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Bacterial Sepsis

Disease Details

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Description: Bacterial sepsis is a life-threatening condition where the body's response to a bacterial infection causes widespread inflammation, potentially leading to organ failure and death.
Type: Bacterial sepsis is an acute condition characterized by a severe, potentially life-threatening infection that leads to widespread inflammation in the body. It is typically not a genetically transmitted disease; rather, it is caused by infection with bacteria, which can enter the body through wounds, surgical sites, or other means. Therefore, bacterial sepsis does not have a specific type of genetic transmission.
Signs And Symptoms: In addition to symptoms related to the actual cause, people with sepsis may have a fever, low body temperature, rapid breathing, a fast heart rate, confusion, and edema. Early signs include a rapid heart rate, decreased urination, and high blood sugar. Signs of established sepsis include confusion, metabolic acidosis (which may be accompanied by a faster breathing rate that leads to respiratory alkalosis), low blood pressure due to decreased systemic vascular resistance, higher cardiac output, and disorders in blood-clotting that may lead to organ failure. Fever is the most common presenting symptom in sepsis, but fever may be absent in some people such as the elderly or those who are immunocompromised.The drop in blood pressure seen in sepsis can cause lightheadedness and is part of the criteria for septic shock.Oxidative stress is observed in septic shock, with circulating levels of copper and vitamin C being decreased.Diastolic blood pressure falls during the early stages of sepsis, causing a widening/increasing of pulse pressure, which is the difference between the systolic and diastolic blood pressures. If sepsis becomes severe and hemodynamic compromise advances, the systolic pressure also decreases, causing a narrowing/decreasing of pulse pressure. A pulse pressure of over 70 mmHg in patients with sepsis is correlated with an increased chance of survival. A widened pulse pressure is also correlated with an increased chance that someone with sepsis will benefit from and respond to IV fluids.
Prognosis: Sepsis will prove fatal in approximately 24.4% of people, and septic shock will prove fatal in 34.7% of people within 30 days (32.2% and 38.5% after 90 days).
Lactate is a useful method of determining prognosis, with those who have a level greater than 4 mmol/L having a mortality of 40% and those with a level of less than 2 mmol/L having a mortality of less than 15%.There are a number of prognostic stratification systems, such as APACHE II and Mortality in Emergency Department Sepsis. APACHE II factors in the person's age, underlying condition, and various physiologic variables to yield estimates of the risk of dying of severe sepsis. Of the individual covariates, the severity of the underlying disease most strongly influences the risk of death. Septic shock is also a strong predictor of short- and long-term mortality. Case-fatality rates are similar for culture-positive and culture-negative severe sepsis. The Mortality in Emergency Department Sepsis (MEDS) score is simpler and useful in the emergency department environment.Some people may experience severe long-term cognitive decline following an episode of severe sepsis, but the absence of baseline neuropsychological data in most people with sepsis makes the incidence of this difficult to quantify or to study.
Onset: The onset of bacterial sepsis can occur very rapidly, often within hours to a few days after the initial infection. It is critical to seek immediate medical attention as sepsis can quickly progress to severe sepsis or septic shock, which are life-threatening conditions. Prompt diagnosis and treatment are essential for improving outcomes in individuals with bacterial sepsis.
Prevalence: The prevalence of bacterial sepsis varies globally and is influenced by factors such as healthcare quality, infection control practices, and population characteristics. In high-income countries, sepsis incidence ranges from 300 to 500 cases per 100,000 person-years. In low- and middle-income countries, the prevalence can be higher due to limited healthcare resources and differing health challenges. Exact global prevalence is challenging to determine due to variations in healthcare reporting and diagnostics.
