De Man, F.

Graber, P.

Lüem, M.

Ochsner, P.

Sendi, P.

Zimmerli, W.

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Broad-Range PCR in Selected Episodesof Prosthetic Joint InfectionThe use of eubacterial PCR of the 16S rRNA (PCR) fordiagnosing prosthetic-joint-associated infections (PJIs) isstill a matter of debate. Several drawbacks need to beconsidered when using this technique, including the lackof susceptibility results (except for methicillin-resistantStaphylococcus aureus) and problems in identifying amixture of bacterial species in a single specimen [1]. Anumber of studies have indicated that the routine use ofPCR in PJIs does not offer a diagnostic advantage overbacterial culture [2–4]. However, this molecular methodcan detect bacterial DNA in samples when conventionalcultures are negative due to previous antimicrobialexposure or unfavorable growth conditions. Taking theseconsiderations into account, we use PCR only if thechance of bacterial growth is low because of previoussurgical and antimicrobial treatment or previous negativeculture results. In order to (re)assess the diagnostic valueof PCR in those selected episodes of suspected PJI inwhich this method had been applied, we performed aretrospective study to define patient characteristics and toestimate the specificity and sensitivity of PCR versusbacterial culture. Our orthopedic surgery clinic is a 48-bedunit that acts as a primary care center for all types oforthopedic surgery of the extremities and as a tertiary carecenter for patients needing revision arthroplasty.The study population consisted of patients with a jointprosthesis who were seen at our clinic from 2001 through2005, and from whom specimens for bacterial culture andPCR were obtained because of possible PJI. The suspicionof PJI was based on clinical signs such as joint pain,effusion, erythema and warmth at the implant site, and/orimplant loosening. Patient history prior to the diagnosticintervention was assessed for (1) antimicrobial treatment,(2) number of revisions performed on the affected joint,(3) confirmed and treated infection involving the affectedjoint within the last 24 months, and (4) implant loosening£ 12 months after implantation without other clinicalsigns of infection. Specimens (synovial fluid and/or biop-sies from periprosthetic tissue) were obtained either dur-ing aspiration prior to surgery or during arthroscopy oropen surgery. Bacterial culture and histopathologic diag-nostics were performed as described previously [5]. Thedecision whether or not to use PCR was made by thephysicians in charge following a review of the patient’shistory and prior to the intervention. However, the phy-sicians were not involved in either analyzing or inter-preting the data. Specimens were sent to a referencelaboratory for analysis [6]. The technique is based on theamplification of bacterial 16S ribosomal DNA [6]. Criteriafor definite PJI included the presence of a sinus tractcommunicating with the prosthesis or purulence sur-rounding the prosthesis at the time of surgery or acute orchronic inflammation consistent with infection on histo-pathologic examination [1, 7]. Infection was excludedwhen the above-mentioned criteria were not fulfilled, noantimicrobial treatment was administered after the epi-sode, and no relapse occurred for at least 1 year.Specimens for both PCR and bacterial culture wereobtained in 29 episodes of possible PJI among 26 patients.This number accounted for 7.6% (23 episodes) of allrevision arthroplasties (n = 301) and 6.8% (6 episodes)of all joint punctures (n = 88) during the study period.Patient characteristics are presented in table 1. Mostepisodes (48%) included a history of three or more sur-gical interventions (median 4, IQR 3–5) on the affectedjoint within a median time of 3.25 years (IQR 0.9–10.5)prior to the diagnostic intervention. The median numberof obtained specimens per patient for bacterial culturewas five (IQR 3–7) and for PCR, one (IQR 1–2).No infection was present in 17 (59%) of the 29 episodes,although the duration of follow-up was £ 12 months inInfection 2009; 37: 292–294DOI 10.1007/s15010-008-8246-1F.H.R. De ManClinic of Orthopaedic Surgery, Kantonsspital, Liestal, SwitzerlandP. GraberUnit of Infectious Diseases, Basel University Medical Clinic Liestal,Liestal, SwitzerlandM. LüemClinic of Orthopaedic Surgery, Kantonsspital, Liestal, SwitzerlandW. ZimmerliUnit of Infectious Diseases, Basel University Medical Clinic Liestal,Liestal, SwitzerlandP.E. OchsnerClinic of Orthopaedic Surgery, Kantonsspital, Liestal, SwitzerlandP. Sendi (corresponding author)Unit of Infectious Diseases, Basel University Medical Clinic Liestal,Rheinstrasse 26, 4410 