Recent advances regarding diagnosis and treatment of fracture-related infection_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

JIANG Nan ^1,2 ,  YU Bin ¹

1. Guangdong Institute of Orthopaedics and Traumatology, Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong, 510515, P. R. China;
2. Department of Trauma Emergency Center, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou Jiangxi, 341000, P. R. China;

Corresponding author：

YU Bin, Email: yubinol@163.com

Keywords：

Fracture-related infection; osteomyelitis; diagnosis; treatment; research progress

DOI：

10.7507/1002-1892.202505073

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the current research status on the diagnosis and treatment of fracture-related infection (FRI). Methods The research literature in the field of FRI both domestically and internationally in recent years were widely reviewed, and the research progress of FRI from the aspects of definition and classification, epidemiological characteristics, diagnosis and treatment elaborated, in order to provide reference for clinical application. Results In recent years, specific classifications for FRI have gradually emerged. FRI is characterized by high incidence, high recurrence, high disability rates, and significant economic costs. Key diagnostic points include clinical signs and symptoms, imaging tests, serological biomarkers, pathogen identification, and histopathological examination. Treatment principles encompass debridement, management of implants (retention or removal), systemic and local antibiotic use, reconstruction of bone and soft tissue defects, and functional and psychological rehabilitation. Conclusion Although FRI is a catastrophic complication following limb bone trauma, early precise diagnosis and standardized treatment are key to improving cure rates, reducing recurrence, and enhancing patients’ quality of life.

