Infection Flashcards
What are some examples of beta lactams and how do they work?
Penicillin, cephalosporins, carbopenems
Work by preventing cross linking of peptidoglycans and so inhibit cell wall synthesis.
What is an example of a glycopeptide and how does it work?
Vancomycin, works by inhibiting cell wall synthesis.
What classes of antibacterials work by targeting protein synthesis?
Tetracyclines, aminoglycosides and macrolides.
What are the ideal features of antimicrobials?
Long half life, few adverse effects, selectively toxic, oral/IV formula (or both!), no interference with other drugs, can reach the site of infection
What are some mechanism by which cells can become resistance to an antimicrobial?
- reduced uptake or increased efflux
- altered target
- drug inactivating enzymes (eg beta lactamases)
- gene mutation
- horizontal gene transfer
What antibacterial can be used against mild gram +ve infections if allergic to penicillin?
Macrolides (eg erythromycin, clarithromycin) bind to 50s ribosomal subunit to inhibit protein synthesis.
List all known gram positive cocci.
Strept pneumoniae
Staph aureus
Coagulase negative staph
Enterococcus faecalis
List all known gram negative cocci.
Neisseria menigitidis
Neisseria gonorrhoeae
List all known gram positive bacilli.
Clostridium difficile
List all known gram negative bacilli.
Salmonella typhi
E. coli
Haemophilus influenzae
Pseudomonas aueruginosa
Are viruses, bacteria, fungi and parasites prokaryotes or eukaryotes?
Viruses and bacteria are prokaryotes.
Fungi (yeasts and molds) and parasites (protozoa and worms) are eukaryotes.
What are 7 methods are infection can be spread?
Contiguous Inoculation Haematogenous Inhalation Vertical Ingestion Vector
What is sepsis?
Life threatening organ dysfunction due to an disregulated host response to infection.
What is septic shock?
Persisting hypotension after an infection, that requires treatment to maintain blood pressure despite fluid resuscitation.
How do we recognise sepsis in patients?
Raised early warning score (RR, BP, temp, HR) or red flags (eg raised RR, low BP, unresponsive)
Clinical features suggestive of source (eg pneumonia, meningitis, UTI)
What is the sepsis six?
- Measure serum lactate
- Take blood cultures
- Measure urine output
- Give O2
- Give fluids
- Give antibiotics IV
How is coagulation linked to sepsis?
Cytokines initiate thrombin formation and promote coagulation. Cytokines inhibit fibrinolysis. This leads to micro vascular thrombosis, and hence organ ischaemia and dysfunction.
What antibacterial is used against meningitis?
Penicillin/ vancomycin (often penicillin resistant strains) and CEFTRIAXONE (penetrates into CSF)
What are some symptoms of meningitis?
Headache Neck stiffness Non-blanching rash Fever Lack of consciousness Photophobia
What are some differences between innate and adaptive immune responses?
Innate: quick, no memory, no change in intensity, lacks specificity
Adaptive: slower, have memory, have specificity, can change in intensity
What are some innate barriers to prevent entry and limit growth of pathogens?
- Physical eg skin, mucous membranes, cilia
- Physiological eg vomiting, diarrhoea, coughing, sneezing
- Chemical eg acidic pH and antimicrobials (lysozyme, gastric acid, IgA, mucus)
- Biological ie normal flora
How do normal flora protect against pathogens?
Compete against them for resources and attachment sites
Synthesis vitamins and antimicrobials
What are monocytes?
Macrophage precursors in the blood
Large kidney-shaped nucleus
What are macrophages?
In all organs, capable of phagocytosis, presented antigens to T cells and produce cytokines & chemokines
What are neutrophils?
Can phagocytose, recruited by chemokines to site of infection. Increase in number during infection.
Multi-lobed nucleus
What are basophils & mast cells?
Release granules of heparin and histamine in allergic responses
What are eosinophils?
Defend against multi cellular parasites (worms)
Bi-lobed nucleus
What are dendritic cells?
Present antigens to T cells
What are natural killer cells?
Kill all abnormal host cells
How are pathogens recognised by the immune system?
Pathogens have PAMPs (pathogen associated molecular patterns) then are recognised by PRRs (pathogen recognition receptors) on macrophages
What is opsonisation and what are some examples of opsonins?
