Infection Flashcards
Define an ‘infection’
Invasion of a host’s tissues by a microorganism
Disease/illness that’s caused by toxins, microbial multiplication or by a host response
What are commensals?
Microorganisms normally carried on skin and mucosal surfaces. They’re normally harmless and can be beneficial but if they’re transferred to other locations, they can be harmful
What are some examples of horizontal transmission of an infection?
Direct contact, inhalation, ingestion
What are some examples of virulence factors?
They’re molecules expressed that help cause disease.
Endotoxins or
Exotoxins such as enzymes, antibody toxins and superantigens
What are the disease determinants involved in developing infections, with specific reference to Patient and Pathogen?
Patient - co-morbidities and infection site
Pathogen - virulence factors and resistance
What are the most important specific investigations that can be carried out in bacteriology?
Microscopy
Culture
Antibiotic susceptibility testing
What are the main functions of the lymphatic system?
Immune defecne
Fluid balance
Fat absorption from gut via lacteals in small intestine
What’s the function of lymphatic capillaries and vessels?
To circulate excess fluid, away from interstitium and into blood stream.
Briefly describe the structure of lymphatic capillaries
Similar to blood capillaries, with one layer of simple squamous epithelium but there is no basement membrane so lymphatics are more permeable than blood vessels.
Briefly describe the structure of lymphatic vessels
Similar to small veins. Have one way valves
What forces help promote flow of lymph in the right direction?
Valves in vessels but also compression due to skeletal muscle contraction, smooth muscle contraction in walls of lymphatic vessels, and pressure changes due to breathing, in the chest
Where do lymphatic vessels drain into?
The right upper limb and the right half of the head, neck and chest drain into the right lymphatic duct which then drains into the right subclavian vein.
The rest of the body’s lymph drains into the thoracic duct which then drains into the left subclavian vein
What are the four main lymphoid organs?
Lymph nodes
spleen
tonsils
thymus gland
When is the thymus at its peak size
Adolescence/ pre puberty
What are the functions of the spleen?
Hold a blood reserve.
Red pulp - removal of old RBCs
White pulp - lymphocyte activation
What is SIRS?
Sytemic Inflammatory Response Syndrome Patient must have 2 of more of these signs Heart rate>90 bpm Temp 38 WBC 12x109 Resp rate >20
What is sepsis?
The systemic response to infection
What is classed as severe sepsis?
SIRS + either organ dysfunction or hypoperfusion
What is classed as septic shock?
Severe sepsis + persistent hypotension, despite IV fluid administration
What is ‘the sepsis six’?
Steps that should be taken in treatment of sepsis High flow oxygen cultures empirical IV antibiotics Measure serum lactate IV fluid resuscitation Urine output measurement
What is the cascade that leads to SIRS?
An endotoxin binds to macrophages and macrophages then stimulate the local release of cytokines such as TNF and IL 1. This stimulates an inflammatory response.
There is then systemic release of cytokines into the blood stream, promoting growth factor, macrophages and platelets to try and restore homeostasis.
If this fails, there is vascular damage and activation of humoral cascade - SIRS
What are the most common causative agents of bacterial meningitis in neonates?
Group B strep
Listeria
E coli
What are the most common causative agents of bacterial meningitis in under 5s?
Neisesseria meningitidis
What are the most common causative agents of bacterial meningitis in the elderly?
Streptococcus pneomoniae
Listeria
What is found in CSF of patients with bacterial meningitis?
Low glucose
High protein
High neutrophils
Why is a Meningitis B vaccine not used?
Group B meningitis agent is too similar to neural tissue so extremely difficult to develop a safe vaccine for use
Where are beta-defensins found?
Epithelia where they’re toxic to microbes
Where are lysozymes found as a chemical barrier?
Sebum, perspiration, urine, where they make holes in cell walls
Why is normal flora an effective biological barrier against infection?
Compete with pathogens for binding sites and other resources
Produce antimicrobial chemicals
Synthesise vitamins, especially B and K
What are the main functions of the immune system?
Minimisation of host damage
Containing and removing infection
Recognition of pathogens
Memory to prevent recurrence
Describe the process of phagocytosis
Innate cells recognise microbes via PAMPs. Microbe is opsonised and then zippered up into phagocyte to form phagosome. This fuses with lysosome to form a phagolysosome. Phagocyte then kills microbe either by enzymatic digestion or oxidative burst
What are the most common opsonins of the innate immune system?
