Quantitative Real-Time Polymerase Chain Reaction May Serve as a Useful Adjunct to Conventional Culture in The Detection of Cutibacterium acnes in the Glenohumeral Joint: A Study of 100 Consecutive Patients

Document Type : RESEARCH PAPER

Authors

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Abstract

Objectives: Synovial fluid or tissue culture is the current gold standard for diagnosis of infection, but 
Cutibacterium acnes (C. acnes) is a frequent cause of shoulder PJI and is a notoriously fastidious 
organism. The purpose of this study was to compare quantitative real-time polymerase chain reaction 
(qRT-PCR) to standard culture as a more rapid, sensitive means of identifying C. acnes from the 
glenohumeral joint. We hypothesized that qRT-PCR would be more effective than standard culture at 
identifying C. acnes and would have greater sensitivity and specificity for detecting infection.
Methods: This was a prospective observational study with 100 consecutive patients undergoing arthroscopic or 
open shoulder surgery with known positive and negative controls. Intraoperatively, synovial fluid and tissue was 
obtained for C. acnes qRT-PCR and results were blinded to the gold standard microbiology cultures.
Results: Clinical review demonstrated 3 patients (3%) with positive cultures, none of which were positive for C. 
acnes. Of the samples tested by the C. acnes qRT-PCR standard curve, 12.2% of tissue samples and 4.5% of fluid 
samples were positive. Culture sensitivity was 60.0%, specificity was 100.0%, PPV was 100.0%, and NPV was 
97.9%. C. acnes qRT-PCR standard curve sensitivity, specificity, PPV, and NPV was 60.0%, 90.3%, 25.0%, and 
97.7% respectively for tissue specimens and 0%, 95.2%, 0%, and 95.2% respectively, for fluid specimens. For 
combination of culture and tissue qRT-PCR, the sensitivity, specificity, PPV and NPV was 100%, 90.3%, 35.7%, 
and 100%, respectively.
Conclusion: We report that qRT-PCR for C. acnes identified the organism more frequently than conventional 
culture. While these findings demonstrate the potential utility of qRT-PCR, the likelihood of false positive results of 
qRT-PCR should be considered. Thus, qRT-PCR may be useful as an adjuvant to current gold standard workup of 
synovial fluid or tissue culture for the diagnosis of infection.
 Level of evidence: II