Opsonin proteins coat the microbes to enhance the attachment of phagocytes and hence microbe clearance. Essential to clear encapsulated bacteria.
Examples of opsonins are CRP (acute phase protein), IgG (antibody), C3b, C4b (complement proteins)
What is the complement system?
Part of the innate immune system, a collection of proteins to complement antibodies and phagocytes ability to clear microbes, promote inflammation, and attacks the pathogens plasma membrane.
What are the roles of:
C3a/C5a
C3b/C4b
C5-9
C3a & C5a recruit phagocytes
C3b & C4b opsonise pathogens
C5-C9 kill pathogens via membrane attack complex
Why are patients with decreased spleen function/ asplenic at increased risk of infection?
Splenic macrophages needed to clear opsonised encapsulated pathogens and remove immune complexes. Spleen also needed to produced antibodies (IgM acute, IgG long term).
Patients present with increased susceptibility and overwhelming infection so need immunisation, prophylactic antibiotics and medical alert bracelet.
What is chronic granulomatous disease?
Genetic defect causing deficiency in NADPH oxidase in phagocytes, which is necessary for respiratory burst. Means superoxide radicals cannot be generated hence granulomatas form and patient is more susceptible to infections.
How can superoxide dismutase and catalase protect against ROS?
SOD converts superoxide to O2 and H2O2.
Catalase then converts H2O2 to H20 + O2.
What is the function of glutathione (GSH)?
Can donate an electron to ROS. GSH then reacts with another GSH to form GSSG, catalysed by glutathione peroxidase.
GSSG then reduced back to 2GSH by glutathione reductase, but this requires electrons by NADPH which is generated by the pentose phosphate pathway. (NADPH -> NADP)
Glutathione peroxidase requires which element?
Selenium
What are free radical scavengers?
Eg vitamin C (water soluble) & vitamins E (lipid soluble), which donate a H+ and e- to free radicals in a non enzymatic reaction.
What is galactosaemia?
Lactose is broken down to glucose and galactose.
If galactose cannot be further broken down due to enzyme deficiency (galactokinase/ uridyl transferase) it is converted to galactitol. This consumes NADPH and can causes cataracts due to weaker defence against ROS.
What is glucose-6-phosphate dehydrogenase (G6PDH) deficiency?
Decreased G6PDH limits the amount of NADPH formed in the pentose phosphate pathway. NADPH is needed to reduce GSSG to 2GSH to protect against damage from oxidative stress.
Hence will cause lipid per oxidation and protein damage, key sign is Heinz bodies from cross linked Hb.
What is ischaemia reperfusion injury?
Cells that are damaged due to ischaemia (but aren’t yet necrotic) can become even more damage if their blood flow is restored. This is due to production of free radicals upon reoxygenation, and also more delivery of neutrophils and complement proteins causes inflammation.
What patient interventions can be done to reduce healthcare infections?
- Optimise their condition (ie quit smoking, control diabetes, diet)
- Antimicrobial prophylaxis
- Hand washing
- Disinfectant body wash
- MRSA screen
- Isolate infected patients and protect those susceptible
What environmental interventions can reduce healthcare infections?
- Design (ie toilets, space b/n beds, wash basins)
- Cleaning furnishing (disinfect, steam cleaning)
- Medical devices (single use/ sterilise/ disinfect)
- Appropriate kitchen facilities w. good food hygiene
- Positive/ negative pressure rooms
What is Clostridium difficile?
Gram positive anaerobic spore-forming bacilli
How does Clostridium difficile exert its pathological effects?
Produces toxins.
Toxin A is an enterotoxin that produces excess fluid secretion and inflammation of the lining of the bowel wall
Toxin B is a cytotoxin and disrupts protein synthesis within cells
What is Norovirus?
A non-enveloped single stranded RNA virus that is a major cause of acute gastroenteritis.
What are some examples of antigen presenting cells?
Dendritic cells (to B & T cells) Langerhans cells (to T) Macrophages (to T) B cells (to T)
What is this function of MHC class I antigens?
Present on all nucleated cells to present peptides from intracellular microbes (eg viruses) to CD8+ T cells.
What is Staphylococcus aureus?
Gram positive cocci
Normal flora in resp tract & not always pathogenic
Can cause skin infection, bacteriaemia, infective endocarditis
Antibiotic resistant strains = MRSA
What is the function of MHC class II microbes?
