Chronic Infection Contributes to the Risk of Limb Amputation in Patients with Diabetic Ulcers: A Literature Review

Authors

  • Wenny Anugraini Universitas Muhammadiyah Yogyakarta
  • Fitri Arofiati Universitas Muhammadiyah Yogyakarta
  • Yanuar Primanda Universitas Muhammadiyah Yogyakarta

DOI:

https://doi.org/10.37287/ijghr.v8i3.1421

Keywords:

chronic infection, diabetic foot ulcer, diabetes mellitus, limb amputation, peripheral arterial disease

Abstract

Diabetic foot ulcers are a chronic complication of diabetes mellitus that often leads to lower extremity amputation and significantly contributes to disability and mortality. Infections, particularly chronic and severe ones, play a significant role in accelerating ulcer progression to amputation, Nevertheless, the synthesis of scientific evidence regarding the contribution of chronic infections as a determinant of amputation is still limited. This literature review aimed to examine the role of chronic infection in the risk of amputation in patients with diabetic foot ulcers. A literature search was conducted on the Scopus, PubMed, and ScienceDirect databases for publications from 2015 to 2025 using keywords related to diabetes mellitus, diabetic foot ulcers, infection, and amputation. Articles were selected based on inclusion and exclusion criteria, 644 articles were identified. After title and abstract screening, followed by full-text review, and critical appraisal using the JBI tools, 10 selected journals were included in the literature synthesis.. The results indicated that moderate to severe infection, osteomyelitis, and pathogen characteristics, particularly Gram-negative and ESBL-producing bacteria, are the main determinants of major amputation. Peripheral artery disease, the severity of ulcers, increased inflammatory parameters, hypoalbuminemia, and certain patient factors also worsen clinical outcomes. It is concluded that chronic infection is a key determinant of amputation in diabetic foot ulcers, making early and aggressive infection prevention and control an essential strategy to reduce amputation rates.

References

Alay, H., Yilmaz, S., & Can, F. K. (2021). An evaluation of risk factors affecting amputation in patients with diabetic foot infection. Journal of Health Sciences and Medicine.

Almohammadi, A. A., Alnashri, M. M., Abdulrahman T Harun, R., Alsamiri, S. M., & Alkhatieb, M. T. (2022). Pattern and type of amputation and mortality rate associated with diabetic foot in Jeddah, Saudi Arabia: A retrospective Cohort Study. Annals of Medicine and Surgery, 73, 103174. https://doi.org/https://doi.org/10.1016/j.amsu.2021.103174

Alvaro, P. B., Joaquin, M. P. A., Ana, E. D. Y., Rolando, C. A., Antonio, Q. C., & Elisa, M. (2024). Risk factors associated with amputations in patients with diabetic foot infection. Seven years of experience in a reference hospital in Panama. The diabetic foot study group at Chiriqui (the FOOTCHI study group). Endocrine and Metabolic Science, 16, 100184. https://doi.org/https://doi.org/10.1016/j.endmts.2024.100184

Armstrong, D. G., Tan, T.-W., Boulton, A. J. M., & Bus, S. A. (2023). Diabetic Foot Ulcers: A Review. JAMA, 330(1), 62–75. https://doi.org/10.1001/jama.2023.10578

Chaudhary, N., Huda, F., Roshan, R., Basu, S., Rajput, D., & Singh, S. K. (2021). Lower Limb Amputation Rates in Patients With Diabetes and an Infected Foot Ulcer: A Prospective Observational Study. Wound Management & Prevention, 67(7), 22–30.

Crocker, R. M., Palmer, K. N. B., Marrero, D. G., & Tan, T.-W. (2021). Patient perspectives on the physical, psycho-social, and financial impacts of diabetic foot ulceration and amputation. Journal of Diabetes and Its Complications, 35(8), 107960. https://doi.org/10.1016/j.jdiacomp.2021.107960

Evran, M., Sert, M., Akkuş, G., Biçer, Ö. S., Kesiktaş, E., Kurtaran, B., Aksungur, E., & Tetiker, T. (2021). Foot Ulcer a Devastating Complication of Diabetes Mellitus: A Single-Center Experience of 400 Patients. Endocrinology Research and Practice. https://doi.org/10.25179/tjem.2021-81583

Federation, I. D. (2024). IDF Diabetes Atlas (10th ed.). International Diabetes Federation.