Keywords

Main Subjects


  1. Beekman PDA, Katusic D, Berghs BM, Karelse A, de Wilde L. One-stage revision for patients with a chronically infected reverse total shoulder replacement. J Bone Joint Surg Br. 2010; 92(6):817-822. doi:10.1302/0301-620X.92B6.23045.
  2. Hudek R, Gohlke F. Endoprotheseninfektionen der Schulter. Orthopade. 2013; 42(7):552-560. doi:10.1007/s00132-012-2026-4.
  3. Sperling JW, Kozak TKW, Hanssen AD, Cofield RH. Infection after Shoulder Arthroplasty. Clin Orthop Relat Res. 2001 :( 382):206-16. doi: 10.1097/00003086-200101000-00028.
  4. Pauzenberger L, Grieb A, Hexel M, Laky B, Anderl W, Heuberer P. Infections following arthroscopic rotator cuff repair: incidence, risk factors, and prophylaxis. Knee Surg Sports Traumatol Arthrosc. 2017; 25(2):595-601. doi: 10.1007/s00167-016-4202-2.
  5. Atesok K, MacDonald P, Leiter J, McRae S, Stranges G, Old J. Postoperative deep shoulder infections following rotator cuff repair. World J Orthop. 2017; 8(8):612. doi:10.5312/WJO.V8.I8.612.
  6. Mayne AIW, Bidwai AS, Clifford R, Smith MG, Guisasola I, Brownson P. The incidence and causative organisms of infection in elective shoulder surgery. Shoulder Elbow. 2018; 10(3):179. doi:10.1177/1758573217711888.
  7. Saltzman MD, Marecek GS, Edwards SL, Kalainov DM. Infection after shoulder surgery. J Am Acad Orthop Surg. 2011; 19(4):208-218. doi:10.5435/00124635-201104000-00005.
  8. Patel A, Calfee RP, Plante M, Fischer SA, Green A. Propionibacterium acnes colonization of the human shoulder. J Shoulder Elbow Surg. 2009; 18(6):897-902. doi:10.1016/J.JSE.2009.01.023.
  9. Patel MS, Singh AM, Gregori P, Horneff JG, Namdari S, Lazarus MD. Cutibacterium acnes: a threat to shoulder surgery or an orthopedic red herring? J Shoulder Elbow Surg. 2020; 29(9):1920-1927. doi:10.1016/J.JSE.2020.02.020.
  10. Hsu JE, Bumgarner RE, Matsen FA. Propionibacterium in Shoulder Arthroplasty: What We Think We Know Today. J Bone Joint Surg Am. 2016; 98(7):597-606. doi:10.2106/JBJS.15.00568.
  11. Elston MJ, Dupaix JP, Opanova MI, Atkinson RE. Cutibacterium acnes (formerly Proprionibacterium acnes) and Shoulder Surgery. Hawaii J Health Soc Welf. 2019; 78(11 Suppl 2):3-5
  12. Dodson CC, Craig E v., Cordasco FA, et al. Propionibacterium acnes infection after shoulder arthroplasty: a diagnostic challenge. J Shoulder Elbow Surg. 2010; 19(2):303-307. doi:10.1016/J.JSE.2009.07.065.
  13. Bossard DA, Ledergerber B, Zingg PO, et al. Optimal Length of Cultivation Time for Isolation of Propionibacterium acnes in Suspected Bone and Joint Infections Is More than 7 Days. J Clin Microbiol. 2016; 54(12):3043. doi:10.1128/JCM.01435-16.
  14. Schäfer 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(11):1403-1409. doi:10.1086/592973.
  15. Jauregui JJ, Tran A, Kaveeshwar S, et al. Diagnosing a periprosthetic shoulder infection: A systematic review. J Orthop. 2021; 26:58-66. doi:10.1016/J.JOR.2021.07.012.
  16. Li C, Renz N, Trampuz A, Ojeda-Thies C. Twenty common errors in the diagnosis and treatment of periprosthetic joint infection. Int Orthop. 2020; 44(1):3-14. doi: 10.1007/s00264-019-04426-7.
  17. Wagner ER, Farley KX, Higgins I, Wilson JM, Daly CA, Gottschalk MB. The incidence of shoulder arthroplasty: rise and future projections compared with hip and knee arthroplasty. J Shoulder Elbow Surg. 2020; 29(12):2601-2609. doi:10.1016/j.jse.2020.03.049.
  18. Prinz J, Schmid B, Zbinden R, et al. Fast and Sensitive Multiplex Real-Time Quantitative PCR to Detect Cutibacterium Periprosthetic Joint Infections. J Mol Diagn. 2022; 24(6):666-673. doi:10.1016/J.JMOLDX.2022.03.003.
  19. Vandercam B, Jeumont S, Cornu O, et al. Amplification-based DNA analysis in the diagnosis of prosthetic joint infection. J Mol Diagn. 2008; 10(6):537-543. doi:10.2353/JMOLDX.2008.070137.
  20. Garrigues GE, Zmistowski B, Cooper AM, et al. Proceedings from the 2018 International Consensus Meeting on Orthopedic Infections: the definition of periprosthetic shoulder infection. J Shoulder Elbow Surg. 2019; 28(6S):S8-S12. doi:10.1016/J.JSE.2019.04.034.
  21. Richards J, Inacio MCS, Beckett M, et al. Patient and procedure-specific risk factors for deep infection after primary shoulder arthroplasty. Clin Orthop Relat Res. 2014; 472(9):2809-2815. doi:10.1007/S11999-014-3696-5.
  22. Baghdadi YMK, Maradit-Kremers H, Dennison T, et al. The hospital cost of two-stage reimplantation for deep infection after shoulder arthroplasty. JSES Open Access. 2017; 1(1):15. doi:10.1016/J.JSES.2017.02.001.
  23. Kennon JC, Songy CE, Marigi E, et al. Cost analysis and complication profile of primary shoulder arthroplasty at a high-volume institution. J Shoulder Elbow Surg. 2020; 29(7):1337-1345. doi:10.1016/j.jse.2019.12.008.
  24. Namdari S, Nicholson T, Abboud J, et al. Cutibacterium acnes is less commonly identified by next-generation sequencing than culture in primary shoulder surgery. Shoulder Elbow. 2020; 12(3):170. doi:10.1177/1758573219842160.
  25. Rao AJ, MacLean IS, Naylor AJ, Garrigues GE, Verma NN, Nicholson GP. Next-generation sequencing for diagnosis of infection: is more sensitive really better? J Shoulder Elbow Surg. 2020; 29(1):20-26. doi:10.1016/j.jse.2019.07.039.