C3a/C5a
CRP
How does the complement cascade result in killing of a microbe?
Forms a membrane attack complex in microbe wall which causes cell lysis
How can the 4 Ps of infection prevention be applied to healthcare infections?
Patient - COnsider patient interactions e.g. with other patients, staff or visitors
Pathogen - consider virulence factors and antibiotic resistance/ interactions
Practice - initiatives and policies, activities of healthcare workers and organisational structure
What patient interventions can be made in infection control?
Optimise patient’s condition and use antibiotic prophylaxis. Halt patient to patient transmission through isolation/protection
What healthcare worker interventions can be made in infection control?
Ensure staff are disease free and vaccinated.
Ensure good sterile clinical techniques are carried out and that personal protective equipment is used
What environmental interventions can be made in infection control?
Try to ensure toilets are well distributed and clean
Consider use of easy-clean furnishings and rooms with positive/negative pressure
Ensure medical devices are sterilised/decontaminated and single use
Describe the characteristics of Clostridium difficile
It’s a gram positive, anaerobic, spore formind bacilli.
What can cause C diff infection?
Antibiotic use diminishing normal gut flora so c diff is allowed to proliferate
How does C diff cause its symptoms?
Releases toxins a and b which inactivate gtpases and reduce amount of actin in cytoskeletons to increase permeability of cell membranes so water leaks out - diarrhoea
What are the characteristics of staphylococcus aureus?
Gram positive cocci
How does staph aureus cause infection?
Produces cell surface toxins that bind to and inactivate antibodies
What are the main species of malaria parasite?
Plasmodium falciparum, vivax, ovale and malariae
What causes enteric fever?
Salmonella enterica - a gram -ve enterobacteriaceae that’s aerobic,a rod and a non-lactose fermenter
What are the symptoms and signs of enteric fever?
Fever, headache, abdominal discomfort, dry cough, rash, hepatosplenomegaly, bradycardia, constipation. Maybe be intestinal perforation and haemorrhage
What abnormalities would be found in an FBC of a patient with enteric fever?
Anaemia and decreased lymphocytes
How is enteric fever treated?
With ceftriaxone of azithromycin for milder cases, for 7-14 days
How should malaria be treated?
Depends on species.
P. Falciparum should be treated with quinine or artemisinin
Other types should be treated with chloroquinine and/or primaquine
What tests should be done to confirm diagnosis of malaria?
Blood smear using giemsa stain to detect parasite
FBC
U and Es
LFTs
Glucose test as metabolism can be affected
What kind of virus is the HIV virus?
Single stranded RNA
What symptoms are there in the primary infection of HIV?
Flu like illness fever pharyngitis weight loss general lymphadenopathy
How does HIV exert its effect?
Attaches to host CD4 cells and then use reverse transcriptase to convert its genome to DNA, which integrates into the host nucleus. Then replicates viral components which assemble and released. As virus attaches to CD4 signals, it stimulates an immune response against CD4 cells, causing CD4 levels to drop and viral load to increase so becomes symptomatic
How is HIV treated?
With Highly Active Antiretroviral Therapy which act to increase CD4 levels and decrease viral load
What investigations should be done in investigating HIV?
Blood test Immunoblot Resistance profile Viral load CD4 levels
What kind of virus is Hep B?
Double stranded DNA
What are the different outcomes of an initial infection with hep b?
Can be acute whereby viral load increases and immune response causes symptoms but immune system clears infection.
Can be chronic where immune system can’t clear infection so causes inflammation and cirrhosis
What are the signs and symptoms of chronic hep B?
Jaundice
ascites
caput medusa
clubbing (signs of liver disease)
What kind of virus is hep c?
Single stranded RNA
What’s the classification of lymphoid organs?
Primary organs that produce mature lymphocytes. i.e. bone marrow and thymus
Secondary organs where lymphocyte activation takes place
What is meant by co-stimulation in T cell activation?
Ensures only harmful antigens are responded to and not self-antigens. Antigen presenting cells containing harmful antigen express a B7 molecule on their surface to bind to CD28 molecule on a T cell which signals that it requires a response. If this doesn’t happen, T cell becomes ‘anergised’
What are the 2 main steps of T cell maturation?
