<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "https://jats.nlm.nih.gov/nlm-dtd/publishing/3.0/journalpublishing3.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="3.0" xml:lang="en">
<front>
<journal-meta>
<journal-id journal-id-type="publisher">JBJI</journal-id>
<journal-title-group>
<journal-title>Journal of Bone and Joint Infection</journal-title>
<abbrev-journal-title abbrev-type="publisher">JBJI</abbrev-journal-title>
<abbrev-journal-title abbrev-type="nlm-ta">J. Bone Joint Infect.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2206-3552</issn>
<publisher><publisher-name>Ivyspring</publisher-name>
<publisher-loc>Göttingen, Germany</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.7150/jbji.22062</article-id>
<title-group>
<article-title>Are There Benefits In Early Diagnosis Of Prosthetic Joint Infection With Multiplex Polymerase Chain Reaction?</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Lausmann</surname>
<given-names>Christian</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Zahar</surname>
<given-names>Akos</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Citak</surname>
<given-names>Mustafa</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Brañes</surname>
<given-names>Julian</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Schmidl</surname>
<given-names>Stefan</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Frommelt</surname>
<given-names>Lars</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gehrke</surname>
<given-names>Thorsten</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gebauer</surname>
<given-names>Matthias</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
</contrib-group><aff id="aff1">
<label>1</label>
<addr-line>Helios ENDO-Klinik Hamburg, Department of Orthopedic Surgery, Hamburg, Germany;</addr-line>
</aff>
<aff id="aff2">
<label>2</label>
<addr-line>Hospital San José, University of Santiago de Chile, Santiago, Chile.</addr-line>
</aff>
<pub-date pub-type="epub">
<day>28</day>
<month>09</month>
<year>2017</year>
</pub-date>
<volume>2</volume>
<issue>4</issue>
<fpage>175</fpage>
<lpage>183</lpage>
<permissions>
<copyright-statement>Copyright: &#x000a9; 2017 Christian Lausmann et al.</copyright-statement>
<copyright-year>2017</copyright-year>
<license license-type="open-access">
<license-p>This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this licence, visit <ext-link ext-link-type="uri"  xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link></license-p>
</license>
</permissions>
<self-uri xlink:href="https://jbji.copernicus.org/articles/2/175/2017/jbji-2-175-2017.html">This article is available from https://jbji.copernicus.org/articles/2/175/2017/jbji-2-175-2017.html</self-uri>
<self-uri xlink:href="https://jbji.copernicus.org/articles/2/175/2017/jbji-2-175-2017.pdf">The full text article is available as a PDF file from https://jbji.copernicus.org/articles/2/175/2017/jbji-2-175-2017.pdf</self-uri>
<abstract>
<p>&lt;p class=&quot;p p-first&quot; id=&quot;__p2&quot;&gt;&lt;em&gt;Purpose&lt;/em&gt; Identification of bacteria and susceptibility are fundamental in periprosthetic joint infection (PJI). Especially in the case of systemic inflammatory response syndrome (SIRS) rapid detection of pathogens is essential for proper therapy. Bacterial cultures are time consuming. The polymerase chain reaction (PCR) is a non-culture molecular method and is able to rapidly identify pathogens and their resistance genes. Multiplex PCR (mPCR) can amplify several different DNA sequences simultaneously. The aim of this study was to show the value of mPCR for early diagnosis of PJI.