Top

Clinical Orthopaedics and Related Research®

Published in:

01-08-2013 | Clinical Research

Novel Biomarkers to Detect Infection in Revision Hip and Knee Arthroplasties

Authors: Mathias Glehr, MD, Joerg Friesenbichler, MD, Günter Hofmann, MD, Gerwin Alexander Bernhardt, MD, Maximilian Zacherl, MD, Alexander Avian, PhD, Reinhard Windhager, MD, Andreas Leithner, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 8/2013

Abstract

Background

A periprosthetic joint infection is one of the most challenging complications associated with THA and TKA. In the diagnostic process for detecting a periprosthetic joint infection, one of the most important steps is analysis of laboratory infection biomarkers.

Questions/purposes

We investigated the sensitivity and specificity of the biomarkers procalcitonin, interleukin 6 (IL-6), and interferon α (IFN-α) as compared with conventional biomarkers (C-reactive protein [CRP], leukocyte level) for a periprosthetic joint infection associated with revision arthroplasties.

Methods

We prospectively included and analyzed 84 patients (124 revision arthroplasties). The blood parameters of interest were procalcitonin, IL-6, IFN-α, leukocyte level, and CRP. Samples were taken preoperatively and on the first, third, and seventh postoperative days. The sensitivity and specificity of these biomarkers then were calculated.

Results

Considering the preoperative values of 84 patients (124 operations), procalcitonin, IL-6, CRP, and leukocyte level correlated with periprosthetic joint infection, whereas IFN-α did not. A procalcitonin cut-off level of 0.35 ng/mL revealed a sensitivity of 80% and specificity of 37%. An IL-6 cut-off level of 2.55 pg/mL had a sensitivity of 92% and specificity of 59%.

Conclusions

In this study procalcitonin and IL-6 were helpful for detecting periprosthetic joint infections in revision arthroplasties, although CRP generally was superior. Procalcitonin and IL-6 may be considered adjuvant tests when the diagnosis of a periprosthetic joint infection is in doubt. This study showed, in addition to conventional biomarkers such as CRP and leukocyte level, procalcitonin and IL-6 were helpful for detecting infections associated with revision arthroplasties.

Level of Evidence

Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Anders HJ, Lichtnekert J, Allam R. Interferon-alpha and -beta in kidney inflammation. Kidney Int. 2010;77:848–854.PubMedCrossRef

Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993;341:515–518.PubMedCrossRef

Bo M, Raspo S, Morra F, Isaia G, Cassader M, Fabris F, Poli L. Body fat and C-reactive protein levels in healthy non-obese men. Nutr Metab Cardiovasc Dis. 2004;14:66–72.PubMedCrossRef

Bottner F, Wegner A, Winkelmann W, Becker K, Erren M, Gotze C. Interleukin-6, procalcitonin and TNF-alpha: markers of peri-prosthetic infection following total joint replacement. J Bone Joint Surg Br. 2007;89:94–99.PubMed

Carrol ED, Thomson AP, Hart CA. Procalcitonin as a marker of sepsis. Int J Antimicrob Agents. 2002;20:1–9.PubMedCrossRef

Costerton JW, Post JC, Ehrlich GD, Hu FZ, Kreft R, Nistico L, Kathju S, Stoodley P, Hall-Stoodley L, Maale G, James G, Sotereanos N, DeMeo P. New methods for the detection of orthopedic and other biofilm infection. FEMS Immunol Med Microbiol. 2011;61:133–140.PubMedCrossRef

Coventry MB. Treatment of infections occurring in total hip surgery. Orthop Clin North Am. 1975;6:991–1003.PubMed

Drago L, Vassena C, Dozio E, Corsi MM, De Vecchi E, Mattina R, Romano C. Procalcitonin, C-reactive protein, interleukin-6, and soluble intercellular adhesion molecule-1 as markers of postoperative orthopaedic joint prosthesis infections. Int J Immunopathol Pharmacol. 2011;24:433–440.PubMed

Esposito S, Leone S. Prosthetic joint infections: microbiology, diagnosis, management and prevention. Int J Antimicrob Agents. 2008;32:287–293.PubMedCrossRef

10.

Fitzgerald RH Jr, Nolan DR, Ilstrup DM, Van Scoy RE, Washington JA 2nd, Coventry MB. Deep wound sepsis following total hip arthroplasty. J Bone Joint Surg Am. 1977;59:847–855.PubMed

11.

