Features of macroorganism reactivity
For a long time, it was believed that the generalization of infection was exclusively associated with a decrease in protective forces. However, sepsis is a specific hyperergic form of response to pathogen invasion. I.V. Davydovsky described this process as a peculiar «immune breakthrough».
Regardless of which specific microorganism caused the disease (and against which antibiotics will be directed), the clinical picture has a distinct character. It lacks the cyclicity typical of infections and is characterized by a severe disruption of tissue repair.
Main clinical manifestations:
- Hectic fever with high temperature swings.
- Pronounced chills followed by profuse sweating.
- Tachycardia and a drop in blood pressure (hypotension).
- Severe toxemia and central nervous system depression.
- Erythrocyte destruction (hemolysis), leading to anemia and suprahepatic jaundice.
The role of cytokines and endotoxin (LPS)
A key link in systemic inflammation is cytokines—proteins that enhance the body's response to bacterial signals. The main mediator is tumor necrosis factor-alpha (TNFα). It stimulates cells to release new portions of mediators, which at high concentrations leads to shock and disseminated intravascular coagulation (DIC). Interleukins (e.g., IL-1β) and interferon-γ are involved in the process, acting on a positive feedback principle: they repeatedly enhance each other's production, creating a «mediator chaos».
Bacterial lipopolysaccharide (LPS) directly embeds into cell membranes via lipid A or binds to specific receptors (CD14, Toll-like receptors) on macrophages and endothelium. This causes:
- Release of endogenous pyrogens.
- Activation of the complement system and clotting factors.
- Suppression of tissue respiration and cell death.
- Release of nitric oxide (NO) by the endothelium, the excess of which provokes profound vascular hypotension.
Endocardial involvement and DIC syndrome
Against the background of systemic inflammation, TNFα causes monocytes and endothelium to produce tissue factor. This activates the extrinsic coagulation pathway. Simultaneously, fibrinolysis is suppressed, and the function of anticoagulant proteins C and S is impaired. DIC syndrome develops: multiple thrombi form initially, followed by bleeding due to the exhaustion of clotting factors.
Any damage to the inner lining of the heart leads to platelet adhesion and the formation of non-bacterial endocarditis. When bacteria enter the bloodstream, they colonize these microthrombi. Microbes become covered with new layers of fibrin on top, which reliably protects them from phagocytes. Vegetations form in which the pathogen actively multiplies, making the selection of penetrating antibacterial therapy extremely important.
Diagnostic criteria and assessment of organ dysfunction
To confirm the diagnosis and assess the severity of damage, a number of inflammatory and hemodynamic markers are used. Leukocytosis (above 12 × 10⁹/L) or leukopenia, elevated C-reactive protein, and procalcitonin are noted in the blood.
Signs of organ dysfunction:
- Hemodynamics: systolic BP drops below 90 mmHg, and mean arterial pressure below 70 mmHg.
- Respiration: PaO2/FiO2 ratio decreases below 300.
- Kidneys: acute oliguria (urine output less than 0.5 mL/kg/h) despite adequate hydration; creatinine rises above 176 µmol/L.
- Blood: thrombocytopenia (less than 100 × 10⁹/L), coagulopathy (INR > 1.5).
- GI tract and liver: intestinal paresis, bilirubin level above 70 µmol/L.
To objectively assess the severity of systemic disorders in clinical practice, the SOFA scale is used, and the APACHE II system is used to determine the patient's general condition.
Briefly: answers to topical questions
Which antibiotic groups are used for initial empirical therapy of sepsis?
The following groups of antibacterial drugs are used for initial empirical therapy of sepsis:
- Cephalosporins — generations II–IV.
- Carbapenems.
- Semisynthetic penicillins.
- Fluoroquinolones.
- Aminoglycosides — used less frequently.
- Macrolides — used less frequently, in combination with imidazoles.
Which antibiotics are prescribed for staphylococcal sepsis caused by MRSA?
In sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA), the drug of choice is vancomycin.
- Vancomycin — administered intravenously; used for sepsis and endocarditis caused by MRSA.
What is the recommended average duration of antibiotic therapy for uncomplicated sepsis?
The total duration of targeted antibacterial therapy for sepsis is 25–30 days or more. The decision to discontinue antibiotics is made based on the following criteria:
- Normalization of temperature — stable body temperature ≤ 37°C for at least 10 days.
- Absence of symptoms — complete disappearance of the clinical picture of sepsis.
- Absence of bacteremia — confirmed by negative blood culture results.
- Normalization of hemogram — restoration of normal blood counts.
Class and exam questions
Why does arterial hypotension develop in sepsis?
Hypotension is caused by the massive release of nitric oxide (NO) by endothelial cells under the influence of cytokines and LPS, which causes sharp vessel dilation (vasodilation).
How do bacteria evade the immune system on heart valves?
They settle on parietal endocardial microthrombi and become covered with a layer of platelets and fibrin, forming vegetations. This layer mechanically blocks the access of phagocytes to the pathogen.
What is the clotting paradox in DIC?
At the beginning of the process, due to the activation of tissue factor, massive intravascular deposition of fibrin (thrombosis) occurs, which depletes the reserves of clotting factors and ultimately leads to severe bleeding.
What else to study on this topic
- Mechanisms of bacterial translocation from the gastrointestinal tract
- Synthesis and functions of eicosanoids (prostaglandins and thromboxanes) in systemic inflammation
- The role of platelet-activating factor (PAF) in tissue damage
- Causes of pulmonary hypertension in endotoxin shock
Master the complete topic in the «Infectious Diseases» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on «Antibiotics in Sepsis» and 3,312 more subject pages
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 41 video lessons on the subject
Other topics in the section "Infections of the Integumentary System and Sepsis"
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.