&lt;/p&gt;&lt;p id=&quot;__p3&quot;&gt;&lt;em&gt;Methods&lt;/em&gt; 60 patients undergoing total hip or knee revisions were recruited in this prospective single-centre-study. Three groups were created: 26 patients with aseptic loosening (negative control), 26 patients with chronic PJI, and 8 patients with acute PJI/SIRS. We compared the results of joint aspirates obtained intraoperatively investigated by mPCR with the microbiology results of tissue specimens.&lt;/p&gt;&lt;p id=&quot;__p4&quot;&gt;&lt;em&gt;Results&lt;/em&gt; The overall sensitivity of mPCR was 78.8% (95% CI, 61.1 - 91.0%), the specificity was 100% (95% CI, 87.2 - 100%), the negative predictive value was 79.4% (95% CI, 62.1 - 91.3%), the positive predictive value was 100% (95% CI, 86.8 - 100%), and the overall accuracy was 88.3% (95% CI, 77.4 - 95.2%). The overall accuracy in acute infections/SIRS (87.5%) was greater than in late chronic PJI (76.9%). In PJI the mPCR was able to provide the results within 5 hours whereas the mean time for cultures was 6.4 days.&lt;/p&gt;&lt;p class=&quot;p p-last&quot; id=&quot;__p5&quot;&gt;&lt;em&gt;Conclusions&lt;/em&gt; Multiplex PCR is a reliable diagnostic tool in PJI management, especially in acute cases complicated with SIRS. Early diagnosis within several hours is possible, targeted antibiotic treatment can be started promptly.&lt;/p&gt;</p>
</abstract>
<counts><page-count count="9"/></counts>
</article-meta>
</front>
<body/>
<back>
<ref-list>
<title>References</title>
<ref id="ref0">
<label>0</label><mixed-citation publication-type="other" xlink:type="simple">Kapadia BH, Berg RA, Daley JA, Fritz J, Bhave A, Mont MA. Periprosthetic joint infection. Lancet. 2016;387:386–94.</mixed-citation>
</ref>
<ref id="ref1">
<label>1</label><mixed-citation publication-type="other" xlink:type="simple">Huotari K, Lyytikainen O, Ollgren J, Virtanen MJ, Seitsalo S, Palonen R. et al. Disease burden of prosthetic joint infections after hip and knee joint replacement in Finland during 1999-2004: capture-recapture estimation. J Hosp Infect. 2010;75:205–8.</mixed-citation>
</ref>
<ref id="ref2">
<label>2</label><mixed-citation publication-type="other" xlink:type="simple">Kurtz SM, Lau E, Watson H, Schmier JK, Parvizi J. Economic burden of periprosthetic joint infection in the United States. J Arthroplasty. 2012;27:61–5. e1.</mixed-citation>
</ref>
<ref id="ref3">
<label>3</label><mixed-citation publication-type="other" xlink:type="simple">Yi SH, Baggs J, Culler SD, Berrios-Torres SI, Jernigan JA. Medicare Reimbursement Attributable to Periprosthetic Joint Infection Following Primary Hip and Knee Arthroplasty. J Arthroplasty. 2015;30:931–8. e2.</mixed-citation>
</ref>
<ref id="ref4">
<label>4</label><mixed-citation publication-type="other" xlink:type="simple">Rezapoor M, Parvizi J. Prevention of Periprosthetic Joint Infection. J Arthroplasty. 2015;30:902–7.</mixed-citation>
</ref>
<ref id="ref5">
<label>5</label><mixed-citation publication-type="other" xlink:type="simple">Parvizi J, Adeli B, Zmistowski B, Restrepo C, Greenwald AS. Management of periprosthetic joint infection: the current knowledge: AAOS exhibit selection. J Bone Joint Surg Am. 2012;94:e104.</mixed-citation>
</ref>
<ref id="ref6">
<label>6</label><mixed-citation publication-type="other" xlink:type="simple">Della Valle C, Parvizi J, Bauer TW, Dicesare PE, Evans RP, Segreti J. et al. Diagnosis of periprosthetic joint infections of the hip and knee. J Am Acad Orthop Surg. 2010;18:760–70.</mixed-citation>
</ref>
<ref id="ref7">
