Sepsis is a critical medical condition^1-5 that kills millions of people every year,⁵ but it’s also one of the most preventable causes of death worldwide.^3,5 Diagnostics play a critical role in combating the global burden of sepsis, empowering doctors to properly treat infections before sepsis occurs, and reducing the misuse or overuse of antimicrobial medication.⁴ By using a combination of inflammatory biomarkers, in-vitro diagnostic (IVD) testing identifies whether an infection is bacterial or viral – allowing doctors to quickly and effectively treat infections.⁴ 

Understanding Sepsis

Why is sepsis a medical emergency?

Sepsis is a life-threatening condition caused by the body’s extreme response to an existing infection.^1,2 While fighting that infection, the immune system damages the body’s own organs and tissues, leading to shock, multi-organ failure and even death.^1-3 People who survive sepsis can also be left with lifelong disabilities or trauma.^3,5 

Specialists consider sepsis to be an ‘inflammation storm’ – an extreme inflammatory response that must be urgently identified and treated.⁴  

Sepsis has a massive global impact, affecting 47–50 million people around the world every year, with at least 11 million fatal cases a year.^3,5 These statistics are especially tragic when we consider that sepsis is highly preventable, so many of these deaths could be avoided.^3,5 

What causes sepsis?

Sepsis can be caused by either a viral or bacterial infection.³ Pneumonia, urinary tract infections, skin or wound infections, meningitis, malaria, influenza and COVID-19 can all lead to sepsis.³  

Why is it so important to distinguish between a bacterial and a viral infection? 

It’s often difficult to distinguish between viral and bacterial infections based on clinical signs and symptoms alone.⁶ This makes it challenging for doctors to decide on the right course of treatment:⁶ is it a bacterial infection that must be treated with antibiotics or a viral infection that will require symptomatic treatment or antiviral medication instead?⁴  

• An untreated or ineffectively treated infection may increase the risk of a patient developing sepsis.^1,4 
• Misdiagnosing a viral infection as bacterial often means the patient is given unnecessary antibiotics, which can play a role in the development of antimicrobial resistance (AMR).⁴ 

This is why doctors need rapid, accurate information about the patient to properly diagnose and treat an infection before it progresses to sepsis.^4,6

Recognizing, Preventing and Treating Sepsis

What does sepsis look like?

The following are all possible symptoms of sepsis: 

• Slurred speech³  
• Confusion and disorientation¹ 
• Shortness of breath^1,3 
• Shivering and/or fever^1.3 
• Muscle pain^1,3 
• Passing no urine all day³ 
• Clammy or sweaty skin¹  
• Mottled or discolored skin³  

Preventing infection, preventing sepsis

Sepsis isn’t contagious, although some of the infections that cause it can be spread from person to person.⁷ Leading global health authorities agree that sepsis can be prevented by avoiding infection in the first place:^3,7  

• Staying up to date with required vaccinations  
• Managing chronic health conditions well 
• Practicing good hand hygiene 
• Keeping cuts and wounds clean and covered until they’ve healed 
• Knowing the common signs and symptoms of sepsis 

Treatment of sepsis 

Sepsis is typically treated with medication, IV fluids and oxygen.⁸ The patient receives urgent medical care in hospital (usually in an intensive care unit) and doctors monitor their vital signs during treatment.^1,8 

Unfortunately, while sepsis caused by a viral infection should be treated with antivirals, patients are often given antibiotics instead (at least initially).⁸ This is because it can take doctors time to figure out the cause of the sepsis but delaying treatment is too dangerous for the patient.⁸  

The Relationship Between Sepsis and Antimicrobial Resistance

AMR happens when microbes like bacteria, viruses, fungi and parasites gradually stop responding to medications, because those medications have been incorrectly used or overused.⁹ This makes infections harder to treat.⁹ In many countries today, bacteria that cause serious infections are showing high rates of drug resistance to antibiotics, which is concerning.⁵ In fact, the World Health Organization has declared AMR a major global public health threat facing humanity.⁵

AMR makes the problem of sepsis more complicated.⁵ Because sepsis is so often treated with broad-spectrum antibiotics (in both bacterial and viral cases),^1,5,8 it can contribute to the rising global issue of AMR.⁵ Fortunately, improving the diagnostic distinction between viral and bacterial infections can help reduce overuse of antibiotics and improve disease control.⁴ 

Diagnosis and Differentiation: The Power of In Vitro Diagnostic Testing

Proper differential diagnostics allows a physician to prescribe the right medication and thereby minimize the risk of a patient developing sepsis. So, how does IVD help to differentiate the numerous infections that can lead to sepsis? 

