Preliminary results of a multicenter study on the use of pathogenetic therapy in patients with severe community-acquired pneumonia depending on the sepsis phenotype

Increasing the effectiveness of intensive sepsis therapy is possible only if a personalized approach is provided with the identification of phenotypes.

The aim of the study was to evaluate the outcomes of blood purification (BP) methods and corticosteroids in the treatment of patients with severe community-acquired pneumonia (SCAP) depending on the phenotypes of sepsis.

Materials and methods: The study included 1,164 intensive care patients with SCAP in 5 multidisciplinary hospitals. The phenotype was determined using a sepsis phenotype calculator developed using the Seymour method (2019).

Results: there were a total of 814 (69.9%) patients with viral and 350 (30.1%) patients with bacterial SCAP, of which 702 (60%) were elderly and senile. In patients with viral SCAP, the α-phenotype dominated (38.5%), while the prevalence of δ was 28.4%, β -20% and γ-13.1%, respectively, p<0.001. Corticosteroids therapy in patients with α-, γ and -phenotypes of viral SCAP showed a decrease in hospital mortality, compared with patients who did not receive corticosteroids (p_a=0.014, p_γ=0.001, p_δ<0.001). An analysis of the use of BP methods in patients with viral SCAP did not reveal significant differences in outcomes. In patients with bacterial SCAP, the δ-phenotype prevailed with a frequency of 53.7%, while α 18%, β-17.7%, γ-10.6%, respectively, p<0.001. In patients with bacterial SCAP with these phenotypes, the frequency of corticosteroids use did not differ (p=0.095). Outcome analysis showed that in patients with the δ-phenotype, corticosteroids therapy was associated with unfavorable outcomes in 82.2% of cases (p< 0.001), while the use of BP techniques in 62.5% of cases with a favorable outcome of the disease (p=0.036). Early start of BP methods in the prospective recruitment group in 44 (91.7%) patients with bacterial SCAP δ-phenotype provided a favorable outcome in 63.6% of cases.

Conclusion: Identification of sepsis phenotypes in elderly and senile patients with severe community-acquired pneumonia allows for optimization of pathogenetic therapy (blood purification and corticosteroids) and improvement of disease outcomes.

1. Salluh J.I.F., Póvoa P., Beane A., Kalil A., Sendagire C., Sweeney D.A., et al. Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines // Intensive Care Med. – 2024 – Vol. 50, №4. – P. 526-538. DOI: 10.1007/s00134-024-07381-z.

2. Gu X., Yang P., Yu L., Yuan J., Zhang Y., Yuan Z et al. Glucocorticoids can reduce mortality in patients with severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials // Eur J Med Res. – 2025. – Vol. 30, №1. P. 215. DOI: 10.1186/s40001-025-02487-6.

3. Torres A., Chalmers J.D., Dela Cruz C.S., Dominedò C., Kollef M., Martin-Loeches I., et al. Challenges in severe community-acquired pneumonia: a point-of-view review. // Intensive Care Med. – 2019. – Vol. 45, №2. – P. 159-171. DOI: 10.1007/s00134-019-05519-y.

4. Kovzel V.A., Davydova L.A., Lapina T.A., Semushkina A.A., Gutnikov A.I. Genetic, Metabolic, and Proteomic Polymorphisms and Clinical Phenotypes of Sepsis // General Reanimatology. – 2024. – Vol. 20, №6, P. 36-53. DOI: 10.15360/1813-9779-2024-6-2470.

5. Seymour C.W., Kennedy J.N., Wang S., Chang C.H., Elliott C.F., Xu Z., et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis //jAMA. – 2019. – Vol. 321. – P. 2003–2017. DOI: 10.1001/jama.2019.5791.

6. Karakike E., Metallidis S., Poulakou G., Kosmidou M., Gatselis N.K., Petrakis V. et al. Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19 // Crit Care Explor. – 2024. – Vol. 6, №9. – P. e1153. DOI: 10.1097/CCE.0000000000001153.

7. Bruse N., Kooistra E.J., Jansen A., van Amstel R.B.E., de Keizer N.F., Kennedy J.N., et al. Clinical sepsis phenotypes in critically ill COVID-19 patients // Crit Care. – 2022. – Vol. 26, №1. – P. 244. DOI: 10.1186/s13054-022-04118-6.

8. Ruslyakova I.A., Shamsutdinova E.Z., Gaikovaya L.B. Relationship Between Sepsis Phenotypes and Treatment Characteristics of Patients with Viral and Bacterial Pneumonia // General Reanimatology. – 2024. – Vol. 20, №2. – P. 29-39. DOI: 10.15360/1813-9779-2024-2-29-40.

9. Sakharov V.I., Mironov P.I., Ruslyakova I.A., Rudnov V.A. Problems of assessing the severity of the state of elderly patients with community-acquired pneumonia caused by Klebsiella pneumoniae // Messenger of ANESTHESIOLOGY AND RESUSCITATION. – 2020. – Vol. 17, №6, P. 45-53. (In Russ.) DOI: 10.21292/2078-5658-2020-17-6-45-53.

10. Cheema H.A., Musheer A., Ejaz A., Paracha A.A., Shahid A., Rehman M.E.U., et al. Efficacy and safety of corticosteroids for the treatment of community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials //j Crit Care. – 2024. – Vol. 80. – P. 154507. DOI: 10.1016/j.jcrc.2023.154507.

11. Terrington I., Cox O., Copley P., Eastwood B., Webb E., McKenzie C. et al. The role of corticosteroids in the management of non-COVID-19 severe community-acquired pneumonia in the intensive care unit: A narrative review //j Intensive Care Soc. – 2025. – P. 17511437251374816. DOI: 10.1177/17511437251374816.

12. Chen Y, Kuang H, Zhu Y, Luo X. The effect and safety of corticosteroid treatment for severe community-acquired pneumonia: a meta-analysis of randomized controlled trials //front Med (Lausanne). – 2024. – Vol. 11. – P. 1457469. DOI: 10.3389/fmed.2024.1457469.

13. Smit J.M., Van Der Zee P.A., Stoof S.C.M., Van Genderen M.E., Snijders D., Boersma W.G., et al. Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials // Lancet Respir Med. – 2025. – Vol. 13, №3. – P. 221-233. DOI: 10.1016/S2213-2600(24)00405-3.

14. Ronco Claudio, Kellum John A. Which Patient Phenotype Is the Ideal Candidate for Hemoadsorption in Acute and Chronic Kidney Disease? // Integrative Medicine in Nephrology and Andrology. – 2024. – Vol. 11, №1. – P. e00001. DOI: 10.1097/IMNA-D-24-00001

15. Kellum J.A., Ronco C. The role of endotoxin in septic shock // Crit Care. – 2023. – Vol. 27, №1. – P. 400. DOI: 10.1186/s13054-023-04690-5.