Bench to Bedside infection CDI is facilitated by alteration of the microbiome following antibiotic administration Antimicrobial therapy directed against the pathogen can treat CDI Unfortunately ID: 938614
Download Pdf The PPT/PDF document "Cell 169 April 20 2017 2017 Elsevier In..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Cell 169, April 20, 2017 © 2017 Elsevier Inc. 375 Bench to Bedside infection (CDI) is facilitated by alteration of the microbiome following antibiotic adminis-tration. Antimicrobial therapy directed against the patho-gen can treat CDI. Unfortunately, ~20% of successfully treated patients will suffer recurrence. Bezlotoxumab, a human monoclonal antibody, binds to toxin B (TcdB), reducing recurrence presumably by limiting epithe-lial damage and facilitating microbiome recovery.Adjuvant therapy to reduce recurrence of CDI in high-risk patients receiving antimicrobial therapy for CDIMOLECULAR TARGETSTcdB, a protein toxin produced by CELLULAR TARGETSNo demonstrated cellular targets; presumably protects host cells from intoxication with TcdBEFFECTS ON TARGETSBezlotoxumab binds to TcdB and inhibits its ability to bind to its cellular surface receptors. Bezlotoxumab is proposed to bind to the N-terminal domain (putative cell-binding region) of TcdB. Antibody-bound TcdB exhibits reduced cell entry and decreased subsequent glycosylation of the Rho family of GTPases, which are the host cell targets of TcdB.Merck Sharp & Dohme Corp. Reducing Recurrence of InfectionMichael G. Dieterle and Vincent B. YoungUniversity of Michigan Medical School, Ann Arbor, MI 48103, USACorrespondence: mdieterl@med.umich.edu; youngvi@med.umich.eduhttp://dx.doi.org/10.1016/j.cell.2017.03.039 TcdBTcdB p itheliu m Predispositionto reinfectionand recurrenceAntimicrobial $4.8 billion$965 million$598 milliontreatment withtreatment withRecurrent casesCost of careCost of care 1935194019701980199019951975198520102015 from stool of healthy infant Kochs postulatesTcdA and TcdBBezlotoxumab approvedfor reducing recurrent CDIreceiving clindamycin (18.3% recurrence)(11.4% recurrence)