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European Spine Journal

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Open Access 26-05-2023 | Antibiotic | Review Article

Pathogen detection in suspected spinal infection: metagenomic next-generation sequencing versus culture

Authors: Haihong Huang, Jiawei Shi, Minghui Zheng, Shenghui Su, Weidong Chen, Jing Ming, Tao Ren, Dongbin Qu

Published in: European Spine Journal | Issue 12/2023

Abstract

Purpose

The aim is to compare the pathogen detection performance of metagenomic next-generation sequencing (mNGS) and the culturing of percutaneous needle biopsy samples obtained from an individual with a suspected spinal infection.

Methods

A retrospective study of 141 individuals with a suspected spinal infection was conducted, and mNGS was performed. The microbial spectra and detection performance between mNGS and the culturing-based method were compared, and the effects of antibiotic intervention and biopsy on the detection performance were assessed.

Results

The microorganisms isolated most commonly via the culturing-based method were Mycobacterium tuberculosis (n = 21), followed by Staphylococcus epidermidis (n = 13). The most common microorganisms detected via mNGS were Mycobacterium tuberculosis complex (MTBC) (n = 39), followed by Staphylococcus aureus (n = 15). The difference in the type of detected microorganisms between culturing and mNGS was observed only in Mycobacterium (P = 0.001). mNGS helped identify potential pathogens in 80.9% of cases, which was significantly higher than the positivity rate of 59.6% observed for the culturing-based method (P < 0.001). Moreover, mNGS had a sensitivity of 85.7% (95% CI, 78.4% to 91.3%), a specificity of 86.7% (95% CI, 59.5% to 98.3%), and sensitivity gains of 35% (85.7% vs. 50.8%; P < 0.001) during culturing, while no differences were observed in the specificity (86.7% vs. 93.3%; P = 0.543). In addition, antibiotic interventions significantly lowered the positivity rate of the culturing-based method (66.0% vs. 45.5%, P = 0.021) but had no effects on the results of mNGS (82.5% vs. 77.3%, P = 0.467).

Conclusion

The use of mNGS could result in a higher detection rate compared to that observed with the culturing-based method in an individual with spinal infection and is particularly valuable for evaluating the effects of a mycobacterial infection or previous antibiotic intervention.

Babic M, Simpfendorfer C (2017) Infections of the spine. Infect Dis Clin North Am 31:279–297. https://doi.org/10.1016/j.idc.2017.01.003CrossRefPubMed

Luzzati R, Giacomazzi D, Danzi M, Tacconi L, Concia E, Vento S (2009) Diagnosis, management and outcome of clinically-suspected spinal infection. J Infect 58:259–265. https://doi.org/10.1016/j.jinf.2009.02.006CrossRefPubMed

Duarte R, Vaccaro A (2013) Spinal infection: state of the art and management algorithm. Eur spine J 22:2787–2799. https://doi.org/10.1007/s00586-013-2850-1CrossRefPubMedPubMedCentral

Go JL, Rothman S, Prosper A, Silbergleit R, Lerner A (2012) Spine infections. Neuroimaging Clin N Am. https://doi.org/10.1016/j.nic.2012.06.002CrossRefPubMed

Herren C, Jung N, Pishnamaz M, Breuninger M, Siewe J, Sobottke R (2017) Spondylodiscitis: diagnosis and treatment options a systematic review. Dtsch Arztebl Int. https://doi.org/10.3238/arztebl.2017.0875CrossRefPubMedPubMedCentral

Nagashima H, Tanishima S, Tanida A (2018) Diagnosis and management of spinal infections. J Orthop Sci 23:8–13. https://doi.org/10.1016/j.jos.2017.09.016CrossRefPubMed

Avenel G, Guyader P, Fiaux E, Alcaix D, Zarnitsky C, Pouplin-Jardin S, Kozyreff-Meurice M, Lequerré T, Vittecoq O (2021) Microbiological diagnosis of suspected vertebral osteomyelitis with a focus on the yield of percutaneous needle biopsy: a 10 year cohort study. Eur J Clin Microbiol Infect Dis 40:297–302. https://doi.org/10.1007/s10096-020-04022-3CrossRefPubMed

Chew FS, Kline MJ (2001) Diagnostic yield of CT-guided percutaneous aspiration procedures in suspected spontaneous infectious diskitis. Radiology 218:211–214. https://doi.org/10.1148/radiology.218.1.r01ja06211CrossRefPubMed

de Lucas E, González Mandly A, Gutiérrez A, Pellón R, Martín-Cuesta L, Izquierdo J, Sánchez E, Ruiz E, Quintana F (2009) CT-guided fine-needle aspiration in vertebral osteomyelitis: true usefulness of a common practice. Clin Rheumatol 28:315–320. https://doi.org/10.1007/s10067-008-1051-5CrossRefPubMed

10.