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2.	McNally M, Govaert G, Dudareva M, et al. Definition and diagnosis of fracture-related infection. EFORT Open Rev, 2020, 5(10): 614-619.
3.	中华医学会骨科学分会创伤骨科学组, 中华医学会骨科学分会外固定与肢体重建学组, 中国医师协会创伤外科医师分会创伤感染专家委员会, 等. 中国骨折内固定术后感染诊断与治疗专家共识 (2018版). 中华创伤骨科杂志, 2018, 20(11): 929-936.
4.	中华医学会骨科学分会创伤骨科学组, 中华医学会骨科学分会外固定与肢体重建学组, 中华医学会创伤学分会, 等. 中国-中亚五国骨折相关感染诊断与治疗指南 (2024). 中华创伤骨科杂志, 2024, 26(1): 6-15.
5.	Metsemakers WJ, Kuehl R, Moriarty TF, et al. Infection after fracture fixation: Current surgical and microbiological concepts. Injury, 2018, 49(3): 511-522.
6.	Cierny G 3rd, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res, 2003(414): 7-24.
7.	Hotchen AJ, Dudareva M, Ferguson JY, et al. The BACH classification of long bone osteomyelitis. Bone Joint Res, 2019, 8(10): 459-468.
8.	Alt V, McNally M, Wouthuyzen-Bakker M, et al. The FRI classification-A new classification of fracture-related infections. Injury, 2024, 55(11): 111831. doi: 10.1016/j.injury.2024.111831.
9.	Foster AL, Warren J, Vallmuur K, et al. A population-based epidemiological and health economic analysis of fracture-related infection. Bone Joint J, 2024, 106-B(1): 77-85.
10.	Khalili P, Brüggemann A, Tevell S, et al. Fracture-related infections after osteosynthesis for hip fracture are associated with higher mortality: A retrospective single-center cohort study. Acta Orthop, 2024, 95: 570-577.
11.	Reátiga Aguilar J, Gonzalez Edery E, Guzmán Badrán J, et al. Open tibial plateau fractures: Infection rate and functional outcomes. Injury, 2023, 54 Suppl 6: 110720. doi: 10.1016/j.injury.2023.04.007.
12.	Pilskog K, Høvding P, Fenstad AM, et al. Risk factors for fracture-related infection after ankle fracture surgery. Injury, 2023, 54(10): 111011. doi: 10.1016/j.injury.2023.111011.
13.	Zhou JQ, Liu ZX, Zhong HF, et al. Single nucleotide polymorphisms in the development of osteomyelitis and prosthetic joint infection: a narrative review. Front Immunol, 2024, 15: 1444469. doi: 10.3389/fimmu.2024.1444469.
14.	Metsemakers WJ, Moriarty TF, Morgenstern M, et al. The global burden of fracture-related infection: can we do better? Lancet Infect Dis, 2024, 24(6): e386-e393.
15.	Woffenden H, Yasen Z, Burden E, et al. Fracture-related infection: Analysis of healthcare utilisation and associated costs. Injury, 2023, 54(12): 111109. doi: 10.1016/j.injury.2023.111109.
16.	Haidari S, Buijs MAS, Plate JDJ, et al. Costs of fracture-related infection: the impact on direct hospital costs and healthcare utilisation. Eur J Trauma Emerg Surg, 2024, 50(4): 1701-1707.
17.	Jiang N, Wu HT, Lin QR, et al. Health care costs of post-traumatic osteomyelitis in China: Current situation and influencing factors. J Surg Res, 2020, 247: 356-363.
18.	Vanvelk N, Van Lieshout EMM, Onsea J, et al. Diagnosis of fracture-related infection in patients without clinical confirmatory criteria: an international retrospective cohort study. J Bone Jt Infect, 2023, 8(2): 133-142.
19.	韩洁, 杨芳. 核医学显像在骨折相关性感染中的研究进展. 中国医学影像学杂志, 2024, 32(11): 1186-1190.
20.	Rupp M, Walter N, Brochhausen C, et al. Fracture related infection-challenges in definition and diagnosis. J Orthop, 2024, 49: 38-41.
21.	Li C, Nie L, Sun Z, et al. 3DFRINet: A framework for the detection and diagnosis of fracture related infection in low extremities based on 18F-FDG PET/CT 3D images. Comput Med Imaging Graph, 2024, 115: 102394. doi: 10.1016/j.compmedimag.2024.102394.
22.	Wang Y, Sun Z, Liang X, et al. Inguinal draining-lymph node in 18F-FDG PET/CT images could be a new indicator for the diagnosis of fracture-related infection in the lower extremities. Front Immunol, 2023, 14: 1206682. doi: 10.3389/fimmu.2023.1206682.
23.	Natoli RM, Malek S. Fracture-related infection blood-based biomarkers: Diagnostic strategies. Injury, 2024, 55 Suppl 6: 111823. doi: 10.1016/j.injury.2024.111823.
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25.	Wang B, Xiao X, Zhang J, et al. Epidemiology and microbiology of fracture-related infection: a multicenter study in Northeast China. J Orthop Surg Res, 2021, 16(1): 490. doi: 10.1186/s13018-021-02629-6.
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28.	Jiang N, Hu YJ, Lin QR, et al. Implant surface culture may be a useful adjunct to standard tissue sampling culture for identification of pathogens accounting for fracture-device-related infection: a within-person randomized agreement study of 42 patients. Acta Orthop, 2022, 93: 703-708.
