Session 7 Flashcards
Understand the concept of microbiota and how do people get infections?
[*] Microbiota = “Commensals” - microorganisms carried on skin and mucosal surfaces.
[*] Normally harmless or even beneficial but when transferred to other sites, can be harmful.
[*] How do people get infections?
- Invasion e.g. Strep pyogenes Pharyngitis
- Migration e.g. Escherichia coli urinary tract infection
- Innoculation e.g. Coagulase negative staphylococcus prosthetic joint (bacteria is on the surface – surgical incision allows bacteria entry into body)
- Haematogenous e.g. viridans Strep endocarditis (bacteria comes from mouth due to bad oral hygiene and settles on heart valves)
What microorganisms are found on the skin?
Viruses
- Papilloma: skin warts, genital warts
- Herpes simplex: cold sores, genital herpes
Gram positive Bacteria
- Staph aureus
- Coagulase negative staphylococci
- Coyrynebacterium (gram positive rods) – contaminate blood cultures
Gram negative Bacteria
- Enterobacteriaceae e.g. in skin ulcers
Fungi
- Yeast (Candida). Organisms like to live in folds of flesh (obese patients)
- Dermatophytes – mould (multicellular) – infect skin, hair, nails. Can cause athlete’s foot.
Parasites:
- Mites – under eyelashes, skin, can lead to scabies, hair loss
Appreciate the range of mucosal flora
- Eye: Coagulase negative staphylococci, diphtheroids, saprophytic Neisseria species, viridans group streptococci
- Nares: staph aureus
- Nasopharynx: Neisseria meningitidis, Streptococcus pneumonia, Haemophilus influenzae
- Mouth: Viridans streptococci, Neisseria, Veillonella, Lactobacillus, Actinomyces, Bacteroides, Capnocytophaga, Eikenella, Prevotella, Fusobacteria, Clostridia, Propionbacteria, Candida, Geotrichum prvird
- Stomach: Helicobacter, streptococci, staphylococci, lactobacilli
- Intestine: Bacteroides, bifidobacterium, eubacterium, lactobacillus, coliforms, aerobic and anaerobic streptococci, clostridium, yeasts
- Urethra: enterobacteriaceae, lactobacilli, diphtheroids, alpha and non-haemolytic streptococci, enterococci
- Vagina: lactobacilli, diphtheroids, micrococci, coagulase-negative staphylococci, Enterocccus faecalis, microaerophilic and anaerobic streptococci, mycoplasmas, ureaplasmas, yeast (some antibiotics can lead to an overgrowth of yeast => thrush, some women may carry Group B streptococci which can be dangerous in pregnant women as babies born via vagina can pick it up)
What are examples of external natural surface infections?
- Cellulitis
- Pharyngitis
- Conjunctivitis
- Gastroenteritis
- Urinary tract infection
- Pneumonia
What are examples of internal natural surface infections?
- Endovascular: endocarditis, vasculitis (inflammation of the blood vessels)
- Septic arthritis (infection outside bone)
- Osteomyelitis (infection inside bone)
- Empyema (pus in the pleural cavity)
What are examples of prosthetic joint surface infections?
- Intravascular lines
- Peritoneal dialysis catheters
- Prosthetic joints
- Cardiac valves (more susceptible to infection than natural valves)
- Pacing wires
- Endovascular grafts
- Ventriculo-peritoneal shunts (release pressure from intracranial fluid)
- Urethral catheters – leading cause of hospital-acquired infections (Catheter-associated urinary tract infection)
Describe the causative organisms of Prosthetic Valve Endocarditis, Prosthetic Joint Infection, Cardiac Pacing Wire Endocarditis
[*] Prosthetic Valve Endocarditis
- Native valve endocarditis and prosthetic valve endocarditis (>1 year post-operation): viridans Streptococci, Enterococcus faecalis, Staph aureus, HACEK group, Candida
- Prosthetic valve endocarditis <1 year post-operation: coagulase negative staphylococci
[*] Prosthetic joint infection – causative organisms: coagulase negative staphylococci, Staphylococcus aureus
[*] Cardiac pacing wire endocarditis – causative organisms: coagulase negative staphylococci, staphylococcus aureus
Describe the pathogenesis of infections at a surface
[*] Adherence to host cells or prosthetic surface via pili or fimbriae
[*] Biofilm formation – a biofilm is any group of microorganisms in which cells stick to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance (EPS). Biofilm prevent complement and antibodies from harming bacteria.
[*] Invasion and multiplication
[*] Host response – pyogenic (neutrophils -> via production of ROS species =>pus) and granulomatous (fibroblasts, lymphocytes, macrophages => nodular inflammatory lesions)
Describe Biofilm Formation
- Starvation can induce bacteria to shrink and adopt a spore-like state known as ultramicrobacteria, which wait in water, soil, rock or tissue until conditions are suitable for active growth.
- Active bacteria can attach to almost any surface. Changes in gene expression transform ‘swimmers’ to ‘stickers’ within minutes.
- Attached bacteria multiply and encase the colonies with a slimy matrix
- Nutrients diffuse into the matrix
- The close proximity of cells in the matrix facilitates the exchange of molecular signals that regulate behaviour
- Chemical gradients create microenvironments for different microbial species or levels of activity
- Although antimicrobials damage outer cell layers, the biofilm community is resistant
- Propelled by shear forces, aggregated cells can become detached, or roll or ripple along a surface in sheets and remain in their protected biofilm state
Describe Quorum sensing in bacteria
[*] Quorum sensing in bacteria: a system of stimulus and response correlated to population density. Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population.