Epidemiology: Sepsis causes millions of deaths globally each year and is the most common cause of death in people who have been hospitalized. The number of new cases worldwide of sepsis is estimated to be 18 million cases per year. In the United States sepsis affects approximately 3 in 1,000 people, and severe sepsis contributes to more than 200,000 deaths per year.Sepsis occurs in 1–2% of all hospitalizations and accounts for as much as 25% of ICU bed utilization. Due to it rarely being reported as a primary diagnosis (often being a complication of cancer or other illness), the incidence, mortality, and morbidity rates of sepsis are likely underestimated. A study of U.S. states found approximately 651 hospital stays per 100,000 population with a sepsis diagnosis in 2010. It is the second-leading cause of death in non-coronary intensive care unit (ICU) and the tenth-most-common cause of death overall (the first being heart disease). Children under 12 months of age and elderly people have the highest incidence of severe sepsis. Among people from the U.S. who had multiple sepsis hospital admissions in 2010, those who were discharged to a skilled nursing facility or long-term care following the initial hospitalization were more likely to be readmitted than those discharged to another form of care. A study of 18 U.S. states found that, amongst people with Medicare in 2011, sepsis was the second most common principal reason for readmission within 30 days.Several medical conditions increase a person's susceptibility to infection and developing sepsis. Common sepsis risk factors include age (especially the very young and old); conditions that weaken the immune system such as cancer, diabetes, or the absence of a spleen; and major trauma and burns.From 1979 to 2000, data from the United States National Hospital Discharge Survey showed that the incidence of sepsis increased fourfold, to 240 cases per 100,000 population, with a higher incidence in men when compared to women. However, the global prevalence of sepsis has been estimated to be higher in women. During the same time frame, the in-hospital case fatality rate was reduced from 28% to 18%. However, according to the nationwide inpatient sample from the United States, the incidence of severe sepsis increased from 200 per 10,000 population in 2003 to 300 cases in 2007 for population aged more than 18 years. The incidence rate is particularly high among infants, with an incidence of 500 cases per 100,000 population. Mortality related to sepsis increases with age, from less than 10% in the age group of 3 to 5 years to 60% by sixth decade of life. The increase in the average age of the population, alongside the presence of more people with chronic diseases or on immunosuppressive medications, and also the increase in the number of invasive procedures being performed, has led to an increased rate of sepsis.
Intractability: Bacterial sepsis can be intractable if not recognized and treated promptly. Early diagnosis and aggressive treatment with antibiotics and supportive care are critical to improving outcomes. Delays in treatment can lead to severe complications and higher mortality rates, making the condition potentially challenging to manage successfully.
Disease Severity: Disease Severity: Bacterial sepsis is a life-threatening condition that occurs when the body's response to a bacterial infection causes widespread inflammation, leading to tissue damage, organ failure, and potentially death if not promptly treated. The severity can range from mild sepsis to severe sepsis and septic shock, with the latter being the most critical and requiring immediate medical intervention.
Healthcare Professionals: Disease Ontology ID - DOID:0040085
Pathophysiology: Sepsis is caused by a combination of factors related to the particular invading pathogen(s) and to the status of the immune system of the host. The early phase of sepsis characterized by excessive inflammation (sometimes resulting in a cytokine storm) may be followed by a prolonged period of decreased functioning of the immune system. Either of these phases may prove fatal. On the other hand, systemic inflammatory response syndrome (SIRS) occurs in people without the presence of infection, for example, in those with burns, polytrauma, or the initial state in pancreatitis and chemical pneumonitis. However, sepsis also causes similar response to SIRS.
Carrier Status: Bacterial sepsis does not typically have a carrier status. It is a severe and life-threatening condition caused by the body's extreme response to a bacterial infection, often originating from another part of the body such as the lungs, urinary tract, abdomen, or bloodstream. Unlike some infectious diseases, individuals do not carry sepsis in a dormant state; it results from active infections that lead to widespread inflammation and potential organ failure.
Mechanism: Bacterial sepsis is a life-threatening condition that occurs when the body's response to a bacterial infection causes widespread inflammation, leading to organ dysfunction and tissue damage.

