Abstract
Background
Without clear signs of infection, spinal implant failure is attributed to mechanical overloads and aseptic loosening. However, how low-grade infections contribute to seemingly aseptic implant failure is unclear.
Purpose
The systematic review examined unexpected positive cultures (UPCs) in revision spine surgery regarding prevalence, isolated pathogens, risk factors, and strategies to reduce infection among asymptomatic patients undergoing revision spine surgery.
Methods
We followed the PRISMA guidelines and searched four main databases (PubMed, EMBASE, SCOPUS, Web of Science) comprehensively until January 2023 for articles reporting UPC after presumed aseptic adult revision spine surgery. The UPC rates were pooled, and risk factors were compared with the culture-negative control group and represented as odds ratio (OR) or mean difference (MD).
Results
Fifteen studies of 1057 individuals were included in two groups: culture-positive or UPCs (n = 317) and culture-negative or control (n = 740). The overall UPC prevalence was 33.2% (317/1057, range: 0 to 53%, 95% CI = 30.2%–36.4%), and Cutibacterium acnes (43.0%, 95% CI = 37.4%–48.8%), Coagulase-negative Staphylococci (CoNS), (39.5%, 95% CI = 33.2%–46.2%), and Staphylococcus species in general (49.5%, 95%CI = 43.7%–55.4%) were reported the most common isolated microbes. 16.1% of the UPCs were polymicrobial. Risk factors associated with UPC rates were female sex (OR = 2.62, 95%CI = 1.76–3.90, P < 0.001), screw loosening (OR = 4.43, 95%CI = 1.31–15.02, P = 0.02), number of operated levels (MD = 0.77, 95%CI = 0.33–1.22, P = 0.0007), and shorter time since index surgery (MD = − 8.57 months, 95%CI = − 14.76, -2.39, P = 0.02).
Conclusions
One-third of patients undergoing spine revision surgery revealed UPC in this study. Each UPC pathogen interpretation and antibiotic use decision should be interpreted case by case.
Level of evidence: IV.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Not applicable.
References
Mok JM, Cloyd JM, Bradford DS, Hu SS, Deviren V, Smith JA et al (2009) Reoperation after primary fusion for adult spinal deformity: rate, reason, and timing. Spine 34(8):832–839
Pichelmann MA, Lenke LG, Bridwell KH, Good CR, O’Leary PT, Sides BA (2010) Revision rates following primary adult spinal deformity surgery: six hundred forty-three consecutive patients followed-up to twenty-two years postoperative. Spine 35(2):219–226
Zhu F, Bao H, Liu Z, Bentley M, Zhu Z, Ding Y et al (2014) Unanticipated revision surgery in adult spinal deformity: an experience with 815 cases at one institution. Spine 39(26B):B36–B44
Dapunt U, Bürkle C, Günther F, Pepke W, Hemmer S, Akbar M (2017) Surgical site infections following instrumented stabilization of the spine. Ther Clin Risk Manag 13:1239
Lewkonia P, DiPaola C, Street J (2016) Incidence and risk of delayed surgical site infection following instrumented lumbar spine fusion. J Clin Neurosci 23:76–80
Kelly MP, Lenke LG, Bridwell KH, Agarwal R, Godzik J, Koester L (2013) The fate of the adult revision spinal deformity patient: a single institution experience. Spine 38(19):E1196
Yilgor C, Sogunmez N, Yavuz Y, Boissiere L, Obeid I, Acaroglu E et al (2017) Global alignment and proportion (GAP) score: development and validation of a new method of analyzing spinopelvic alignment to predict mechanical complications after adult spinal deformity surgery. Spine J 17(10):S155–S156
