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Bloodstream Infections

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  • Authors: Raquel M. Martinez1, Donna M. Wolk2
  • Editors: Randall T. Hayden3, Donna M. Wolk4, Karen C. Carroll5, Yi-Wei Tang6
    Affiliations: 1: Department of Laboratory Medicine, Geisinger Health System, Danville, PA 17822; 2: Department of Laboratory Medicine, Geisinger Health System, Danville, PA 17822; 3: St. Jude Children’s Research Hospital, Memphis, TN; 4: Geisinger Clinic, Danville, PA; 5: Johns Hopkins University Hospital, Baltimore, MD; 6: Memorial Sloan-Kettering Institute, New York, NY
  • Source: microbiolspec August 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.DMIH2-0031-2016
  • Received 05 May 2016 Accepted 23 May 2016 Published 12 August 2016
  • Donna M. Wolk, [email protected]
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  • Abstract:

    Bacteremia and sepsis are conditions associated with high mortality and are of great impact to health care operations. Among the top causes of mortality in the United States, these conditions cause over 600 fatalities each day. Empiric, broad-spectrum treatment is a common but often a costly approach that may fail to effectively target the correct microbe, may inadvertently harm patients via antimicrobial toxicity or downstream antimicrobial resistance. To meet the diagnostic challenges of bacteremia and sepsis, laboratories must understand the complexity of diagnosing and treating septic patients, in order to focus on creating algorithms that can help direct a more targeted approach to antimicrobial therapy and synergize with existing clinical practices defined in new Surviving Sepsis Guidelines. Significant advances have been made in improving blood culture media; as yet no molecular or antigen-based method has proven superior for the detection of bacteremia in terms of limit of detection. Several methods for rapid molecular identification of pathogens from blood cultures bottles are available and many more are on the diagnostic horizon. Ultimately, early intervention by molecular detection of bacteria and fungi directly from whole blood could provide the most patient benefit and contribute to tailored antibiotic coverage of the patient early on in the course of the disease. Although blood cultures remain as the best means of diagnosing bacteremia and candidemia, complementary testing with antigen tests, microbiologic investigations from other body sites, and histopathology can often aid in the diagnosis of disseminated disease, and application of emerging nucleic acid test methods and other new technology may greatly impact our ability to bacteremic and septic patients, particularly those who are immunocompromised.

  • Citation: Martinez R, Wolk D. 2016. Bloodstream Infections. Microbiol Spectrum 4(4):DMIH2-0031-2016. doi:10.1128/microbiolspec.DMIH2-0031-2016.


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Bacteremia and sepsis are conditions associated with high mortality and are of great impact to health care operations. Among the top causes of mortality in the United States, these conditions cause over 600 fatalities each day. Empiric, broad-spectrum treatment is a common but often a costly approach that may fail to effectively target the correct microbe, may inadvertently harm patients via antimicrobial toxicity or downstream antimicrobial resistance. To meet the diagnostic challenges of bacteremia and sepsis, laboratories must understand the complexity of diagnosing and treating septic patients, in order to focus on creating algorithms that can help direct a more targeted approach to antimicrobial therapy and synergize with existing clinical practices defined in new Surviving Sepsis Guidelines. Significant advances have been made in improving blood culture media; as yet no molecular or antigen-based method has proven superior for the detection of bacteremia in terms of limit of detection. Several methods for rapid molecular identification of pathogens from blood cultures bottles are available and many more are on the diagnostic horizon. Ultimately, early intervention by molecular detection of bacteria and fungi directly from whole blood could provide the most patient benefit and contribute to tailored antibiotic coverage of the patient early on in the course of the disease. Although blood cultures remain as the best means of diagnosing bacteremia and candidemia, complementary testing with antigen tests, microbiologic investigations from other body sites, and histopathology can often aid in the diagnosis of disseminated disease, and application of emerging nucleic acid test methods and other new technology may greatly impact our ability to bacteremic and septic patients, particularly those who are immunocompromised.

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The host response in severe sepsis. The host response to sepsis is characterized by both proinflammatory responses (top of panel, in red) and anti-inflammatory immunosuppressive responses (bottom of panel, in blue). The direction, extent, and duration of these reactions are determined by both host factors (e.g., genetic characteristics, age, coexisting illnesses, and medications) and pathogen factors (e.g., microbial load and virulence). Inflammatory responses are initiated by interaction between pathogen-associated molecular patterns expressed by pathogens and pattern-recognition receptors expressed by host cells at the cell surface (toll-like receptors [TLRs] and C-type lectin receptors [CLRs]), in the endosome (TLRs) or in the cytoplasm (retinoic acid inducible gene 1-like receptors [RLRs] and nucleotide-binding oligomerization domain-like receptors [NLRs]). The consequence of exaggerated inflammation is collateral tissue damage and necrotic cell death, which results in the release of damage-associated molecular patterns, so-called danger molecules that perpetuate inflammation at least in part by acting on the same pattern-recognition receptors that are triggered by pathogens. Reprinted from reference ( 3 ), with permission.

Source: microbiolspec August 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.DMIH2-0031-2016
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Organ failure in severe sepsis and dysfunction of the vascular endothelium and mitochondria. Sepsis is associated with microvascular thrombosis caused by concurrent activation of coagulation (mediated by tissue factor) and impairment of anticoagulant mechanisms as a consequence of reduced activity of endogenous anticoagulant pathways (mediated by activated protein C, antithrombin, and tissue factor pathway inhibitor), plus impaired fibrinolysis owing to enhanced release of plasminogen activator inhibitor type 1 (PAI-1). The capacity to generate activated protein C is impaired at least in part by reduced expression of two endothelial receptors: thrombomodulin (TM) and the endothelial protein C receptor. Thrombus formation is further facilitated by neutrophil extracellular traps (NETs) released from dying neutrophils. Thrombus formation results in tissue hypoperfusion, which is aggravated by vasodilatation, hypotension, and reduced red-cell deformability. Tissue oxygenation is further impaired by the loss of barrier function of the endothelium owing to a loss of function of vascular endothelial (VE) cadherin, alterations in endothelial cell-to-cell tight junctions, high levels of angiopoietin 2, and a disturbed balance between sphingosine-1 phosphate receptor 1 (S1P1) and S1P3 within the vascular wall, which is at least in part due to preferential induction of S1P3 through protease-activated receptor 1 (PAR1) as a result of a reduced ratio of activated protein C to thrombin. Oxygen use is impaired at the subcellular level because of damage to mitochondria from oxidative stress. Reprinted from reference ( 3 ), with permission.

Source: microbiolspec August 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.DMIH2-0031-2016
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Algorithms for diagnosis, prognostication, and prediction of response to therapy. FA = fluorescent antibody stain; AFB = acid-fast bacilli; mAFB = modified AFB; SSTI = skin and soft tissue infection; LDT = Laboratory developed test.

Source: microbiolspec August 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.DMIH2-0031-2016
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Summary of interesting reviews and publications related to viral and miscellaneous pathogen bloodstream infections

Source: microbiolspec August 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.DMIH2-0031-2016
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Predisposing factors that contribute to immunosuppression

Source: microbiolspec August 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.DMIH2-0031-2016

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