Liestal, Switzerland; Phone: (+41/61) 925-2180,Fax: -2804, e-mail: sendi-pa@magnet.chReceived: July 21, 2008 Æ Revision accepted: October 6, 2008Published online: April 23, 2009Infection Correspondence292 Infection 37 Æ 2009 Æ No. 3  URBAN & VOGELtwo cases (4, 11 months) due to non-episode-relateddeath and loss to follow-up, respectively. The PCR wasnegative in all 17 cases with clinically excluded infection.In contrast, there was bacterial growth in five episodes,but these were interpreted as contamination. In theinfection episodes, one inaccurate PCR result was con-sidered to be a false-positive. Based on these findings,the specificity for bacterial culture was 71% and forPCR 94%.The criteria for PJI were fulfilled in 12 (41%) of the29 episodes; this accounted for 8.5% of 142 confirmedPJI episodes (including 62% referred cases) during thestudy period. The results of bacterial culture and PCRare presented in table 2. In five episodes, both diagnosticapproaches identified the same microorganism. However,in two of these, PCR revealed only one pathogen, whiletwo distinct microorganisms grew in culture. In twofurther episodes, the pathogen was identified eitheronly by bacterial culture or only by PCR. Hence, thesensitivity for bacterial culture was 58% and for PCR,50%.Little information is available for assisting clinicalpractitioners in selecting episodes in which PCR may besuperior or complementary to bacterial culture for diag-nosing PJI. The previous history of the patients includedin this study (Table 1) highlights the importance of dis-tinguishing PJI from other causes of joint failure. Basedon this history, we decided it was reasonable to expanddiagnostic means by an additional tool in these selectedepisodes.Broad-range PCR and more advanced molecularmethods show a high specificity (96%–100%) [3, 4, 8–12],but often a poor sensitivity (£ 50%) in diagnosing PJI[3, 4, 8, 10, 12]. Similarly, the specificity was excellent inTable 1Demographic data and history of 26 patients with 29 episodesof suspected prosthetic-joint-associated infections (PJIs) fromwhom specimens for bacterial culture and broad-range PCRwere obtained.Characteristic Number ofepisodes (%)Median age (years) 70.5 (range 53–80)SexMale 13Female 13Affected jointHip 13 (44.8%)Knee 16 (55.2%)Patient history prior to presentation‡ 3 revisions performed at theaffected joint14 (48%)Confirmed and treated infection at theaffected joint within £ 24 months9 (31%)Previous antimicrobial treatment 8 (27.5%)0–2 Weeks prior to intervention 32–4 Weeks prior to intervention 14–8 weeks prior to intervention 4Implant loosening £ 12 months afterimplantation without other clinical signsof infection6 (21%)Table 2Results of bacterial culture and broad-range PCR in 12 episodes of confirmed PJI.Episode Sample origin Bacterial culture 16S rRNA-PCRNumber of positive/total numberof specimensPathogen Number of positive/total number ofspecimensPathogen1 Synovial fluid 2/2 Streptococcus pyogenes 1/1 Streptococcus pyogenes2a Periprosthetic tissue 2/13 Propionibacterium sp. 1/8 Streptococcus infantis3 Synovial fluid 1/1 Staphylococcus aureus 1 Negative4 Periprosthetic tissue 1 No growth 1 Negative5 Periprosthetic tissue 1 No growth 1 Negative6 Synovial fluid 1 No growth 1/1 Streptococcus bovis7 Periprosthetic tissue 5/11 Staphylococcus aureus 1/1 Staphylococcus aureus1/11 Enterococcus faecalis8 Periprosthetic tissue 6 No growth 2 Negative9 Periprosthetic tissue 6/9 Staphylococcus epidermidis 1/1 Staphylococcus epidermidis10 Periprosthetic tissue 5/6 Pseudomonas aeruginosa 2/2 Pseudomonas aeruginosa1/6 Enterococcus faecalis11 Periprosthetic tissue 1/5b Staphylococcus epidermidis 1/1 Staphylococcus epidermidis12 Periprosthetic tissue 5 No growth 1 Negativea Identification of the pathogen in this episode was inconclusive, since in both diagnostic methods the ratio of number of positive: totalnumber of specimens was low. However, based on the previous history (duration of symptoms 19 months) and the small fragment foramplification isolated from the biopsy, Propionibacterium sp. was interpreted as possible pathogen, and Streptococcus infantis as contami-nation; b Results from diagnostic arthroscopy. Four weeks later, one-stage exchange was performed and Staphylococcus epidermidis grew in 8 of16 obtained biopsiesF.H.R. De Man et al. PCR in PJIInfection 37 Æ 2009 Æ No. 3  URBAN & VOGEL 293our selected episodes. In all episodes with a previoushistory of multiple revisions or previously treated PJI,PCR remained negative when no infection was present.Also, in only one out of six episodes with early implantloosening (£ 12 months after implantation) but no otherclinical signs of PJI was an infection present, and