Introduction Quorum-sensing (QS) molecules produced by Gram-negative bacteria regulate virulence and host–pathogen interactions, but their systemic role in human septic shock remains largely unexplored. We hypothesized that QS molecules are detectable in the circulation of burn patients with septic-shock–associated acute kidney injury (SA-AKI), are associated with disease severity, and are amenable to removal by extracorporeal treatment. Methods In this observational pilot study, plasma concentrations of eight Gram-negative–derived QS molecules were quantified by HPLC-MS/MS in 12 burn patients with refractory septic shock and SA-AKI on continuous kidney replacement therapy (CKRT) and CytoSorb hemoadsorption. Serial blood samples (0, 0.5, 6, 12, and 24 h) were collected during the 24-hour sessions of the 23 studied cartridges. QS molecule removal by the sorbent cartridge and hemofilter was assessed, and associations between baseline QS molecule levels and systemic lactate concentrations were explored. Results Out of 8 QS molecules tested, C6-homoserine lactone, 3-hydroxy-C12-HSL, C7-PQS, HQNO, HHQ, and C9-PQS were detectable in systemic plasma, whereas 3-oxo-acyl-homoserine lactones (3-oxo-C10/3-oxo-C12) were below the limit of quantification. Cytosorb induced a significant early reduction in plasma QS molecule concentrations of C6-HSH, 3-OH-C12-HSL, and C7-PQS, whereas hemofilter clearance of QS molecules was negligible (< 4 ml/min). Adsorption was followed by partial rebound at later time points, consistent with sorbent saturation and desorption after 12 h. Baseline lactate levels showed a significant positive correlation with the relative plasma concentrations of QS molecules 3-OH-C12-HSL (r = 0.76818, p < 0.002) and C7-PQS (r = 0.64961, p < 0.03), an association that remained significantly robust for both QS molecules in selected patients with Pseudomonas aeruginosa bloodstream infection (r = 0.87698, p < 0.02 and r = 0.55547, p < 0.03, respectively). Conclusion Gram-negative QS molecules are detectable in the systemic circulation of burn patients with SA-AKI, are associated with systemic lactate concentrations, and can be removed by hemoadsorption but not by the hemofilter. These findings support a potential pathophysiological role of bacterial communication signals in critical illness, and a potential therapeutic target of hemoadsorption in critical illness.
CytoSorb in burn patients with septic shock and acute kidney injury on continuous kidney replacement therapy efficiently reduces the levels of Gram-negative-derived quorum-sensing molecules associated with lactate increases
Mariano, Filippo
First
;Carpenito, Nicolo';Mella, Alberto;Di Vico, Maria Cristina;Pensa, Anna;Depetris, Nadia;Gambino, Roberto;Biancone, Luigi
2026-01-01
Abstract
Introduction Quorum-sensing (QS) molecules produced by Gram-negative bacteria regulate virulence and host–pathogen interactions, but their systemic role in human septic shock remains largely unexplored. We hypothesized that QS molecules are detectable in the circulation of burn patients with septic-shock–associated acute kidney injury (SA-AKI), are associated with disease severity, and are amenable to removal by extracorporeal treatment. Methods In this observational pilot study, plasma concentrations of eight Gram-negative–derived QS molecules were quantified by HPLC-MS/MS in 12 burn patients with refractory septic shock and SA-AKI on continuous kidney replacement therapy (CKRT) and CytoSorb hemoadsorption. Serial blood samples (0, 0.5, 6, 12, and 24 h) were collected during the 24-hour sessions of the 23 studied cartridges. QS molecule removal by the sorbent cartridge and hemofilter was assessed, and associations between baseline QS molecule levels and systemic lactate concentrations were explored. Results Out of 8 QS molecules tested, C6-homoserine lactone, 3-hydroxy-C12-HSL, C7-PQS, HQNO, HHQ, and C9-PQS were detectable in systemic plasma, whereas 3-oxo-acyl-homoserine lactones (3-oxo-C10/3-oxo-C12) were below the limit of quantification. Cytosorb induced a significant early reduction in plasma QS molecule concentrations of C6-HSH, 3-OH-C12-HSL, and C7-PQS, whereas hemofilter clearance of QS molecules was negligible (< 4 ml/min). Adsorption was followed by partial rebound at later time points, consistent with sorbent saturation and desorption after 12 h. Baseline lactate levels showed a significant positive correlation with the relative plasma concentrations of QS molecules 3-OH-C12-HSL (r = 0.76818, p < 0.002) and C7-PQS (r = 0.64961, p < 0.03), an association that remained significantly robust for both QS molecules in selected patients with Pseudomonas aeruginosa bloodstream infection (r = 0.87698, p < 0.02 and r = 0.55547, p < 0.03, respectively). Conclusion Gram-negative QS molecules are detectable in the systemic circulation of burn patients with SA-AKI, are associated with systemic lactate concentrations, and can be removed by hemoadsorption but not by the hemofilter. These findings support a potential pathophysiological role of bacterial communication signals in critical illness, and a potential therapeutic target of hemoadsorption in critical illness.| File | Dimensione | Formato | |
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