Cilengitide- A novel therapy in sepsis to prevent antimicrobial resistance
Journal Title: International Journal of Research in Pharmacology & Pharmacotherapeutics (IJRPP) - Year 2019, Vol 8, Issue 3
Abstract
Sepsis is a fast progressing disease, triggered by the host response to infection. If untreated, sepsis can rapidly evolve to multi-organ dysfunction and septic shock. Despite numerous advances in palliative intensive care and antibiotic treatment, sepsis remains a major cause of morbidity and mortality. The vascular endothelium is a major target of sepsis-induced events. Upon entry to the bloodstream, bacteria attach to the endothelium within 15s. Attachment triggers dysregulated signals that result in endothelial cell (EC) death and loss of barrier integrity, which give rise to increased capillary permeability clinically associated with hypotension, subcutaneous and body-cavity edema and impaired tissue oxygenation. Early and adequate antimicrobial therapy is the cornerstone of the therapy in sepsis. Broad empirical antimicrobial therapy should be administered as soon as possible after at least two sets of blood cultures have been obtained. This has lead to high load of antimicrobial use and in turn resulted to an emergent problem that is antimicrobial resistance. Cilengitide, the most advanced integrin inhibitor in clinical development, is a cyclized pentapeptide peptidomimetic designed to compete for the arginine–glycine–aspartic acid (RGD) peptide sequence that regulates integrin-ligand binding. Specifically, cilengitide selectively and potently blocks the ligation of the αvβ3 and αvβ5 integrins to provisional matrix proteins such as vitronectin, fibronectin, fibrinogen, von Willebrand factor. Cilengitide is capable of competitively antagonizing bacterial binding to ECs and as a result removes the signal that perpetuates vascular EC involvement in sepsis and thus presents as a potential as new complementary strategy for the treatment of established sepsis and as prophylaxis in high risk patients. This indeed can result in lowering of the antimicrobials used and will reduce resistance.
Authors and Affiliations
Juzer Sabuwala
Keywords
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