the PCRresults matched accordingly. Importantly, in five episodes,PCR was useful in identifying false-positive results frombacterial culture.The sensitivity of the PCR, however, was poor (50%).The overall sensitivity in diagnosing PJI increased to 67%when both PCR and bacterial culture were consideredtogether (i.e. one or other or both positive). Since ourstudy was performed retrospectively, and patients selectedfor PCR were not recruited according to strictly prede-fined criteria, the study could have been influenced by aselection bias. Therefore, no immediate recommendationabout the use of PCR in PJI can be made.However, the expense and diagnostic value of PCR incomparison to bacterial culture [2–4] warrant the use ofthis molecular method only selectively and not routinely,and in addition to bacterial culture. In our center, PCR hasbeen performed in fewer than 10% of all revision arthro-plasties (i.e. in patients with a complex history of jointdisease) and found to have only a limited diagnostic value.In fewer than 20% of the episodes, PCR was helpful inrecognizing false-positive culture results. In terms of theapplicability of PCR in clinical practice, more studies arerequired to identify both a patient population and a diag-nostic strategy in which the use of such a molecular tool isbeneficial in diagnosing or excluding PJIs.F.H.R. De Man, P. Graber, M. Lu¨em, W. Zimmerli,P.E. Ochsner, P. SendiAcknowledgmentsThis work was presented in part at the 45th Interscience Con-ference on Antimicrobial Agents and Chemotherapy, Washing-ton D.C., 16–19 December 2005 (abstract K-876). We thank Dr.Susanne Graf and the laboratory technicians from our Unit ofMicrobiology for their superb assistance. Financing disclosure:F.H.R. De Man received grants from the AO foundation, and M.Lu¨em received grants from the Wissenschaftfonds OrthopaedieKantonsspital Liestal.Conflict of interest statement. None of the authors have aconflict of interest.References1. Trampuz A, Steckelberg JM, Osmon DR, Cockerill FR, HanssenAD, Patel R: Advances in the laboratory diagnosis of prostheticjoint infection. Rev Med Microbiol 2003; 14: 1–14.2. Panousis K, Grigoris P, Butcher I, Rana B, Reilly JH, Hamblen DL:Poor predictive value of broad-range PCR for the detection ofarthroplasty infection in 92 cases. Acta Orthop 2005; 76: 341–346.3. Kordelle J, Hossain H, Stahl U, Schleicher I, Haas H: Usefulnessof 16S rDNA polymerase-chain-reaction (PCR) in the intraoper-ative detection of infection in revision of failed arthroplasties.Z Orthop Ihre Grenzgeb 2004; 142: 571–576.4. Kordelle J, Klett R, Stahl U, Hossain H, Schleicher I, Haas H:Infection diagnosis after knee-TEP-implantation. Z Orthop IhreGrenzgeb 2004; 142: 337–343.5. Zappe B, Graf S, Ochsner PE, Zimmerli W, Sendi P: Propioni-bacterium spp. in prosthetic joint infections: a diagnostic chal-lenge. Arch Orthop Trauma Surg 2008; 128: 1039–1046.6. Bosshard PP, Kronenberg A, Zbinden R, Ruef C, Bottger EC,Altwegg M: Etiologic diagnosis of infective endocarditis bybroad-range polymerase chain reaction: a 3-year experience.Clin Infect Dis 2003; 37: 167–172.7. Berbari EF, Marculescu C, Sia I, Lahr BD, Hanssen AD,Steckelberg JM, Gullerud R, Osmon DR: Culture-negativeprosthetic joint infection. Clin Infect Dis 2007; 45: 1113–1119.8. Mariani BD, Martin DS, Levine MJ, Booth RE Jr, Tuan RS: TheCoventry Award. Polymerase chain reaction detection ofbacterial infection in total knee arthroplasty. Clin Orthop RelatRes 1996; 331: 11–22.9. Moojen DJ, Spijkers SN, Schot CS, Nijhof MW, Vogely HC, Fleer A,Verbout AJ, Castelein RM, Dhert WJ, Schouls LM: Identificationof orthopaedic infections using broad-range polymerase chainreaction and reverse line blot hybridization. J Bone Joint SurgAm 2007; 89: 1298–1305.10. Fihman V, Hannouche D, Bousson V, Bardin T, Liote F, Raskine L,Riahi J, Sanson-Le Pors MJ, Bercot B: Improved diagnosis speci-ficity in bone and joint infections using molecular techniques.J Infect 2007; 55: 510–517.11. Fenollar F, Roux V, Stein A, Drancourt M, Raoult D: Analysis of525 samples to determine the usefulness of PCR amplificationand sequencing of the 16S rRNA gene for diagnosis of bone andjoint infections. J Clin Microbiol 2006; 44: 1018–1028.12. Hoeffel DP, Hinrichs SH, Garvin KL: Molecular diagnostics forthe detection of musculoskeletal infection. Clin Orthop RelatRes 1999; 360: 37–46.F.H.R. De Man et al. PCR in PJI294 Infection 37 Æ 2009 Æ No. 3  URBAN & VOGEL

Broad-Range PCR in Selected Episodes of Prosthetic Joint Infection

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Broad-Range PCR in Selected Episodes of Prosthetic Joint Infection

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