Journal of Diagnostics Concepts & Practice >
Current status and challenges in sepsis diagnosis and treatment
Received date: 2025-10-10
Revised date: 2025-11-20
Online published: 2025-12-25
Sepsis leads to approximately 11 million deaths globally each year, and its incidence is still on the rise, particularly in aging societies. Elderly patients, due to multiple underlying diseases and declined immune function, often progress rapidly to sepsis after infection, resulting in poor prognosis. Additionally, immunosuppressed patients, such as those who have undergone organ transplantation or have malignant tumors, exhibit a significantly higher incidence of sepsis compared to the general population. From 2017 to 2019, the annual standardized incidence of sepsis among hospitalized patients in China was (328.25-421.85) per 100 000, with over 57% of cases occurring in individuals aged 65 and above. As a syndrome of organ dysfunction caused by a systemic hyperinflammatory response to infection, sepsis remains a significant disease contributing to high mortality and healthcare burden worldwide. Although diagnostic and therapeutic strategies have been continuously improved with in-depth research on sepsis mechanisms in recent years, clinical practice still faces several core challenges: ① difficulties in early diagnosis due to limitations of current assessment systems and biomarkers; ② increasingly severe antibiotic resistance, which significantly restricts treatment options; and ③ extremely high heterogeneity of the disease, which leads to poor efficacy of standardized treatment schemes and limited adoption of individualized therapy. In recent years, at the diagnostic level, the application of novel biomarkers, molecular diagnostic technologies, and artificial intelligence is driving innovations in early identification and precise subtyping capabilities. At the therapeutic level, the concepts of individualized and precision medicine are increasingly applied, and novel therapeutic strategies such as immunomodulation demonstrate great potential in addressing disease complexity. The key to overcoming the above three core challenges lies in integrating the concept of precision medicine throughout the entire diagnostic and therapeutic process: by leveraging multi-omics data to deepen the understanding of disease heterogeneity, utilizing advanced technologies to achieve accurate diagnosis and subtyping, and developing targeted therapies based on this foundation, ultimately achie-ving the goal of improving patient prognosis.
Key words： Sepsis; Diagnosis; Treatment; Biomarkers; Antibiotic resistance; Precision medicine
HUANG Man , DING Shuo . Current status and challenges in sepsis diagnosis and treatment[J]. Journal of Diagnostics Concepts & Practice, 2025 , 24(06) : 583 -592 . DOI: 10.16150/j.1671-2870.2025.06.003
| [1] | TEGGERT A, DATTA H, ALI Z. Biomarkers for point-of-care diagnosis of sepsis[J]. Micromachines, 2020, 11(3):286. |
| [2] | FAY K, SAPIANO M R P, GOKHALE R, et al. Assessment of health care exposures and outcomes in adult patients with sepsis and septic shock[J]. JAMA Netw Open, 2020, 3(7):e206004. |
| [3] | WENG L, XU Y, YIN P, et al. National incidence and mortality of hospitalized sepsis in China[J]. Crit Care, 2023, 27(1):84. |
| [4] | XU J, GAO Y, HUANG X, et al. S100A9 in sepsis: A biomarker for inflammation and a mediator of organ damage[J]. Biochem Biophys Res Commun, 2025, 752:151484. |
| [5] | AUGUSTIN B, WU D, BLACK L P, et al. Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality[J]. Crit Care, 2024, 28(1):431. |
| [6] | CAO M, WANG G, XIE J. Immune dysregulation in sepsis: Experiences, lessons and perspectives[J]. Cell Death Discov, 2023, 9(1):465. |
| [7] | TAHA S, BINDAYNA K, ALJISHI M, et al. Transcriptomic profiling reveals distinct immune dysregulation in early-stage sepsis patients[J]. Int J Mol Sci, 2025, 26(14):6647. |
| [8] | COLORETTI I, TOSI M, BIAGIONI E, et al. Management of sepsis in the first 24 hours: Bundles of care and individualized approach[J]. Semin Respir Crit Care Med, 2024, 45(4):503-509. |
