Browsing publications of the research group Microbial Proteomics (MPRO) by Authors
Clearance of chloroquine and hydroxychloroquine by the Seraph® 100 Microbind® Affinity blood filter - approved for the treatment of COVID-19 patients.Seffer, Malin-Theres; Martens-Lobenhoffer, Jens; Schmidt, Julius J; Eden, Gabriele; Bode-Böger, Stefanie M; Kielstein, Jan T; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Wiley, 2020-06-19)On April 17th 2020 the US Food and Drug Administration granted Coronavirus Disease 2019 (COVID-19) emergency use authorizations for the Seraph® 100 Microbind® Affinity Blood Filter. The medical device is aimed to treat critically ill COVID-19 patients with confirmed or imminent respiratory failure. The aim of this life size in vitro pharmacokinetic study was to investigate the in-vitro adsorption of chloroquine and hydroxychloroquine from human plasma using equipment that is also used at the bedside. After start of the hemoperfusion Pre (Cpre ) Seraph® plasma levels were obtained at 5 (C5 ), 10 (C10 ), 15 (C15 ), 30 (C30 ), 60 (C60 ) and 120 (C120 ) minutes into the procedure. At two timepoints (5 min and 120 min) post (Cpost ) Seraph® plasma levels were determined that were used to calculate the plasma clearance. Both drugs were determined using a validated HPLC method Median [IQR] plasma clearance of the Seraph for chloroquine / hydroxychloroquine was 1.71 [0.51-4.38] ml/min / 1.79 [0.21-3.68] ml/min respectively. The lack of elimination was also confirmed by the fact that plasma levels did not change over the 120 min treatment. As neither chloroquine nor hydroxychloroquine were removed by the treatment with the Seraph dose adjustments in COVID-19 patients undergoing this treatment are not necessary. This article is protected by copyright. All rights reserved.
Elimination of Staphylococcus aureus from the bloodstream using a novel biomimetic sorbent haemoperfusion device.Seffer, Malin-Theres; Eden, Gabriele; Engelmann, Susanne; Kielstein, Jan T (2020-08-24)Removal of bacteria from the blood by means of extracorporeal techniques has been attempted for decades. In late 2019, the European Union licensed the first ever haemoperfusion device for removal of bacteria from the blood. The active ingredient of Seraph 100 Microbind Affinity Blood Filter is ultrahigh molecular weight polyethylene beads with endpoint-attached heparin. Bacteria have been shown to bind to heparin as they would usually do to the heparan sulfate on the cell surface, thereby being removed from the blood stream. We describe the first case of a female chronic haemodialysis patient in which this device was clinically used for a Staphylococcus aureus infection that persisted for 4 days despite antibiotic therapy. After a single treatment, the bacterial load decreased and the blood cultures at the end of a 4 hour haemoperfusion exhibited no bacterial growth.
Heparin 2.0: A New Approach to the Infection Crisis.Seffer, Malin-Theres; Cottam, Daniel; Forni, Lui G; Kielstein, Jan T; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Karger AG, 2020-07-02)In April 2020, the US Food and Drug Administration granted emergency use authorization for certain medical devices to be used in patients with coronavirus disease 2019 (CO-VID-19). This included extracorporeal blood purification devices. This narrative review will give a brief overview regarding some of the extracorporeal devices that could be used to treat COVID-19 patients, including the Seraph® 100 Microbind® Affinity Blood Filter, produced by ExThera Medical (Martinez, CA, USA), first licensed in the European Economic Area in 2019. The Seraph® 100 contains ultrahigh molecular weight polyethylene beads with end point-attached heparin and is approved for the reduction of pathogens from the bloodstream either as a single agent or as an adjunct to conventional anti-infective agents. Bacteria, viruses, fungi, and toxins have been shown to bind to the immobilized heparin in a similar way to the interaction with heparan sulfate on the cell surface. This binding is nonreversible and as such, the pathogens are removed from the bloodstream. In this review, we describe the pathophysiological basis and rationale for using heparin for pathogen removal from the blood as well as exploring the technology behind the adaptation of heparin to deprive it of its systemic anticoagulant activity. In addition, we summarize the in vitro data as well as the available preclinical testing and published clinical reports. Finally, we discuss the enormous potential of this technology in an era of increasing antibiotic resistance and high mortality associated with sepsis and consider the application of this as a possible treatment option for COVID-19.