The Performance of a Dithiothreitol-Based Diagnostic System in Diagnosing Periprosthetic Joint Infection Compared to Sonication Fluid Cultures and Tissue Biopsies

Abstract

Purpose The aim of this study was to evaluate the performance of a commercially available dithiothreitol (DTT) kit for routine use in diagnosing periprosthetic joint infections (PJIs) in comparison to conventional microbiological tissue specimens and sonication procedures in a maximal care hospital.

Methods We applied the DTT system in 40 consecutive cases of revision arthroplasty (23 PJIs and 17 aseptic revisions), with an exchange or a removal of components. The hardware components were split between the DTT system and the conventional sonication procedure. At least three tissue biopsies and a joint fluid specimen were sent for microbiological and histopathological analysis. Data was analysed retrospectively to compare between the different methods.

Results Cultures of the DTT fluid showed a sensitivity of 65% and specificity of 100%, as referenced to conventional microbiological cultures. Sonication had better sensitivity (75%) but lower specificity (85%). The categorical agreement of DTT cultures compared to sonication fluid cultures was 78% (31/40). Neither pathogen type, infection duration nor antibiotic pretreatment influenced the accuracy of the DTT, but a low pH in the DTT seemed to be associated with false-negative results.

Conclusion DTT was inferior in sensitivity when diagnosing PJIs compared to sonication fluid cultures and tissue biopsies. A low pH in the DTT fluid correlated with false-negative results. Nevertheless, the closed system of the DTT kit avoids contamination and false-positive results, and DTT can be an alternative where sonication is not available.

Zusammenfassung

Ziel Das Ziel dieser Studie war die Bewertung eines kommerziell verfügbaren Diagnostik-Kits, welches durch den Einsatz von Dithiothreitol (DTT) in einem Doppelkammerbeutel den Biofilm von Explantaten bei periprothetischen Infektionen (PJI) lösen und der mikrobiologischen Diagnostik zugänglich machen soll. Die Ergebnisse des DTT-Systems wurden gegen konventionelle Mikrobiologie und klassische Sonikation getestet und bewertet.

Methoden Das System wurde gemäß seiner Zulassung bei insg. 40 konsekutiven Prothesenrevisions-Fällen eingesetzt (23 mit PJI, 17 mit aseptischer Revisionsursache), wenn ein Wechsel der Prothese oder einzelner Komponenten vorgenommen wurde. Die Explantate wurden auf konventionelle Sonikation und das DTT-System verteilt. Das Gelenkpunktat, sowie mindestens 3 Gewebeproben wurden in jedem Fall mikrobiologisch und histologisch untersucht. Die Datenanalyse und Auswertung erfolgte retrospektiv.

Ergebnis Die Kultur aus der DTT-Flüssigkeit zeigte seine Sensitivität von 65% und Spezifität von 100% zur Detektion eines periprothetischen Infektes, bezogen auf die Ergebnisse der konventionellen Mikrobiologie. Die normale Sonikation hatte mit 75% eine höhere Sensitivität, aber dafür schlechtere Spezifität (85%). DTT und Sonikation stimmten in 78% der Fälle (31/40) im Bezug auf den Keimnachweis überein. Weder beeinflussten bestimmte Erreger, noch die Infektdauer oder eine antibiotische Vorbehandlung die Genauigkeit des DTT-Testes. Ein niedriger pH-Wert im DTT schien mit falsch-negativen Ergebnissen assoziiert.

Schlussfolgerung Das DTT-Kit zeigte eine schlechtere Sensitivität als Sonikation und konventionelle Gewebeproben. Ein niedriger pH-Wert im DTT scheint mit falsch-negativen Proben assoziiert sein. Trotzdem bietet das in sich geschlossene und CE-zertifizierte System eine mögliche Alternative zur Untersuchung von explantiertem Material, wenn die Sonikation nicht eingesetzt werden kann.