Kim C, Song K, Park W, Kim E, Park S, Kim H, Oh M, Kim N (2012) Microbiologically and clinically diagnosed vertebral osteomyelitis: impact of prior antibiotic exposure. Antimicrob Agents Chemother 56:2122–2124. https://doi.org/10.1128/aac.05953-11CrossRefPubMedPubMedCentral

11.

Simner PJ, Miller S, Carroll KC (2018) As a diagnostic tool for infectious diseases. Clin Infect Dis 66:778–788. https://doi.org/10.1093/cid/cix881CrossRefPubMed

12.

Gu W, Miller S, Chiu CY (2019) Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev Pathol 14:319–338. https://doi.org/10.1146/annurev-pathmechdis-012418-012751CrossRefPubMed

13.

Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, Federman S, Stryke D, Briggs B, Langelier C, Berger A, Douglas V, Josephson SA, Chow FC, Fulton BD, DeRisi JL, Gelfand JM, Naccache SN, Bender J, Dien Bard J, Murkey J, Carlson M, Vespa PM, Vijayan T, Allyn PR, Campeau S, Humphries RM, Klausner JD, Ganzon CD, Memar F, Ocampo NA, Zimmermann LL, Cohen SH, Polage CR, DeBiasi RL, Haller B, Dallas R, Maron G, Hayden R, Messacar K, Dominguez SR, Miller S, Chiu CY (2019) Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis. New Engl J Med 380:2327–2340. https://doi.org/10.1056/NEJMoa1803396CrossRefPubMed

14.

Huang ZD, Zhang ZJ, Yang B, Li WB, Zhang CJ, Fang XY, Zhang CF, Zhang WM, Lin JH (2020) Pathogenic detection by metagenomic next-generation sequencing in osteoarticular infections. Front Cell Infect Microbiol 10:471. https://doi.org/10.3389/fcimb.2020.00471CrossRefPubMedPubMedCentral

15.

Tarabichi M, Shohat N, Goswami K, Alvand A, Silibovsky R, Belden K, Parvizi J (2018) Diagnosis of periprosthetic joint infection: the potential of next-generation sequencing. J Bone Joint Surg Am 100:147–154. https://doi.org/10.2106/JBJS.17.00434CrossRefPubMed

16.

Berbari E, Kanj S, Kowalski T (2015) 2015 Infectious diseases society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin infect dis 61:e26-46. https://doi.org/10.1093/cid/civ482CrossRefPubMed

17.

Levitt A, Shah LM, Parsons MS, Agarwal V, Baldwin K, Bhattacharyya S, Boulter DJ, Burns J, Fink KR, Hunt CH, Hutchins TA, Kao LS, Khan MA, Lo BM, Moritani T, Reitman C, Repplinger MD, Shah VN, Singh S, Timpone VM, Corey AS (2021) ACR appropriateness criteria® suspected spine infection. J Am Coll Radiol 18:S488-s501. https://doi.org/10.1016/j.jacr.2021.09.001CrossRefPubMed

18.

Horan T, Gaynes R, Martone W, Jarvis W, Emori T (1992) CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol 13:606–608. https://doi.org/10.1086/646436CrossRefPubMed

19.

Miao Q, Ma Y, Wang Q, Pan J, Zhang Y, Jin W, Yao Y, Su Y, Huang Y, Wang M, Li B, Li H, Zhou C, Li C, Ye M, Xu X, Li Y, Hu B (2018) Microbiological diagnostic performance of metagenomic next-generation sequencing when applied to clinical practice. Clin Infect Dis 67:S231-s240. https://doi.org/10.1093/cid/ciy693CrossRefPubMed

20.

Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25:1754–1760. https://doi.org/10.1093/bioinformatics/btp324CrossRefPubMedPubMedCentral

21.

