Sepsis: Symptoms, Causes, Treatment & Prevention

Sepsis is a life-threatening condition that happens when the body overreacts to an infection releasing chemicals into the bloodstream. This overreaction causes widespread inflammation, which can damage tissues, harm organs, and, if not treated quickly, lead to death. Sepsis affects millions of people around the world every year and is one of the main causes of preventable deaths. 

Anyone can develop sepsis, but newborns, older adults, and people with weak immune systems, chronic diseases, or severe infections are at higher risk. Early signs can be hard to spot because they are similar to many other illnesses. These include fever, chills, fast heartbeat, rapid breathing, and confusion. 

If sepsis worsens, it can progress to septic shock, a severe stage marked by very low blood pressure and failure of multiple organs. Treatment requires immediate hospital care with powerful antibiotics (such as piperacillin–tazobactam, meropenem, ceftriaxone, or vancomycin), intravenous fluids, and support for breathing or other organ functions when needed. 

Sepsis can often be prevented by treating infections early, following good infection-control practices in hospitals, getting vaccinated against common diseases, and properly managing long-term health conditions.

Historical Background

The term sepsis originates from the Greek word meaning “putrefaction” or “decay.” In ancient medicine, sepsis was linked to the concept of rotting flesh and was often seen as an unavoidable consequence of severe wounds or infections. Hippocrates and later Galen described it as a process of bodily corruption, though without knowledge of microbes.

By the Middle Ages, sepsis was still poorly understood and was often considered a fatal outcome of injury or childbirth. It was not until the 19th century, with the rise of germ theory, that its infectious nature began to be clarified. The work of Louis Pasteur and Robert Koch established the role of microorganisms in disease, while Joseph Lister introduced antiseptic techniques in surgery, significantly reducing postoperative sepsis. Around the same time, Ignaz Semmelweis demonstrated that handwashing with disinfectants drastically lowered maternal deaths from puerperal sepsis in maternity wards.

In the 20th century, the introduction of antibiotics such as penicillin and sulfonamides transformed sepsis treatment, leading to sharp declines in mortality. Advances in intensive care, intravenous fluid therapy, and mechanical ventilation further improved survival. However, despite these advances, sepsis continued to cause high death rates, prompting efforts to standardize diagnosis and treatment.

Modern understanding emphasizes that sepsis arises not only from infection itself but from the body’s dysregulated immune response to infection. This led to the development of clinical definitions and diagnostic criteria. In the 1990s, the Systemic Inflammatory Response Syndrome (SIRS) criteria were introduced to identify patients at risk. In 2001, the first international sepsis definitions conference expanded these criteria. Most recently, the Sepsis-3 definitions, published in 2016, redefined sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection,” providing a framework that is widely used in clinical practice today.

Sepsis Versus Septicemia

The terms sepsis and septicemia are often used interchangeably in everyday language, but in medical science they have distinct meanings.

Septicemia refers specifically to the presence of viable microorganisms, most commonly bacteria in the bloodstream. The term literally means “blood poisoning” and was historically used to describe cases where bacteria entered and multiplied within the blood, often producing toxins that contributed to systemic illness. Septicemia is therefore closely related to bacteremia, which is the medical term for bacteria detected in the blood, although bacteremia may be transient and asymptomatic, whereas septicemia implies active infection with clinical consequences. In older medical literature, septicemia was frequently used as a general label for severe bloodstream infections. Today, the term is considered imprecise and is less commonly used in clinical guidelines, which instead emphasize bacteremia, fungemia (fungal organisms in the blood), or viremia (viruses in the blood) to describe the specific condition.

Sepsis, by contrast, is defined not by the mere presence of microorganisms in the blood but by the body’s systemic response to infection. Modern definitions, such as the Sepsis-3 criteria (2016), describe sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection.” Sepsis may result from infections located in any part of the body—including the lungs (pneumonia), urinary tract, abdominal cavity, skin, or soft tissue—and does not require bacteria to be present in the bloodstream. For example, severe pneumonia or peritonitis can trigger sepsis without bacteremia being detectable.

The relationship between the two terms can therefore be summarized as follows:

• Septicemia always involves microorganisms circulating in the bloodstream.
• Sepsis reflects a harmful systemic reaction to infection, which may or may not involve microorganisms in the blood.
• Not all cases of septicemia progress to sepsis.
• Sepsis can occur in the absence of septicemia.