Present on all professional APCs to present peptides from extra cellular microbes to CD4+ T cells.
What are common causative organisms of prosthetic joint infections?
Staph aureus
Coagulase negative staph
(Form a biofilm)
What are key aspects of a travel history?
- any unwell companions
- pre travel vaccinations/ prophylaxis
- recreational activities
- location
- symptoms
- timing
What is the vector in malaria?
Female anopheles mosquito
What are the main species of Plasmodium?
Falciparum
Vivax
Ovalae
What are some signs and symptoms of a malaria infection?
Cycle of fever, chills & sweats every 3-4 days
+/- enlarged spleen, nausea, muscle aches, fatigue, muscle pain, dry cough, vomiting
What is the incubation period for malaria?
Minimum 6 days
How should suspected malaria be investigated?
Blood smear x3 (as many not show at first)
FBC, U&Es, LFTs, glucose, coagulation, head CT if CNS symptoms, CXR
How can malaria be prevented?
ABC
A: assess risky areas
B: bite prevention (clothes, nets, repellent)
C: chemoprophylaxis (before and after trip)
What is causative organism of enteric fever?
Salmonella typhi/ parathyphi
Where is enteric fever prevalent?
Mainly Asia, due to poor sanitation. Transmitted via faecal oral route.
How can enteric fever be prevented?
Typhoid vaccine
Food and water hygiene precautions
What are the signs and symptoms of enteric fever?
Bacteriaemia, fever, headache, abdominal discomfort, constipation, dry cough, bradycardia
What is the incubation period for enteric fever?
7-14 days
What is the treatment for enteric fever?
Ceftriaxone or azithromycin 7-14 days
Where is dengue fever prevalent?
Africa, Asia, India SC
What are signs and symptoms of dengue fever?
Often asymptomatic. Characterising skin rash, fever, headache, vomiting, muscle pains
Can develop into dengue haemmorrhagic fever or dengue shock fever
How is dengue fever spread?
Several species of mosquito
What is the incubation period for dengue fever?
4-7 days
What treatments can be given for dengue fever?
Supportive eg fluids
DONT GIVE NSAIDs eg ibuprofen as these may aggravate risk of bleeding
Which T cells does HIV affect?
CD4 T cells
CD4 count can stage what severity HIV is at
What are some signs and symptoms of HIV?
Mouth sores Malaise Weight loss Nausea Fever Headache Rash
How is HIV transmitted?
Sexual transmission
Injecting equipment
Vertical transmission (in utero, during child birth or breast feeding)
Medical procedures (blood transfusion, organ donations, skin grafts etc)
How can HIV be diagnosed?
Test blood for both HIV antigen and antibody
Which drugs are used to treat HIV?
Use 3 drugs (minimise chance of resistance)
Use 2 NRTIs (nucleotide reverse transcriptase inhibitor) + NNRTI/ protease inhibitor + integrase inhibitor
Lifelong anti retro viral therapy
Can Hep C & B be cured?
Only Hep C by antiviral drug combo (but can get reinfected)
Hep B cannot be cured but can give lifelong antivirals to suppress viral replication
Are vaccines available for Hep B and C?
Only a vaccine available for Hep B
Vaccination of genetically engineered surface Ag which produces surface Ab response = lifelong immunity
How do symptoms of Hep B and C differ?
Both commonly presents with jaundice, nausea, fatigue, anorexia, vomiting, abdominal pain
But Hep C is mostly asymptomatic
How can Hep B & C be transmitted?
IVDU, infants with +ve mums, needlestick
Hep B can be transmitted sexually
Hep C can be transmitted by those who had blood transfusions before 1991
Can both Hep B & C become chronic infections?
Both can, but Hep B rarely becomes chronic (only if Ag still present after 6 months) whereas most Hep C infections will become chronic
What is the serology of a hepatitis B infection?
Surface antigen -> e antigen -> core antibody (IgM) -> e antibody -> surface antibody -> core antibody (IgG)
What are the important cells of the stomach and what are their secretions?
G cells: gastrin Parietal cells: HCl & intrinsic factor D cells: somatostatin Mucous cells: mucous ECL cells: histamine Chief cells: pepsinogen
(Cells are within the gastric pits)
How is HCl secretion controlled?
Stimulated by gastrin from G cells, and histamine from ECL cells
What is the endemic rate of disease?
