Articles | Volume 11, issue 3
https://doi.org/10.5194/jbji-11-373-2026
© Author(s) 2026. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
https://doi.org/10.5194/jbji-11-373-2026
© Author(s) 2026. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
Integrating molecular and conventional diagnostics in native vertebral osteomyelitis: a narrative review
Farzad Pourghazi
Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minnesota, 55905, USA
Omar Mahmoud
Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minnesota, 55905, USA
Francesco Petri
Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minnesota, 55905, USA
Department of Infectious Diseases, ASST Fatebenefratelli Sacco University Hospital, Regional Center for Infectious Diseases (CEREMI), Lombardy Region, Milan, Italy
Said El Zein
Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minnesota, 55905, USA
Gina A. Suh
Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minnesota, 55905, USA
Takahiro Matsuo
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA
Andrea Gori
Department of Infectious Diseases, ASST Fatebenefratelli Sacco University Hospital, Regional Center for Infectious Diseases (CEREMI), Lombardy Region, Milan, Italy
Department of Biomedical and Clinical Sciences, University of Milan, Milan, 20157, Italy
Centre for Multidisciplinary Research in Health Science (MACH), University of Milan, Milan, 20157, Italy
Audrey N. Schuetz
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, 55905, USA
Elie F. Berbari
CORRESPONDING AUTHOR
Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minnesota, 55905, USA
Related authors
No articles found.
Hussam Tabaja, Matteo Passerini, Irene G. Sia, Elena Beam, and Gina A. Suh
J. Bone Joint Infect., 11, 77–82, https://doi.org/10.5194/jbji-11-77-2026, https://doi.org/10.5194/jbji-11-77-2026, 2026
Short summary
Short summary
In Lyme-endemic regions, Lyme disease should be considered in culture-negative periprosthetic joint infection (PJI). Diagnosis relies on microbial DNA detection, particularly Borrelia-targeted polymerase chain reaction (PCR) on synovial fluid or tissue. We present 10 cases highlighting the value of PCR for early recognition of this pathogen, which is not detectable by conventional culture media. Surgical debridement remains the standard of care, though several cases were successfully treated medically, an observation that merits further investigation.
Seyed Mohammad Amin Alavi, Fabio Borgonovo, Francesco Petri, Takahiro Matsuo, Andrea Gori, Jeremy D. Shaw, Aaron J. Tande, and Elie F. Berbari
J. Bone Joint Infect., 10, 451–457, https://doi.org/10.5194/jbji-10-451-2025, https://doi.org/10.5194/jbji-10-451-2025, 2025
Short summary
Short summary
The rising rate of spinal surgeries has led to more postoperative infections, yet no standardized diagnostic criteria exist. We analyzed over 100 studies and found considerable variation in definitions. Our findings underscore the need for a unified diagnostic framework that integrates clinical signs, laboratory data, and imaging to enhance diagnostic accuracy, support clinical decision-making, and improve consistency in future research.
Fabio Borgonovo, Francesco Petri, Takahiro Matsuo, Rita Igwilo-Alaneme, Seyed Mohammad Amin Alavi, Omar K. Mahmoud, Said El Zein, Matteo Passerini, Mohammad Hassan Murad, Daniel C. DeSimone, Ahmad Nassr, Aaron J. Tande, Andrea Gori, and Elie F. Berbari
J. Bone Joint Infect., 10, 425–435, https://doi.org/10.5194/jbji-10-425-2025, https://doi.org/10.5194/jbji-10-425-2025, 2025
Short summary
Short summary
We studied a serious double infection affecting the heart and spine, often seen in older or immunocompromised patients. By analyzing systematic data from the literature, we found that this condition leads to high death rates, especially when caused by the bacterium Staphylococcus aureus. Our work highlights the urgent need for higher-quality studies and better coordinated care. These findings may help guide future treatment strategies and improve outcomes for affected patients.
Chiara Mariani, Matteo Passerini, Lucia Galli, Alice Covizzi, Marta Colaneri, Martina Offer, Margherita Faenzi, Stefania Merli, Simona Landonio, Marta Fusi, Alberto Dolci, Andrea Gori, and Dario Cattaneo
J. Bone Joint Infect., 10, 255–263, https://doi.org/10.5194/jbji-10-255-2025, https://doi.org/10.5194/jbji-10-255-2025, 2025
Short summary
Short summary
Bone and joint infections often require prolonged antibiotic treatments over 12 weeks. Dalbavancin, an intravenous antibiotic given at spaced intervals, offers a promising option. Our study developed a method to optimize dosing schedules using two blood tests to measure drug levels. This ensures effective treatment while avoiding excessive accumulation. These findings suggest dalbavancin is a safe, effective choice for managing long-term infections.