Trampuz A, Piper KE, Jacobson MJ, Hanssen AD, Unni KK, Osmon DR et al (2007) Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med 357(7):654–663
Pumberger M, Bürger J, Strube P, Akgün D, Putzier M (2019) Unexpected positive cultures in presumed aseptic revision spine surgery using sonication. Bone Joint J. 101-b(5):621–624
Saleh A, Guirguis A, Klika AK, Johnson L, Higuera CA, Barsoum WK (2014) Unexpected positive intraoperative cultures in aseptic revision arthroplasty. J Arthroplasty 29(11):2181–2186
Bongers J, Jacobs AM, Smulders K, Goosen JH (2020) Reinfection and re-revision rates of 113 two-stage revisions in infected TKA. J Bone Joint Infect 5(3):137–144
Di Benedetto P, Dalla Vecchia G, Dante F, Gisonni R, Cainero V, Causero A (2019) Leukocyte esterase strip test as a reliable intraoperative PJIs biomarker. Our experience. Acta Bio Medica Atenei Parmensis. 90(Suppl 12):43
Portillo ME, Salvadó M, Alier A, Sorli L, Martínez S, Horcajada JP et al (2013) Prosthesis failure within 2 years of implantation is highly predictive of infection. Clin Orthop Related Res. 471(11):3672–3678
Rasouli MR, Harandi AA, Adeli B, Purtill JJ, Parvizi J (2012) Revision total knee arthroplasty: infection should be ruled out in all cases. J Arthroplasty 27(6):1239-1243.e2
Tubb CC, Polkowksi GG, Krause B (2020) Diagnosis and prevention of periprosthetic joint infections. JAAOS-J Am Acad Orthop Surg 28(8):e340–e348
van den Kieboom J, Tirumala V, Box H, Oganesyan R, Klemt C, Kwon Y-M (2021) One-stage revision is as effective as two-stage revision for chronic culture-negative periprosthetic joint infection after total hip and knee arthroplasty: a retrospective cohort study. Bone Joint J 103(3):515–521
Del Pozo JL, Patel R (2009) Infection associated with prosthetic joints. N Engl J Med 361(8):787–794
Marculescu C, Berbari E, Hanssen A, Steckelberg J, Osmon DR (2005) Prosthetic joint infection diagnosed postoperatively by intraoperative culture. Clin Orthop Related Res 439:38–42
Moojen DJF, van Hellemondt G, Vogely HC, Burger BJ, Walenkamp GH, Tulp NJ et al (2010) Incidence of low-grade infection in aseptic loosening of total hip arthroplasty: a prospective multicenter study using extensive routine and broad-range 16S PCR with reverse line blot diagnostics. Acta Orthop 81(6):667–673
Ribera A, Morata L, Moranas J, Agulló J, Martínez J, Lopez Y et al (2014) Clinical and microbiological findings in prosthetic joint replacement due to aseptic loosening. J Infect 69(3):235–243
Chaichana KL, Bydon M, Santiago-Dieppa DR, Hwang L, McLoughlin G, Sciubba DM et al (2014) Risk of infection following posterior instrumented lumbar fusion for degenerative spine disease in 817 consecutive cases. J Neurosurg Spine 20(1):45–52
Kasliwal MK, Tan LA, Traynelis VC (2013) Infection with spinal instrumentation: review of pathogenesis, diagnosis, prevention, and management. Surg Neurol Int 4(Suppl 5):S392
Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350:g7647
Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberati A, Moschetti I, Phillips B, Thornton H (2011). The 2011 Oxford CEBM Levels of Evidence (Introductory Document). Oxford Centre for Evidence-Based Medicine. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence
Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558
Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ et al (2019) Cochrane handbook for systematic reviews of interventions. Wiley, New York
Hu X, Lieberman IH (2018) Revision spine surgery in patients without clinical signs of infection: how often are there occult infections in removed hardware? Eur Spine J 27(10):2491–2495
