL and/or positive microbiological culture of the aspirate) | 1.89 | 47% | 95% |
Elgeidi et al., Int Orthop, 2014 [15] | ≥1 of the following criteria: (1) visible pus surrounding prosthesis, (2) sinus tract communicating to implant, (3) growth of bacteria on culture (≥2 intraoperative cultures or growth of a virulent organism in a single specimen) | 10.4 | 100% | 93% |
Randau et al., Plos One, 2014 [16] | ≥1 of the following criteria: (1) purulent synovial fluid or ≥1700 leukocytes/µL or ≥65% neutrophils in the joint aspirate (TKA) (≥3600 leukocytes/µL or ≥80% neutrophils (THA)), (2) histological confirmation of PJI, (3) pathogen detection in sterile joint aspiration or in at least two intraoperative tissue specimen, or (4) definitive signs of PJI clinically or intraoperatively (e.g., sinus tract) | 2.6 6.6 | 79% 49% | 58% 88% |
Ettinger et al., CID, 2015 [18] | MSIS 2011 | 5.12 | 80% | 88% |
Yu et al., BMC Musculoskeletal Disorders, 2020 [23] | MSIS 2011 | 8.07 | 80% | 76% |
Klim et al., Int Orthop, 2020 [25] | MSIS 2011 | 5.7 | 77% | 70% |
Procalitonin | Infection Definition | Cut-Off (ng/mL) | Sensitivity | Specificity |
---|---|---|---|---|
Bottner et al., JBJS Br, 2007 [11] | Based on findings of intraoperative culture and histology | 0.3 | 33% | 98% |
Glehr et al., CORR, 2013 [13] | MSIS 2011 | 0.35 0.75 | 90% 48% | 33% 100% |
Randau et al., Plos One, 2014 [16] | ≥1 of the following criteria: (1) purulent synovial fluid or ≥1700 leukocytes/µL or ≥65% neutrophils in the joint aspirate (TKA) (≥3600 leukocytes/µL or ≥80% neutrophils (THA)), (2) histological confirmation of PJI, (3) pathogen detection in sterile joint aspiration or in at least two intraoperative tissue specimen, or (4) definitive signs of PJI clinically or intraoperatively (e.g., sinus tract) | 0.46 | 13% | 100% |
Yuan et al., Surgical Infection, 2015 [17] | ≥1 of the following criteria: (1) ≥1 positive tissue culture, (2) pus surrounding the prosthesis, or (3) positive histopathology | 0.5 | 80% | 74% |
Ettinger et al., CID, 2015 [18] | MSIS 2011 | 0.25 | 90% | 28% |
Klim et al., Int Orthop, 2020 [25] | MSIS 2011 | 0.1 | 40% | 90% |
Serum Parameter | Cut-Off | Sensitivity | Specificity |
---|---|---|---|
C-reactive Protein (CRP) | 3–32 mg/L | 62–100% | 64–96% |
Erythrocyte sedimentation rate (ESR) | 13–46 mm/h | 33–95% | 60–100% |
White blood cell count (WBC) | 5.48–10.5 × 109 cells/L | 21–42% | 89–94% |
Percentage of neutrophils (%N) | 68–69% | 52–66% | 67–75% |
Neutrophils to lymphocytes ratio (NLR) | 2.13–3.82 | 63–85% | 68–73% |
Platelet count to mean platelet volume ratio (PC/mPV) | 29.4–31.7 | 43–55% | 81% |
Fibrinogen | 360–574 mg/dL | 69–94% | 66–95% |
D-dimer | 410–1170 ng/mL | 60–96% | 32–93% |
Interleukin 6 (IL-6) | 1.89–12 pg/mL | 47–100% | 53–95% |
Procalcitonin (PCT) | 0.1–0.75 ng/mL | 13–90% | 28–100% |
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Sigmund, I.K.; Puchner, S.E.; Windhager, R. Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections. Biomedicines 2021, 9, 1128. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091128
Sigmund IK, Puchner SE, Windhager R. Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections. Biomedicines. 2021; 9(9):1128. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091128
Chicago/Turabian StyleSigmund, Irene K., Stephan E. Puchner, and Reinhard Windhager. 2021. "Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections" Biomedicines 9, no. 9: 1128. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091128