Pansachee Damronglerd, Ryan Bijan Khodadadi, Said El Zein, Jack William McHugh, Omar M. Abu Saleh, Mark Edward Morrey, Aaron Joseph Tande, and Gina Ann Suh
J. Bone Joint Infect., 10, 25–31, https://doi.org/10.5194/jbji-10-25-2025, https://doi.org/10.5194/jbji-10-25-2025, 2025
Short summary
Short summary
Our 10-year multicenter study examines the epidemiology, presentation, management, and outcomes of elbow native joint septic arthritis, a rare condition with risks like reoperation and mortality. Common symptoms included pain and swelling. Synovial fluid white blood cell counts were often low, with monosodium urate crystals also noted. Staphylococcus aureus was the main pathogen, and 72.2 % of patients underwent open debridement.
Francesco Petri, Omar Mahmoud, Said El Zein, Ahmad Nassr, Brett A. Freedman, Jared T. Verdoorn, Aaron J. Tande, and Elie F. Berbari
J. Bone Joint Infect., 9, 173–182, https://doi.org/10.5194/jbji-9-173-2024, https://doi.org/10.5194/jbji-9-173-2024, 2024
Short summary
Short summary
In recent years, there has been an increase in scientific production on native vertebral osteomyelitis (NVO), a condition whose incidence is rising and that can be highly detrimental to health. However, there is no consensus on the definition of this syndrome in the medical community. Therefore, we propose a new framework to synthesize the diagnostic tools at our disposal. This can help to advance research further and guide patient care more effectively.
Daisuke Furukawa, Megan Dunning, Sa Shen, Amy Chang, Jenny Aronson, Derek F. Amanatullah, Gina A. Suh, and Shanthi Kappagoda
J. Bone Joint Infect., 9, 143–148, https://doi.org/10.5194/jbji-9-143-2024, https://doi.org/10.5194/jbji-9-143-2024, 2024
Short summary
Short summary
The role of long-term antibiotics after debridement, antibiotics, and implant retention (DAIR) for periprosthetic joint infections is unclear. Patients with eventual cessation of antibiotics had similar outcomes to those who remained on chronic antibiotic suppression (failure rate of 11 % for both groups). This study importantly highlights a potential opportunity to prevent unnecessary antibiotic use and spare patients from the risk of side effects and development of resistant organisms.
Said El Zein, Elie F. Berbari, Allison M. LeMahieu, Anil Jagtiani, Parham Sendi, Abinash Virk, Mark E. Morrey, and Aaron J. Tande
J. Bone Joint Infect., 9, 107–115, https://doi.org/10.5194/jbji-9-107-2024, https://doi.org/10.5194/jbji-9-107-2024, 2024
Short summary
Short summary
Our study investigated olecranon septic bursitis treatment, focusing on postsurgical antibiotic use. Analyzing 22 years of Mayo Clinic data, we found that smoking and not administering antibiotics following surgery led to poorer outcomes. A 3-week antibiotic course following surgery was most effective. Our findings suggest that a subset of patients may benefit from longer courses of antibiotics; however, further research is needed to confirm these findings.
Matteo Passerini, Julian Maamari, Don Bambino Geno Tai, Robin Patel, Aaron J. Tande, Zelalem Temesgen, and Elie F. Berbari
J. Bone Joint Infect., 8, 143–149, https://doi.org/10.5194/jbji-8-143-2023, https://doi.org/10.5194/jbji-8-143-2023, 2023
Short summary
Short summary
Physicians have difficulties interpreting the isolation of Cutibacterium acnes in the spine tissue. Here we provide the experience of our center about this topic, adding data that can help physicians in their choices. Our results show that some clinical, radiological, and microbiological features can help distinguish patients to treat or not to treat. Moreover, treatment with parenteral beta-lactams appears to be effective, but targeted oral therapy could be a valid alternative.
Eibhlin Higgins, Don Bambino Geno Tai, Brian Lahr, Gina A. Suh, Elie F. Berbari, Kevin I. Perry, Matthew P. Abdel, and Aaron J. Tande
J. Bone Joint Infect., 8, 125–131, https://doi.org/10.5194/jbji-8-125-2023, https://doi.org/10.5194/jbji-8-125-2023, 2023
Short summary
Short summary
This retrospective case-matched study evaluated males and females with staphylococcal PJI (periprosthetic joint infection) treated with two-stage exchange arthroplasty. We matched 156 males and females for age, type of staphylococcal infection, and joint involved. We compared clinical parameters related to presentation, treatment, and outcome. We did not find a statistically significant difference in outcome between males and females treated with the same surgical approach at our institution.