Causes of Sepsis

Sepsis arises from infections that trigger a severe immune response. These infections come from different types of pathogens, which each affect the body in specific ways and require distinct treatments.

Bacterial Infections

Bacteria are the leading cause of sepsis worldwide. Common culprits include Escherichia coli, Staphylococcus aureus, and Streptococcus species. These organisms typically originate from localized infections such as pneumonia (lungs), urinary tract infections, abdominal infections (e.g., peritonitis), or skin and soft tissue infections.

When bacteria gain access to the bloodstream, the condition is sometimes referred to as bacteremia. Bacterial products such as endotoxins (from Gram-negative bacteria) and exotoxins (from certain Gram-positive bacteria) can trigger a massive release of inflammatory mediators by the host immune system. This “cytokine storm” contributes to widespread tissue injury, impaired blood flow, and organ failure.

Antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae, present significant treatment challenges, as delays in administering effective antibiotics increase mortality risk.

Viral Infections

Although less common than bacterial causes, viruses can also precipitate sepsis. Viral sepsis occurs when the body’s immune system overreacts to a viral infection, or when viral illness predisposes individuals to severe secondary bacterial infections. Examples include influenza, coronavirus disease 2019 (COVID-19), and herpes simplex virus.

Viral sepsis is particularly dangerous in immunocompromised individuals, such as those undergoing chemotherapy, transplant recipients, or people with advanced HIV infection. Treatment typically combines antiviral medications—when available—with organ-supportive therapies. For many viral infections, supportive care remains the mainstay.

Fungal 

Fungal pathogens, especially Candida species, represent an important cause of sepsis in hospitalized patients. Invasive candidiasis often occurs in people with prolonged antibiotic use, central venous catheters, or weakened immune systems. Other fungi, such as Aspergillus species, may also cause systemic infection in severely immunocompromised hosts.

Fungal sepsis often presents with subtle clinical signs, and blood cultures may be slow to confirm the diagnosis. Management requires antifungal therapy, such as echinocandins or amphotericin B, in combination with removal of infected lines or catheters.

Parasitic Causes

Parasitic causes of sepsis are rare but medically significant. The most notable example is severe malaria caused by Plasmodium falciparum. In this condition, parasite-infected red blood cells obstruct small blood vessels, provoking widespread inflammation, impaired oxygen delivery, and multi-organ failure. Other parasites, including Leishmania or Trypanosoma species, can occasionally cause systemic inflammatory responses resembling sepsis.

Treatment of parasitic sepsis depends on antiparasitic drugs tailored to the specific organism, alongside intensive supportive care.

Risk Factors

Sepsis risk is influenced by age, health conditions, and immune function. Certain groups have a higher likelihood of developing sepsis due to biological or medical vulnerabilities.

Demographic Factors

Age is one of the strongest determinants of sepsis risk. Infants, particularly those younger than one year, are vulnerable because of immature immune defenses, limited vaccine protection, and a higher likelihood of infections acquired during childbirth or early infancy. At the other end of the spectrum, older adults (typically those over 65 years) face increased risk due to age-related decline in immune function (immunosenescence), reduced physiological reserves, and the higher prevalence of chronic diseases. Elderly individuals are also more likely to undergo hospitalization and invasive procedures, further increasing their susceptibility.

Gender also plays a role; males generally face a slightly higher risk of sepsis and worse outcomes than females. Potential explanations include hormonal influences, differences in immune regulation, and behavioral factors such as health-seeking patterns. However, some female populations, such as pregnant or postpartum women, may face unique risks due to physiological changes and exposure to obstetric infections.

Poverty, limited access to healthcare, poor living conditions, and malnutrition all contribute to increased vulnerability to infections that may progress to sepsis. Delayed recognition and treatment in resource-limited settings lead to higher mortality. In high-income countries, disparities in health insurance coverage, geographic access to healthcare facilities, and preventive care similarly influence sepsis outcomes.

Differences in sepsis incidence and mortality across ethnic groups have been observed. For example, in the United States, Black and Indigenous populations experience disproportionately higher rates of sepsis-related deaths. These disparities are attributed to structural inequalities, barriers to timely care, higher prevalence of chronic conditions, and limited healthcare resources in certain communities.