<label>7</label><mixed-citation publication-type="other" xlink:type="simple">Parvizi J, Gehrke T, Chen AF. Proceedings of the International Consensus on Periprosthetic Joint Infection. Bone Joint J. 2013;95B:1450–2.</mixed-citation>
</ref>
<ref id="ref8">
<label>8</label><mixed-citation publication-type="other" xlink:type="simple">Bonanzinga T, Zahar A, Dutsch M, Lausmann C, Kendoff D, Gehrke T. How Reliable Is the Alpha-defensin Immunoassay Test for Diagnosing Periprosthetic Joint Infection? A Prospective Study. Clin Orthop Relat Res. 2017;475:408–15. [PMC free article]</mixed-citation>
</ref>
<ref id="ref9">
<label>9</label><mixed-citation publication-type="other" xlink:type="simple">McArthur BA, Abdel MP, Taunton MJ, Osmon DR, Hanssen AD. Seronegative infections in hip and knee arthroplasty: periprosthetic infections with normal erythrocyte sedimentation rate and C-reactive protein level. Bone Joint J. 2015;97B:939–44.</mixed-citation>
</ref>
<ref id="ref10">
<label>10</label><mixed-citation publication-type="other" xlink:type="simple">Schafer P, Fink B, Sandow D, Margull A, Berger I, Frommelt L. Prolonged bacterial culture to identify late periprosthetic joint infection: a promising strategy. Clin Infect Dis. 2008;47:1403–9.</mixed-citation>
</ref>
<ref id="ref11">
<label>11</label><mixed-citation publication-type="other" xlink:type="simple">Parvizi J, Erkocak OF, Della Valle CJ. Culture-negative periprosthetic joint infection. J Bone Joint Surg Am. 2014;96:430–6.</mixed-citation>
</ref>
<ref id="ref12">
<label>12</label><mixed-citation publication-type="other" xlink:type="simple">Gehrke T, Zahar A, Kendoff D. One-stage exchange: it all began here. Bone Joint J. 2013;95B:77–83.</mixed-citation>
</ref>
<ref id="ref13">
<label>13</label><mixed-citation publication-type="other" xlink:type="simple">Qu X, Zhai Z, Li H, Li H, Liu X, Zhu Z. et al. PCR-based diagnosis of prosthetic joint infection. J Clin Microbiol. 2013;51:2742–6. [PMC free article]</mixed-citation>
</ref>
<ref id="ref14">
<label>14</label><mixed-citation publication-type="other" xlink:type="simple">Melendez DP, Greenwood-Quaintance KE, Berbari EF, Osmon DR, Mandrekar JN, Hanssen AD. et al. Evaluation of a Genus- and Group-Specific Rapid PCR Assay Panel on Synovial Fluid for Diagnosis of Prosthetic Knee Infection. J Clin Microbiol. 2016;54:120–6. [PMC free article]</mixed-citation>
</ref>
<ref id="ref15">
<label>15</label><mixed-citation publication-type="other" xlink:type="simple">Gallo J, Raska M, Dendis M, Florschutz AV, Kolar M. Molecular diagnosis of prosthetic joint infection. A review of evidence. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2004;148:123–9.</mixed-citation>
</ref>
<ref id="ref16">
<label>16</label><mixed-citation publication-type="other" xlink:type="simple">Hartley JC, Harris KA. Molecular techniques for diagnosing prosthetic joint infections. J Antimicrob Chemother. 2014;69(Suppl 1):i21–4.</mixed-citation>
</ref>
<ref id="ref17">
<label>17</label><mixed-citation publication-type="other" xlink:type="simple">Kriegsmann J, Arens N, Altmann C, Kriegsmann M, Casadonte R, Otto M. [Molecular pathological diagnostics of infections in orthopedic pathology] Pathologe. 2014;35(Suppl 2):225–31.</mixed-citation>
</ref>
<ref id="ref18">
<label>18</label><mixed-citation publication-type="other" xlink:type="simple">Jamal W, Al Roomi E, AbdulAziz LR, Rotimi VO. Evaluation of Curetis Unyvero, a multiplex PCR-based testing system, for rapid detection of bacteria and antibiotic resistance and impact of the assay on management of severe nosocomial pneumonia. J Clin Microbiol. 2014;52:2487–92. [PMC free article]</mixed-citation>
</ref>
<ref id="ref19">
