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An alternate pathophysiologic paradigm of sepsis and septic shock: Implications for optimizing antimicrobial therapy

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a...

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Autor principal: Kumar, Anand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916387/
https://www.ncbi.nlm.nih.gov/pubmed/24184742
http://dx.doi.org/10.4161/viru.26913
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author Kumar, Anand
author_facet Kumar, Anand
author_sort Kumar, Anand
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description The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role.
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spelling pubmed-39163872014-03-06 An alternate pathophysiologic paradigm of sepsis and septic shock: Implications for optimizing antimicrobial therapy Kumar, Anand Virulence Review The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. Landes Bioscience 2014-01-01 2013-11-01 /pmc/articles/PMC3916387/ /pubmed/24184742 http://dx.doi.org/10.4161/viru.26913 Text en Copyright © 2014 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Review
Kumar, Anand
An alternate pathophysiologic paradigm of sepsis and septic shock: Implications for optimizing antimicrobial therapy
title An alternate pathophysiologic paradigm of sepsis and septic shock: Implications for optimizing antimicrobial therapy
title_full An alternate pathophysiologic paradigm of sepsis and septic shock: Implications for optimizing antimicrobial therapy
title_fullStr An alternate pathophysiologic paradigm of sepsis and septic shock: Implications for optimizing antimicrobial therapy
title_full_unstemmed An alternate pathophysiologic paradigm of sepsis and septic shock: Implications for optimizing antimicrobial therapy
title_short An alternate pathophysiologic paradigm of sepsis and septic shock: Implications for optimizing antimicrobial therapy
title_sort alternate pathophysiologic paradigm of sepsis and septic shock: implications for optimizing antimicrobial therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916387/
https://www.ncbi.nlm.nih.gov/pubmed/24184742
http://dx.doi.org/10.4161/viru.26913
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