Residence in long-term care facilities, such as nursing homes, or prolonged stays in hospitals increases exposure to antibiotic-resistant pathogens and invasive devices (e.g., urinary catheters, central lines, ventilators). These settings are also associated with outbreaks of multidrug-resistant organisms, which raise the risk of sepsis following infection.

Immunocompromised States

Immunosuppression—whether inherited, disease-related, or medically induced—substantially raises the risk of sepsis.

• HIV/AIDS: Progressive depletion of immune cells weakens the body’s ability to control bacterial, viral, and fungal infections. Opportunistic pathogens such as Pneumocystis jirovecii and Mycobacterium tuberculosis are particularly associated with sepsis in these patients.
• Cancer and Chemotherapy: Chemotherapeutic drugs impair bone marrow function and neutrophil production, increasing susceptibility to bloodstream infections, especially from Gram-negative bacteria.
• Organ Transplantation: Transplant recipients require long-term immunosuppressive medications to prevent graft rejection. These drugs reduce immune surveillance and increase risk of severe bacterial, fungal, and viral infections.
• Immunosuppressive Medications: Corticosteroids, biologic therapies (e.g., TNF-alpha inhibitors), and other agents used to treat autoimmune diseases diminish immune responses and can allow infections to spread rapidly.
• Congenital or Primary Immunodeficiencies: Rare genetic conditions impair the development or function of immune cells, rendering affected individuals highly vulnerable to severe systemic infections that can evolve into sepsis.

In all these cases, diminished immune defenses permit pathogens to multiply unchecked, heightening the risk of overwhelming infection and septic progression.

Chronic Diseases

The presence of chronic illnesses is a major risk factor for sepsis, both because these conditions impair the immune system and because they often necessitate hospital-based interventions.

• Diabetes Mellitus: Poorly controlled blood glucose weakens neutrophil function and impairs wound healing, allowing bacterial infections of the skin, urinary tract, and lungs to progress to sepsis more readily.
• Chronic Kidney Disease (CKD): Patients on dialysis are at increased risk due to repeated vascular access and weakened immune regulation. CKD also impairs clearance of toxins, amplifying inflammatory responses during infection.
• Liver Disease and Cirrhosis: Cirrhosis disrupts the liver’s role in filtering bacteria and producing immune proteins, leading to increased rates of spontaneous bacterial peritonitis and sepsis.
• Cardiovascular Disease: Conditions such as heart failure or peripheral artery disease impair circulation and oxygen delivery, reducing the body’s capacity to respond effectively to infection.
• Chronic Lung Diseases: Chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis create persistent airway inflammation, reduce clearance of pathogens, and predispose patients to respiratory infections that may trigger sepsis.
• Malignancies: Beyond treatment-related immunosuppression, certain cancers themselves disrupt normal immune regulation and increase vulnerability to systemic infection.

Pathophysiology of Sepsis

Sepsis arises from an abnormal immune response triggered by infection, causing widespread inflammation. This response affects multiple organs and may lead to severe circulatory changes, resulting in tissue damage and failure.

Systemic Inflammatory Response

The earliest phase of sepsis is marked by a systemic inflammatory response triggered by microbial components such as lipopolysaccharide (LPS) from Gram-negative bacteria or lipoteichoic acid from Gram-positive organisms. These pathogen-associated molecular patterns (PAMPs) are recognized by host pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), on immune cells.

Activation of these receptors leads to a rapid release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). These cytokines orchestrate leukocyte activation, fever induction, and upregulation of adhesion molecules on vascular endothelium.

Endothelial cells, once activated, increase vascular permeability, allowing plasma proteins and immune cells to migrate into tissues. While intended to fight infection, this process also results in capillary leakage, tissue edema, and reduced intravascular volume. Simultaneously, the coagulation cascade is activated through tissue factor pathways, while anticoagulant mechanisms such as protein C and antithrombin become impaired. This imbalance promotes the formation of microthrombi within small vessels, leading to disseminated intravascular coagulation (DIC) and contributing to tissue ischemia.

The combined effect of widespread inflammation, endothelial injury, and coagulopathy transforms what begins as a localized host defense into a systemic, self-damaging process.