The body produces molecules called biomarkers (or markers), which can indicate the presence of a condition or disease,¹⁰ and doctors can use IVD tests to examine the levels of certain markers in a patient’s blood (or other body fluids).^4,6,10  

Looking at various markers together helps a clinician to understand their patient’s immune response (which differs between a viral and a bacterial infection), providing clues about the most appropriate treatment.^4,6,10 These markers can also be used to check severity of infection and how the patient is responding to treatment.^4,10 

Combining biomarkers 

Because many of the biomarkers used in testing may be an indication of either a bacterial or viral disease, the best diagnostic tests are those that use a combination of multiple markers.^4,6 These types of tests make it easier for doctors to differentiate between the two.^4,6 There are numerous marker combinations that can provide reliable, sensitive and specific diagnostic results.⁴ 

Examples of important markers that indicate the presence of infection include:   

• Serum amyloid A (SAA), a protein produced by the liver.¹¹ SAA levels rise sharply during acute inflammation.¹¹ Both bacterial and viral infections can cause an increase in SAA.¹²  
  
• C-reactive protein (CRP), another protein made by the liver.¹³ CRP often increases with bacterial infection but can also be elevated during a viral infection.¹⁴ 
  
• Interleukin 6 (IL-6), an immune protein produced as a response to acute or chronic infection, tissue injuries and some cancers.^15,16 It’s also a pyrogen, meaning it produces fever.¹⁶ 
  
• The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), involved in the body’s immune response to viral infections, as well as tumors and metastases.¹⁷ 
  
• Neutrophil gelatinase-associated lipocalin (NGAL), which plays a role in the immune response to bacterial infections.¹⁹ It’s often used as a marker for diagnosing acute kidney injury (AKI).²⁰ 
  
• Procalcitonin (PCT), a peptide that’s normally found in very low levels in a healthy person.²¹ PCT levels rise during bacterial infection but not viral infection.²¹ This makes PCT a very reliable marker for diagnosing bacterial infection.²¹ 
  
• Neutrophil-derived heparin binding protein (HBP), a well-known marker for bacterial infections, but some severe viral infections (like COVID-19 and H1N1 influenza) can also show elevated HBP levels.²²  
  
• Interferon-inducible protein 10 (IP-10), which has been used as a marker for bacterial infections in preterm babies,²³ and for acute respiratory infections in adults.²⁴ 

Moving forward: Preventing sepsis with quality IVD testing 

To help combat the threat of sepsis by providing better diagnostic differentiation and slow the expansion of antimicrobial resistance, partner with Medix Biochemica – an independent international IVD raw materials provider. 

Medix Biochemica is a global, market-leading supplier of antigens, antibodies, and molecular diagnostic reagents to the IVD industry.  Our optimized, industrial-scale manufacturing procedures, certified batch-to-batch consistency, and expert customer service make us an ideal raw material supply partner for your IVD tests. Whether you’re developing an immunoassay for measuring any of the mentioned biomarkers, looking for a control antigen, or have any other IVD need, contact us today to discuss how we can help.  

To discuss your needs with one of our experts, please get in touch today.

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References: 

1. Sepsis is the body’s extreme response to an infection. Centers for Disease Control and Prevention. Accessed April 3, 2023. https://www.cdc.gov/sepsis/what-is-sepsis.html.
2. Sepsis. World Health Organization. Accessed April 3, 2023. https://www.who.int/news-room/fact-sheets/detail/sepsis.
3. Sepsis. Global Sepsis Alliance. Accessed April 3, 2023. https://www.global-sepsis-alliance.org/sepsis.
4. Expert opinion. Interview with Gerben Zuiderveld, Sr. Global Product Manager, Medix Biochemica. March 2023. 
5. Global report on the epidemiology and burden of sepsis: current evidence, identifying gaps and future directions. World Health Organization. 2020. Licence: CC BY-NC-SA 3.0 IGO.
6. Distinguish between bacterial and viral infections in 15 minutes. MeMed. Accessed April 3, 2023. https://www.me-med.com/memed-bv/.
7. Protect yourself and your family from sepsis. Centers for Disease Control and Prevention. Accessed April 3, 2023. https://www.cdc.gov/sepsis/education/patient-resources.html.
8. Antimicrobial resistance. World Health Organization. Accessed April 3, 2023. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance.
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11. Chen M, Wu Y, Jia W, et al. The predictive value of serum amyloid A and C-reactive protein levels for the severity of coronavirus disease 2019. Am J Transl Res. 2020;12(8):4569-4575. 
12. C-reactive protein test. Mayo Clinic. Accessed April 3, 2023. https://www.mayoclinic.org/tests-procedures/c-reactive-protein-test/about/pac-20385228.
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15. What is Interleukin 6? News Medical. Accessed April 3, 2023. https://www.news-medical.net/health/What-is-Interleukin-6.aspx.
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19. Zhang J, Han J, Liu J, et al. Clinical significance of novel biomarker NGAL in early diagnosis of acute renal injury. Exp Ther Med. 2017;14(5):5017-5021. doi:10.3892/etm.2017.5150. 
20. Chang AM, Oakland M. Chapter 12 - biomarkers in shortness of breath. In: Nambi V, ed. Biomarkers in Cardiovascular Disease. Elsevier; 2019:129-137. doi:10.1016/B978-0-323-54835-9.00012-0.
21. Mellhammar L, Thelaus L, Elén S, et al. Heparin binding protein in severe COVID-19—a prospective observational cohort study. PLoS One. 2021;16(4):e0249570. doi:10.1371/journal.pone.0249570.
22. Ng PC, Li K, Chui KM, et al. IP-10 is an early diagnostic marker for identification of late-onset bacterial infection in preterm infants. Pediatr Res. 2007;61(1):93-98. doi:10.1203/01.pdr.0000250207.95723.96.
23. Hayney MS, Henriquez KM, Barnet JH, et al. Serum IFN-γ-induced protein 10 (IP-10) as a biomarker for severity of acute respiratory infection in healthy adults. J Clin Virol. 2017;90:32-37. doi:10.1016/j.jcv.2017.03.003.
24. About us. Medix Biochemica. Accessed April 3, 2023. https://about.medixbiochemica.com/.