Kareme D. Alder, Anthony P. Fiegen, Matthew M. Rode, Don Bambino Geno Tai, Gina A. Suh, Abinash Virk, and Nicholas Pulos
J. Bone Joint Infect., 8, 39–44, https://doi.org/10.5194/jbji-8-39-2023, https://doi.org/10.5194/jbji-8-39-2023, 2023
Short summary
Short summary
We present the first published case of bilateral extensor tenosynovitis caused by Coxiella burnetii. C. burnetii should be considered in patients with inflammatory osteoarticular disease, including tenosynovitis, when conventional cultures are negative especially in elderly, male, or immunocompromised patients with exposure to animals.
Matteo Passerini, Julian Maamari, Tarek Nayfeh, Leslie C. Hassett, Aaron J. Tande, Mohammad H. Murad, Zelalem Temesgen, and Elie F. Berbari
J. Bone Joint Infect., 7, 249–257, https://doi.org/10.5194/jbji-7-249-2022, https://doi.org/10.5194/jbji-7-249-2022, 2022
Short summary
Short summary
Despite a growing interest in oral therapy for native vertebral osteomyelitis, there is no evidence to recommend oral or parenteral therapy. From our single-center experience combined with a systematic review and a meta-analysis of the available literature, there is insufficient evidence to conclude that there is a difference in proportion of failure and relapse between an early switch to oral antibiotics and prolonged parenteral therapy. Further studies are needed to increase the evidence.
Talha Riaz, Matthew Howard, Felix Diehn, Aaron Joseph Tande, Courtney Ross, Paul Huddleston, and Elie Berbari
J. Bone Joint Infect., 7, 213–219, https://doi.org/10.5194/jbji-7-213-2022, https://doi.org/10.5194/jbji-7-213-2022, 2022
Short summary
Short summary
In this study, we prospectively enrolled patients with a suspected diagnosis of native vertebral osteomyelitis (NVO) undergoing image-guided needle aspiration of the intervertebral disc. Based on this pilot study, a high manual cell count or a high neutrophilic predominance from the disc aspirate was associated with the diagnosis of NVO.
Katharine Dobos, Gina A. Suh, Aaron J. Tande, and Shanthi Kappagoda
J. Bone Joint Infect., 7, 137–141, https://doi.org/10.5194/jbji-7-137-2022, https://doi.org/10.5194/jbji-7-137-2022, 2022
Short summary
Short summary
This paper describes five cases of prosthetic joint infection (PJI) caused by Mycobacterium avium complex (MAC). Infections occurred in both immune competent and immunosuppressed patients. Interestingly, using the Musculoskeletal Infection Society diagnostic criteria for PJI may miss some cases of MAC PJI. Treatment courses and outcomes are described.
Julian Maamari, Aaron J. Tande, Felix Diehn, Don Bambino Geno Tai, and Elie F. Berbari
J. Bone Joint Infect., 7, 23–32, https://doi.org/10.5194/jbji-7-23-2022, https://doi.org/10.5194/jbji-7-23-2022, 2022
Short summary
Short summary
The yearly incidence of native vertebral osteomyelitis (NVO) is increasing. In 2013 the prevalence of NVO in the USA was 5.4 cases per 100 000. Delays in the diagnosis of NVO remain common, in part due to the insidious nature of the infection and its related symptoms. The mean time between the onset of symptoms to diagnosis of NVO is 45.5 d. We herein review available and novel diagnostic modalities at the disposal of healthcare providers to reach an accurate and timely diagnosis of NVO.
Miao Xian Zhou, Elie F. Berbari, Cory G. Couch, Scott F. Gruwell, and Alan B. Carr
J. Bone Joint Infect., 6, 363–366, https://doi.org/10.5194/jbji-6-363-2021, https://doi.org/10.5194/jbji-6-363-2021, 2021
Short summary
Short summary
This was written to outline Mayo Clinic guidelines on prophylactic antibiotics prior to invasive procedures in patients with prosthetic joints. There is an emphasis on maintaining optimal oral health to reduce the risk of infection to minimize the patient’s risk of PJI.
Talha Riaz, Mark Collins, Mark Enzler, Marco Rizzo, Audrey N. Schuetz, Julia S. Lehman, Douglas Osmon, and Irene G. Sia
J. Bone Joint Infect., 6, 355–361, https://doi.org/10.5194/jbji-6-355-2021, https://doi.org/10.5194/jbji-6-355-2021, 2021
Short summary
Short summary
Tenosynovitis due to Histoplasma capsulatum in an immunocompromised host warrants special attention. Following surgical debridement, the patient initially improved on antifungal therapy, but as immunosuppression was decreased, she presented with a flare, requiring further debridement. With negative fungal cultures and declining antigenemia, it was felt that her interim worsening was as a consequence of immune reconstitution inflammatory syndrome (IRIS).
