Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study

Gabriele Eden, Julius J Schmidt, Stefan Büttner, Philipp Kümpers, Carsten Hafer, Alexandros Rovas, Benjamin Florian Koch, Bernhard M W Schmidt, Jan T Kielstein, Gabriele Eden, Julius J Schmidt, Stefan Büttner, Philipp Kümpers, Carsten Hafer, Alexandros Rovas, Benjamin Florian Koch, Bernhard M W Schmidt, Jan T Kielstein

Abstract

Background: Bacterial burden as well as duration of bacteremia influence the outcome of patients with bloodstream infections. Promptly decreasing bacterial load in the blood by using extracorporeal devices in addition to anti-infective therapy has recently been explored. Preclinical studies with the Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100), which consists of heparin that is covalently bound to polymer beads, have demonstrated an effective binding of bacteria and viruses. Pathogens adhere to the heparin coated polymer beads in the adsorber as they would normally do to heparan sulfate on cell surfaces. Using this biomimetic principle, the Seraph® 100 could help to decrease bacterial burden in vivo.

Methods: This first in human, prospective, multicenter, non-randomized interventional study included patients with blood culture positive bloodstream infection and the need for kidney replacement therapy as an adjunctive treatment for bloodstream infections. We performed a single four-hour hemoperfusion treatment with the Seraph® 100 in conjunction with a dialysis procedure. Post procedure follow up was 14 days.

Results: Fifteen hemodialysis patients (3F/12 M, age 74.0 [68.0-78.5] years, dialysis vintage 28.0 [11.0-45.0] months) were enrolled. Seraph® 100 treatment started 66.4 [45.7-80.6] hours after the initial positive blood culture was drawn. During the treatment with the Seraph® 100 with a median blood flow of 285 [225-300] ml/min no device or treatment related adverse events were reported. Blood pressure and heart rate remained stable while peripheral oxygen saturation improved during the treatment from 98.0 [92.5-98.0] to 99.0 [98.0-99.5] %; p = 0.0184. Four patients still had positive blood culture at the start of Seraph® 100 treatment. In one patient blood cultures turned negative during treatment. The time to positivity (TTP) was increased between inflow and outflow blood cultures by 36 [- 7.2 to 96.3] minutes. However, overall TTP increase was not statistical significant.

Conclusions: Seraph® 100 treatment was well tolerated. Adding Seraph® 100 to antibiotics early in the course of bacteremia might result in a faster resolution of bloodstream infections, which has to be evaluated in further studies.

Trail registration: ClinicalTrials.gov Identifier: NCT02914132 , first posted September 26, 2016.

Keywords: Bacteraemia; Bloodstream infections; Extracorporeal devices; Haemodialysis.

Conflict of interest statement

JJS, SB and JTK received research support from ExThera Medical.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Vital signs including heart rate (A), systolic blood pressure (B), diastolic blood pressure (C) and oxygen saturation (D) before and after treatment with the Seraph® 100
Fig. 2
Fig. 2
Routine blood tests of white blood cell count (A), hemoglobin (B), hematocrit (C), platelets (D), antithrombin activity (E), fibrinogen (F), D-dimers (G), albumin (H), total protein (I), immunoglobulins (J), aspartate transaminase (K), alanine transaminase (L), total bilirubin (M), direct bilirubin (N), indirect bilirubin (O), alkaline phosphatase (P), creatinine (Q) and urea (R) before and after Seraph® 100 therapy
Fig. 2
Fig. 2
Routine blood tests of white blood cell count (A), hemoglobin (B), hematocrit (C), platelets (D), antithrombin activity (E), fibrinogen (F), D-dimers (G), albumin (H), total protein (I), immunoglobulins (J), aspartate transaminase (K), alanine transaminase (L), total bilirubin (M), direct bilirubin (N), indirect bilirubin (O), alkaline phosphatase (P), creatinine (Q) and urea (R) before and after Seraph® 100 therapy
Fig. 3
Fig. 3
Overview of the change in time to positivity (TTP) during the treatment. A shows inflow and outflow TTP values of the Seraph® 100 at every time point when positive blood cultures at inflow and outflow were measured. B shows all positive inflow and outflow blood cultures with their respected TTP. C shows a heat map of the course of the TTP in the inflow (in) and outflow (out) blood cultures at every time point. Red represents a high TTP, white are negative blood cultures

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Source: PubMed

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