Infection Flashcards
How do organisms cause disease?
Exposure- Adherence- invasion - multiplication - dissemination
Virulence factors endo and exo toxins
Host inflammatory response, oxidative damage, not oxygen dependent.
Disease determinants
Site of injury Size of inoculation Co morbidities Age Genetics Immunity Immune function Antibiotic resistance
How so you determine infection
History, examination, investigation
Supportive - fbcs, us and es, crp, liver function tests, blood microscopy, imaging, histiopathology
Specific -
Bacteria - stain, microscopy, PCR, antigen/ antibiotic susceptibility, nucleic acid detection.
Virus- antigen, PCR, antibody
Beta lactams
Penicillins e.g. Amoxicillin (gram neg), flucloxacillin (staph and strep), penicillin V (most staph)
Cephalosporins e.g. (Broad spec cause C diff, not anaerobes) e.g. Ceftriaxone
Carbrapenems- (broad spec) e.g. Meropenem mostly gneg
Monobactams
Cell wall synthesis
Glycopeptides
Cell wall synth
Vancomyosin MRSA
G pos
Macrolides
Erythromycin - gram positive e.g. Strep pneumonea and H. Influ (penicillin allergy)
Protein synth
Aminoglycosides
Protein synth
Pseudomonas aeoriginosa and other g neg and some mycobacteria e.g. Tobramyosin
Gentamicin - g neg sepsis reserved for
Polymixins
Cell membrane function
Quinolones
Fluroquinolone
Nucleic acid synth
G neg
Ciprofloxacin
Tetracyclines
Doxycycline Protein synth G pos, broad spec I'm penicillin resistance Atypical pathogens in pneumonia Chlamydia and some protozoa
How do bacteria become resistant?
Vertical
Horizontal - transformation(from environment), conjugation, transduction (vector).
Mutations
Describe most common pathogen of sepsis and give pathogenesis including multi organ failure
Neisseria menigitidis. Gram negative diplococci. Aerobic.
Capsule prevents phagocytosis, promotes adherence and triggers inflammatory response. Cytokines, (IL1 and TNFa) released which cause clotting (more thrombin and less fibrinolysis). Coagulation damaging micro vasculature and leading to organ ischemia.
When is SIRS
Systemic inflammatory response syndrome
RR >20
HR >90
Temp >38 12x109/l
Give the history, examination and investigation of Sepsis
History- nausea, vomiting, photophobia, fever, malaise, confusion
Examination- hot/ cold, high rr, high BP, purpuric rash (not blanching
Investigations:
Sepsis 6 and
Fbcs
Us and es
Lfts
Crp
Blood culture and stain, PCR, antigen ect.
Possible lumbar puncture for csf
Blood sugar
Clotting study
Blood gas
Sats
Possible complications include: lung failure, renal damage, raised inter cranial pressure, irreversible hypotension, ischeamia of digits
Describe treatment of sepsis
Sepsis 6 IV antibiotics e.g. For N meningitidis then ceftriaxone Blood culture Serum lactate O2 IV fluids Urine output measure
Blood of csf to confirm
Prevention of n menigitidis
Prophylactic antibiotics and group C vaccine
Difference between innate and adaptive immunity
Constant intensity
Non specific (but recognises groups of pathogens)
No memory
Immediate
Describe the barrier to infection
Physical - skin, epithelium, cilia
Chemical - Saliva (lysozyme) tears (IgA) acid in stomach and vagina, gastric acid, pepsin, mucus , beta defensins (epithelium - form pores in cell membranes)
Biological - skin flora and mucosal flora e.g. Lactobacillus spp. Synthesise vit K and vit B12
Physiological - vomiting, sneezing, diarrhoea, coughing, mucocillary escalator?
When can biological barriers become damage routs
Transfer to sterile environment e.g. Bladder or surgery.
Antibiotics e.g. C diff
Affected immune system e.g. DM leading to overgrown flora
Poor dental work - bacteraemia especially with altered spleen function.
Skin - staph aureus, epididymis, strep pyrogens, Candida albicans, clostridium perfingens
Nasopharynx - haemophilus influenzae, neisseria meningitidis and strep pneumonea
Describe cells of the innate immune system
Macrophage- PRRs (pathogen recognition receptor) recognise PAMPs (pathogen associated molecular patterns) on bacteria. Phagocytose. Kill via O2 dependent and independent e.g. Lysozyme, lactoferrinor transferrin, Cationic proteins, and proteolytic/ hydrolytic enzymes.