Gong, H., Ren, Y., Li, Z., Zha, P., Bista, R., Li, Y., Chen, D., Gao, Y., Chen, L., Ran, X., & Wang, C. (2023). Clinical characteristics and risk factors of lower extremity amputation in the diabetic inpatients with foot ulcers. Frontiers in Endocrinology, 14([not specified]), [not specified]-[not specified]. https://doi.org/10.3389/fendo.2023.1144806

Hwang, Y. (2024). Analysis of Predictor Factors and Comorbidities About Lower-Extremity Repetitive Amputation in Diabetic Foot Ulcer and Infection: A Retrospective Study. Foot & Ankle Orthopaedics. https://doi.org/10.1177/2473011424s00135

Kilic, M., Olgun, N., Dündar, M., Celik Advan, S., Kücük, F. Z., Okcuoglu, S., Sahin, S., Kır Bicer, E., Ülker, Y., Sahin, P., & Taskiran, Z. (2025). Prevalence, risk level and risk factors of diabetic foot ulcer among adult individuals with diabetes in the Southeastern Anatolia Region of Turkiye. Journal of Tissue Viability, 34(1), 100839. https://doi.org/https://doi.org/10.1016/j.jtv.2024.12.003

Kim, J. (2023). The pathophysiology of diabetic foot: a narrative review. Journal of Yeungnam Medical Science, 40(4), 328–334. https://doi.org/10.12701/jyms.2023.00731

Lee, J. H., Yoon, J. S., Lee, H. W., Won, K. C., Moon, J. S., Chung, S. M., & Lee, Y. Y. (2020). Risk factors affecting amputation in diabetic foot. Journal of Yeungnam Medical Science, 37(4), 314–320. https://doi.org/10.12701/yujm.2020.00129

Leibovitch, M., Cahn, A., Gellman, Y. N., Haze, A., Peled, S., Amit, S., Elishoov, O., & Olshtain-Pops, K. (2021). Predictors and outcomes of diabetic foot ulcer infection with ESBL-producing bacteria in a large tertiary center. International Journal of Infectious Diseases, 113, 318–324. https://doi.org/https://doi.org/10.1016/j.ijid.2021.10.016

Lin, C., Liu, J., & Sun, H. (2020). Risk factors for lower extremity amputation in patients with diabetic foot ulcers: A meta-analysis. PLOS ONE. https://doi.org/10.1371/journal.pone.0239236

Mansoor, Z., & Modaweb, A. (2022). Predicting Amputation in Patients With Diabetic Foot Ulcers: A Systematic Review. Cureus, 14(7), e27245. https://doi.org/10.7759/cureus.27245

Matheson, E. M., Bragg, S. W., & Blackwelder, R. S. (2021). Diabetes-related foot infections: diagnosis and treatment. American Family Physician, 104(4), 386–394. https://www.aafp.org/pubs/afp/issues/2021/1000/p386.html

N, J. S., Punitha, S., & Rakshana, M. (2025). Outcome Predictors for Wound Healing and Amputation Risk in Patients with Diabetic Foot Ulcer. International Journal of Innovative Science and Research Technology, 10(9), 127–134. https://doi.org/10.38124/ijisrt/25sep188

Rodríguez-Rodríguez, N., Martínez-Jiménez, I., García-Ojalvo, A., Mendoza-Mari, Y., Guillén-Nieto, G., Armstrong, D. G., & Berlanga-Acosta, J. (2022). Wound Chronicity, Impaired Immunity and Infection in Diabetic Patients. MEDICC Review, 24(1), 44–58. https://doi.org/10.37757/MR2021.V23.N3.8

Roy, R., Singh, R. K., & Shafikhani, S. H. (2024). Infection in Diabetes: Epidemiology, Immune Dysfunctions, and Therapeutics. Contemporary Diabetes.