Shiban E, Joerger AK, Janssen I, Issa M, Lange N, Wagner A et al (2020) Low-grade infection and implant failure following spinal instrumentation: a prospective comparative study. Neurosurgery 87(5):964–970
Leitner L, Malaj I, Sadoghi P, Amerstorfer F, Glehr M, Vander K et al (2018) Pedicle screw loosening is correlated to chronic subclinical deep implant infection: a retrospective database analysis. Eur Spine J 27(10):2529–2535
Ohrt-Nissen S, Fritz B, Valentin L, Kragh KN, Manniche C, Dahl B et al (2019) Is pseudarthrosis after spinal instrumentation caused by a chronic infection? Eur Spine J 28(12):2996–3002
Prinz V, Bayerl S, Renz N, Trampuz A, Czabanka M, Woitzik J et al (2019) High frequency of low-virulent microorganisms detected by sonication of pedicle screws: a potential cause for implant failure. J Neurosurg Spine 31(3):424–429
Siller S, Skrap B, Grabein B, Trabold R, Zausinger S, Tonn JC (2022) Routine intraoperative microbiological smear testing in patients with reoperation after elective degenerative non-instrumented spine surgery-useful or negligible adjunct. Acta Neurochir (Wien) 164(3):891–901
Agarwal A, Mooney M, Agarwal AG, Jayaswal D, Saakyan G, Goel V et al (2020) High prevalence of biofilms on retrieved implants from aseptic pseudarthrosis cases. Spine Surg Relat Res 5(2):104–108
Burkhard MD, Loretz R, Uçkay I, Bauer DE, Betz M, Farshad M (2021) Occult infection in pseudarthrosis revision after spinal fusion. Spine J 21(3):370–376
Dupré DA, Cheng B, Kreft R, Nistico L, Ehrlich GD, Averick S et al (2022) The presence of biofilms in instrumented spinal fusions. Genet Test Mol Biomarkers 26(7–8):375–381
Shifflett GD, Bjerke-Kroll BT, Nwachukwu BU, Kueper J, Burket J, Sama AA et al (2016) Microbiologic profile of infections in presumed aseptic revision spine surgery. Eur Spine J 25(12):3902–3907
Burkhard MD, Hassanzadeh A, Andronic O, Götschi T, Uçkay I, Farshad M (2022) Clinical relevance of occult infections in spinal pseudarthrosis revision. N Am Spine Soc J (NASSJ) 12:100172
García-Pérez D, Lagares A, Castaño-León AM, Panero I, Munarriz PM, Delgado-Fernández J et al (2021) Implant microbial colonization detected by sonication as a cause for spinal device failure: a prospective study. Spine 46(21):1485–1494
Steinhaus ME, Salzmann SN, Lovecchio F, Shifflett GD, Yang J, Kueper J et al (2019) Risk factors for positive cultures in presumed aseptic revision spine surgery. Spine 44(3):177–184
Burkhard MD, Hassanzadeh A, Andronic O, Götschi T, Uçkay I, Farshad M (2022) Clinical relevance of occult infections in spinal pseudarthrosis revision. N Am Spine Soc J (NASSJ). 12:100172
Callanan TC, Abjornson C, DiCarlo E, Henry M, Sama AA, Girardi FP et al (2021) Prevalence of occult infections in posterior instrumented spinal fusion. Clin Spine Surg 34(1):25–31
Richards BS (1995) Delayed infections following posterior spinal instrumentation for the treatment of idiopathic scoliosis. J Bone Joint Surg Am 77(4):524–529
Updegrove GF, Armstrong AD, Kim HM (2015) Preoperative and intraoperative infection workup in apparently aseptic revision shoulder arthroplasty. J Shoulder Elbow Surg 24(3):491–500
Purudappa PP, Sharma OP, Priyavadana S, Sambandam S, Villafuerte JA (2020) Unexpected positive intraoperative cultures (UPIC) in revision Hip and knee arthroplasty—a review of the literature. J Orthop 17:1–6