Cited articles
Afshinnekoo, E., Chou, C., Alexander, N., Ahsanuddin, S., Schuetz, A. N., and Mason, C. E.: Precision Metagenomics: Rapid Metagenomic Analyses for Infectious Disease Diagnostics and Public Health Surveillance, J. Biomol. Tech., 28, 40–45, https://doi.org/10.7171/jbt.17-2801-007, 2017.
Alavi, S. M. A., Petri, F., Mahmoud, O. K., Igwilo-Alaneme, R., El Zein, S., Nassr, A. N., Gori, A., and Berbari, E. F.: Culture-negative native vertebral osteomyelitis: a narrative review of an underdescribed condition, J. Clin. Med., 13, 5802, https://doi.org/10.3390/jcm13195802, 2024.
Asthana, V., Nieves, E. M., Bugga, P., Smith, C., Dunn, T., Narayanasamy, S., Dickson, R. P., and VanEpps, J. S.: A rapid, inexpensive, culture-free, universal bacterial identification system using internal transcribed spacer targeting primers: a proof-of-principle study, bioRxiv [preprint], https://doi.org/10.1101/2024.09.15.613074, 2024.
Berbari, E. F., Kanj, S. S., Kowalski, T. J., Darouiche, R. O., Widmer, A. F., Schmitt, S. K., Hendershot, E. F., Holtom, P. D., Huddleston, P. M., and Petermann, G. W.: 2015 infectious diseases society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adultsa, Clin. Infect. Dis., 61, e26–e46, https://doi.org/10.1093/cid/civ482, 2015.
Beroukhim, G., Shah, R., and Bucknor, M. D.: Factors predicting positive culture in CT-guided bone biopsy performed for suspected osteomyelitis, Am. J. Roentgenol., 212, 620–624, https://doi.org/10.2214/AJR.18.20125, 2019.
Chang, C. Y., Simeone, F. J., Nelson, S. B., Taneja, A. K., and Huang, A. J.: Is biopsying the paravertebral soft tissue as effective as biopsying the disk or vertebral endplate? 10-year retrospective review of CT-guided biopsy of diskitis-osteomyelitis, Am. J. Roentgenol., 205, 123–129, https://doi.org/10.2214/AJR.14.13545, 2015.
Channer, L., Krol, O., Philipp, T., Wright, C., Kark, J., Smith, S., and Yoo, J.: Incidence and Risk Factors for Native Vertebral Osteomyelitis: A Retrospective Cohort Study Using a National Claims Database, Spine J., https://doi.org/10.1016/j.spinee.2025.10.002, 2025.
Chew, F. S. and Kline, M. J.: 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.r01ja06211, 2001.
Chiang, H. Y., Chung, C. W., Kuo, C. C., Lo, Y. C., Chang, W. S., and Chi, C. Y.: First-4-week erythrocyte sedimentation rate variability predicts erythrocyte sedimentation rate trajectories and clinical course among patients with pyogenic vertebral osteomyelitis, PLoS One, 14, e0225969, https://doi.org/10.1371/journal.pone.0225969, 2019.
Chiu, C. Y. and Miller, S. A.: Clinical metagenomics, Nat. Rev. Genet., 20, 341–355, https://doi.org/10.1038/s41576-019-0113-7, 2019.
Choe, H., Aota, Y., Kobayashi, N., Nakamura, Y., Wakayama, Y., Inaba, Y., and Saito, T.: Rapid sensitive molecular diagnosis of pyogenic spinal infections using methicillin-resistant Staphylococcus-specific polymerase chain reaction and 16S ribosomal RNA gene-based universal polymerase chain reaction, Spine J., 14, 255–262, https://doi.org/10.1016/j.spinee.2013.10.044, 2014.
Colmenero, J. D., Morata, P., Ruiz-Mesa, J. D., Bautista, D., Bermúdez, P., Bravo, M. J., and Queipo-Ortuño, M. I.: Multiplex real-time polymerase chain reaction: a practical approach for rapid diagnosis of tuberculous and brucellar vertebral osteomyelitis, Spine (Phila Pa 1976), 35, E1392–1396, https://doi.org/10.1097/BRS.0b013e3181e8eeaf, 2010.
Czuczman, G. J., Marrero, D. E., Huang, A. J., Mandell, J. C., Ghazikhanian, V., and Simeone, F. J.: Diagnostic yield of repeat CT-guided biopsy for suspected infectious spondylodiscitis, Skeletal Radiol., 47, 1403–1410, https://doi.org/10.1007/s00256-018-2972-y, 2018.