**Mechanism:**
1. **Infection Entry:** Bacteria enter the bloodstream through a localized infection, such as pneumonia, urinary tract infections, or wounds.
2. **Immune Response:** The immune system detects the bacteria and releases cytokines and other inflammatory mediators to combat the infection.
3. **Systemic Inflammatory Response:** The excessive release of these inflammatory mediators leads to an exaggerated immune response, causing widespread inflammation.
4. **Endothelial Damage:** The inflammation damages the endothelial cells lining blood vessels, increasing vascular permeability and causing fluid leakage into tissues.
5. **Disseminated Intravascular Coagulation (DIC):** The coagulation system is activated, leading to the formation of small blood clots throughout the bloodstream, which can impair blood flow to organs.
6. **Organ Dysfunction:** The combination of inflammation, endothelial damage, and DIC disrupts normal organ function, potentially leading to multiple organ failure.

**Molecular Mechanisms:**
1. **Pattern Recognition Receptors (PRRs):** Cells of the innate immune system use PRRs, such as Toll-like receptors (TLRs), to recognize pathogen-associated molecular patterns (PAMPs) on bacteria.
2. **Cytokine Release:** Activation of PRRs leads to the release of pro-inflammatory cytokines (such as TNF-α, IL-1, and IL-6), further amplifying the immune response.
3. **Complement System Activation:** The complement system is activated, enhancing opsonization, inflammatory response, and bacterial lysis.
4. **Nuclear Factor-kappa B (NF-κB) Pathway:** NF-κB is a key transcription factor activated by PRRs, leading to the expression of genes involved in the inflammatory response.
5. **Reactive Oxygen Species (ROS) Production:** Phagocytes, such as neutrophils and macrophages, produce ROS to kill bacteria but excessive ROS can damage host tissues.
6. **Endotoxin (LPS) Recognition:** Gram-negative bacteria release endotoxins such as lipopolysaccharides (LPS), which are recognized by TLR4 on immune cells, triggering a strong inflammatory response.
7. **Mitochondrial Dysfunction:** Inflammation and oxidative stress can impair mitochondrial function, leading to decreased ATP production and increased cell death.

Understanding these mechanisms is crucial for developing targeted therapies to manage and treat bacterial sepsis effectively.
Treatment: The primary treatment for bacterial sepsis involves:

1. **Antibiotics:** Broad-spectrum antibiotics are typically administered intravenously as soon as possible, often within the first hour of recognizing severe sepsis or septic shock.
2. **Fluids:** Intravenous fluids are given to maintain blood pressure and circulation to vital organs.
3. **Vasoactive Medications:** Medications such as norepinephrine may be used if blood pressure remains low despite fluid replacement.
4. **Source Control:** Identifying and treating the source of infection (e.g., drainage of an abscess, removal of an infected catheter).
5. **Supportive Care:** Oxygen, mechanical ventilation (if needed), and other supportive treatments to stabilize organ function.

Prompt and aggressive treatment is crucial to improving outcomes in bacterial sepsis.
Compassionate Use Treatment: For bacterial sepsis, compassionate use treatments and off-label or experimental treatments are considered when standard therapies are ineffective or unavailable. Some options include:

1. **Activated Protein C (Drotrecogin alfa)**: Once used for severe sepsis under the brand name Xigris, it was withdrawn from the market due to lack of efficacy in further studies but was an example of an experimental approach.

2. **Vitamin C, Thiamine, and Hydrocortisone**: This combination therapy has been explored as an off-label treatment aimed at reducing organ failure and mortality, based on some promising but not yet definitive studies.

3. **Monoclonal Antibodies**: Research into monoclonal antibodies targeting specific components of the body's immune response to sepsis is ongoing, but these are still largely experimental.

4. **Bacteriophages**: The use of viruses that infect and kill bacteria is being explored, especially for antibiotic-resistant infections. This is an emerging area of research and may be considered under compassionate use for multi-drug-resistant sepsis.

These treatments are typically only considered when the patient's condition is critical, and all other options have been exhausted. Approval from regulatory bodies and institutional review boards is often required for compassionate use.
Lifestyle Recommendations: For bacterial sepsis, lifestyle recommendations include:

1. **Hygiene Practices**:
- Wash hands regularly with soap and water.
- Maintain good oral hygiene.
- Keep any wounds clean and properly dressed.