The usual background rate
What is an outbreak?
Two or more cases linked in time and place
What is an epidemic?
A rate of infection greater than the usual background rate.
What is a pandemic?
A very high rate of infection spread across many regions, countries, continents
What is R0?
The average number of cases one case generates over its infective period in an otherwise uninflected, non-immune population
What does R0:
Greater than one indicate?
Equal to one?
Less than one?
- increase in cases
- stable number of cases
- decrease in cases
What are some reasons for outbreak, epidemics and pandemics?
- new pathogen (eg mutation, antigen shift)
- new host (ie children)
- new practice (eg introduction of central lines, body piercings)
What is the mechanism of herd immunity?
Indirect protection against an infectious disease when a large proportion of the population are immune to it
What is antimicrobial stewardship?
Interventions to ensure appropriate use of antimicrobials to reduce adverse affects, reduce costs and reduce selection for resistant strains.
(Restrictive vs persuasive techniques)
Has antimicrobial stewardship shown results?
Restricted prescriptions of cephalosporins has shown a drop in C diff infection
Why does diabetes lead to an increased risk of infection?
Microvascular and macrovascular changes leads to reduced perfusion of affected tissue, and so less delivery of complement and nutrients
Also diminished sensation (neuropathy) so infected skin may go unnoticed and can worsen
Hyperglycaemia is linked with reduced neutrophil and lymphocyte function
What organism is a major cause of lung infections in CF patients?
Pseudomonas aeruginosa
What are some ENT infections that diabetics are susceptible to?
-Necrotising otitis externa
(Pseudomonas aeruginosa, starts in external auditory canal and spreads to adjacent soft tissue cartilage bone etc. Severe ear pain and discharge)
-Rhinocerebral mucormycosis
(Mould funghi colonises nose and paranasal sinuses and can spread to adjacent soft tissue causing necrosis and bony erosion)
Why are people with Down’s syndrome sometimes more infection prone?
Poorer neutrophil and monocytes function, lower antibody response, lower T cell function, abnormal cytokine production etc
What type of hypersensitivity reaction is an allergy?
Type 1 (IgE)
Is the incidence of allergies higher in rural or urban areas?
Urban
Generally smaller families, less exposure, higher antibiotic use, better sanitation, lower helminth burden
Which is the main cell involved in an allergic response?
Mast cell
Once activated it was undergo degranulation and release its contents to cause effects (eg vasodilation, bronchoconstriction, increase vascular permeability)
What is different between the first and second exposure of an allergen?
The first is clinically silent
What are some symptoms of anaphylaxis?
Systemic activation of mast cells can lead to breathing difficulty, hypotension, cardiovascular collapse (shock), swollen face (angioedema), generalised urticaria (hives rash)
How can an anaphylactic shock be treated?
Intramuscular (quicker than SC) epinephrine (adrenaline)
-reverses vasodilation, reduces hypotension and oedema, increases myocardial contraction force, reverse airway obstruction, inhibits mast cell activation
How can allergies be managed?
Antihistamines
Corticosteroids
Anti-IgE
Allergy densensitisation (special hospital units giving increasing dose of allergen over period of years)
How should asplenic patients be managed?
Lifelong penicillin prophylaxis
Medic alert bracelet
Immunisation against encapsulated bacteria
What are some examples of secondary immune deficiencies?
Malnutrition
Infection (HIV)
Liver diseases
Splenectomy (due to infarction eg sickle cell, trauma, congenital, coeliac disease, malignancy)
What is CRP and where is it produced?
An acute phase protein produced in the liver
CRP production triggered by microbial toxins
CRP acts as an opsonin that can bind to a microbial surface to enhance attachment of phagocyte and clearance of microbes
What is aspergillus?
Fungus (hence is a eukaryotes unlike bacteria send viruses which are prokaryotes)
This means it has a difference cell wall so won’t respond to standard antibiotics, need an antifungal
Aspergillus can be found in dust in buildings
Does not normally cause disease in normal hosts but is a major problem for Immunocompromised patients
What infection does varicella zoster cause?
Chicken pox (Belongs to the herpes virus)
What is an example of an antibacterial that affects nucleic acid synthesis?
Quinolones eg ciprofloxacin (inhibits a DNA enzyme)
What is chronic granulomatous disease?
Cannot activate respiratory burst so granulomas form in the body