Controls
- Sporulation
- Biofilm formation
- Virulence factor secretion
Three principles
- Signalling molecules – autoinducers (AI) – released into bacterial environment
- Autoinducers float across and bind to cell surface or cytoplasmic receptors on other bacteria (signal to these bacteria that there’s a lot of bacteria around, indicating good area for replication)
- Gene expression => cooperative behaviours and more AI production (positive feedback). This leads onto biofilm production.
Describe Diagnosis and Management (Treatment) of Surface Infections
[*] Diagnosis – aim is to identify infecting organism and its antimicrobial susceptibilities
Challenges
- Adherent organisms
- Low metabolic state/small colony variants (so difficult to culture)
Blood cultures
Tissue/prosthetic material sonication (to get rid of biofilm) and culture
[*] ** Treatment**
- Aim: sterilise tissue and reduce bioburden
- Antibacterials
- Remove prosthetic material
- Surgery – resect (remove) infected material
Challenges
- Poor antibacterial penetration into biofilm
- Low metabolic activity of biofilm micro-organisms
- Dangers/difficulties of surgery
Describe Prevention of Surface Infections
Natural surface
- Maintain surface integrity
- Prevent bacterial surface colonisation
- Remove colonising bacteria
- E.g. disinfecting before surgery, carrying out operations in ultra-cleaned air (our sterilised by filtration)
Prosthetic surfaces
- Prevent contamination
- Inhibit surface colonisation
- Remove colonising bacteria
[*] Summary
- Natural and prosthetic surfaces are frequent sites of infection
- Biofilms are a common feature of surface infections
- Bacteria are protected from host and antibacterial attack by biofilms
What is hypersensitivity and describe its common features
[*] Hypersensitivity: the antigen-specific (antigen-driven) immune responses that are either inappropriate or excessive and result in harm to host. The mechanisms underlying these aberrant immune responses are those employed by the host to fight infections
[*] Common feature of hypersensitivity reactions
- Sensitization phase – first encounter with the antigen (allergen in allergy). The individual starts producing immune response. No clinical manifestation at this stage.
- Effector phase: clinical pathology upon re-exposure to the same antigen (clinical manifestation)
What are the types of hypersensitivity reactions?
- Type I or immediate (<30 mins, depending on how the allergen gets into the blood plasma): Allergies
- In response to environmental non-infectious antigens (allergens), driven by IgE
- Type II or antibody mediated (5-12 hours) – driven by IgM and IgG – directed against membrane or tissue complex on cell surface (host cell perceived by the immune system as foreign, leading to cellular destruction)
- Type III or immune complexes mediated (3-8 hours): driven by IgM and IgG, soluble antigen => forms immune complex. IgG binds to soluble antigen forming a circulating immune complex. This is often deposited in the vessel walls of the joints and kidney, initiating a local inflammatory reaction
- Type IV or cell mediated (24-48 hours) – most T cells aided by macrophages against environmental infectious agents and self-antigens
Describe the epidemiology of allergies
- Increasing worldwide prevalence
- UK is in Top 3 countries with the highest incidence of allergy
- >50% of chidren in the UK
- 13 million <45 years old have 2 or more allergies
- 1 in 50 children has peanut allergy
- Life-threatening reactions (anaphylactic shock)
- Systemic reaction to allergen (insect venom, food)
- £900 million/annum (primary care)
Why do people get allergies?
[*] A lack of early childhood exposure to infectious agents, symbiotic microorganisms (e.g. gut flora or probiotics) and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system. In particular the lack of exposure is thought to lead to defects in the establishment of immune tolerance.
- Immune system is not educated – does not learn to recognise pathogen from non-harmful.
- In people with allergies, they have TH2 phenotype – increased IgE production which is involved in allergic responses
- In people who have non-allergic genes, they have TH1 phenotype
What are common allergens and describe clinical cross-reactivity
- House dust mite (sufferers are sensitive to proteins present in the droppings, not actual bug), cockroaches
- Animals, especially domestic pets such as cats and dogs
- Tree and grass pollens
- Insect venom such as that contained in wasp and bee stings
- Medicines for example the antibiotic penicillin
- Chemicals such as latex
- Food such as milk, peanuts, nuts, etc
[*] Clinical cross-reactivity: if a patient has an allergen, increased risk of developing allergies to other allergens due to structural homology
Describe the immune mechanism of the allergic reaction
- Allergen 1st exposure: antigen-specific IgE antibody made => IgE-mediated triggering of mast cell (binds to high affinity IgE receptor). This is clinically silent ‘allergenic sensitisation).
- Allergen 2nd exposure: antigen binds to 2 IgE molecules “cross-linking” signalling mast cells to degranulate and release their mediators wherever they are in the body
Triggering release of granule contents (histamine, chemokines)
Synthesis of new mediators – leukotrienes, prostaglandins
This all leads to increased vascular permeability, vasodilation, bronchial constriction
Direct activation of mast cells also occur via irritants such as C3a and C5a.
Diagnosis: blood/serum levels of mast cell products e.g. histamine, tryptase are indications of systemic mast cell activation/degranulation
Describe the skin prick test for allergy
[*] Skin Prick Test for Allergy: detects the existence of antigen-specific IgE antibodies (indicates sensitization) by injecting allergen into the epidermis
- Wheal-and-Flare reaction: the characteristic immediate reaction to a skin test, in which an irregular blanched wheel appears surrounded by an area of redness – caused a release of histamine => fluid leaks under the skin from surrounding capillaries.
- Characterised by redness and swelling
Describe the treatment of anaphylactic shock
[*] Treatment of anaphylactic shock: intramuscular adrenaline
- Reverses peripheral vasodilation and reduces oedema
- Reverses airway obstruction/bronchospasm
- Increases the force of myocardial contraction
- Inhibits mast cell activation
- DO NOT DELAY TREATMENT – window of 30 minutes between allergen and cardiac arrest in more sensitive patients
- Monitor pulse, blood pressure, ECG, oximetry