<label>19</label><mixed-citation publication-type="other" xlink:type="simple">Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ. et al. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011;469:2992–4. [PMC free article]</mixed-citation>
</ref>
<ref id="ref20">
<label>20</label><mixed-citation publication-type="other" xlink:type="simple">Guenther D, Kokenge T, Jacobs O, Omar M, Krettek C, Gehrke T. et al. Excluding infections in arthroplasty using leucocyte esterase test. Int Orthop. 2014;38:2385–90.</mixed-citation>
</ref>
<ref id="ref21">
<label>21</label><mixed-citation publication-type="other" xlink:type="simple">Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R. et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med. 2008;34:17–60. [PMC free article]</mixed-citation>
</ref>
<ref id="ref22">
<label>22</label><mixed-citation publication-type="other" xlink:type="simple">Borde JP, Hacker GA, Guschl S, Serr A, Danner T, Hubner J. et al. Diagnosis of prosthetic joint infections using UMD-Universal Kit and the automated multiplex-PCR Unyvero i60 ITI((R)) cartridge system: a pilot study. Infection. 2015;43:551–60.</mixed-citation>
</ref>
<ref id="ref23">
<label>23</label><mixed-citation publication-type="other" xlink:type="simple">Aggarwal VK, Bakhshi H, Ecker NU, Parvizi J, Gehrke T, Kendoff D. Organism profile in periprosthetic joint infection: pathogens differ at two arthroplasty infection referral centers in Europe and in the United States. J Knee Surg. 2014;27:399–406.</mixed-citation>
</ref>
<ref id="ref24">
<label>24</label><mixed-citation publication-type="other" xlink:type="simple">Workgroup Convened by the Musculoskeletal Infection S. New definition for periprosthetic joint infection. J Arthroplasty. 2011;26:1136–8.</mixed-citation>
</ref>
<ref id="ref25">
<label>25</label><mixed-citation publication-type="other" xlink:type="simple">Springer BD. The Diagnosis of Periprosthetic Joint Infection. J Arthroplasty. 2015;30:908–11.</mixed-citation>
</ref>
<ref id="ref26">
<label>26</label><mixed-citation publication-type="other" xlink:type="simple">Fenollar F, Raoult D. Molecular genetic methods for the diagnosis of fastidious microorganisms. APMIS. 2004;112:785–807.</mixed-citation>
</ref>
<ref id="ref27">
<label>27</label><mixed-citation publication-type="other" xlink:type="simple">Portillo ME, Salvado M, Sorli L, Alier A, Martinez S, Trampuz A. et al. Multiplex PCR of sonication fluid accurately differentiates between prosthetic joint infection and aseptic failure. J Infect. 2012;65:541–8.</mixed-citation>
</ref>
<ref id="ref28">
<label>28</label><mixed-citation publication-type="other" xlink:type="simple">Villa F, Toscano M, De Vecchi E, Bortolin M, Drago L. Reliability of a multiplex PCR system for diagnosis of early and late prosthetic joint infections before and after broth enrichment. Int J Med Microbiol. 2017 in press.</mixed-citation>
</ref>
<ref id="ref29">
<label>29</label><mixed-citation publication-type="other" xlink:type="simple">Lodes U, Bohmeier B, Lippert H, Konig B, Meyer F. PCR-based rapid sepsis diagnosis effectively guides clinical treatment in patients with new onset of SIRS. Langenbecks Arch Surg. 2012;397:447–55.</mixed-citation>
</ref>
<ref id="ref30">
<label>30</label><mixed-citation publication-type="other" xlink:type="simple">Jacovides CL, Kreft R, Adeli B, Hozack B, Ehrlich GD, Parvizi J. Successful identification of pathogens by polymerase chain reaction (PCR)-based electron spray ionization time-of-flight mass spectrometry (ESI-TOF-MS) in culture-negative periprosthetic joint infection. J Bone Joint Surg Am. 2012;94:2247–54.</mixed-citation>