Davis, W. T., April, M. D., Mehta, S., Long, B., Boys, G., and Shroyer, S.: Sensitivity of C-reactive protein cut-off values for pyogenic spinal infection in the emergency department, Cjem, 22, 836–843, https://doi.org/10.1017/cem.2020.402, 2020.
Di Bonaventura, G., Angeletti, S., Ianni, A., Petitti, T., and Gherardi, G.: Microbiological laboratory diagnosis of human brucellosis: an overview, Pathogens, 10, 1623, https://doi.org/10.3390/pathogens10121623, 2021.
Echeverria, A. P., Cohn, I. S., Danko, D. C., Shanaj, S., Blair, L., Hollemon, D., Carli, A. V., Sculco, P. K., Ho, C., Meshulam-Simon, G., Mironenko, C., Ivashkiv, L. B., Goodman, S. M., Grizas, A., Westrich, G. H., Padgett, D. E., Figgie, M. P., Bostrom, M. P., Sculco, T. P., Hong, D. K., Hepinstall, M. S., Bauer, T. W., Blauwkamp, T. A., Brause, B. D., Miller, A. O., Henry, M. W., Ahmed, A. A., Cross, M. B., Mason, C. E., and Donlin, L. T.: Sequencing of Circulating Microbial Cell-Free DNA Can Identify Pathogens in Periprosthetic Joint Infections, J. Bone Joint Surg. Am., 103, 1705–1712, https://doi.org/10.2106/JBJS.20.02229, 2021.
Fenollar, F. and Raoult, D.: Molecular genetic methods for the diagnosis of fastidious microorganisms, Apmis, 112, 785–807, https://doi.org/10.1111/j.1600-0463.2004.apm11211-1206.x,2004.
Fenollar, F., Lévy, P.-Y., and Raoult, D.: Usefulness of broad-range PCR for the diagnosis of osteoarticular infections, Curr. Opin. Rheumatol., 20, 463–470, https://doi.org/10.1097/BOR.0b013e3283032030, 2008.
Flurin, L., Wolf, M. J., Mutchler, M. M., Daniels, M. L., Wengenack, N. L., and Patel, R.: Targeted metagenomic sequencing-based approach applied to 2146 tissue and body fluid samples in routine clinical practice, Clin. Infect. Dis., 75, 1800–1808, https://doi.org/10.1093/cid/ciac247, 2022.
Fuursted, K., Arpi, M., Lindblad, B. E., and Pedersen, L. N.: Broad-range PCR as a supplement to culture for detection of bacterial pathogens in patients with a clinically diagnosed spinal infection, Scand. J. Infect. Dis., 40, 772–777, https://doi.org/10.1080/00365540802119994, 2008.
Grif, K., Heller, I., Prodinger, W., Lechleitner, K., Lass-Flörl, C., and Orth, D.: Improvement of detection of bacterial pathogens in normally sterile body sites with a focus on orthopedic samples by use of a commercial 16S rRNA broad-range PCR and sequence analysis, J. Clin. Microbiol., 50, 2250–2254, https://doi.org/10.1128/jcm.00362-12,2012.
Grumaz, S., Grumaz, C., Vainshtein, Y., Stevens, P., Glanz, K., Decker, S. O., Hofer, S., Weigand, M. A., Brenner, T., and Sohn, K.: 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.0000000000003658, 2019.
Gu, W., Miller, S., and Chiu, C. Y.: Clinical metagenomic next-generation sequencing for pathogen detection, Annu. Rev. Pathol.-Mech., 14, 319–338, https://doi.org/10.1146/annurev-pathmechdis-012418-012751, 2019.
Higgins, E., Suh, G. A., and Tande, A. J.: Enhancing diagnostics in orthopedic infections, J. Clin. Microbiol., 60, e02196-02121, https://doi.org/10.1128/jcm.02196-21, 2022.
Hilt, E. E. and Ferrieri, P.: Next generation and other sequencing technologies in diagnostic microbiology and infectious diseases, Genes, 13, 1566, https://doi.org/10.3390/genes13091566, 2022.
Hoang, D., Fisher, S., Oz, O. K., La Fontaine, J., and Chhabra, A.: Percutaneous CT guided bone biopsy for suspected osteomyelitis: diagnostic yield and impact on patient's treatment change and recovery, Eur. J. Radiol., 114, 85–91, https://doi.org/10.1016/j.ejrad.2019.01.032, 2019.