| [9] | ANTCLIFFE D B, BURRELL A, BOYLE A J, et al. Sepsis subphenotypes, theragnostics and personalized sepsis care[J]. Intensive Care Med, 2025, 51(4):756-768. |
| [10] | SINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA, 2016, 315(8):801-810. |
| [11] | RANZANI O T, SINGER M, SALLUH J I F, et al. Development and validation of the Sequential Organ Failure Assessment (SOFA)-2 score[J]. JAMA, 2025. |
| [12] | VAN OERS J A H, DE JONG E, KEMPERMAN H, et al. Diagnostic accuracy of procalcitonin and C-reactive protein is insufficient to predict proven infection: A retrospective cohort study in critically ill patients fulfilling the sepsis-3 criteria[J]. J Appl Lab Med, 2020, 5(1):62-72. |
| [13] | PRKNO A, WACKER C, BRUNKHORST F M, et al. Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock: A systematic review and meta-analysis[J]. Crit Care, 2013, 17(6):R291. |
| [14] | BOUADMA L, LUYT C E, TUBACH F, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): A multicentre randomised controlled trial[J]. Lancet, 2010, 375(9713):463-474. |
| [15] | SIRIWARDENA A K, JEGATHEESWARAN S, MASON J M. A procalcitonin-based algorithm to guide antibiotic use in patients with acute pancreatitis (PROCAP): A single-centre, patient-blinded, randomised controlled trial[J]. Lancet Gastroenterol Hepatol, 2022, 7(10):913-921. |
| [16] | KIP M M A, VAN OERS J A, SHAJIEI A, et al. Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients: Results from a randomised controlled multicentre trial in the Netherlands[J]. Crit Care, 2018, 22(1):293. |
| [17] | MARIN M J, VAN WIJK X M R, CHAMBLISS A B. Advances in sepsis biomarkers[J]. Adv Clin Chem, 2024, 119:117-166. |
| [18] | RIDKER P M. C-reactive protein: Eighty years from discovery to emergence as a major risk marker for cardiovascular disease[J]. Clin Chem, 2009, 55(2):209-215. |
| [19] | SAXENA J, DAS S, KUMAR A, et al. Biomarkers in sepsis[J]. Clin Chim Acta, 2024, 562:119891. |
| [20] | PFEIFFER D, RO?MANITH E, LANG I, et al. miR-146a, miR-146b, and miR-155 increase expression of IL-6 and IL-8 and support HSP10 in an in vitro sepsis model[J]. PLoS One, 2017, 12(6):e0179850. |
| [21] | BINDAYNA K. microRNA as sepsis biomarkers: A comprehensive review[J]. Int J Mol Sci, 2024, 25(12):6476. |
| [22] | MA Y, LIU Y, HOU H, et al. miR-150 predicts survival in patients with sepsis and inhibits LPS-induced inflammatory factors and apoptosis by targeting NF-κB1 in human umbilical vein endothelial cells[J]. Biochem Biophys Res Commun, 2018, 500(3):828-837. |
| [23] | GALLIERA E, MASSACCESI L, DE VECCHI E, et al. Clinical application of presepsin as diagnostic biomarker of infection: Overview and updates[J]. Clin Chem Lab Med CCLM, 2019, 58(1):11-17. |
| [24] | JIANG J, WANG X, CHENG T, et al. Dynamic monito-ring of sTREM-1 and other biomarkers in acute cholangitis[J]. Mediators Inflamm, 2020, 2020:8203813. |
| [25] | AKINRINMADE O A, CHETTY S, DARAMOLA A K, et al. CD64: An attractive immunotherapeutic target for M1-type macrophage mediated chronic inflammatory diseases[J]. Biomedicines, 2017, 5(3):56. |
| [26] | AL MANSOUR N, AL MAHMEED A, BINDAYNA K. Effect of HMGB1 and HBD-3 levels in the diagnosis of sepsis- A comparative descriptive study[J]. Biochem Biophys Rep, 2023, 35:101511. |
| [27] | HE Y, HU Q, SAN S, et al. CRISPR-based biosensors for human health: A novel strategy to detect emerging infectious diseases[J]. Trends Analyt Chem, 2023,168. |
| [28] | WU M, DU X, GU R, et al. Artificial intelligence for clinical decision support in sepsis[J]. Front Med, 2021, 8:665464. |
| [29] | BARKAS G I, DIMEAS I E, KOTSIOU O S. Bug wars: Artificial intelligence strikes back in sepsis management[J]. Diagnostics, 2025, 15(15):1890. |
| [30] | YANG J, HAO S, HUANG J, et al. The application of artificial intelligence in the management of sepsis[J]. Med Rev, 2023, 3(5):369-380. |
| [31] | EVANS L, RHODES A, ALHAZZANI W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021[J]. Intensive Care Med, 2021, 47(11):1181-1247. |