Hodakowski AJ, Cohn MR, Mehta N, Menendez ME, McCormick JR, Garrigues GE (2022) An evidence-based approach to managing unexpected positive cultures in shoulder arthroplasty. J Shoulder Elbow Surg 31(10):2176–2186
Kim SJ, Kim JH (2014) Unexpected positive cultures including isolation of Propionibacterium acnes in revision shoulder arthroplasty. Chin Med J (Engl) 127(22):3975–3979
Kloos J, Vander Linden K, Vermote S, Berger P, Vandenneucker H (2022) Prevalence, interpretation, and management of unexpected positive cultures in revision TKA: a systematic review. Knee Surg Sports Traumatol Arthrosc 30(12):3998–4009
Levy O, Iyer S, Atoun E, Peter N, Hous N, Cash D et al (2013) Propionibacterium acnes: an underestimated etiology in the pathogenesis of osteoarthritis? J Shoulder Elbow Surg 22(4):505–511
Kempthorne JT, Ailabouni R, Raniga S, Hammer D, Hooper G (2015) Occult infection in aseptic joint loosening and the diagnostic role of implant sonication. Biomed Res Int 2015:946215
Zhai Z, Li H, Qin A, Liu G, Liu X, Wu C et al (2014) Meta-analysis of sonication fluid samples from prosthetic components for diagnosis of infection after total joint arthroplasty. J Clin Microbiol 52(5):1730–1736
Sampedro MF, Huddleston PM, Piper KE, Karau MJ, Dekutoski MB, Yaszemski MJ et al (2010) A biofilm approach to detect bacteria on removed spinal implants. Spine 35(12):1218–1224
Nelson CL, McLaren AC, McLaren SG, Johnson JW, Smeltzer MS (2005) Is aseptic loosening truly aseptic? Clin Orthop Relat Res 437:25–30
Agarwal A, Mooney M, Agarwal AG, Jayaswal D, Saakyan G, Goel V et al (2021) High prevalence of biofilms on retrieved implants from aseptic pseudarthrosis cases. Spine Surg Relat Res 5(2):104–108
Uçkay I, Dinh A, Vauthey L, Asseray N, Passuti N, Rottman M et al (2010) Spondylodiscitis due to Propionibacterium acnes: report of twenty-nine cases and a review of the literature. Clin Microbiol Infect 16(4):353–358
Bémer P, Corvec S, Tariel S, Asseray N, Boutoille D, Langlois C et al (2008) Significance of Propionibacterium acnes-positive samples in spinal instrumentation. Spine 33(26):E971–E976
Chahoud J, Kanafani Z, Kanj S (2014) Surgical Site infections following spine surgery: eliminating the controversies in the diagnosis. Front Med 1:7
Acknowledgements
None.
Funding
There is no funding source for authors to declare.
Author information
Authors and Affiliations
Contributions
PM introduced the concept, analyzed the data, wrote the manuscript, and edited the final draft. AJ and HG contributed to the screening, material preparation, data extraction, and writing the first manuscript. MADO contributed to the search strategy, designed tables and figures, and edited the manuscript. Supervising, editing, and finalizing the manuscript was performed by PM., NE contributed to the study conceptualization, manuscript revision and response to reviewer’s comment. All authors commented on previous versions of the manuscript and revised it. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors have no relevant financial or non-financial interests to disclose.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Appendix 1: All isolated microorganisms (N, %)
Appendix 1: All isolated microorganisms (N, %)
Study | Pooled rate and 95%CI | Shifflett 2016 Steinhaus 2019 | Hu 2018 | Pumberger 2019 | Shiban 2020 | Agarwal 2021 | Burkhard 2021 Burkhard 2022 | Callanan 2021(9) | García-Pérez 2021 | Dupre´ 2022 | Ohrt-Nissen | Prinz | Leitner | Siller et al |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
