Infection Flashcards
What are the pharmacodynamic principles of antibacterials?
Each has a MIC, minimum inhibitory concentration and MBC, minimum bacteriocidal concentration.
The MIC and MBC decide the potency and effectiveness of the drug
What are the desirable properties of Antimicrobials?
- Reach the site of infection
- No adverse effects
- Selective toxicity
- Long half life
- Oral / IV formulation
- No interference with other drugs
What are the mechanisms of antimicrobial resistance?
- Drug inactivating enzymes
- Altered target
- Decrease permeability for the drug
- Increase efflux
Give an example of an antimicrobial whose resistance is due to drug inactivating enzymes
Beta lactams, amino glycosides
B lactamases, amino glycoside enzymes
Give an example of a drug whose resistance is conferred due to altered target, giving the drug a lower affinity for the bacteria
Methicillin, macrolides, trimethoprim
Name a drug whose resistance is due to decreased permeability
Beta lactams
Name a drug which resistance is due to increased efflux
Tetracycline
What is antimicrobial stewardship?
Combined interventions designed to improve and measure the appropriate use of antimicrobials
What are the complications of acute sepsis?
Irreversible hypotension Respiratory failure Renal failure Raised intracranial pressure- compromises cerebral function- chronic problems Ischaemic necrosis of the extremities
What is SIRS?
Response to insult eg ischaemia, trauma, infection
2 or more of the following: Resp rate >20 Temp 38*C Heart rate >90bpm WBC <12x10^9/L
What is sepsis?
Systemic response to infection. SIRS with a documented or presumed infection
Define septicaemia
Generalised sepsis, usually due to bacteraemia
Define severe sepsis
SIRS and organ dysfunction due to organ hypoperfusion. Presents as renal failure with decreased urine output
Define septic shock
Severe sepsis with persistently low blood pressure despite IV fluids
What is the sepsis 6?
- High flow oxygen
- Take blood and other cultures, consider source control
- Empirical IV antibiotics
- Measure serum lactate- indicates oxygen levels
- IV fluid resuscitation
- Accurate urine output measurement- indicate renal function
State 3 physical barriers against infection
Skin
Mucous membranes
Bronchial cilia
State 4 physiological barriers against pathogens
Diarrhoea
Vomiting
Coughing
Sneezing
State 2 chemical barriers against pathogens
Low pH of skin, stomach and vagina
Antimicrobial molecules
IgA- secreted by mucus membranes, found in tears and saliva. Prevents attachment
Lysozymes- found in sebum, perspiration, urine. Makes holes in bacteria
Mucus- traps pathogens
Beta defensins- epithelial cells’ defence against viruses
Gastric acid and pepsin
Describe the biological barriers against pathogens
Commensal microorganisms found in strategic locations (nasopharyngeal, vagina, mouth/ throat, GI tract) compete with pathogens for attachment sites and resources and produce antimicrobial chemicals. Some synthesise vitamins
Describe the second line of defence against pathogens
PRRs (toll like receptors) on phagocytes recognise PAMPS on the microbe. Phagocytosis occurs, forming a phagosome. A lysosome fuses to form a phagolysosome. Enzymes digest the microbe using the oxygen dependent or oxygen independent intracellular killing mechanism, and the indigestible material forms residual bodies. Waste materials are discharged.
What do cytokines do?
- Act on the liver to produce CRP and MBL - opsonise microbes and MBL activates the complement system
- Bone marrow to mobilise neutrophils
- Hypothalamus to increase body temperature
- Vasodilation
- Increase vascular permeability
- Adhesion molecules to attract neutrophils
How is the complement system activated?
Alternative Pathway- initiated by cell surface microbial constituents
MBL Pathway- initiated when MBL (acute phase protein) binds to mannose containing residues of proteins
What is the MBL pathway?
A way of activating the complement system, initiated when MBL (acute phase protein) binds to mannose containing residues of proteins
What does the complement system do?
Produced by hepatocytes, circulate as inactivated precursors. When activated they: Opsonise (C3b-C4b) Chemotaxis (C3a and C5a) Cell lysis (C5-C9) Agglutination - clumping of cells