Positive selection - cells that bind to foreign antigens survive and replicate
Negative selection - cells that bind to self-tissues are deleted
What are the 2 types of MHCs and what do they present?
Class 1 MHCs present intracellular pathogens to CD8 cytotoxic cells, via exogenous pathway
Class 2 MHCs present extracellular pathogens to CD4 cells, via endogenous pathway
What type of antibody is found in breast milk?
IgA
What type of antibody can cross the placenta?
IgG
What type of antibody is responsible for primary response to an antigen?
IgM
What type of antibody is involved in allergic responses?
IgE
How do CD8 T cells exert their cytotoxic effect?
Release perforins which make a pore in the cell membrane then release granzymes which enter through this pore and stimulate apoptosis
How can commensals cause infection?
Through migration, inoculation, invasion and through blood stream
What is qurum sensing?
Process by which bacteria monitor local population. Uses signalling molecules called autoinducers, cell surface and cytoplasmic receptors and gene expression to increase autoinducer formation and control behaviour of bacteriae
What’s difficult about treating surface infections?
Biofilms are difficult to penetrate with antimicrobials and then microorganisms aren’t very metabolically active so don’t take up drugs quickly so drugs are inneffective.
resection of infection is also risky due to risks of surgery
What causes rhesus disease?
When mother is eg rhesus negative and foetus is rhesus positive. If small amount of blood passes from foetal - maternal circulation (ie through small haemorrhage) then foetal Rh stimulates inflammatory response in mother and IgM - IgG are produced. IgG then crosses placenta and causes haemolytic anaemia in foetus.
How is rhesus disease treated?
Give anti-RhD antibodies to mother
Why do primary immunodeficiencies tend to present roughly 1 month after birth?
As until then, they still have some maternal immunity via IgG which crosses the placenta. After that’s gone - present with immune problems
What is the mechanisms behind Common Variable Immunodeficiency?
Failure of B cells to mature into plasma cells so there’s low IgG, IgA and IgM
What is Bruton’s disease?
X-linked agammaglobulinaemia. There’s no tyrosine kinase so B cells can’t mature. There’s low IgG and undetectable IgA
Causes failure to thrive and recurrent bacterial respiratory infections and diarrhoea which can be fatal. Also undetectable tonsils and adenoids
What is chronic granulomatous disease?
Neutrophils fail to make oxygen radicals so ixidative burst fails in killing of bacteria. Therefore many granulomas form (frustrated phagocytosis)
There’s failure to thrive and increase in deep seated infections, especially staph aureus infections of the skin that need surgical removal.
What is DiGeorge syndrome?
T cell CATCH 22 disease. With cardiac abnormalities, abnormal facies, tymus aplasia, cleft palate and hypocalcaemia/ hypoparathyroidism, due to defect on 22nd chromosome. There’s failure of 3rd and 4 th pharyngeal arch development. Thymus aplasia means T cells can’t mature so there’s increased susceptibility to infection
What is Severe Combined Immunodeficiency?
Deficiency in T and B cells so cellular and humoral components of adaptive immune system are absent. There are recurrent severe respiratory infections and diarrhoea after first month of life and can be fatal if untreated. (boy in bubble syndrome)
How is SCID treated?
Reverse barrier nursing
Prophylactic antibiotics
IV immunoglobulins
Potentially bone marrow transplant
When does neutropenic sepsis normally occur?
In cytotoxic chemotherapy. Kills neutrophils. Neutropenia leads to increased susceptibility to infection so can be sepsis.
What is a ‘dead end infection’?
One that spreads from non-human source to human but can’t pass between humans
What can cause an outbreak/epidemic/pandemic?
Pathogen that’s either never been around before or that has new characteristics such as virulence factors, antibacterial resistanceor antigens
Host that’s either never been seen in that location before or host that used to be immune but isn’t anymore
New practice - either social or healthcare related
What is basic reproduction number?
Average number of cases of disease that one original case causes in an otherwise non-infected non-immune population
What are some disadvantages of infection control?
Decreased exposure decreases immunity so outbreaks on re-exposure are more common
Also an increase in average exposure age can increase the severity upon infectionsuch as in chickenpox
What are some common adverse effects of antibiotic use?
GI upsets Allergies/skin rashes Organ toxicity Super infections Haematological disturbances
How do beta lactams exert their effects?
By inhibiting peptidoglycan cross-linkages in bacterial cell walls.