UPIC/ Negative culture | 45/67 (40%) | 15/147 (9%) | 75/91 (45%) | 25/35 (41%) | 7/3 (70%) | 13/115 (10%) | 33/17 (66%) | 11/27 (28%) | 5/6 (45%) | 17/15 (53%) | 22/60 (26%) | 32/78 (29%) | 8/53 (15%) | |
Species | ||||||||||||||
Coagulase-negative staphylococci (CoNS) | 101/308 (40.8%) (34.6%–47.3%) | 5/45 (11%) | 6/15 (40%) | 35/75 (47%) | 5/13 (3.9%) | 9/33 (27%) | 5/11 (47%) | 4/17 (23%) | 15/22 (68%) | 17/32 (53%) | ||||
Cutibacterium acnes | 129/308 (43.1%; 37.5- 48.8%) | 22/45 (49%) | 7/15 (46%) | 34/75 (45%) | 9/25 (36%) | 6 /13 (4.7%) | 12/33 (36%) | 3/11 (25%) | 3/5 (60%) | 9/17 (52%) | 6/22 (27%) | 13/32 (40%) | 5/8 (62%) | |
Staphylococcus epidermidis | 46/308 (27%; 20.8–34.2%) | 1/45 (2%) | 23/75 (31%) | 7/25 (28%) | 4 /13 (3.1%) | 1/5 (20%) | 7/32 (21%) | 3/8 (37%) | ||||||
Staphylococcus capitis | 8/308 (6.1%; 3.1%-11.8%) | 4/75 (5%) | 2/25 (8%) | 1/32 (6%) | 1/8 (12%) | |||||||||
Staphylococcus hominis | 5/308 (4.8%; 2- 11%) | 3/75 (4%) | 2/32 (12%) | |||||||||||
Staphylococcus haemolyticus | 2/308 (2.7%; 0.7- 1%) | 2/75 (3%) | ||||||||||||
Staphylococcus cohnii | 2/308 (2.7%; 0.7–1%) | 2/75 (3%) | ||||||||||||
Staphylococcus warneri | 1/308 (1.3%; 0.2–8.9%) | 1/75 (1%) | ||||||||||||
Staphylococcus lugdunensis | 6/308 (4.8%; 2.1–10.2%) | 3/45 (6%) | 1/75 (1%) | 1/25 (4%) | 1 /13 (0.8%) | |||||||||
Staphylococcus saccharolyticus | 8/308 (6.2%; 3.1–12%) | 1/45 (2%) | 1/75 (1%) | 4/33 (12%) | – | 2/32 (12%) | ||||||||
Staphylococcus aureus | 5/308 (6.5%; 2.7–14.7%) | 2/75 (3%) | 3/25 (12%) | |||||||||||
oxacillin-sensitive Staphylococcus aureus | 7/308 (15.6%)(7.6%–29.2%) | 7/45 (15%) | ||||||||||||
Streptococcus Viridans | 2/308 (4.4%)(1.1%–16.1%) | 2/45 (4.4%) | ||||||||||||
Proteus mirabilis | 1/308 (2.2%)(0.3%–14.2%) | 1/45 (2%) | ||||||||||||
Methicillin-resistant Staphylococcus epidermidis | 4/308 (8.9%)(3.4%–21.4%) | 4/45 (9%) | ||||||||||||
Methicillin-sensitive Staphylococcus epidermidis | 4/308 (8.9%)(3.4%–21.4%) | 4/45 (9%) | ||||||||||||
Methicillin-resistant Staphylococcus aureus | 4/308 (5.9%; 2.2–14.6%) | 3/45 (6%) | 1/25 (4%) | |||||||||||
E. Coli | 5/308 (7.2%; 3–16.1%) | 3/45 (6%) | 2/25 (8%) | |||||||||||
Diphtheroids | 3/308 (6.7%; 2.2–18.7%) | 3/45 (6%) | ||||||||||||
Pseudomonas aeruginosa | 1/308 (6.7%; 0.9–35.2%) | 1/15 (6%) | ||||||||||||
Polymicrobial | 10/308 (13.3%; 7.3–23%) | 10/75 (13%) | ||||||||||||
Corynebact confusum | 1/308 (4%; 0.6–23.5%) | 1/25 (4%) | ||||||||||||
E. faecalis | 3/308 (9.6%; 3.1–26.2%) | 1/25 (4%) | 2 /13 (1.6%) | |||||||||||
Finegoldia magna | 1/308 (4%; 0.6–23.5%) | 1/25 (4%) | ||||||||||||
Pseudomonas chlororaphis | 1/308 (4%; 0.6–23.5%) | 1/25 (4%) | ||||||||||||
Achromobacter spp. | 1/308 (4%; 0.6–23.5%) | 1/25 (4%) | ||||||||||||
Kalbesila pneumonia | 1/308 (3%; 0.4–18.6%) | 1/33 (3%) | ||||||||||||
Trueperella bernardia | 1/308 (3%; 0.4–18.6%) | 1/33 (3%) | ||||||||||||
Roseomonas mucosa | 1/308 (20%; 2.7–69.1%) | 1/5 (20%) | ||||||||||||
Enterococcus faecalis | 1/308 (4.5%; 0.6–26.1%) | 1/22 (4%) | ||||||||||||
Bacillus circulans | 1/308 (12.5%; 1.7–53.7%) | 1/8 (12%) | ||||||||||||
Propionibacterium avidum | 1/308 (5.9%; 0.8–32%) | 1/17 (5%) |
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Mirghaderi, P., Gholamshahi, H., Jahromi, A. et al. Unexpected positive culture (UPC) in adults revision spine surgery: a systematic review and meta-analysis of incidence, risk factors, and management. Eur Spine J (2024). https://doi.org/10.1007/s00586-024-08229-2
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00586-024-08229-2