| [32] | ALI W A, BAZAN N S, ELBERRY A A, et al. A randomi-zed trial to compare procalcitonin and C-reactive protein in assessing severity of sepsis and in guiding antibacterial therapy in Egyptian critically ill patients[J]. Ir J Med Sci, 2021, 190(4):1487-1495. |
| [33] | SHAHN Z, SHAPIRO N I, TYLER P D, et al. Fluid-limiting treatment strategies among sepsis patients in the ICU: A retrospective causal analysis[J]. Crit Care, 2020, 24(1):62. |
| [34] | GHOSH I, SANGHA S S, PANDEY G, et al. Author response: Insights into immunomodulatory therapy for sepsis[J]. Indian J Crit Care Med, 2025, 29(1):91. |
| [35] | LIU Y C, SHOU S T, CHAI Y F. Immune checkpoints in sepsis: New hopes and challenges[J]. Int Rev Immunol, 2022, 41(2):207-216. |
| [36] | NAVEGANTES-LIMA K C, MONTEIRO V V S, DE FRAN?A GASPAR S L, et al. Agaricus brasiliensis mushroom protects against sepsis by alleviating oxidative and inflammatory response[J]. Front Immunol, 2020, 11:1238. |
| [37] | AMLAND R C, HAHN-COVER K E. Republished: Clinical decision support for early recognition of sepsis[J]. Am J Med Qual, 2019, 34(5):494-501. |
| [38] | VAN DER AART T J, VISSER M, VAN LONDEN M, et al. The smell of sepsis: Electronic nose measurements improve early recognition of sepsis in the ED[J]. Am J Emerg Med, 2025, 88:126-133. |
| [39] | KIM M H, CHOI J H. An update on sepsis biomarkers[J]. Infect Chemother, 2020, 52(1):1-18. |
| [40] | LEGESE M H, ASRAT D, SWEDBERG G, et al. Sepsis: Emerging pathogens and antimicrobial resistance in Ethiopian referral hospitals[J]. Antimicrob Resist Infect Control, 2022, 11(1):83. |
| [41] | ANGULO-ZAMUDIO U A, VELAZQUEZ-MEZA M L, MARTINEZ-GARCIA J J, et al. Characteristics of neonates with sepsis associated with antimicrobial resistance and mortality in a tertiary hospital in Mexico: A retrospective observational study[J]. Pathogens, 2025, 14(6):588. |
| [42] | CURREN E J, LUTGRING J D, KABBANI S, et al. Advancing diagnostic stewardship for healthcare-associated infections, antibiotic resistance, and sepsis[J]. Clin Infect Dis, 2022, 74(4):723-728. |
| [43] | VIKTORSSON S A, TURNBULL I R. Sepsis in surgical patients: Personalized medicine in the future treatment of sepsis[J]. Surgery, 2024, 176(2):544-546. |
| [44] | WANG N, HUANG H, TAN Y, et al. Research progress of biomarkers for sepsis and precision medicine[J]. Emerg Med Int, 2025, 2025:4585495. |
| [45] | SEYMOUR C W, KENNEDY J N, WANG S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis[J]. JAMA, 2019, 321(20):2003-2017. |
| [46] | BRUSE N, MOTOS A, VAN AMSTEL R, et al. Clinical phenotyping uncovers heterogeneous associations between corticosteroid treatment and survival in critically ill COVID-19 patients[J]. Intensive Care Med, 2024, 50(11):1884-1896. |
| [47] | BURNHAM K L, DAVENPORT E E, RADHAKRISHNAN J, et al. Shared and distinct aspects of the sepsis transcriptomic response to fecal peritonitis and pneumonia[J]. Am J Respir Crit Care Med, 2017, 196(3):328-339. |
| [48] | SCICLUNA B P, VAN VUGHT L A, ZWINDERMAN A H, et al. Classification of patients with sepsis according to blood genomic endotype: A prospective cohort study[J]. Lancet Respir Med, 2017, 5(10):816-826. |
| [49] | SWEENEY T E, AZAD T D, DONATO M, et al. Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters[J]. Crit Care Med, 2018, 46(6):915-925. |
| [50] | SWEENEY T E, LIESENFELD O, WACKER J, et al. Validation of inflammopathic, adaptive, and coagulopathic sepsis endotypes in coronavirus disease 2019[J]. Crit Care Med, 2021, 49(2):e170-e178. |
| [51] | WONG H R, CVIJANOVICH N, LIN R, et al. Identification of pediatric septic shock subclasses based on genome-wide expression profiling[J]. BMC Med, 2009, 7:34. |
| [52] | LI F, WANG S, GAO Z, et al. Harnessing artificial intelligence in sepsis care: Advances in early detection, persona-lized treatment, and real-time monitoring[J]. Front Med, 2025, 11:1510792. |
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