Kim B, Lee J, Kim S, Lee G, Kang H (2013) Diagnostic yield of fluoroscopy-guided biopsy for infectious spondylitis. AJNR Am J Neuroradiol 34:233–238. https://doi.org/10.3174/ajnr.A3120CrossRefPubMedPubMedCentral

22.

Woo P, Lau S, Teng J, Tse H, Yuen K (2008) Then and now: use of 16S rDNA gene sequencing for bacterial identification and discovery of novel bacteria in clinical microbiology laboratories. Clin microbiol infect 14:908–934. https://doi.org/10.1111/j.1469-0691.2008.02070.xCrossRefPubMed

23.

Ma C, Wu H, Chen G, Liang C, Wu L, Xiao Y (2021) The potential of metagenomic next-generation sequencing in diagnosis of spinal infection: a retrospective study. Eur Spine J. https://doi.org/10.1007/s00586-021-07026-5CrossRefPubMed

24.

Grumaz S, Grumaz C, Vainshtein Y, Stevens P, Glanz K, Decker SO, Hofer S, Weigand MA, Brenner T, Sohn K (2019) Enhanced performance of next-generation sequencing diagnostics compared with standard of care microbiological diagnostics in patients suffering from septic shock. Crit Care Med 47:e394–e402. https://doi.org/10.1097/ccm.0000000000003658CrossRefPubMedPubMedCentral

25.

Salipante S, Hoogestraat D, Abbott A, SenGupta D, Cummings L, Butler-Wu S, Stephens K, Cookson B, Hoffman N (2014) Coinfection of fusobacterium nucleatum and actinomyces israelii in mastoiditis diagnosed by next-generation DNA sequencing. J Clin Microbiol 52:1789–1792. https://doi.org/10.1128/jcm.03133-13CrossRefPubMedPubMedCentral

26.

McIntyre A, Ounit R, Afshinnekoo E, Prill R, Hénaff E, Alexander N, Minot S, Danko D, Foox J, Ahsanuddin S, Tighe S, Hasan N, Subramanian P, Moffat K, Levy S, Lonardi S, Greenfield N, Colwell R, Rosen G, Mason C (2017) Comprehensive benchmarking and ensemble approaches for metagenomic classifiers. Genome Biol 18:182. https://doi.org/10.1186/s13059-017-1299-7CrossRefPubMedPubMedCentral

27.

Jakobsen T, Eickhardt S, Gheorghe A, Stenqvist C, Sønderholm M, Stavnsberg C, Jensen P, Odgaard A, Whiteley M, Moser C, Hvolris J, Hougen H, Bjarnsholt T (2018) Implants induce a new niche for microbiomes. APMIS 126:685–692. https://doi.org/10.1111/apm.12862CrossRefPubMed

28.

Thoendel M, Jeraldo P, Greenwood-Quaintance K, Yao J, Chia N, Hanssen A, Abdel M, Patel R (2017) Impact of contaminating DNA in Whole-Genome amplification kits used for metagenomic Shotgun sequencing for infection diagnosis. J Clin Microbiol 55:1789–1801. https://doi.org/10.1128/jcm.02402-16CrossRefPubMedPubMedCentral

29.

Hasan M, Rawat A, Tang P, Jithesh P, Thomas E, Tan R, Tilley P (2016) Depletion of human DNA in spiked clinical specimens for improvement of sensitivity of pathogen detection by next-generation sequencing. J Clin Microbiol 54:919–927. https://doi.org/10.1128/jcm.03050-15CrossRefPubMedPubMedCentral

30.

Salzberg S, Breitwieser F, Kumar A, Hao H, Burger P, Rodriguez F, Lim M, Quiñones-Hinojosa A, Gallia G, Tornheim J, Melia M, Sears C, Pardo C (2016) Next-generation sequencing in neuropathologic diagnosis of infections of the nervous system. Neurol neuroimmunol neuroinflam 3:e251. https://doi.org/10.1212/nxi.0000000000000251CrossRef

Title: Pathogen detection in suspected spinal infection: metagenomic next-generation sequencing versus culture
Authors: Haihong Huang
Jiawei Shi
Minghui Zheng
Shenghui Su
Weidong Chen
Jing Ming
Tao Ren
Dongbin Qu
Publication date: 26-05-2023
Publisher: Springer Berlin Heidelberg
Keyword: Antibiotic
Published in: European Spine Journal / Issue 12/2023
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-023-07707-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Pathogen detection in suspected spinal infection: metagenomic next-generation sequencing versus culture

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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