Saltoglu, N., Yemisen, M., Ergonul, O., Kadanali, A., Karagoz, G., Batirel, A., Ak, O., Eraksoy, H., Cagatay, A., Vatan, A., Sengoz, G., Pehlivanoglu, F., Aslan, T., Akkoyunlu, Y., Engin, D., Ceran, N., Erturk, B., Mulazimoglu, L., Oncul, O., … Ozyazar, M. (2015). Predictors for limb loss among patient with diabetic foot infections: an observational retrospective multicentric study in Turkey. Clinical Microbiology and Infection, 21(7), 659–664. https://doi.org/https://doi.org/10.1016/j.cmi.2015.03.018

Sánchez Correa, C. A., Briceño Sanín, I., Bautista Valencia, J. J., Niño, M. E., & Robledo Quijano, J. (2025). [Translated article] Reamputation prevalence after minor feet amputations in patients with diabetic foot: A cross sectional study. Revista Española de Cirugía Ortopédica y Traumatología, 69(1), T70–T76. https://doi.org/https://doi.org/10.1016/j.recot.2024.11.012

Santra, S., Rawat, A., Pattarayan, D., & Roy, S. (2020). Chapter 3 - Chronic infection and inflammation: Hallmarks of diabetic foot ulcers (D. Bagchi, A. Das, & S. B. T.-W. H. Roy Tissue Repair, and Regeneration in Diabetes (eds.); pp. 39–47). Academic Press. https://doi.org/https://doi.org/10.1016/B978-0-12-816413-6.00003-4

Snyder, H. (2019). Literature review as a research methodology: An overview and guidelines. Journal of Business Research, 104, 333–339. https://doi.org/https://doi.org/10.1016/j.jbusres.2019.07.039

Toledo, M. C. B., Soares, S., & Costa, A. M. (2025). A relação entre o “pé diabético” e amputações dos membros inferiores: uma revisão sistemática. Revista CPAQV. https://doi.org/10.36692/v17n1-19r

Ugwu, E., Adeleye, O., Gezawa, I., Okpe, I., Enamino, M., & Ezeani, I. (2019). Predictors of lower extremity amputation in patients with diabetic foot ulcer: findings from MEDFUN, a multi-center observational study. Journal of Foot and Ankle Research, 12, 34. https://doi.org/10.1186/s13047-019-0345-y

Wang, D., & Jupiter, D. C. (2025). Associations of Diabetic Foot Infection with Ulcer Prognosis and Amputation Timing in Patients with Type 2 Diabetes Mellitus. Journal of the American Podiatric Medical Association, 115(6). https://doi.org/10.7547/23-230

Wang, X., Yuan, C.-X., Xu, B., & Yu, Z. (2022). Diabetic foot ulcers: Classification, risk factors and management. World Journal of Diabetes, 13(12), 1049–1065. https://doi.org/10.4239/wjd.v13.i12.1049

Wukich, D. K., Johnson, M. J., & Raspovic, K. M. (2022). Limb Salvage in Severe Diabetic Foot Infection. Foot and Ankle Clinics, 27(3), 655–670. https://doi.org/https://doi.org/10.1016/j.fcl.2022.02.004

Xu, S., Herrera, A., Schechter, C., Tabassum, H., Milosavljevic, J., Lopez Fanas, R., Daily, J. P., & Myers, A. K. (2024). The Risk of and Associated Demographic and Laboratory Variables for Amputations for Inpatients with Diabetic Foot Ulcers. Endocrine Practice, 30(8), 758–764. https://doi.org/https://doi.org/10.1016/j.eprac.2024.04.019

Zhang, Y., Cramb, S. M., McPhail, S. M., Pacella, R., van Netten, J. J., Kinnear, E. M., & Lazzarini, P. A. (2025). The incidence of and risk factors for hospitalisations and amputations for people with diabetes-related foot ulcers in Queensland, 2011-19: an observational cohort study. The Medical Journal of Australia, 223(3), 149–158. https://doi.org/10.5694/mja2.52703

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Published

2026-05-29

How to Cite

Anugraini, W., Arofiati, F., & Primanda, Y. (2026). Chronic Infection Contributes to the Risk of Limb Amputation in Patients with Diabetic Ulcers: A Literature Review. Indonesian Journal of Global Health Research, 8(3), 1069–1080. https://doi.org/10.37287/ijghr.v8i3.1421

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