Acquisition Origin Matters: Clinical, Microbiological and Immunological Characteristics and Treatment Effects in Community- vs. Hospital-Acquired Septic Shock

<b>Background</b>: Septic shock is a leading cause of mortality worldwide, with community-acquired (CA) and hospital-acquired (HA) infections representing distinct clinical entities. The differences in clinical characteristics, immune response profiles, and effects of sepsis treatments between CA and HA septic shock have not been fully elucidated. <b>Methods</b>: This retrospective cohort study included 726 adults with septic shock who were admitted to two ICUs at Modena University Hospital between January 2006 and September 2024. Patients were classified as having CA or HA septic shock based on the origin of the infection. Clinical, microbiological, and immunological data, treatments, and outcomes were analysed. Immune cell dynamics were assessed during the first week after the onset of the shock. Multivariable Cox regression models were used to identify predictors and the effects of treatment on ICU mortality. <b>Results</b>: Among 344 patients with CA and 382 with HA septic shock, those with CA had higher severity scores but lower ICU and in-hospital mortality. Patients with HA exhibited a higher prevalence of multidrug-resistant organisms and more comorbidities. Immunologically, CA survivors showed increasing lymphocyte counts over time, whereas HA survivors mainly demonstrated recovery in T helper cells. Therapeutic strategies were similar between groups; however, continuous renal replacement therapy was more frequent in patients with HA. Neither appropriate empiric antibiotics nor steroids or immunoglobulin therapy independently improved mortality in the multivariate analyses. <b>Conclusions</b>: CA and HA septic shock differ significantly in terms of clinical severity, microbiological aetiology, immune recovery patterns, and outcomes. The lack of mortality benefit from standard treatments highlights the need for personalised management strategies that integrate clinical, immunological, and microbiological data to optimise care in septic shock subpopulations.