What are penicillins active against?
Penicillin - streptococci
Amoxicillin - Streptococci and gram negatives
Flucloxacillin - Streptococci and staphylococci
What are cephalosporins active against?
Made in generations.
Increasingly active against gram negative and decreasingly active against gram positives. Not effective against anaerobes.
Ceftriaxone has good CSF action
What are carbopenems active against?
Very broad but predominantly anaerobes and gram negatives. Can be safe in mild penicillin allergies
What are beta-lactamase inhibitor combinations used for?
Coamoxiclav used for streptococci, staphylococci, gram negative and anaerobes
Piperacillin/Tazobactam used for streptococci, staphylococci, anaerobes and more gram negatives, including pseudomonas
How do glycopeptides exert their effects?
Inhibit peptidoglycan cross-linking in gram positive organisms.
Which antibacterials affect protein synthesis?
Tetracyclines, aminoglycosides and macrolides
How do tetracyclines work and what are they used for?
Bind to 30S ribosomal subunit to block aminoacyl tRNA and prevent protein transcription.
Used especially in penicillin allergies against gram positive organisms. Also active in chlamydia and atypical pneumonia
What are aminoglycosides used for?
e.g gentamycin. Mostly reserved for gram negative sepsis as they are potentially nephrotoxic and ototoxic and so need therapeutic drug monitoring.
What are macrolides used for?
eg erythromycin.
Used against gram positive cocci, anaerobes (not bacteroides), mycoplasma, chlamydia and atypical respiratory infections. Can be used as penicillin alternative in gram positive infection.
What antibacterial affect nucleic acid synthesis?
Quinolones, eg ciprofloxacin
Sulphonamids and trimethprim eg nitrofurantoin
How do quinolones work?
Inhibit DNA gyrase. Highly active against gram negatives and atypical pathogens but have C. difficile association
How do sulphonamides work?
Inhibit folic acid synthesis by inhibiting tetrahydrofolate. Can be combined with sulphamethoxazole to give co-trimoxazole, used in PCP and MRSA
How does aciclovir work?
By inhibiting DNA polymerase. Used to treat herpes simplex virus and varicella zoster
What is metronidazole used for?
As an antibacterial against anaerobes and as an antiviral.
Effective against amoebae, such as those that cause dysentery, giardia that cause diarrhoea and against trichomas that causes vaginitis.
What is a common antifungal agent?
Azoles such as fluconazole inhibits cell membrane synthesis so used in candida infections
How can problems with antibiotic resistance be reduced?
Antimicrobial stewardship which involves antimicrobials are taken correctly
Infection control involving reducing exposure of bacteria to antibiotics and preventing spread of resistant bacteria
What is the role of disc sensitivity testing and E tests.
Discs analyse what antibiotics a certain bacteria is resistant to and then E tests analyse the extent of susceptibility/resistance so at what concentration is a bacteria resistant
What are the differences in cell wall structure of gram negative and gram positive organisms?
Gram negative have plasma membrane, periplasmic surface, thin peptidoglycan wall, another periplasmic surface and a lipopolysaccharide protien layer.
Gram positive bacteria have cell membrane, periplasmic surface and a thick peptidoglycan layer?
How does cell wall structure effect gram staining result?
Gram staining involves adding crystal violet and iodine. This complex is retained by the peptidoglycan layer. There is then decolourisation by alcohol/acetone. This only works in gram negative bacteria as their peptidoglycan layer is thinner so doesn’t retain the crystal violet/iodine. Then red dye is added. This dyes the uncoloured gram negative bacteria red but gram positive stay blue/purple
What kind of bacteria is E coli?
Gram negative bacilli
How is E coli treated?
If UTI - nitrofurantoin and trimethoprim
In general, Cephalosporin or Co-amoxiclav
What does staph aureus look like under a microscope?
Purple/blue if gram stained. Forms grape like clusters
How is staph aureus treated?
Methicillin/ flucoxacillin
If MRSA, use vancomycin/teicoplanin
How is strep pneumoniae treated?
Preferably penicillin
If resistant, use vancomycin
How is C diff infection treated?
Fluids and remove causative antibiotics if possible.
Can also use Oral metronidazole/vancomycin
What kind of bacteria is haemohilus influenzae?
Gram negative coccobacilli. Facultative anaerobe
How is H. influenzae treated?
Co amoxiclav