Organ Dysfunction

Sustained inflammation and microvascular dysfunction impair oxygen delivery and utilization at the tissue level. Endothelial injury disrupts microcirculatory blood flow, producing tissue hypoxia even when systemic oxygen supply is adequate. This phenomenon is compounded by mitochondrial dysfunction, which reduces the ability of cells to generate adenosine triphosphate (ATP) and shifts metabolism toward anaerobic glycolysis.

Key organ systems affected include:

• Kidneys: Reduced renal perfusion and direct inflammatory damage result in acute kidney injury, a common early complication of sepsis.
• Lungs: Endothelial and epithelial barrier breakdown leads to pulmonary edema and impaired gas exchange, manifesting clinically as acute respiratory distress syndrome (ARDS).
• Liver: Sepsis disrupts hepatic clearance of toxins and immune mediators, leading to cholestasis and impaired metabolic function.
• Heart: Myocardial depression arises from both circulating cytokines and mitochondrial dysfunction, contributing to reduced cardiac output.
• Central Nervous System: Sepsis-associated encephalopathy is thought to result from altered blood–brain barrier permeability, microglial activation, and neurotransmitter imbalance.

The convergence of hypoperfusion, cellular metabolic failure, and immune-mediated injury explains why multiple organs can fail simultaneously during sepsis.

Septic Shock

Septic shock represents the most severe stage of sepsis and is characterized by persistent hypotension despite adequate fluid resuscitation. This hemodynamic collapse arises from several mechanisms:

• Vasodilation: Excessive production of nitric oxide and other vasodilators leads to loss of vascular tone and severe reductions in systemic vascular resistance.
• Capillary Leak: Persistent endothelial dysfunction causes ongoing fluid extravasation, reducing circulating blood volume.
• Myocardial Depression: Cytokines and nitric oxide impair cardiac contractility, limiting the ability of the heart to compensate for falling blood pressure.
• Metabolic Failure: With inadequate tissue perfusion, cells rely increasingly on anaerobic metabolism, generating lactate and resulting in lactic acidosis.

Clinically, septic shock carries a high mortality rate and requires prompt intervention with intravenous fluids, vasopressors (commonly norepinephrine), and intensive organ support.

Clinical Presentation

Sepsis exhibits a range of symptoms that change as the condition worsens. The presentation varies notably depending on patient age and the stage of illness. Recognizing specific signs early impacts treatment decisions and outcomes.

Early Signs and Symptoms

Initial manifestations often include fever, chills, and an elevated heart rate above 90 beats per minute. Patients may report rapid breathing and confusion or disorientation. Skin may appear pale, clammy, or mottled due to poor perfusion.

Other early indicators include decreased urine output and general weakness. Laboratory findings frequently show elevated white blood cell count and increased lactate levels, signaling tissue hypoxia. Prompt identification at this stage is critical.

Progression of Severity

As sepsis advances, hypotension resistant to fluid resuscitation may develop, leading to septic shock. Multi-organ dysfunction becomes evident, characterized by altered mental status, acute kidney injury, and coagulation abnormalities.

Patients encounter respiratory failure requiring mechanical ventilation and cardiac insufficiency. The Sequential Organ Failure Assessment (SOFA) score increases, reflecting rising morbidity. Mortality risk rises sharply with organ involvement.

Pediatric and Geriatric Differences

Children often exhibit nonspecific symptoms such as irritability, poor feeding, and cold extremities rather than classic fever. Their immune response may lead to rapid deterioration, necessitating close monitoring.

In elderly patients, confusion and lethargy are common early signs, sometimes without fever. Comorbidities and atypical presentations complicate diagnosis. Clinicians must consider subtle changes from baseline function to detect sepsis promptly.

Diagnostic Criteria

Sepsis diagnosis relies on identifying specific clinical signs, laboratory abnormalities, and assessment tools that indicate infection-induced organ dysfunction. Accurate detection combines biochemical markers, imaging results, and validated scoring systems to guide timely intervention.

Laboratory Tests

Laboratory evaluation emphasizes markers of infection and organ dysfunction. Elevated white blood cell count (WBC) or leukopenia can reflect immune response alterations. Procalcitonin and C-reactive protein (CRP) levels serve as biomarkers indicating bacterial infection and systemic inflammation, respectively.

Blood cultures are essential to identify causative pathogens but may take 24-48 hours. Lactate measurement is critical, with levels above 2 mmol/L suggesting tissue hypoperfusion and increased mortality risk.