Monocytes
Basophils
Eosinophils
Describe the complement system
Activated via alternate pathway- cell surface constituents on microbes, or via MBL pathway binding to mannose residues of proteins.
C3a and 5a are chemoattractants for phagocytes
C3b and 4b opsonise
C5-9 form membrane attack complex
Decribe the roles of TNFa, il1 and il6 released from macrophages
Stimulate neutrophil production and migration from bone marrow.
Dilate vessels, increase blood flow and make more permeable.
Increase body temp (hypothalamus)
CRP and MBL from liver
Describe malaria and it’s pathogenesis and investigations
Female anopheles mosquito carries- hepatocytes- RBC
4 types plasmodium falciparum, ovalae, malariae, vivax.
1-3 week incubation
Falciparumw causes RBCs to become sticky
Causes fever, arthralgia, myalgia, headache, chills, fatigue, cough
Possible splenomegaly, cerebral features e.g. Coma, respiratory distress
Treatment for malaria
ID physician Can be seen under microscopy If CNS then do a head CT If falciparum then quinine or artemisinin If other then chloroquine or primaquine
Pathogenesis enteric fever
Typhoid or paratyphoid caused by salmonella enterica subspecies. G neg bacilli
Faecal oral route
Use fimbriae to cover and adhere to epithelium over ilieal lymphoid tissue causing payers patches. Invasion allows intracellular invasion. Endotoxins antigen VI
Symptoms enteric fever
Fever Malaise Abdo pain Constipation Hepatospenomegaly Dry cough Bradycardia Intestinal haemorrhage/ perforation Occasional rash - paratyphoid not as bad
Investigation of enteric fever
Anaemia
Feacal/ blood culture
Raised LFTs
Relative lymphopenia
Treatment of enteric fever
Ceftriaxone or azithromyosin (macrolide)
Typhoid vaccine to VI antigen or a live attenuated vaccine but not 100%
Also s typhimurium or enteritidis
Briefly describe brucellosis
From animals, milk or cut, gram neg bacilli (Brucella)
Fever non specif symptoms, myalgia, arthralgia and epidydimitis
Doxy or rifam
Isolation required
Understand where and how to look up information on travel related infections
CDC - centres for disease control
WHO
Describe influenza virus and it’s transmission and management
Aerosol
Influenza A -ss RNA
Fluids and painkiller
Describe legionella pneumophila and an example of its clinical importance.
Water Bourne amoebae. Legionella pneumophila g neg bacilli Multiply inside macrophage Fever, diarrhoea, chills, cough, muscle ache, tiredness, loss of appetite. Affected liver function Similar to pneumonia May develop potanic fever similar to flu
Difference between antigenic drift and antigenic shift
Antigenic drift - mutations in antigens
Antigenic shift- combination of different strains
Describe features of an APC
Found in a variety of places - SALT, MALT, lymphoid organs, blood stream.
Phagocytose of micropinocytosis (soluble particles from pathogen)
Describe extracellular PAMPs and how they are identified
Phagocytosed by APC.
Phagosome fuses with vesicle containing MHC class II, antigen bound to MHC.
CD4 T cell binds to the MHC with TCR and CD28-B7.
This activates TH2 - activates B cells, eosinophils and mast cells.
It activates TH17 - neutrophils - phagocytosis.
Extracellular = humeral immunity
Pathogens= bacteria, parasites, fungi
Describe intracellular PAMPs and how they are identified
Antigen enters ER, binds to MHC1. On membrane MHC1 binds to CD8 (not also found MHC2).
MHC 2 binds to CD4- TH1 which activates CD8 on MHC1. CD8 activates CTL which use perform and granzymes after binding to MHC1.
TH1 activates B cells and macrophages
Cellular immunity
Pathogens- virus and bacteria
Properties of MHC
Co dominant
Polymorphic binding clefts
Must be able to fit/ match antigen for it to express
E.g. Some can’t express gp120 so have rapid progression.
Can cause organ rejectin
Some hLA (form of MHC) varient cause autoimmune disease.
T cells and cytokines?
TH1 - TNFa, IFN gamma
Th2- Il4,5,10
TH17- Il17
Apply the infection model to a patient with HIV
Pathogen Ss +RNA Gp120 binds to enter Reverse transcriptase and integrase Sex, blood vertically Incubation 1-3 weeks. Seroconversion long. Infection- chronic, suppresses immune system so pneumonia, meningitis, encephalopathy, peripheral neuropathy Acute - presents as cold/ flu with rash Detected by PCR and p24 antigen via ELISA- 6 months to be sure. Treatment HAART: Nucleoside reverse transcriptase inhibitors Non nucleoside rti Integrase invibitors Protease inhibitors Fusion inhibitors Co receptor entry inhibitor
Apply the infection model to Hep B
Pathogen replicates in hepatocytes
Blood Bourne, sex
Chronic affects children, symptomatic in adults
Different antigens screened
Jaundice, liver failure, cirrhsis and liver cancer
Acutely- fever malaise and jaundice around 2-6 months
Vaccination not 100%
Made worse by HepD
Understand the concept of microbiota
Commensal bacteria both symbiotic and pathogenic that live on a body surface.