29.	Chen P, Lin QR, Huang MZ, et al. Devascularized bone surface culture: A novel strategy for identifying osteomyelitis-related pathogens. J Pers Med, 2022, 12(12): 2050. doi: 10.3390/jpm12122050.
30.	Marais LC, Zalavras CG, Moriarty FT, et al. The surgical management of fracture-related infection. Surgical strategy selection and the need for early surgical intervention. J Orthop, 2023, 50: 36-41.
31.	Li B, Liu C, Alt V, et al. Multidisciplinary approach and host optimization for fracture-related infection management. Injury, 2024, 55 Suppl 6: 111899. doi: 10.1016/j.injury.2024.111899.
32.	Langit MB, Tay KS, Al-Omar HK, et al. Surgical debridement in long bone chronic osteomyelitis: is wide tumour-like resection necessary? Bone Jt Open, 2023, 4(8): 643-651.
33.	Baertl S, Rupp M, Alt V. The DAIR-procedure in fracture-related infection-When and how. Injury, 2024, 55 Suppl 6: 111977. doi: 10.1016/j.injury.2024.111977.
34.	Tsang SJ, Ferreira N. The role of implant retention and conservative management in the management of fracture-related infection. J Orthop, 2023, 48: 47-51.
35.	Besal R, Adamič P, Beović B, et al. Systemic antimicrobial treatment of chronic osteomyelitis in adults: A narrative review. Antibiotics (Basel), 2023, 12(6): 944. doi: 10.3390/antibiotics12060944.
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39.	Depypere M, Kuehl R, Metsemakers WJ, et al. Recommendations for systemic antimicrobial therapy in fracture-related infection: A consensus from an international expert group. J Orthop Trauma, 2020, 34(1): 30-41.
40.	de Oliveira Campos TV, de Andrade MAP, de Oliveira E Britto Perucci M, et al. The duration of antibiotic therapy for fracture related infection does not affect recurrence but leads to increased adverse effects: a comparison among 6, 12 and 24 weeks of treatment. Eur J Orthop Surg Traumatol, 2024, 34(8): 3995-4000.
41.	Ceccarelli G, Perciballi B, Russo A, et al. Chronic suppressive antibiotic treatment for Staphylococcal bone and joint implant-related infections. Antibiotics (Basel), 2023, 12(5): 937. doi: 10.3390/antibiotics12050937.
42.	Lovatti S, Tiecco G, Mulé A, et al. Dalbavancin in bone and joint infections: A systematic review. Pharmaceuticals (Basel), 2023, 16(7): 1005. doi: 10.3390/ph16071005.
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44.	Ferry T, Onsea J, Roussel-Gaillard T, et al. Bacteriophage therapy in musculoskeletal infections: from basic science to clinical application. EFORT Open Rev, 2024, 9(5): 339-348.
45.	Chen B, Moriarty TF, Metsemakers WJ, et al. Phage therapy: A primer for orthopaedic trauma surgeons. Injury, 2024, 55 Suppl 6: 111847. doi: 10.1016/j.injury.2024.111847.
46.	Liu K, Zhang H, Maimaiti X, et al. Bifocal versus trifocal bone transport for the management of tibial bone defects caused by fracture-related infection: a meta-analysis. J Orthop Surg Res, 2023, 18(1): 140. doi: 10.1186/s13018-023-03636-5.
47.	Liu K, Jia Q, Wang X, et al. Complications associated with single-level bone transport for the treatment of tibial bone defects caused by fracture-related infection. BMC Musculoskelet Disord, 2023, 24(1): 514. doi: 10.1186/s12891-023-06527-2.
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1. Metsemakers WJ, Morgenstern M, McNally MA, et al. Fracture-related infection: A consensus on definition from an international expert group. Injury, 2018, 49(3): 505-510.
2. McNally M, Govaert G, Dudareva M, et al. Definition and diagnosis of fracture-related infection. EFORT Open Rev, 2020, 5(10): 614-619.
3. 中华医学会骨科学分会创伤骨科学组, 中华医学会骨科学分会外固定与肢体重建学组, 中国医师协会创伤外科医师分会创伤感染专家委员会, 等. 中国骨折内固定术后感染诊断与治疗专家共识 (2018版). 中华创伤骨科杂志, 2018, 20(11): 929-936.
4. 中华医学会骨科学分会创伤骨科学组, 中华医学会骨科学分会外固定与肢体重建学组, 中华医学会创伤学分会, 等. 中国-中亚五国骨折相关感染诊断与治疗指南 (2024). 中华创伤骨科杂志, 2024, 26(1): 6-15.
5. Metsemakers WJ, Kuehl R, Moriarty TF, et al. Infection after fracture fixation: Current surgical and microbiological concepts. Injury, 2018, 49(3): 511-522.
6. Cierny G 3rd, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res, 2003(414): 7-24.
7. Hotchen AJ, Dudareva M, Ferguson JY, et al. The BACH classification of long bone osteomyelitis. Bone Joint Res, 2019, 8(10): 459-468.
8. Alt V, McNally M, Wouthuyzen-Bakker M, et al. The FRI classification-A new classification of fracture-related infections. Injury, 2024, 55(11): 111831. doi: 10.1016/j.injury.2024.111831.
