In-vitro-Effektivität der Imprägnierung von Gefäßprothesen mit keimspezifischen Bakteriophagen für die Prävention von Protheseninfektionen

Bisdas, Theodosios; Bagaev, Eric; Burgwitz, Karin; Marsch, Georg; Wilhelmi, Mathias; Haverich, Axel; Teebken, Omke E.

doi:10.1007/s00772-011-0950-y

Cited by 1 publication

(2 citation statements)

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“…Considering also the limitation of antibiotic resistance, bacteriophage-based enzymes, so called endolysins, have been also suggested as potential non-antibiotic impregnation agents [16]. Endolysins are phage-encoded peptidoglycan hydrolases employed by the majority of bacteriophages to enzymatically degrade the peptidoglycan layer of the host bacterium [17].…”

Section: Introductionmentioning

confidence: 99%

“…Numerous antibiotic agents (e.g., rifampin, daptomycin, and vancomycin) have been tested in vitro and in preclinical studies as potential candidates, with conflicting results [ 13 – 15 ]. Considering also the limitation of antibiotic resistance, bacteriophage-based enzymes, so called endolysins, have been also suggested as potential non-antibiotic impregnation agents [ 16 ]. Endolysins are phage-encoded peptidoglycan hydrolases employed by the majority of bacteriophages to enzymatically degrade the peptidoglycan layer of the host bacterium [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Vascular Graft Impregnation with Antibiotics: The Influence of High Concentrations of Rifampin, Vancomycin, Daptomycin, and Bacteriophage Endolysin HY-133 on Viability of Vascular Cells

Herten

Idelevich²,

Sielker

et al. 2017

Med Sci Monit Basic Res

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BackgroundRifampin-soaked synthetic prosthetic grafts have been widely used for prevention or treatment of vascular graft infections (VGIs).This in vitro study investigated the effect of the antibiotics daptomycin and vancomycin and the new recombinant bacteriophage endolysin HY-133 on vascular cells, as potential alternatives compared to rifampin.Material/MethodsPrimary human ECs, vascular smooth muscle cells (vSMC), and fibroblasts were cultivated in 96-well plates and incubated with rifampin, daptomycin, vancomycin, and endolysin HY-133 for 24 h. Subsequently, after washing, cell viability was determined by measuring mitochondrial ATP concentration. Antibiotics were used in their corresponding minimum and maximum serum concentrations, in decimal multiples and in maximum soaking concentration. The experiments were performed in triplicate.ResultsThe 10-fold max serum concentrations of rifampin, daptomycin, and vancomycin did not influence viability of EC and vSMC (100 μg/ml, p>0.170). Higher concentrations of rifampin (>1 mg/ml) significantly (p<0.001) reduced cell viability of all cell types. For the other antibiotics, high concentrations (close to maximum soaking concentration) were most cytotoxic for EC and vSMC and fibroblasts (p<0.001). Endolysin did not display any cytotoxicity towards vascular cells.ConclusionsResults of this in vitro study show the high cytotoxicity of rifampin against vascular cells, and may re-initiate the discussion about the benefit of prophylactic pre-soaking in high concentrations of rifampin. Further studies are necessary to determine the influence of rifampin on the restoration of vessel functionality versus its prophylactic effect against VGIs. Future use of recombinant phage endolysins for alternative prophylactic strategies needs further investigations.

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Section: Introductionmentioning

confidence: 99%