Empiric Antimicrobial Therapy in Severe Sepsis and Septic Shock: Optimizing Pathogen Clearance

Abstract

Mortality and morbidity in severe sepsis and septic shock remain high despite significant advances in critical care. Efforts to improve outcome in septic conditions have focused on targeted, quantitative resuscitation strategies utilizing intravenous fluids, vasopressors, inotropes, and blood transfusions to correct disease-associated circulatory dysfunction driven by immune-mediated systemic inflammation. This review explores an alternate paradigm of septic shock in which microbial burden is identified as the key driver of mortality and progression to irreversible shock. We propose that clinical outcomes in severe sepsis and septic shock hinge upon the optimized selection, dosing, and delivery of highly potent antimicrobial therapy.

Sepsis and Other Infectious Disease Emergencies in the Elderly

“…38 While several paradigms have been proposed to explain the role of infection in triggering and sustaining the immunologic cascade leading to cellular injury, irreversible organ damage, and death in severe sepsis and septic shock, appropriate antimicrobial therapy is critical to rapidly reducing pathogen load and improving mortality. 39,40 Empiric antimicrobial therapy is considered appropriate if it has in vitro activity against a causative pathogen before it has been identified in the laboratory workup ( e.g. , microbiologic culture, rapid molecular diagnostics).…”

“…39 Initial antimicrobial therapy should start at the maximum recommended dose while taking into account baseline renal or hepatic insufficiency that may predispose an elder to drug toxicity. Age-related changes in body composition, total body water, and serum albumin all impact drug concentrations.…”

Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases?

“…Importantly, excessive inflammation reactions can also induce acute oxidative stress [2]. Together, both cytokine storm and oxidative stress promote each other and induce MODS, result in high mortality rate [15].…”

“…Oxidative stress and systemic inflammatory response syndrome have been confirmed to play critical roles in tissue and organ damages after polymicrobial sepsis injury, acute peritonitis injury, and peritonitis, which can develop into lethal sepsis with inappropriate treatment [13,14]. In spite of some available antibiotic therapies for the some stages of sepsis, Multiple Organ Dysfunction Syndrome (MODS) induced by sepsis is still the leading cause of death in the Intensive Care Unit (ICU) [15,16]. Recent studies reveal potential protective effects of hydrogen against sepsis and acute peritonitis by decreasing proinflammatory responses, oxidative stress, and apoptosis, which indicate hydrogen medicine as a new no-toxic therapy for bacterial infections [13,14].…”

New developments in proprotein convertase subtilisin–kexin 9's biology and clinical implications

“…Severe sepsis, where sepsis is accompanied by dysfunction of at least one organ, affects 0.3-1% of individuals/year in the USA with mortality rates of 30% [54]. It has been suggested that improving microbial clearance, and thus reducing the spread of infection, minimizes the severity of sepsis [55]. Promising therapies have been developed on this basis, including hemoperfusion filters that specifically bind lipopolysaccharide (LPS) in the blood to remove it from circulation [56].…”