9. Foster AL, Warren J, Vallmuur K, et al. A population-based epidemiological and health economic analysis of fracture-related infection. Bone Joint J, 2024, 106-B(1): 77-85.
10. Khalili P, Brüggemann A, Tevell S, et al. Fracture-related infections after osteosynthesis for hip fracture are associated with higher mortality: A retrospective single-center cohort study. Acta Orthop, 2024, 95: 570-577.
11. Reátiga Aguilar J, Gonzalez Edery E, Guzmán Badrán J, et al. Open tibial plateau fractures: Infection rate and functional outcomes. Injury, 2023, 54 Suppl 6: 110720. doi: 10.1016/j.injury.2023.04.007.
12. Pilskog K, Høvding P, Fenstad AM, et al. Risk factors for fracture-related infection after ankle fracture surgery. Injury, 2023, 54(10): 111011. doi: 10.1016/j.injury.2023.111011.
13. Zhou JQ, Liu ZX, Zhong HF, et al. Single nucleotide polymorphisms in the development of osteomyelitis and prosthetic joint infection: a narrative review. Front Immunol, 2024, 15: 1444469. doi: 10.3389/fimmu.2024.1444469.
14. Metsemakers WJ, Moriarty TF, Morgenstern M, et al. The global burden of fracture-related infection: can we do better? Lancet Infect Dis, 2024, 24(6): e386-e393.
15. Woffenden H, Yasen Z, Burden E, et al. Fracture-related infection: Analysis of healthcare utilisation and associated costs. Injury, 2023, 54(12): 111109. doi: 10.1016/j.injury.2023.111109.
16. Haidari S, Buijs MAS, Plate JDJ, et al. Costs of fracture-related infection: the impact on direct hospital costs and healthcare utilisation. Eur J Trauma Emerg Surg, 2024, 50(4): 1701-1707.
17. Jiang N, Wu HT, Lin QR, et al. Health care costs of post-traumatic osteomyelitis in China: Current situation and influencing factors. J Surg Res, 2020, 247: 356-363.
18. Vanvelk N, Van Lieshout EMM, Onsea J, et al. Diagnosis of fracture-related infection in patients without clinical confirmatory criteria: an international retrospective cohort study. J Bone Jt Infect, 2023, 8(2): 133-142.
19. 韩洁, 杨芳. 核医学显像在骨折相关性感染中的研究进展. 中国医学影像学杂志, 2024, 32(11): 1186-1190.
20. Rupp M, Walter N, Brochhausen C, et al. Fracture related infection-challenges in definition and diagnosis. J Orthop, 2024, 49: 38-41.
21. Li C, Nie L, Sun Z, et al. 3DFRINet: A framework for the detection and diagnosis of fracture related infection in low extremities based on 18F-FDG PET/CT 3D images. Comput Med Imaging Graph, 2024, 115: 102394. doi: 10.1016/j.compmedimag.2024.102394.
22. Wang Y, Sun Z, Liang X, et al. Inguinal draining-lymph node in 18F-FDG PET/CT images could be a new indicator for the diagnosis of fracture-related infection in the lower extremities. Front Immunol, 2023, 14: 1206682. doi: 10.3389/fimmu.2023.1206682.
23. Natoli RM, Malek S. Fracture-related infection blood-based biomarkers: Diagnostic strategies. Injury, 2024, 55 Suppl 6: 111823. doi: 10.1016/j.injury.2024.111823.
24. Trenkwalder K, Hackl S, Weisemann F, et al. The value of current diagnostic techniques in the diagnosis of fracture-related infections: Serum markers, histology, and cultures. Injury, 2024, 55 Suppl 6: 111862. doi: 10.1016/j.injury.2024.111862.
25. Wang B, Xiao X, Zhang J, et al. Epidemiology and microbiology of fracture-related infection: a multicenter study in Northeast China. J Orthop Surg Res, 2021, 16(1): 490. doi: 10.1186/s13018-021-02629-6.
26. Govaert GAM, Kuehl R, Atkins BL, et al. Diagnosing fracture-related infection: Current concepts and recommendations. J Orthop Trauma, 2020, 34(1): 8-17.
27. Hoffmann A, Hoffmann J, Ruegamer T, et al. New diagnostic techniques for diagnosing facture-related infections. Injury, 2024, 55 Suppl 6: 111898. doi: 10.1016/j.injury.2024.111898.
28. Jiang N, Hu YJ, Lin QR, et al. Implant surface culture may be a useful adjunct to standard tissue sampling culture for identification of pathogens accounting for fracture-device-related infection: a within-person randomized agreement study of 42 patients. Acta Orthop, 2022, 93: 703-708.
29. Chen P, Lin QR, Huang MZ, et al. Devascularized bone surface culture: A novel strategy for identifying osteomyelitis-related pathogens. J Pers Med, 2022, 12(12): 2050. doi: 10.3390/jpm12122050.
30. Marais LC, Zalavras CG, Moriarty FT, et al. The surgical management of fracture-related infection. Surgical strategy selection and the need for early surgical intervention. J Orthop, 2023, 50: 36-41.
31. Li B, Liu C, Alt V, et al. Multidisciplinary approach and host optimization for fracture-related infection management. Injury, 2024, 55 Suppl 6: 111899. doi: 10.1016/j.injury.2024.111899.