Hogan, C. A., Yang, S., Garner, O. B., Green, D. A., Gomez, C. A., Dien Bard, J., Pinsky, B. A., and Banaei, N.: Clinical Impact of Metagenomic Next-Generation Sequencing of Plasma Cell-Free DNA for the Diagnosis of Infectious Diseases: A Multicenter Retrospective Cohort Study, Clin. Infect. Dis., 72, 239–245, https://doi.org/10.1093/cid/ciaa035, 2020.
Hu, T., Chitnis, N., Monos, D., and Dinh, A.: Next-generation sequencing technologies: An overview, Hum. Immunol., 82, 801–811, https://doi.org/10.1016/j.humimm.2021.02.012, 2021.
Husseini, J. S. and Huang, A. J.: Discitis-osteomyelitis: optimizing results of percutaneous sampling, Skeletal Radiol., 52, 1815–1823, https://doi.org/10.1007/s00256-022-04151-0, 2023.
Jensen, A. G., Espersen, F., Skinhøj, P., and Frimodt-Møller, N.: Bacteremic Staphylococcus aureus spondylitis, Arch. Intern. Med., 158, 509–517, https://doi.org/10.1001/archinte.158.5.509, 1998.
Kim, C.-J., Kang, S.-J., Choe, P., Park, W., Jang, H.-C., Jung, S.-I., Song, K.-H., Kim, E., Kim, H., and Park, K.-H.: Which tissues are best for microbiological diagnosis in patients with pyogenic vertebral osteomyelitis undergoing needle biopsy?, Clin. Microbiol. Infec., 21, 931–935, 2015.
Kremers, H. M., Nwojo, M. E., Ransom, J. E., Wood-Wentz, C. M., Melton III, L. J., and Huddleston III, P. M.: Trends in the epidemiology of osteomyelitis: a population-based study, 1969 to 2009, J. Bone Joint Surg., 97, 837–845, https://doi.org/10.2106/JBJS.N.01350, 2015.
Kullar, R., Chisari, E., Snyder, J., Cooper, C., Parvizi, J., and Sniffen, J.: Next-generation sequencing supports targeted antibiotic treatment for culture negative orthopedic infections, Clin. Infect. Dis., 76, 359–364, https://doi.org/10.1093/cid/ciac733, 2023.
Lacasse, M., Derolez, S., Bonnet, E., Amelot, A., Bouyer, B., Carlier, R., Coiffier, G., Cottier, J., Dinh, A., and Maldonado, I.: 2022 SPILF-Clinical Practice guidelines for the diagnosis and treatment of disco-vertebral infection in adults, Infect. Dis., 53, 104647, https://doi.org/10.1016/j.idnow.2023.01.007, 2023.
Lazzeri, E., Bozzao, A., Cataldo, M. A., Petrosillo, N., Manfrè, L., Trampuz, A., Signore, A., and Muto, M.: Joint EANM/ESNR and ESCMID-endorsed consensus document for the diagnosis of spine infection (spondylodiscitis) in adults, Eur. J. Nucl. Med. Mol. I., 46, 2464–2487, https://doi.org/10.1007/s00259-019-04393-6, 2019.
Lee, H. T., Pukenas, B. A., and Sebro, R.: Change in Bone CT Attenuation and C-reactive Protein Are Predictors of Bone Biopsy Culture Positivity in Patients With Vertebral Discitis/Osteomyelitis, Spine (Phila Pa 1976), 45, 1208–1214, https://doi.org/10.1097/brs.0000000000003504, 2020.
Li, Y.-C., Liu, Y.-X., Li, L., Wang, H., Zhao, Z.-R., and Yao, Z.-Y.: Metagenomic next-generation sequencing (mNGS) versus tissue culture technique (TCT) in diagnosis of spinal infection: a systematic review and meta-analysis, Sci. Rep., 15, 20926, https://doi.org/10.1038/s41598-025-06759-3, 2025a.
Li, Z., Zhang, Q., Lian, X., Yin, C., Lin, Y., Wang, Y., Han, Z., Shen, F., Xu, Y., and Wang, H.: Value of metagenomic next-generation sequencing in the diagnosis of native pyogenic spinal infections: a multicenter, retrospective observational study, Spine J., 25, 640–648, https://doi.org/10.1016/j.spinee.2024.11.004, 2025b.