Appreciate the range of normal microbiota
HPV and herpes simplex GP: Staph aureus Coag neg staph aureus e.g. Epidermidis Viridens strep Group b haemolytic strep Corynebacterium (rods) GN: Enterobacteriacae Fungi and yeasts - dermatophytes athletes foot
Describe pathogenesis of infections at a surface
Adherence to prosthetic surface via pili or frimbriae
Invasion and multiplication
Formation of biofilm/ slime
Bacteria produce matrix and nutrient diffuse.
Quorum sensing - uses signals, auto inducers, receptors and gene expression to regulate sporulation, biofilm formation and virulence factor secretion.
Host response is pyrogens or granulomatous
Describe the management of infected sites
Diagnose with blood culture, sonication.
ntibacterials
Surgery to respect
Prevent by maintaining surface integrity and prevent colonisation
Prosthetic- prevent contamination, inhibit e.g. Silver.
Describe the range and origins of surface infections on both natural and prosthetic surfaces
Strep throat - strep pyrogens pharyngitis
UTI- candida
Inoculation- coag neg staph and prosthetic
Uaem
Haematogenous- viridens from teeth/ mouth
Empyema- pleural cavity
Vasculitis- pleural cavity
Native vales- viridens, enterococcus faecalis, HACEK, candida. Turbulence
Prosthetic less than 1 year then coag neg.
Prosthetic:
IV lines
Catheter
Joints
Valves
Pacing wires
Describe the different types of hypersensitivity reactions
Type 1- IgE mediated, non infectious allergens, less than 30 mins
Type 2 - IgG/M mediated, non soluble antigen 5-12 hour
Type 2- IgG/M mediated antibody complex, soluble antigen 3-8 hour
Type 4- cell mediated, environmental infectious agents and self. 24-48 hour
Understand the pathophysiology behind the type I hypersensitivity reaction
First antigen contact- IgE produced
Second contact- antigen binds to IgE on mast cell or activates it directly via C3a and 5a.
Mast cell releases chemoattractants, cytokines, histamines causing exudation, dilation and vascular leakage.
Location differs the effects:
Epidermis- urticaria
Dermis- angioedema can be fatal in URT
Systemic- anaphylaxis, hypotension, CVS collapse, urticaria, wheezing
Treatment of type I anaphylaxis
Adrenaline
Monitor EXG, BP, pulse and oximetry
Management of type 1
Education e.g. Epipen
Avoid allergens
Sensitivity testing, graded exposure
Manage with antihistamines, steroids, anti IgE
Apply the infection model to a patient presenting with a hospital aquired infection
Within 48 hours of admission including visitors and HCW
Practice and place health care infections
Practice- activities of HCA, organisation structure and engagement, leadership, government iniative
Place- healthcare environment, fixed features and variable features
Understand the range of hospital acquired infections
Ventilator pneumonia Mrsa Candida albicans Pseudomonas aeruginosa Clostridium difficile TB Legionaries UTI
Describe the use of personal protective equipment with regard to a hospital setting
Vomiting/ diarrhoea then gloves and apon
Full Ppe suit for highly contagious diseases such as Ebola.
Pathogenesis of C. difficile
Gram neg spore forming aerobic bacillus.
Occurs with antibiotics. (Normally b lactams)
ToxinA (endotoxin) and toxin B (cytotoxin) affect actin production and Rho GTPases.
Check with stools and Elisa
Management of C. difficile
Metronidazole
Vancomyosin
Often stopping causative antibiotic will sort it out.
Characteristics of staph aureus with regard to hospital aquired infections and drug resistance
Some resistant to most B lactams antibiotics, eg. Methicillin. Gentimicin some resistance. Vancomyosin little resistance
Characteristics of norovirus
Aerosol
Winter vomiting disease
+ssRNA non enveloped
Bleach and disinfectants, isolation to prevent spread
Significance of reproduction number (Ro) and levels of outbreak
Reproduction number (Ro) = average number of cases each new case/infected individual causes
Endemic- normal background rate
Epidemic- greater than normal
Pandemic- much greater than normal
Consider the principles of infection prevention
Pathogen- avoid/ kill, elimate breeding sites
Patient- keep healthy, immunisations
Practice- behaviour, geography or action to prevent contact between pathogen and patient
Place - environmental engineering, good design ect.