Fottner A, Birkenmaier C, von Schulze Pellengahr C, Wegener B, Jansson V. Can serum procalcitonin help to differentiate between septic and nonseptic arthritis? Arthroscopy. 2008;24:229–233.

12.

Galbraith JG, Butler JS, Browne TJ, Mulcahy D, Harty JA. Infection or metal hypersensitivity? The diagnostic challenge of failure in metal-on-metal bearings. Acta Orthop Belg. 2011;77:145–151.PubMed

13.

Gendrel D, Bohuon C. Procalcitonin, a marker of bacterial infection. Infection. 1997;25:133–134.PubMedCrossRef

14.

Gendrel D, Raymond J, Assicot M, Moulin F, Iniguez JL, Lebon P, Bohuon C. Measurement of procalcitonin levels in children with bacterial or viral meningitis. Clin Infect Dis. 1997;24:1240–1242.PubMedCrossRef

15.

Ghanem E, Azzam K, Seeley M, Joshi A, Parvizi J. Staged revision for knee arthroplasty infection: what is the role of serologic tests before reimplantation? Clin Orthop Relat Res. 2009;467:1699–1705.PubMedCrossRef

16.

Gonzalez MH, Mekhail AO. The failed total knee arthroplasty: evaluation and etiology. J Am Acad Orthop Surg. 2004;12:436–446.PubMed

17.

Haleem AA, Berry DJ, Hanssen AD. Mid-term to long-term followup of two-stage reimplantation for infected total knee arthroplasty. Clin Orthop Relat Res. 2004;428:35–39.PubMedCrossRef

18.

Hatzistilianou M. Diagnostic and prognostic role of procalcitonin in infections. ScientificWorldJournal. 2010;10:1941–1946.PubMedCrossRef

19.

Hogdall D, Hvolris JJ, Christensen L. Improved detection methods for infected hip joint prostheses. APMIS. 2010;118:815–823.PubMedCrossRef

20.

Hugle T, Schuetz P, Mueller B, Laifer G, Tyndall A, Regenass S, Daikeler T. Serum procalcitonin for discrimination between septic and non-septic arthritis. Clin Exp Rheumatol. 2008;26:453–456.PubMed

21.

Hunziker S, Hugle T, Schuchardt K, Groeschl I, Schuetz P, Mueller B, Dick W, Eriksson U, Trampuz A. The value of serum procalcitonin level for differentiation of infectious from noninfectious causes of fever after orthopaedic surgery. J Bone Joint Surg Am. 2010;92:138–148.PubMedCrossRef

22.

Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97:215–252.PubMedCrossRef

23.

Martinot M, Sordet C, Soubrier M, Puechal X, Saraux A, Liote F, Guggenbuhl P, Legre V, Jaulhac B, Maillefert JF, Zeisel M, Coumaros G, Sibilia J. Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients. Clin Exp Rheumatol. 2005;23:303–310.PubMed

24.

Moulin F, Raymond J, Iniguez JL, Ravilly S, Lebon P, Gendrel D. Serum alpha-interferon in lower respiratory tract infections of children. Pediatr Infect Dis J. 1996;15:883–886.PubMedCrossRef

25.

Moya F, Nieto A, R-Candela JL. Calcitonin biosynthesis: evidence for a precursor. Eur J Biochem. 1975;55:407–413.PubMedCrossRef

26.

Nascimento-Carvalho CM, Cardoso MR, Barral A, Araujo-Neto CA, Guerin S, Saukkoriipi A, Paldanius M, Vainionpaa R, Lebon P, Leinonen M, Ruuskanen O, Gendrel D. Procalcitonin is useful in identifying bacteraemia among children with pneumonia. Scand J Infect Dis. 2010;42:644–649.PubMedCrossRef

27.

Owen N, Poulton T, Hay FC, Mohamed-Ali V, Steptoe A. Socioeconomic status, C-reactive protein, immune factors, and responses to acute mental stress. Brain Behav Immun. 2003;17:286–295.PubMedCrossRef

28.

Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ, Garvin KL, Mont MA, Wongworawat MD, Zalavras CG. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011;469:2992–2994.

29.

Pramod J, Singh A. Sepsis biomarkers. Am J Med. 2008;121:e11; author reply e13.

30.