2. **Preventative Healthcare**:
- Ensure vaccinations are up to date.
- Avoid close contact with individuals who have infections.
- Seek medical care promptly for any signs of infection.

3. **Healthy Living**:
- Maintain a balanced diet to support immune function.
- Engage in regular physical activity.
- Get adequate sleep and manage stress levels.

4. **Chronic Condition Management**:
- Properly manage any underlying health conditions such as diabetes, heart disease, or chronic lung conditions by adhering to treatment plans and regular medical check-ups.

5. **Avoiding Infections**:
- Use antibiotics responsibly and only as prescribed by a healthcare provider.
- Avoid unnecessary invasive procedures that may increase the risk of infection.
Medication: In cases of bacterial sepsis, treatment generally involves the administration of broad-spectrum antibiotics initially, which may later be adjusted based on specific bacterial identification and susceptibilities. Common antibiotics used include piperacillin-tazobactam, meropenem, vancomycin, and ceftriaxone. Apart from antibiotics, supportive care such as intravenous fluids, vasopressors, and oxygen therapy may be necessary to manage the symptoms and stabilize the patient.
Repurposable Drugs: Several existing drugs have been explored for repurposing in the treatment of bacterial sepsis. These include:

1. **Statins**: Known primarily for their cholesterol-lowering effects, statins have anti-inflammatory and immunomodulatory properties that might be beneficial in sepsis.
2. **Corticosteroids**: Drugs like hydrocortisone can help modulate the immune response and are sometimes used in septic shock.
3. **Metformin**: Commonly used for type 2 diabetes, metformin has shown potential due to its anti-inflammatory effects.
4. **Aspirin**: With its anti-inflammatory and antithrombotic properties, aspirin might help reduce complications in sepsis.
5. **Vitamin C**: High-dose intravenous vitamin C has been studied for its potential antioxidant and anti-inflammatory effects in sepsis.

These therapies are usually considered adjunctive and should be evaluated in conjunction with standard treatments like antibiotics and supportive care.
Metabolites: In the context of bacterial sepsis, specific metabolites can serve as markers for diagnosis and monitoring. These include:

1. **Lactate**: Elevated levels indicate tissue hypoxia and metabolic stress.
2. **Procalcitonin**: Typically increased in bacterial infections and sepsis.
3. **C-reactive protein (CRP)**: An acute-phase protein that rises in response to inflammation.
4. **Cytokines (e.g., IL-6, TNF-alpha)**: Pro-inflammatory markers that are elevated in sepsis.
5. **Glucose**: Abnormal glucose levels can be a result of metabolic dysregulation in sepsis.

These metabolites help in understanding the severity and progression of bacterial sepsis.
Nutraceuticals: Nutraceuticals are foods or food products that provide medical or health benefits, including the prevention and treatment of disease. In the context of bacterial sepsis, some nutraceuticals being investigated for their potential benefits include:

1. Omega-3 Fatty Acids: These have anti-inflammatory properties and may help modulate the immune response.
2. Probiotics: These can enhance gut microbiota and may boost immune function, potentially aiding in the defense against systemic infections.
3. Antioxidants: Vitamins C and E, as well as coenzyme Q10, may help reduce oxidative stress and inflammation associated with sepsis.

Current research is ongoing to establish the efficacy and safety of these nutraceuticals in the management of bacterial sepsis. Always consult healthcare professionals before using any nutraceuticals for medical purposes.
Peptides: For bacterial sepsis:

- Peptides: Sepsis treatment research includes studying antimicrobial peptides (AMPs) for their potential to directly kill bacteria and modulate the immune response. AMPs can enhance the body's ability to fight infections by disrupting bacterial membranes and altering immune signaling pathways.
- Nan: Nanomedicine approaches, such as using nanoparticles, are being investigated for their ability to deliver antimicrobial agents efficiently to the site of infection, reduce toxicity, and improve the effectiveness of sepsis treatment. Nanoparticles can encapsulate antibiotics or AMPs, enhancing their stability and targeting capability.