Key words

septic arthritis - periprosthetic joint infection - sonication - revision arthroplasty - biofilm

Schlüsselwörter

septische Arthritis - periprothetische Infektion - Sonikation - Revisionsendoprothetik - Biofilm

Publication History

Article published online:
11 May 2020

• References

• 1 Lange J, Troelsen A, Thomsen RW. et al. Chronic infections in hip arthroplasties: comparing risk of reinfection following one-stage and two-stage revision: a systematic review and meta-analysis. Clin Epidemiol 2012; 4: 57-73 doi:10.2147/CLEP.S29025
• 2 Parvizi J, Ghanem E, Sharkey P. et al. Diagnosis of infected total knee: findings of a multicenter database. Clin Orthop Relat Res 2008; 466: 2628-2633 doi:10.1007/s11999-008-0471-5
• 3 Peersman G, Laskin R, Davis J. et al. Infection in total knee replacement: a retrospective review of 6489 total knee replacements. Clin Orthop Relat Res 2001; (392) 15-23
• 4 Tan TL, Maltenfort MG, Chen AF. et al. Development and Evaluation of a Preoperative Risk Calculator for Periprosthetic Joint Infection Following Total Joint Arthroplasty. J Bone Joint Surg Am 2018; 100: 777-785 doi:10.2106/JBJS.16.01435
• 5 Kurtz SM, Lau E, Watson H. et al. Economic burden of periprosthetic joint infection in the United States. J Arthroplasty 2012; 27 (8 Suppl.): 61-65.e1 doi:10.1016/j.arth.2012.02.022
• 6 Müller M, Trampuz A, Winkler T. et al. The Economic Challenge of Centralised Treatment of Patients with Periprosthetic Infections. Z Orthop Unfall 2018; DOI: 10.1055/s-0044-100732.
• 7 Randau TM, Friedrich MJ, Wimmer MD. et al. Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening. PLoS One 2014; 9: e89045 doi:10.1371/journal.pone.0089045
• 8 Saleh A, George J, Faour M. et al. Serum biomarkers in periprosthetic joint infections. Bone Joint Res 2018; 7: 85-93 doi:10.1302/2046-3758.71.BJR-2017-0323
• 9 Balato G, Franceschini V, Ascione T. et al. Diagnostic accuracy of synovial fluid, blood markers, and microbiological testing in chronic knee prosthetic infections. Arch Orthop Trauma Surg 2018; 138: 165-171 doi:10.1007/s00402-017-2832-6
• 10 Friedrich MJ, Randau TM, Wimmer MD. et al. Lipopolysaccharide-binding protein: a valuable biomarker in the differentiation between periprosthetic joint infection and aseptic loosening?. Int Orthop 2014; 38: 2201-2207 doi:10.1007/s00264-014-2351-9
• 11 Lee YS, Koo KH, Kim HJ. et al. Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis. J Bone Joint Surg Am 2017; 99: 2077-2084 doi:10.2106/JBJS.17.00123
• 12 Morawietz L, Classen RA, Schröder JH. et al. Proposal for a histopathological consensus classification of the periprosthetic interface membrane. J Clin Pathol 2006; 59: 591-597 doi:10.1136/jcp.2005.027458
• 13 Krenn V, Morawietz L, Perino G. et al. Revised histopathological consensus classification of joint implant related pathology. Pathol Res Pract 2014; 210: 779-786 doi:10.1016/j.prp.2014.09.017
• 14 Jun Y, Jianghua L. Diagnosis of Periprosthetic Joint Infection Using Polymerase Chain Reaction: An Updated Systematic Review and Meta-Analysis. Surg Infect (Larchmt) 2018; 19: 555-565 doi:10.1089/sur.2018.014
• 15 Achermann Y, Vogt M, Leunig M. et al. Improved diagnosis of periprosthetic joint infection by multiplex PCR of sonication fluid from removed implants. J Clin Microbiol 2010; 48: 1208-1214 doi:10.1128/JCM.00006-10
• 16 Hischebeth GTR, Randau TM, Buhr JK. et al. Unyvero i60 implant and tissue infection (ITI) multiplex PCR system in diagnosing periprosthetic joint infection. J Microbiol Methods 2016; 121: 27-32 doi:10.1016/j.mimet.2015.12.010