Other tests include:

• Serum creatinine for renal function
• Bilirubin for hepatic involvement
• Coagulation profiles (INR, platelet count) for coagulopathy detection

Imaging Findings

Imaging helps locate infection sources and evaluate organ damage. Chest X-rays can reveal pneumonia, a common sepsis origin.

Ultrasound detects abscesses or fluid collections, guiding drainage. CT scans provide detailed views of intra-abdominal or soft tissue infections.

Imaging findings alone do not confirm sepsis but support clinical and laboratory data to identify infection focus and complications like organ ischemia or edema.

Sepsis Scoring Systems

Several scoring systems assess sepsis severity and predict outcomes. The Sequential Organ Failure Assessment (SOFA) score quantifies organ dysfunction using six parameters: respiration, coagulation, liver, cardiovascular, central nervous system, and renal functions.

A SOFA score increase of 2 points or more from baseline indicates sepsis.

Another tool, the quick SOFA (qSOFA), uses three criteria:

• Altered mental status
• Respiratory rate ≥22/min
• Systolic blood pressure ≤100 mmHg

Presence of two or more indicates a greater risk of poor outcomes.

The Systemic Inflammatory Response Syndrome (SIRS) criteria, once widely used, focus on temperature, heart rate, respiratory rate, and WBC count but lack specificity.

Treatment Strategies

Sepsis treatment requires immediate and targeted interventions to control infection, restore circulation, and maintain organ function. Three primary approaches focus on antimicrobial use, fluid management, and circulatory support.

Antibiotic Therapy

Clinical guidelines recommend the administration of empiric broad-spectrum antibiotics within the first hour of sepsis recognition, as delays are strongly associated with increased mortality. The empiric regimen is selected to provide coverage against a wide range of likely pathogens, including Gram-positive organisms (such as Staphylococcus aureus), Gram-negative bacilli (such as Escherichia coli and Pseudomonas aeruginosa), and anaerobes, depending on the suspected infection source.

Once microbiological cultures and sensitivity results are available, antibiotic therapy is refined to target the identified pathogen, a process known as de-escalation. This tailored approach improves efficacy while reducing the risk of antimicrobial resistance and minimizing unnecessary drug exposure. The duration of therapy is typically 7–10 days, but treatment length is adjusted according to clinical response, the site of infection, and patient comorbidities.

Fluid Resuscitation

Sepsis-induced hypoperfusion and capillary leakage necessitate aggressive fluid resuscitation to restore intravascular volume and tissue perfusion. Initial management generally involves the rapid infusion of crystalloids, such as normal saline or lactated Ringer’s solution, with current guidelines recommending an initial bolus of 30 mL/kg within the first three hours of recognition.

The effectiveness of resuscitation is assessed through continuous monitoring of hemodynamic parameters, including mean arterial pressure (MAP), urine output, central venous pressure, and lactate clearance. Excessive fluid administration, however, may result in pulmonary edema and worsen respiratory compromise; therefore, fluid therapy is guided by dynamic assessment of fluid responsiveness. Colloids, such as albumin, may be considered in select cases, though they are not routinely favored over crystalloids.

Vasopressors

In patients who remain hypotensive despite adequate fluid resuscitation, vasopressor therapy is essential to restore vascular tone and maintain tissue perfusion. Norepinephrine is the first-line vasopressor due to its potent α-adrenergic effects, which increase systemic vascular resistance and raise MAP, while also providing modest β-adrenergic support for cardiac output.

When norepinephrine alone is insufficient, additional agents such as vasopressin or epinephrine may be introduced. Vasopressin serves as an adjunct that can reduce norepinephrine requirements, whereas epinephrine provides combined α- and β-adrenergic stimulation. The therapeutic goal is typically to maintain a MAP of at least 65 mmHg, thereby ensuring adequate organ perfusion. Continuous hemodynamic monitoring is required to titrate vasopressor doses while minimizing risks such as arrhythmias, ischemia, or excessive vasoconstriction.

Supportive Care Measures

Supportive care in sepsis focuses on stabilizing critical body functions and providing adequate nutrition to aid recovery. Close monitoring and tailored interventions are essential to prevent organ failure and meet metabolic demands.