Maamari, J. B., Tande, A. J., Tai, D. B. G., Diehn, F. E., Ross, C., Lahr, B., Suh, G. A., and Berbari, E. F.: Factors impacting the yield of image-guided biopsy in native vertebral osteomyelitis: a 10-year retrospective study, Open Forum Infectious Diseases, ofac616, https://doi.org/10.1093/ofid/ofac616, 2022
Mahmoud, O. K., Petri, F., El Zein, S., Fida, M., Diehn, F. E., Verdoorn, J. T., Schuetz, A. N., Murad, M. H., Nassr, A., and Berbari, E. F.: What Is the Accuracy of 16S PCR Followed by Sanger Sequencing or Next-generation Sequencing in Native Vertebral Osteomyelitis? A Systematic Review and Meta-analysis, Clin. Orthop. Relat. R., 483, 930–938, https://doi.org/10.1097/CORR.0000000000003314, 2025.
Matsuo, T., Borgonovo, F., Lahr, B. D., Petri, F., Igwilo-Alaneme, R., Mulett, S. L. A., Alavi, S. M. A., Challener, D. W., Nassr, A., Huddleston, P. M., Tande, A. J., and Berbari, E. F.: Clinical Manifestations, Long-Term Trends, and Risk Factors for Treatment Failure in Native Vertebral Osteomyelitis: A 26-Year Mayo Clinic Experience, Clin. Infect. Dis., https://doi.org/10.1093/cid/ciag048, 2026.
McBride, J. A., Moua, M., Sterkel, A., Matkovic, E., Rehrauer, W., Eickhoff, J., Schweizer, M. L., and Andes, D.: 16S rRNA bacterial identification in evaluation of orthopedic infections and its limited role in antimicrobial stewardship, Open Forum Infectious Diseases, https://doi.org/10.1093/ofid/ofag262, 2026.
McNamara, A., Dickerson, E., Gomez-Hassan, D., Cinti, S., and Srinivasan, A.: Yield of image-guided needle biopsy for infectious discitis: a systematic review and meta-analysis, Am. J. Neuroradiol., 38, 2021–2027, https://doi.org/10.3174/ajnr.A5337, 2017.
Michalopoulos, G. D., Yolcu, Y. U., Ghaith, A. K., Alvi, M. A., Carr, C. M., and Bydon, M.: Diagnostic yield, accuracy, and complication rate of CT-guided biopsy for spinal lesions: a systematic review and meta-analysis, J. Neurointer. Surg., 13, 841–847, https://doi.org/10.1136/neurintsurg-2021-017419, 2021.
Nagashima, H., Tanishima, S., and Tanida, A.: Diagnosis and management of spinal infections, J. Orthop. Sci., 23, 8–13, https://doi.org/10.1016/j.jos.2017.09.016, 2018.
Nickerson, E. K. and Sinha, R.: Vertebral osteomyelitis in adults: an update, Brit. Med. Bull., 117, https://doi.org/10.1093/bmb/ldw003, 2016.
Passerini, M., Maamari, J., Geno Tai, D. B., Patel, R., Tande, A. J., Temesgen, Z., and Berbari, E. F.: Cutibacterium acnes in spine tissue: characteristics and outcomes of non-hardware-associated vertebral osteomyelitis, J. Bone Joint Infect., 8, 143–149, https://doi.org/10.5194/jbji-8-143-2023, 2023.
Petri, F., Mahmoud, O. K., Ranganath, N., El Zein, S., Abu Saleh, O., Berbari, E. F., and Fida, M.: Plasma Microbial Cell-free DNA Next-generation Sequencing Can Be a Useful Diagnostic Tool in Patients With Osteoarticular Infections, Open Forum Infectious Diseases, 11, https://doi.org/10.1093/ofid/ofae328, 2024.
Pupaibool, J., Vasoo, S., Erwin, P. J., Murad, M. H., and Berbari, E. F.: The utility of image-guided percutaneous needle aspiration biopsy for the diagnosis of spontaneous vertebral osteomyelitis: a systematic review and meta-analysis, Spine J., 15, 122–131, https://doi.org/10.1016/j.spinee.2014.07.003, 2015.
Reller, L. B., Weinstein, M. P., and Petti, C. A.: Detection and identification of microorganisms by gene amplification and sequencing, Clin. Infect. Dis., 44, 1108–1114, https://doi.org/10.1086/512818, 2007.
Rhoads, D. D.: Stenotrophomonas maltophilia susceptibility testing challenges and strategies, J. Clin. Microbiol., 59, https://doi.org/10.1128/jcm.01094-21, 2021.
Rossoff, J., Chaudhury, S., Soneji, M., Patel, S. J., Kwon, S., Armstrong, A., and Muller, W. J.: Noninvasive Diagnosis of Infection Using Plasma Next-Generation Sequencing: A Single-Center Experience, Open Forum Infectious Diseases, 6, https://doi.org/10.1093/ofid/ofz327, 2019.