Prat C, Dominguez J, Rodrigo C, Gimenez M, Azuara M, Jimenez O, Gali N, Ausina V. Procalcitonin, C-reactive protein and leukocyte count in children with lower respiratory tract infection. Pediatr Infect Dis J. 2003;22:963–968.PubMedCrossRef

31.

Rau B, Steinbach G, Gansauge F, Mayer JM, Grunert A, Beger HG. The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis. Gut. 1997;41:832–840.PubMedCrossRef

32.

Roos BA, Okano K, Deftos LJ. Evidence for a pro-calcitonin. Biochem Biophys Res Commun. 1974;60:1134–1140.PubMedCrossRef

33.

Ruiz-Alvarez MJ, Garcia-Valdecasas S, De Pablo R, Sanchez Garcia M, Coca C, Groeneveld TW, Roos A, Daha MR, Arribas I. Diagnostic efficacy and prognostic value of serum procalcitonin concentration in patients with suspected sepsis. J Intensive Care Med. 2009;24:63–71.

34.

Sanzen L, Sundberg M. Periprosthetic low-grade hip infections: erythrocyte sedimentation rate and C-reactive protein in 23 cases. Acta Orthop Scand. 1997;68:461–465.PubMedCrossRef

35.

Savarino L, Baldini N, Tarabusi C, Pellacani A, Giunti A. Diagnosis of infection after total hip replacement. J Biomed Mater Res B Appl Biomater. 2004;70:139–145.PubMedCrossRef

36.

Savarino L, Tigani D, Baldini N, Bochicchio V, Giunti A. Pre-operative diagnosis of infection in total knee arthroplasty: an algorithm. Knee Surg Sports Traumatol Arthrosc. 2009;17:667–675.PubMedCrossRef

37.

Schuetz P, Batschwaroff M, Dusemund F, Albrich W, Burgi U, Maurer M, Brutsche M, Huber AR, Muller B. Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey. Eur J Clin Microbiol Infect Dis. 2010;29:269–277.PubMedCrossRef

38.

Selberg O, Hecker H, Martin M, Klos A, Bautsch W, Kohl J. Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6. Crit Care Med. 2000;28:2793–2798.PubMedCrossRef

39.

Van Kleunen JP, Knox D, Garino JP, Lee GC. Irrigation and debridement and prosthesis retention for treating acute periprosthetic infections. Clin Orthop Relat Res. 2010;468:2024–2028.PubMedCrossRef

40.

Wirtz DC, Heller KD, Miltner O, Zilkens KW, Wolff JM. Interleukin-6: a potential inflammatory marker after total joint replacement. Int Orthop. 2000;24:194–196.PubMedCrossRef

41.

Worthington T, Dunlop D, Casey A, Lambert R, Luscombe J, Elliott T. Serum procalcitonin, interleukin-6, soluble intercellular adhesin molecule-1 and IgG to short-chain exocellular lipoteichoic acid as predictors of infection in total joint prosthesis revision. Br J Biomed Sci. 2010;67:71–76.PubMed

42.

Zhang SY, Boisson-Dupuis S, Chapgier A, Yang K, Bustamante J, Puel A, Picard C, Abel L, Jouanguy E, Casanova JL. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense. Immunol Rev. 2008;226:29–40.PubMedCrossRef

Title: Novel Biomarkers to Detect Infection in Revision Hip and Knee Arthroplasties
Authors: Mathias Glehr, MD
Joerg Friesenbichler, MD
Günter Hofmann, MD
Gerwin Alexander Bernhardt, MD
Maximilian Zacherl, MD
Alexander Avian, PhD
Reinhard Windhager, MD
Andreas Leithner, MD
Publication date: 01-08-2013
Publisher: Springer US
Published in: Clinical Orthopaedics and Related Research® / Issue 8/2013
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-013-2998-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Novel Biomarkers to Detect Infection in Revision Hip and Knee Arthroplasties

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

Level of Evidence

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

Level of Evidence

Please log in to get access to this content

Other articles of this Issue 8/2013

Symposium: Advanced Hip Arthroscopy: Editorial Comment

The Crossover Sign Overestimates Acetabular Retroversion

Joint Space Predicts THA After Hip Arthroscopy in Patients 50 Years and Older

Results of Treatment of Femoroacetabular Impingement in Adolescents with a Surgical Hip Dislocation Approach

Iterative Curettage is Associated with Local Control in Giant Cell Tumors Involving the Distal Tibia

Obituary: Kevin D. Harrington MD (1938–2013)