Organ Support

Organ support encompasses measures to sustain essential physiological functions when natural compensatory mechanisms fail.

• Respiratory support: Severe sepsis frequently progresses to acute respiratory distress syndrome (ARDS), requiring mechanical ventilation. Protective ventilation strategies—such as low tidal volume (6 mL/kg predicted body weight) and limitation of plateau pressures (<30 cm H₂O)—are standard to reduce ventilator-induced lung injury. Adjunctive therapies may include prone positioning, neuromuscular blockade in refractory hypoxemia, and extracorporeal membrane oxygenation (ECMO) in selected cases.
• Hemodynamic stabilization: Persistent hypotension after fluid resuscitation necessitates vasopressor support. Norepinephrine remains the first-line agent, titrated to achieve a mean arterial pressure (MAP) ≥65 mmHg, with vasopressin or epinephrine considered as adjuncts. Inotropes such as dobutamine may be used in patients with evidence of myocardial depression or low cardiac output despite adequate filling pressures. Continuous monitoring of cardiac function, perfusion indices, and lactate clearance guides therapy adjustments.
• Renal support: Acute kidney injury is a common complication of sepsis. Renal replacement therapy (RRT) is indicated for refractory fluid overload, severe electrolyte abnormalities (e.g., hyperkalemia), metabolic acidosis, or uremia. Both continuous (CRRT) and intermittent modalities may be used, with early initiation suggested in patients with worsening organ dysfunction.

Nutrition and Metabolic Management

Sepsis is a hypermetabolic and catabolic state, making timely nutritional support essential for recovery.

• Enteral nutrition: Enteral feeding is initiated once hemodynamic stability is achieved, as it helps maintain gut integrity, reduces bacterial translocation, and lowers infection risk. Early enteral nutrition, within 24–48 hours of stabilization, is generally preferred over parenteral routes.
• Energy and protein requirements: Energy needs are ideally calculated by indirect calorimetry, though predictive equations are often used when unavailable. Protein intake of 1.2–2.0 g/kg/day is recommended to counteract catabolism and support tissue repair.
• Glycemic control: Stress-induced hyperglycemia is common in sepsis. Blood glucose is usually maintained between 140 and 180 mg/dL, as tighter control increases the risk of hypoglycemia. Insulin infusion may be required, with frequent monitoring to ensure safety.
• Micronutrient and electrolyte balance: Electrolyte derangements (e.g., hypokalemia, hypomagnesemia, hypophosphatemia) are common due to increased cellular uptake and renal losses. Regular monitoring and supplementation are necessary. Vitamins and trace elements, particularly vitamin C, thiamine, selenium, and zinc, have been investigated for adjunctive benefits, though evidence for routine use remains limited.
• Parenteral nutrition: Parenteral feeding is reserved for patients in whom enteral nutrition is contraindicated, poorly tolerated, or insufficient to meet caloric needs. When used, it should be introduced gradually and combined with enteral feeding whenever possible.

Complications of Sepsis

Sepsis can cause serious disruptions throughout the body, leading to severe damage to vital organs. Patients often face both immediate and long-term health challenges after an episode of sepsis.

Acute Organ Failure

Acute organ dysfunction is the hallmark of sepsis and results from impaired perfusion, endothelial injury, and dysregulated inflammatory cascades.

• Respiratory failure: Acute respiratory distress syndrome (ARDS) is a common complication, characterized by non-cardiogenic pulmonary edema, hypoxemia, and reduced lung compliance. Patients often require mechanical ventilation, and mortality rates remain high despite advances in supportive care.
• Renal failure: Sepsis-induced acute kidney injury (AKI) is associated with high mortality. Reduced renal blood flow, tubular cell injury, and microvascular thrombosis can necessitate renal replacement therapy such as dialysis or continuous renal replacement therapy (CRRT).
• Liver dysfunction: Hepatic involvement manifests as cholestasis, impaired drug metabolism, coagulopathy, and hypoglycemia. Severe cases may progress to acute liver failure, compounding the risk of bleeding and secondary infections.
• Cardiac dysfunction: Septic cardiomyopathy is characterized by depressed myocardial contractility, arrhythmias, and impaired ventricular function, often reversible but potentially fatal if left unrecognized.
• Circulatory collapse: Septic shock represents the most severe form of circulatory failure, with profound vasodilation, capillary leakage, and refractory hypotension. The resulting inadequate tissue oxygenation can precipitate multiple organ dysfunction syndrome (MODS), defined as failure of two or more organ systems, which carries a markedly increased risk of death.