Santagada, D. A., Perna, A., Tullo, G., Proietti, L., Vitiello, R., Ferraro, S., Giovannini, S., Gasbarrini, A., Franceschi, F., Maccauro, G., Tamburrelli, F. C., and Covino, M.: Could serum procalcitonin play a role in an emergency setting for patients with pyogenic spondylodiscitis?, Eur. Rev. Med. Pharmacol. Sci., 26, 66–77, https://doi.org/10.26355/eurrev_202211_30284, 2022.
Schiro, S., Foreman, S. C., Bucknor, M., Chin, C. T., Joseph, G. B., and Link, T. M.: Diagnostic performance of CT-guided bone biopsies in patients with suspected osteomyelitis of the appendicular and axial skeleton with a focus on clinical and technical factors associated with positive microbiology culture results, J. Vasc. Interv. Radiol., 31, 464–472, https://doi.org/10.1016/j.jvir.2019.08.013, 2020.
Sehn, J. K. and Gilula, L. A.: Percutaneous needle biopsy in diagnosis and identification of causative organisms in cases of suspected vertebral osteomyelitis, Eur. J. Radiol., 81, 940–946, https://doi.org/10.1016/j.ejrad.2011.01.125, 2012.
Shen, C. J., Wu, M. S., Lin, K. H., Lin, W. L., Chen, H. C., Wu, J. Y., Lee, M. C., and Lee, C. C.: The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis, Eur. J. Clin. Microbiol. Infect. Dis., 32, 807–814, https://doi.org/10.1007/s10096-012-1812-6, 2013.
Simner, P. J., Miller, S., and Carroll, K. C.: Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases, Clin. Infect. Dis., 66, 778–788, https://doi.org/10.1093/cid/cix881, 2018.
Tarabichi, M., Shohat, N., Goswami, K., Alvand, A., Silibovsky, R., Belden, K., and Parvizi, J.: Diagnosis of periprosthetic joint infection: the potential of next-generation sequencing, J. Bone Joint Surg., 100, 147–154, https://doi.org/10.2106/JBJS.17.00434, 2018.
Thatcher, S. A.: DNA/RNA Preparation for Molecular Detection, Clin. Chem., 61, 89–99, https://doi.org/10.1373/clinchem.2014.221374, 2015.
Wang, Y., He, T., Shen, Z., and Wu, C.: Antimicrobial Resistance in Stenotrophomonas spp., Microbiology Spectrum, 6, https://doi.org/10.1128/microbiolspec.arba-0005-2017, 2018.
Weihe, R., Taghlabi, K., Lowrance, M., Reeves, A., Jackson, S. R., Burton, D. C., and El Atrouni, W.: Culture yield in the diagnosis of native vertebral osteomyelitis: a single tertiary center retrospective case series with literature review, Open Forum Infectious Diseases, ofac026, https://doi.org/10.1093/ofid/ofac026, 2022
Winkler, W. L., George, I. A., Gandra, S., Baker, J. C., Tomasian, A., Northrup, B., Vander Velde, T. L., Hillen, T. J., Luo, C., and Imaoka, R.: Diagnostic efficacy and clinical impact of image-guided core needle biopsy of suspected vertebral osteomyelitis, Int. J. Infect. Dis., 144, 107027, https://doi.org/10.1016/j.ijid.2024.107027, 2024.
Yeh, K. J., Husseini, J. S., Hemke, R., Nelson, S. B., and Chang, C. Y.: CT-guided discitis-osteomyelitis biopsies with negative microbiology: how many days should we wait before repeating the biopsy?, Skeletal Radiol., 49, 619–623, 2020.
Yoon, Y. K., Jo, Y. M., Kwon, H. H., Yoon, H. J., Lee, E. J., Park, S. Y., Park, S. Y., Choo, E. J., Ryu, S. Y., Lee, M. S., Yang, K. S., and Kim, S. W.: Differential diagnosis between tuberculous spondylodiscitis and pyogenic spontaneous spondylodiscitis: a multicenter descriptive and comparative study, Spine J., 15, 1764–1771, https://doi.org/10.1016/j.spinee.2015.04.006, 2015.
Zimmerli, W.: Clinical practice. Vertebral osteomyelitis, N. Engl. J. Med., 362, 1022–1029, https://doi.org/10.1056/NEJMcp0910753, 2010.
Short summary
Native vertebral osteomyelitis, a spinal bone infection, is difficult to diagnose, and delays can worsen outcomes. This review examines how traditional laboratory tests and newer genetic techniques can be integrated to improve identification of the responsible microorganism. We show that combining these approaches within the diagnostic pathway may increase accuracy and support earlier diagnosis, enabling more timely and informed treatment decisions.
Native vertebral osteomyelitis, a spinal bone infection, is difficult to diagnose, and delays...