</ref>
<ref id="ref31">
<label>31</label><mixed-citation publication-type="other" xlink:type="simple">Achermann Y, Vogt M, Leunig M, Wust J, Trampuz A. Improved diagnosis of periprosthetic joint infection by multiplex PCR of sonication fluid from removed implants. J Clin Microbiol. 2010;48:1208–14. [PMC free article]</mixed-citation>
</ref>
<ref id="ref32">
<label>32</label><mixed-citation publication-type="other" xlink:type="simple">Gomez E, Cazanave C, Cunningham SA, Greenwood-Quaintance KE, Steckelberg JM, Uhl JR. et al. Prosthetic joint infection diagnosis using broad-range PCR of biofilms dislodged from knee and hip arthroplasty surfaces using sonication. J Clin Microbiol. 2012;50:3501–8. [PMC free article]</mixed-citation>
</ref>
<ref id="ref33">
<label>33</label><mixed-citation publication-type="other" xlink:type="simple">Cazanave C, Greenwood-Quaintance KE, Hanssen AD, Karau MJ, Schmidt SM, Gomez Urena EO. et al. Rapid molecular microbiologic diagnosis of prosthetic joint infection. J Clin Microbiol. 2013;51:2280–7. [PMC free article]</mixed-citation>
</ref>
<ref id="ref34">
<label>34</label><mixed-citation publication-type="other" xlink:type="simple">Rak M, KavcIc M, Trebse R, Co RA.  Detection of bacteria with molecular methods in prosthetic joint infection: sonication fluid better than periprosthetic tissue. Acta Orthop; 2016. pp. 1–7. [PMC free article]</mixed-citation>
</ref>
<ref id="ref35">
<label>35</label><mixed-citation publication-type="other" xlink:type="simple">Metso L, Maki M, Tissari P, Remes V, Piiparinen P, Kirveskari J. et al. Efficacy of a novel PCR- and microarray-based method in diagnosis of a prosthetic joint infection. Acta Orthop. 2014;85:165–70. [PMC free article]</mixed-citation>
</ref>
<ref id="ref36">
<label>36</label><mixed-citation publication-type="other" xlink:type="simple">Marin M, Garcia-Lechuz JM, Alonso P, Villanueva M, Alcala L, Gimeno M. et al. Role of universal 16S rRNA gene PCR and sequencing in diagnosis of prosthetic joint infection. J Clin Microbiol. 2012;50:583–9. [PMC free article]</mixed-citation>
</ref>
<ref id="ref37">
<label>37</label><mixed-citation publication-type="other" xlink:type="simple">Li Z, Yu A. Diagnostic value of a PCR-based technique for prosthetic joint infection. J Clin Microbiol. 2014;52:2281–2. [PMC free article]</mixed-citation>
</ref>
<ref id="ref38">
<label>38</label><mixed-citation publication-type="other" xlink:type="simple">Bemer P, Plouzeau C, Tande D, Leger J, Giraudeau B, Valentin AS. et al. Evaluation of 16S rRNA gene PCR sensitivity and specificity for diagnosis of prosthetic joint infection: a prospective multicenter cross-sectional study. J Clin Microbiol. 2014;52:3583–9. [PMC free article]</mixed-citation>
</ref>
<ref id="ref39">
<label>39</label><mixed-citation publication-type="other" xlink:type="simple">Ryu SY, Greenwood-Quaintance KE, Hanssen AD, Mandrekar JN, Patel R. Low sensitivity of periprosthetic tissue PCR for prosthetic knee infection diagnosis. Diagn Microbiol Infect Dis. 2014;79:448–53.</mixed-citation>
</ref>
<ref id="ref40">
<label>40</label><mixed-citation publication-type="other" xlink:type="simple">Panousis K, Grigoris P, Butcher I, Rana B, Reilly JH, Hamblen DL. Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92 cases. Acta Orthop. 2005;76:341–6.</mixed-citation>
</ref>
<ref id="ref41">
<label>41</label><mixed-citation publication-type="other" xlink:type="simple">Levy PY, Fenollar F. The role of molecular diagnostics in implant-associated bone and joint infection. Clin Microbiol Infect. 2012;18:1168–75.</mixed-citation>
</ref>
</ref-list>
</back>
</article>