Bloodstream Infections - Bacterial and Viral

How do we define sepsis?

Systemic inflammatory response syndrome to infection

• Documented or suspected

What is bacteraemia?

Bacteraemia is presence of bacteria in the blood - may have no disease implications

What is septicaemia?

Septicaemia is presence of bacteria in the blood with clinical symptoms

Can you have symptoms of septicaemia with no bacteria in the blood?

Yes

• You may show clinical signs, but the blood culture can be negative

What are the three bacteremic patterns?

1. Transient

2. Intermittent

3. Continuous

What does a transient bacteremic pattern indicate?

Transient

Bacteria are present in the bloodstream for a short time, usually minutes to hours, before being cleared by the body. This type of bacteremia is usually harmless in healthy people.

What does an intermittent bacteremic pattern indicate?

Intermittent

Bacteria are present in the bloodstream in a recurring pattern, often due to an undrained abscess or biofilm.

What does an persistent bacteremic pattern indicate?

Persistent

Bacteria are continuously present in the bloodstream, which can be fatal if left untreated.

What is systemic inflammatory response syndrome?

Systemic inflammatory response syndrome (SIRS) - systemic signs of inflammation (infection, trauma, burns, surgery, thrombo- embolism, autoimmune disease, chemical poisoning, vasculitis)

What are uncomplicated infections?

not sepsis, no systemic features of organ failure, localized

What is severe sepsis?

Sepsis induced organ dysfunction or tissue hypo-perfusion

What is septic shock?

sepsis induced hypotension, which does not respond to fluid resuscitation

Describe the continuum from infection to septic shock.

Infection leads to sepsis, leading to organ dysfunction, severe sepsis and then septic shock and multiple organ dysfunction

What are the main causes of sepsis?

• Bacteria, Gram positive and Gram negative and their products

• Fungi - yeasts and filamentous fungi

• Some systemic and localised viral infections, eg - canine parvovirus, influenza, ebola

• Malaria

Describe the normal inflammatory response, and the systemic proinflammatory state should it progress to sepsis.

Host response to infection is normally a localized inflammatory process mediated by phagocytic cells with little host tissue damage or physiological derangement

Pattern recognition receptors on these cells, (toll-like receptors) bind to molecular patterns on invading pathogens, triggering a balance of proinflammatory and anti-inflammatory reactions, thereby eliminating the infection. In sepsis this balance is unseated.

The systemic proinflammatory state of sepsis, severe sepsis, and septic shock is orchestrated by cytokine (e.g., IL-1, TNF-a) and non-cytokine (e.g., nitric oxide) mediators. The anti-inflammatory state is marked by immunosuppression and anergy.

How can you get sepsis from a severe soft tissue infection (No bacteria in blood)?

Due to bacterial components in the blood

• A localised infection (e.g., lung, urinary tract, skin, soft tissue) releases bacterial components (peptidoglycan, LPS) into the blood causing clinical symptoms

• There are no live bacteria in the blood (blood cultures are negative)

Describe what gram-negative bacteria may release into the body, causing sepsis and altering normal physiology?

- Endotoxin = lipid A of lipopolysaccharide promotes IL1, TNF & complement activation

Describe what gram-positive bacteria may release into the body, causing sepsis and altering normal physiology?

- peptidoglycan

- Exotoxins, act as super-antigens similar pathways as above

Clinically, can you differentiate between gram-negative and gram-positive infections?

no, very difficult to distinguish

What do superantigens released by gram-positive bacteria cause?

• Certain bacterial toxins called Superantigens cause the systemic symptoms of shock

• Bacteria involved in skin or soft tissue infection release these toxins which have systemic effects

How many T-cells do normal antigens stimulate?

How many T-cells do super antigens stimulate, what may this cause?

• Stimulate < 0.01% of T Cells

• Stimulate 2 - 20% of T Cells

  • Causing massive release of pro-inflammatory cytokines → leading to shock

  • Often S.aureus and streptococcus, or step. canis

Describe the sepsis cascade.

• Infection (Bacterial, viral, fungal, parasitic, endotoxins)

• Increased inflammation, coagulation, decreased fibrinolysis

• Causing endothelial dysfunction and microvascular thrombosis

• Leading to hypofusion ischemia

• Causing acute organ dysfunction

How do hosts recognize foreign invaders?

Recognise conserved molecules present on many pathogens

- Pathogen-associated molecular patterns (PAMPs)

- NB - present on non-pathogens

What are some examples of structures or bacterial molecules which are recognized by the host cells?

- Lipid A (LPS), G -ve bacteria

- Peptidoglycan, G +ve (G-ve) bacteria

- Bacterial DNA, all bacteria

- Bacterial lipoproteins, all bacteria

What are host-cell pattern-recognition receptors? (PRRs)

These are recognition molecules, which link between the organism and activation of the immune response or sepsis response in the host - toll like receptors (TLR's)

• TLR-2 - Peptidoglycan, lipoproteins

• TLR-4 - LPS, Lipid A

• TLR-5 - Flagellin

• TLR-9 - Bacterial DNA

**There are also intracellular TLRs for viruses or intracellular bacteria.

Why is the macrophage important in developing an immune response?

• Once activated they release cytokines, leading to…

  • Decreased muscle tone of heart and arteries

  • Fever

  • Increased leakage of plasma from blood vessels

  • Causing shock and impaired O2 exchange

• Also activate the complement

  • Leukocytes attracted to lung tissue

  • Increased capillary leakage of plasma

  • Lysosomal enzymes released from leukocytes

  • Causing Lung Tissue Damage

• Also activate clotting

  • Clotting in tissues (Used up all of CF in tissue)

  • Causing hemorrhage

What are clinical complications of severe sepsis/septic shock?

• Acute Respiratory Distress Syndrome (ARDS)

• Cardiac output initially rises then falls

• Hypotension often leads to renal failure

• Haematology: increased white cells, decreased platelets

• Disseminated Intravascular Coagulation (DIC)

• Widespread tissue ischemia & organ failure

• Increased bleeding

What therapy is used to treat sepsis?

• Sepsis requires 'goal directed therapy'

  • Want to restore normal and maintain of physiological parameters as close to normal as possible

• Fluid management - maintain arterial and venous pressures

• Respiratory support - oxygen or ventilator

• Renal support

  • When BP fails, kidneys suffer, requiring renal support

• Antimicrobial chemotherapy within 1 hour of diagnosis

Viral infections may cause…

Clinical signs of sepsis

What is primary viraemia?

What is secondary viraemia?

• Primary Viremia

  The presence of a large amount of viruses in the blood. It's a common part of most viral infections. 

• Secondary viremia

  When a virus spreads from the initial infection site to other tissues through the bloodstream. This can lead to more severe infections

  • After reinvading the bloodstream after the primary