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

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.

Staphylococcus aureus binding to Seraph® 100 Microbind® Affinity Filter: Effects of surface protein expression and treatment duration

“…In the first in-patient applications, patients with persistent blood stream infections were treated with the Seraph 1 100 Microbind 1 Affinity Blood Filters for four hours at a blood flow rate of 225 to 300 ml/min, which is significantly higher than in the present study. A reduction in bacterial counts was observed, but this varied widely between patients and did not reach statistical significance [49,50]. There are many reasons for the high variability between patients and the resulting differences in treatment outcomes.…”

“…As S. aureus Newman is unable to form a robust biofilm [48], it is not possible to conclude from this study whether S. aureus biofilm formation has a significant effect on S. aureus reduction by Seraph. However, it is not expected that the S. aureus cells bound to the heparin-coated beads will be able to form a massive biofilm during a treatment period of four hours, as has been used in previous clinical situations with Seraph [49,50]. If longer treatment times are planned, biofilm formation by the bacteria bound on the beads should be excluded.…”

Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment

“…There has been a case report of the effective removal of S. aureus from the blood of an infected haemodialysis patient by the use of an extracorporeal blood filter incorporating heparin immobilised onto polyethylene beads, followed more recently by a small trial [ 64 , 65 ]. The effective use of heparin as a direct competitor with HS in anti-bacterial therapy requires delivery of heparin in high concentration to the location of the infection, and in this case extracorporeal circulation delivered the infection to the therapy.…”

“…There are also ways of using heparin without allowing it to enter the circulation. One of these is the technique described above for extracorporeal removal of pathogens from the blood [ 65 ], in which the therapeutic heparin is immobilised on a column; another is the use of nebulised heparin to allow direct access to the lung epithelium and associated pathogens without entering the bloodstream [ 14 ].…”

Hämoperfusion und Plasmapherese auf der Intensivstation

“…Die dort behandelten 15 Hämodialysepatient:innen mit Blutstrominfektionen vertrugen die Therapie gut. Der primäre Endpunkt – die Sicherheit – erbrachte keine negativen Signale [ 14 ]. In Bezug auf die Effektivität, den sekundären Endpunkt der Studie, konnte die TTP („time to positivity“) der Blutkultur durch die Therapie um mehr als 22 min erhöht werden, was einer Senkung der Bakterienzahl entspricht.…”