Long-Term Outcomes

Advances in critical care have increased survival rates, but many patients endure persistent complications collectively known as post-sepsis syndrome.

• Physical impairments: Prolonged immobilization in the intensive care unit (ICU) contributes to muscle wasting, neuropathy, and chronic fatigue. Some patients develop long-term disabilities that limit mobility and independence.
• Neurocognitive dysfunction: Cognitive impairments such as memory loss, poor concentration, and reduced executive function are frequent among survivors, particularly older adults. These deficits can persist for years, impairing social and occupational reintegration.
• Psychological sequelae: Depression, anxiety disorders, and post-traumatic stress disorder (PTSD) are common in sepsis survivors, influenced by both the critical illness experience and lingering neuroinflammatory effects.
• Recurrent health problems: Survivors remain at elevated risk of recurrent infections, hospital readmissions, and new-onset chronic conditions such as cardiovascular disease. Mortality rates remain higher in sepsis survivors than in age-matched populations for several years after discharge.
• Quality of life: The cumulative burden of physical, cognitive, and psychological sequelae significantly reduces quality of life. Long-term rehabilitation, psychological counseling, and multidisciplinary follow-up are often required to optimize recovery.

Prevention of Sepsis

Preventing sepsis involves targeted strategies to reduce infection risk. These include immunizations and strict infection control measures, which significantly lower the chances of developing sepsis from common pathogens.

Vaccination

Immunizations stimulate protective immune responses against common bacterial and viral pathogens, thereby lowering both the frequency and severity of infections.

Annual influenza vaccination reduces the risk of viral pneumonia and secondary bacterial infections, which are frequent precursors of sepsis. Pneumococcal vaccination is strongly recommended for older adults, immunocompromised individuals, and patients with chronic illnesses such as diabetes or chronic lung disease, as pneumococcal pneumonia is a leading cause of sepsis.

Vaccines against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis are crucial in reducing life-threatening bloodstream infections and meningitis in children, which can rapidly evolve into septicemia.

Vaccination strategies are often tailored to population subgroups based on age, occupation, and underlying medical conditions. For instance, meningococcal vaccines are recommended for adolescents, military recruits, and travelers to endemic regions.

By reducing the incidence of these primary infections, vaccines indirectly but effectively lower the global burden of sepsis.

Infection Control Practices

Infection control in healthcare and community settings is essential to prevent sepsis. In healthcare settings, hand hygiene remains the most effective strategy for preventing nosocomial infections. Routine and thorough handwashing by healthcare personnel significantly reduces the risk of pathogen transmission between patients. Another major focus is the prevention of device-associated infections. Central venous catheters, urinary catheters, and ventilators are common entry points for pathogens, making them a leading cause of bloodstream and systemic infections. 

To address this, guidelines recommend minimizing device use, ensuring sterile insertion techniques, and removing devices as soon as they are no longer clinically necessary. Additionally, the use of personal protective equipment (PPE) and isolation protocols is critical to contain the spread of multidrug-resistant organisms, which increasingly contribute to septic episodes. Equally important is environmental cleaning and sterilization: thorough disinfection of hospital surfaces and proper sterilization of surgical instruments greatly reduce cross-contamination risks.

In community settings, infection control practices are equally important for sepsis prevention. Prompt cleaning and proper covering of wounds limit bacterial entry, particularly for organisms like Staphylococcus aureus. Safe food and water practices, such as correct food handling, thorough cooking, and maintaining clean water supplies, are essential in preventing gastrointestinal infections that may progress to septicemia. General hygiene measures, including regular handwashing especially after contact with sick individuals or contaminated surfaces further reduce the spread of pathogens in households, schools, and other communal environments.

Sepsis in Special Populations

Sepsis presents unique challenges and risks in specific groups due to physiological differences, immune status, and clinical considerations. Treatment approaches and outcomes vary significantly, requiring tailored management strategies.

Neonates

Neonates are highly vulnerable to sepsis because of their immature immune systems. Early onset sepsis usually results from vertical transmission of bacteria such as Group B Streptococcus or Escherichia coli during delivery. Symptoms are often nonspecific, including temperature instability, lethargy, and respiratory distress, making early diagnosis difficult.

