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Sepsis

Understanding sepsis and the challenges in diagnosis and delivering care

Sepsis is a condition that can be caused by bacteria, fungi or viruses in the blood and is the result of the body’s response to infection. Approximately 22.5% of cases of severe sepsis are fatal.1 The mortality rate is even higher for fungal infections.2 Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.3 20% of deaths worldwide are sepsis-related1 and patient survival decreases by ~8% with each hour of delay before effective treatment.4


With 49 million cases worldwide each year, its impact on human life and healthcare systems5 is staggering.


Sepsis is most likely to develop in immunocompromised, paediatric, and elderly populations; or those who have an indwelling medical device or catheter. Sepsis rates are on the rise because of a rising elderly population, increased longevity of individuals with chronic diseases such as cancer, technological advances in medicine that lead to more frequent use of invasive medical devices, and the extensive use of antibiotics.5

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Sepsis represents a big global epidemiological burden

Sepsis - Patient journey

1. High risk of sepsis complications

Newborns, elderly and immunocompromised patients are at particular high risk6

2. Prevalence

It is estimated to affect approximately 49 million people worldwide every year, potentially leading to 11 million deaths6

3. Diagnosis

Early sepsis diagnosis can be challenging and is critical to reducing mortality.4

4. High mortality

The incidence of sepsis and the number of sepsis-related risk deaths are increasing.3 In hospital sepsis mortality remains high (>15%).7

5. Therapy selection

An inappropriate initial antibiotic therapy is associated with an increase in mortality and morbidity8

6. Therapy control


It is key to identify the cause of sepsis infections early so that patients can be treated with the appropriate therapy as soon as possible to improve survival rates, reduce adverse effects of antimicrobials and reduce antimicrobial resistance.

 

Three stages of a sepsis infection9

Sepsis-Stage-1-General-Inflammation

Stage 1: General inflammation


A local infection – e.g. in the lung – overcomes the body’s defense mechanisms. Pathogens and the toxins they produce leave the original site of infection and enter the circulatory system.

2B-Sepsis-Stage2-Organ-dysfunctional

Stage 2: Organ dysfunction


A general inflammatory response called SIRS (systemic inflammatory response syndrome) causes an individual organ to deteriorate or fail. Sepsis occurs when more than one organ begins to deteriorate.

2C-Sepsis-Stage3-Septic-shock

Stage 3: Septic shock


Septic shock occurs when multiple organs stop functioning and cardio-circulatory failure leads to a sudden drop in blood pressure.

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Blood culture identification

A clinician makes a rapid assessment of the patient's likelihood for having sepsis or septic shock and will decide to administer antimicrobial empiric therapy.  Blood culture identification is also done to rule in or out blood stream infection and determine how best to direct and optimize antimicrobial therapy.6

Challenges in diagnosis and delivering care
Timely treatment
Timely treatment


Rapid identification of the causative agent(s) of bloodstream infections (BSIs) is critical. Traditional methods can take days to identify the cause of an infection and mortality can increase up to 8% for every hour effective antibiotics are delayed.4

Rapid identification of BSIs, in combination with antimicrobial stewardship has been shown to decrease time to targeted therapy by roughly 24 hours, while decreasing hospital length of stay by 2.5 days.10,11

Antimicrobial stewardship
Antimicrobial stewardship

 

The rapid emergence of resistant microorganisms has led to an antibiotic resistance crisis. Up to 50% of antibiotics prescribed in hospitals are either unnecessary or inappropriate12 and it is estimated that roughly 10 million people will die annually due to antimicrobial resistance by the year 2050.13 Taking antibiotics when not needed can put patients at risk for serious adverse events and lead to the development of resistance. As such, careful and judicious use of antimicrobial agents has become a key component of mitigating the risk posed by resistant organisms.

Fungal infections
Fungal infections


Fungal pathogens are a growing cause of BSIs and are associated with some of the highest rates of inappropriate therapy and mortality. The hospital mortality rate of invasive candidiasis is estimated between 46%-75%, with costs attributed to candidemia as high as $92,000 per case.2 Non-albicans species of Candida and other emerging fungi are increasing in incidence, with immunocompromised patients at greatest risk. A delay in antifungal prescribing of >12 hours from the time of blood sample collection increased mortality by 2.09-fold.14

 

Blood culture contamination
Blood culture contamination


Contaminants in blood cultures are common and can lead to unnecessary use of antibiotics that increase cost and toxicity. These contaminants can represent up to 15-30% of the organisms isolated in some hospitals.15The optimized identification of pathogens when combined with antibiotic stewardship, has been shown to decrease the duration of antibiotic therapy for blood culture contaminants by 17.8 hours.10

Blood culture contaminants can have a significant impact on hospital costs:

  • Length of stay can increase by 2 days16

  • Total cost of care per patient has been shown to increase by over $4,70016

  • Lab charges and pharmacy costs can increase more than $100017,18

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    References

    1. Rudd KE, et al. Lancet 2020;395(10219):200-211 
    2. Pfaller MA, et al. (2007) Clin Microbiol Rev;20(1):133-63. 
    3. Singer et al. JAMA (2016) 315(8):801-810.
    4. Kumar A. et al. Grit Care Med. 2006; 34(6): 1589-1596
    5. https:/www.global-sepsis-alliance.org/sepsis 
    6. https://who.int/news-room/fact-sheets/detail/sepsis 
    7. Rhee, C. et al. (2017) JAMA 318(13):1241-1249.
    8. Zilberberg, et. al., (2014) Critical Care (18):596.
    9. Fact Sheet Sepsis. V2_Sepsis Fact Sheet. World Sepsis Day. Global Sepsis Alliance. Center for Sepsis Control & Care.
    10. Box, et al., (2016) Pharmacotherapy, 35 (3): 269-276 
    11. Timbrook, et al. (2017) Clin Infect Dis. 64 (1): 15-23 
    12. Antibiotic Resistance Threats in the United States. 2013. U.S. Dept of Health & Human Services. Centers for Disease Control and Prevention 
    13. The Review on Antimicrobial Resistance, Chaired by Jim O'Neill, December 2014 
    14. Morrell, et. al. (2005) Antimicrobial Agents and Chemotherapy. 49(9):3640-5.
    15. Murray, P. et al. (2012), Crit Care Med, Current Approaches to the Diagnosis of Bacterial and Fungal Bloodstream Infections for the ICU. 40(12):3277-3282. 
    16. Skoglund E, et al. (2019), JCM; 57(1): 1105-18 
    17. Bates, D. et al. (1991), JAMA; 265(3):365-9. 
    18. Hall. K. et al. (2006) Clinical Microbiology Reviews. Updated Review of Blood Culture Contamination. 19(4):788-802