Abstract
Sepsis management demands early diagnosis and timely treatment that includes source control, antimicrobial therapy, and resuscitation. Currently employed diagnostic tools are ill-equipped to rapidly diagnose sepsis and isolate the offending pathogen, which limits the ability to offer targeted and lowest-toxicity treatment. Cutting edge diagnostics and therapeutics in development may improve time to diagnosis and address two broad management principles: (1) source control by removing the molecular infectious stimulus of sepsis, and (2) attenuation of the pathological immune response allowing the body to heal. This review addresses novel diagnostics and therapeutics and their role in the management of sepsis.
Highlights
Sepsis begins with the activation of an innate immune response mediated by the detection of damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs) by pattern-recognition receptors (PRRs) on host cells
Pathogen-associated molecular patterns (PAMPs) are unique motifs found on microbes that are recognized by PRRs, and allow the innate immune system to distinguish self from non-self, while Damage-associated molecular patterns (DAMPs) are a sign that there is damage to the host
Soluble triggering receptors expressed on myeloid cells are mainly distributed on the surface of polymorphonuclear cells and mature monocytes and are upregulated by bacterial lipopolysaccharides (LPS)
Summary
Sepsis is a clinical syndrome resulting from a dysregulated inflammatory response to infection. Delayed identification and incorrect treatment lead to worse outcomes, increased costs, and higher mortality [2]. Managing sepsis in the contemporary era revolves around early diagnosis, administration of antimicrobials, hemodynamic support with fluids and vasopressors, and source control via procedural drainage and removal of the inciting pathogen. While these interventions have led to a decrease in hospital mortality, significant shortcomings in early recognition and treatment of the underlying cause of sepsis remain: the biomolecular triggering and subsequent inciting of an uncontrolled inflammatory response [4]. Overreliance on culture data delays identification of an infectious etiology and increases the possibility of inappropriate antimicrobial selection.
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