Treatment involves prompt administration of broad-spectrum antibiotics and supportive care in a neonatal intensive care unit. Monitoring for complications like meningitis is critical, as neonates have a higher risk of severe outcomes. Preventive measures include maternal screening and intrapartum antibiotic prophylaxis.

Pregnant Women

Pregnant women have altered immune responses and physiological changes that increase susceptibility to sepsis. Common sources include urinary tract infections, chorioamnionitis, and cesarean section wounds. Sepsis during pregnancy requires urgent multidisciplinary care to protect both mother and fetus.

Clinical signs may be masked by pregnancy-related changes, so vigilance is necessary. Antibiotic therapy must consider fetal safety. Delivery planning, often expedited, depends on infection severity and gestational age. Early recognition reduces maternal and neonatal morbidity and mortality.

Immunosuppressed Patients

Immunosuppressed individuals, such as those with HIV, cancer, or on immunosuppressive drugs, face higher sepsis risk and atypical presentations. Opportunistic infections from fungi and viruses are more common in this group, complicating diagnosis and management.

Treatment demands broad antimicrobial coverage and careful attention to drug interactions. Immune status often dictates prognosis, with increased risk of septic shock. Regular monitoring, prophylactic antimicrobials, and supportive therapies are essential components of care in these patients.

Population	Common Pathogens	Key Considerations	Treatment Focus
Neonates	Group B Strep, E. coli	Early nonspecific symptoms, meningitis risk	Broad-spectrum antibiotics, NICU care
Pregnant Women	UTI pathogens, Staphylococcus aureus	Altered immune physiology, fetal safety	Antibiotic choice, delivery timing
Immunosuppressed	Fungi, viruses, multidrug-resistant bacteria	Atypical presentations, drug interactions	Broad coverage, immune monitoring

Epidemiology and Global Impact

In 2017, there were an estimated 48.9 million incident cases of sepsis worldwide. Within the same year, sepsis was responsible for approximately 11.0 million deaths, representing about 19.7–20% of all global deaths. Nearly 20 million of these cases occurred in children under five years of age, with around 2.9 million deaths in this age group.

The majority of sepsis cases and deaths occur in low- and middle-income countries. About 85% of global cases in 2017 were concentrated in these regions. Countries with the highest death rates from sepsis include the Central African Republic (771.1 deaths per 100,000), Chad (566.3), and South Sudan (551.4), while the lowest death rates were recorded in Qatar (10.8 per 100,000), Kuwait (17.6), Lebanon (24.2), Oman (24.8), and Bahrain (27.1).

Over time, global trends show a decline in sepsis burden. In 1990, there were approximately 60.2 million incident cases of sepsis, which decreased to 48.9 million by 2017. The age-standardised incidence dropped from about 1,074.7 cases per 100,000 in 1990 to 677.5 per 100,000 in 2017, representing a 37% reduction. Mortality from sepsis also decreased, with the age-standardised mortality rate declining by roughly 52.8% between 1990 and 2017.

Sepsis affects different populations disproportionately. Children and adolescents aged 5–19 years experienced around 454,000 sepsis-related deaths in 2017. Maternal sepsis remains a concern, with an estimated global cumulative incidence of 13.16 per 10,000 pregnant women. Regional variation is significant: in Africa, maternal sepsis incidence reached 129.17 per 10,000, compared with 6.31 per 10,000 in the Americas.

Case fatality and hospitalization rates remain high. In pediatric intensive care units across 26 countries, hospital mortality for severe sepsis was reported at around 25%. In Brazil, case-fatality for pediatric bacterial sepsis was approximately 20–21% in studies conducted from 1992 to 2006, and remained around 19.8% in a 2019 study.

Economic Burden

Sepsis incurs substantial healthcare costs, including prolonged hospital stays, intensive care interventions, and rehabilitation services. In the United States alone, sepsis-related hospital expenses exceed $24 billion annually.

Indirect costs include lost productivity and long-term disability among survivors. These economic impacts strain healthcare systems and societies, especially in countries with limited resources.

Investment in prevention, early detection, and standardized care protocols may reduce both clinical and financial burdens. Economic evaluations underscore sepsis as a high-priority target for health policy and funding initiatives.