• 17 Portillo ME, Salvadó M, Sorli L. et al. Multiplex PCR of sonication fluid accurately differentiates between prosthetic joint infection and aseptic failure. J Infect 2012; 65: 541-548 doi:10.1016/j.jinf.2012.08.018
• 18 Renz N, Feihl S, Cabric S. et al. Performance of automated multiplex PCR using sonication fluid for diagnosis of periprosthetic joint infection: a prospective cohort. Infection 2017; 45: 877-884 doi:10.1007/s15010-017-1073-5
• 19 Trampuz A, Piper KE, Jacobson MJ. et al. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med 2007; 357: 654-663 doi:10.1056/NEJMoa061588
• 20 Kobayashi N, Bauer TW, Tuohy MJ. et al. Brief ultrasonication improves detection of biofilm-formative bacteria around a metal implant. Clin Orthop Relat Res 2007; 457: 210-213 doi:10.1097/BLO.0b013e3180312042
• 21 Tande AJ, Patel R. Prosthetic joint infection. Clin Microbiol Rev 2014; 27: 302-345 doi:10.1128/CMR.00111-13
• 22 Redanz S, Podbielski A, Warnke P. Improved microbiological diagnostic due to utilization of a high-throughput homogenizer for routine tissue processing. Diagn Microbiol Infect Dis 2015; 82: 189-193 doi:10.1016/j.diagmicrobio.2015.03.018
• 23 Gomez-Urena EO, Tande AJ, Osmon DR. et al. Diagnosis of Prosthetic Joint Infection: Cultures, Biomarker and Criteria. Infect Dis Clin North Am 2017; 31: 219-235 doi:10.1016/j.idc.2017.01.008
• 24 Drago L, Signori V, De Vecchi E. et al. Use of dithiothreitol to improve the diagnosis of prosthetic joint infections. J Orthop Res 2013; 31: 1694-1699 doi:10.1002/jor.22423
• 25 Wimmer MD, Randau TM, Petersdorf S. et al. Evaluation of an interdisciplinary therapy algorithm in patients with prosthetic joint infections. Int Orthop 2013; 37: 2271-2278 doi:10.1007/s00264-013-1995-1
• 26 Hischebeth GTR, Kohlhof H, Wimmer MD. et al. Detection of Pantoea agglomerans in hip prosthetic infection by sonication of the removed prosthesis: the first reported case. Technol Health Care 2013; 21: 613-618 doi:10.3233/THC-130757
• 27 Schmolders J, Hischebeth GTR, Friedrich MJ. et al. Evidence of MRSE on a gentamicin and vancomycin impregnated polymethyl-methacrylate (PMMA) bone cement spacer after two-stage exchange arthroplasty due to periprosthetic joint infection of the knee. BMC Infect Dis 2014; 14: 144 doi:10.1186/1471-2334-14-144
• 28 Parvizi J, Gehrke T. Definition of periprosthetic joint infection. J Arthroplasty 2014; 29: 1331 doi:10.1016/j.arth.2014.03.009
• 29 Trampuz A, Hanssen AD, Osmon DR. et al. Synovial fluid leukocyte count and differential for the diagnosis of prosthetic knee infection. Am J Med 2004; 117: 556-562 doi:10.1016/j.amjmed.2004.06.022
• 30 Schäfer P, Fink B, Sandow D. et al. Prolonged bacterial culture to identify late periprosthetic joint infection: a promising strategy. Clin Infect Dis 2008; 47: 1403-1409 doi:10.1086/592973
• 31 Portillo ME, Salvadó M, Alier A. et al. Advantages of sonication fluid culture for the diagnosis of prosthetic joint infection. J Infect 2014; 69: 35-41 doi:10.1016/j.jinf.2014.03.002
• 32 Sambri A, Cadossi M, Giannini S. et al. Is Treatment With Dithiothreitol More Effective Than Sonication for the Diagnosis of Prosthetic Joint Infection?. Clin Orthop Relat Res 2018; 476: 137-145 doi:10.1007/s11999.0000000000000060
• 33 Janz V, Wassilew GI, Perka CF. et al. Increased rate of bacterial colonization on PE-components in total joint arthroplasty: An evaluation through sonication. Technol Health Care 2017; 25: 137-142 doi:10.3233/THC-161257
• 34 Choi TJ, Geletu TT. High level expression and purification of recombinant flounder growth hormone in E. coli. J Genet Eng Biotechnol 2018; 16: 347-355 doi:10.1016/j.jgeb.2018.03.006