32. Langit MB, Tay KS, Al-Omar HK, et al. Surgical debridement in long bone chronic osteomyelitis: is wide tumour-like resection necessary? Bone Jt Open, 2023, 4(8): 643-651.
33. Baertl S, Rupp M, Alt V. The DAIR-procedure in fracture-related infection-When and how. Injury, 2024, 55 Suppl 6: 111977. doi: 10.1016/j.injury.2024.111977.
34. Tsang SJ, Ferreira N. The role of implant retention and conservative management in the management of fracture-related infection. J Orthop, 2023, 48: 47-51.
35. Besal R, Adamič P, Beović B, et al. Systemic antimicrobial treatment of chronic osteomyelitis in adults: A narrative review. Antibiotics (Basel), 2023, 12(6): 944. doi: 10.3390/antibiotics12060944.
36. Li HK, Rombach I, Zambellas R, et al. Oral versus intravenous antibiotics for bone and joint infection. N Engl J Med, 2019, 380(5): 425-436.
37. Hawkins MR, Thottacherry E, Juthani P, et al. Implementing oral antibiotics for bone and joint infections: Lessons learned and opportunities for improvement. Open Forum Infect Dis, 2024, 11(12): ofae683. doi: 10.1093/ofid/ofae683.
38. Major Extremity Trauma Research Consortium (METRC); Obremskey WT, O’Toole RV, et al. Oral vs intravenous antibiotics for fracture-related infections: The POvIV randomized clinical trial. JAMA Surg, 2025, 160(3): 276-284.
39. Depypere M, Kuehl R, Metsemakers WJ, et al. Recommendations for systemic antimicrobial therapy in fracture-related infection: A consensus from an international expert group. J Orthop Trauma, 2020, 34(1): 30-41.
40. de Oliveira Campos TV, de Andrade MAP, de Oliveira E Britto Perucci M, et al. The duration of antibiotic therapy for fracture related infection does not affect recurrence but leads to increased adverse effects: a comparison among 6, 12 and 24 weeks of treatment. Eur J Orthop Surg Traumatol, 2024, 34(8): 3995-4000.
41. Ceccarelli G, Perciballi B, Russo A, et al. Chronic suppressive antibiotic treatment for Staphylococcal bone and joint implant-related infections. Antibiotics (Basel), 2023, 12(5): 937. doi: 10.3390/antibiotics12050937.
42. Lovatti S, Tiecco G, Mulé A, et al. Dalbavancin in bone and joint infections: A systematic review. Pharmaceuticals (Basel), 2023, 16(7): 1005. doi: 10.3390/ph16071005.
43. Jacob CC, Daw JH, Santiago-Torres J. The efficacy of antibiotic-impregnated calcium sulfate (AICS) in the treatment of infected non-union and fracture-related infection: a systematic review. J Bone Jt Infect, 2023, 8(2): 91-97.
44. Ferry T, Onsea J, Roussel-Gaillard T, et al. Bacteriophage therapy in musculoskeletal infections: from basic science to clinical application. EFORT Open Rev, 2024, 9(5): 339-348.
45. Chen B, Moriarty TF, Metsemakers WJ, et al. Phage therapy: A primer for orthopaedic trauma surgeons. Injury, 2024, 55 Suppl 6: 111847. doi: 10.1016/j.injury.2024.111847.
46. Liu K, Zhang H, Maimaiti X, et al. Bifocal versus trifocal bone transport for the management of tibial bone defects caused by fracture-related infection: a meta-analysis. J Orthop Surg Res, 2023, 18(1): 140. doi: 10.1186/s13018-023-03636-5.
47. Liu K, Jia Q, Wang X, et al. Complications associated with single-level bone transport for the treatment of tibial bone defects caused by fracture-related infection. BMC Musculoskelet Disord, 2023, 24(1): 514. doi: 10.1186/s12891-023-06527-2.
48. Frank FA, Stubbs D, Ferguson JY, et al. A practical definition of pin site infection. Injury, 2024, 55(2): 111230. doi: 10.1016/j.injury.2023.111230.
49. Masquelet A, Kanakaris NK, Obert L, et al. Bone repair using the Masquelet technique. J Bone Joint Surg (Am), 2019, 101(11): 1024-1036.
50. Frese J, Schulz AP, Kowald B, et al. Treatment outcome of the Masquelet technique in 195 infected bone defects-A single-center, retrospective case series. Injury, 2023, 54(10): 110923. doi: 10.1016/j.injury.2023.110923.
51. McCullough MC, Arkader A, Ariani R, et al. Surgical outcomes, complications, and long-term functionality for free vascularized fibula grafts in the pediatric population: A 17-year experience and systematic review of the literature. J Reconstr Microsurg, 2020, 36(5): 386-396.
52. Bezstarosti H, Metsemakers WJ, van Lieshout EMM, et al. Management of critical-sized bone defects in the treatment of fracture-related infection: a systematic review and pooled analysis. Arch Orthop Trauma Surg, 2021, 141(7): 1215-1230.
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