Hemoperfusion with Seraph-100 in septic patients removes pathogens and improves clinical outcomes

Abstract

Hemoperfusion (HP) represents a treatment option for sepsis. This study evaluated Seraph-100 in septic patients admitted to the intensive care unit (ICU) after cardiac surgery due to infective endocarditis (IE). Thirteen septic patients were enrolled and treated by Seraph-100 hemoperfusion. Fiftenne patients, not treated by HP, represented a control group. Pathogens were assessed before (T0) and after 4 h of HP treatment (T4). The difference between the two- quantification cycle (Cq) values (T0 and T4), namely ∆Cq at the polymerase chain reaction, was a surrogate marker of pathogen removal. The bacterial load decreased after Seraph-100 HP, with a mean ∆Cq values of 4.6 ± 2.4, as corroborated by conventional haemoculture's results. Field Emission Scanning Electron Microscopy analyses confirm the Seraph' adsorptive properties. Procalcitonin, C reactive protein and lactates significantly decreased, with a reduced ICU stay in the Seraph group. After HP, only 15% of patients had AKI requiring renal replacement therapy (RRT), significantly lower than that found in the control group (40%). The Seraph-100 HP induces a decrease of vasopressor doses, a hemodynamic stability and a reduction of AKI and RRT, improving the clinical course, reflected as a reduced ICU stay.

Keywords: AKI; Hemoperfusion; ICU stay; Sepsis; Seraph-100.

Fig. 1

Enrolment plan with inclusion and exclusion criteria. Abbreviations: ICU: intensive care Unit; IE: infective endocarditis; PCR: polymerase chain reaction.

Fig. 2

qPCR test performed in a Seraph-treated septic patient. The bloodstream pathogen load was assessed before (orange curve) and at the end (blu curve) of the hemoperfusion session (4 h). The Cq values, defined as the fractional number of cycles that were needed for the RFU to reach the quantification threshold, were inversely related to the pathogen burden. The difference of the two Cq values, defined as ∆Cq, assessed at the beginning and at the end of the hemoperfusion session, is a surrogate marker of the bloodstream pathogen burden reduction, reflecting the capacity of the adsorber filter to remove the pathogen. Abbreviations: Cq: quantification cycle; LOD: limit of detection; RFU: fluorescence; ∆Cq: differences between the two Cq values revealed before and after the Seraph treatment.

Fig. 3

Representative pictures of a blood sample seeded in TSA culture medium plates before (left) and after (right) Seraph hemoperfusion session in which is well visible the Staphilococcus aureus growth. The reduction of the bacterial load is clearly visible from the reduction of the colony-forming units (CFU).

Fig. 4

Representative FE-SEM pictures, at different magnification (scale bar 2 µm, 1 µm and 0.1 µm for A, B and C respectively), of the Seraph-100 stationary phase at the end of the hemoperfusion session (4 h), in which is evident the presence of a bacterium comparable in shape and size with Staphilococcus aureus identified by MALDI-TOF analysis.

Fig. 5

VIS Score and MAP values in the Seraph and Control groups during the first 72 h of ICU stay. Abbreviations: VIS: vasoactive-inotropic score; MAP: mean arterial pressure;

Fig. 6

Variations of infective and inflammatory biomarker levels pre and post Seraph-100 treatment. Abbreviations: PCT: procalcitonin; CRP: C reactive protein: IL: interleukin; ADM: Mid-regional pro-adrenomedullin.

Fig. 7

Correlations between ∆Cq and infective and inflammatory biomarkers. Abbreviations: PCT: procalcitonin; CRP: C reactive protein: IL: interleukin; ADM: Mid-regional pro-adrenomedullin; ∆Cq: differences between the two Cq values revealed before and after the Seraph-100 treatment.