Appreciate the consequences of antibiotic resistance
MDR! XDR, PDR
Treatment failure
Prophylactic failure - surgery
Economic cost of ITU
Principles of anti microbial stewardship
Appropriate use of antibiotics Minimise adverse effects and toxicity Maximise optimal clinical outcome Reduce cost of infectiom Limit the selection for anti microbial strains
What does anti microbial stewardship require?
Multidisciplinary team
Leadership to challenge
Interventions- persuasive, restrictive or structural
Surveillance
Leadership and support
Integrate into patient safety
Process measures (use and adherence) vs outcome measures (resistance and patient outcomes)
Describe the diversity of chronic infections
Vascular Infection Trauma Autoimmune Metabolic Inflammatory Neoplasm Congenital Degenerative Environmental Idiopathic
Describe CF and infection
Autosomal recessive delta f508 Thickened mucus Often H influenzae infections Later staph aureus Then atypical mycobacteria, candida, aspergillus, pseudomonas aeruginosa Eventually COPD Increased mucus Acute exacerbation with HI, PA or RSV
Describe DM and infections
Hyperglycaemia and acidosis affects humoral immunity (antibodies) and neutrophil and lymphocyte functioning.
Damage to vasculature means poor perfusion and decreased host response
Neuropathy - diminished sensations.
More susceptible to:
net e.g. Otis externa- external auditory canal soft stis sues, pain and discharge (otorrhea).
Rhinocerbral mucormycosis- mould infection of sinuses in DKA, soft tissue necrosis and bony erosion.
UTIs common
Down’s syndrome and infection
More susceptible to viral infection in earlier years. Mucus? Structure?
Humoral:
Affected immunoglobulin production. Decreased neutrophil and monocyte functioning (chemo taxis)
Cellular:
Altered T cell function and distribution, cytokines production and nK cell function
The role of pseudomonas aeruginosa in CF
Highly resistant
Forms biofilms (mucoid)
G neg aerobic bacillus
Typical patient in an immunocompromising host
Male
Most diagnosed over 18 but 7-9 years between onset and diagnosis
Symptoms of an immunocompromised host
Severe
Persistent
Unusual
Recurrent
Investigating immunodeficiencies
History - family (X), viral and fungal ingestion Then T cell? Bacterial and fungal then B cell? IgG IgA IgM IgG to specific antigen Immunisation testing Neutrophil function Individual complement components Adhesion molecule expression (LAD T cell test in vireo Lymphocyte subset analysis Test immunisation with antibody Definitive test e.g. Molecule re and genetic
B cell deficiencies
CVID - inability of B cells to mature, presents at any point IgA deficiency IgG subclass deficiency- but total IgG fine bruton's (problem in B cell development- X linked) Hyper IgM syndrome- cannot switch to IgG
Phagocyte deficiencies
Cyclic neutropenia - unknown
Leukocyte adhesion deficiency (LAD)
Chronic granulomatous disease- failure of oxidative burst/ killing
Chediak-higashi syndrome- failure of phagocytosis
Describe T cell deficiencies
Di George- catch 22, cardia, abnormal faeces, thymus hypoplasia, cleft palate, hypocalcaemia- surgey, antibiotics, calcium, bone marrow transplant, X irradiated and cmv- blood, no live vaccine
SCID- stem cell defect or death of tymocytes
Omenns disease/ SCID- defective T cell development
Discuss causes of secondary immuno deficiency
Loss of immune components: Infection e.g. HIV Malnutrition Liver disease Lymphoproliferative disease A splenic patients Neutropenia: Drug induced e.g. Alcohol, chemotherapy, organophosphate, benzene Autoimmune Bone marrow malignancy Aplastic anaemia Vitamins B12, folate or iron deficiency Radiotherapy
Discuss a splenic patients
More susceptible to encapsulated bacteria e.g. H influenzae strep pneumoniae and n meningitidis.
Prophylactic penicillin, immunisations, medical alert bracelet
OPSI- overwhelming sepsis and meningitis
Role of the spleen
Removes encapsulated bacteria, synthesises antibodies, macrophages to remove opsonised bacteria and immune complexes.
Consequences of a primary antibody deficiency and treatment
Resp bacterial infections GI complications Lymphoma, gastric carcinoma Arthropathies Autoimmune disease. Management: Prophylaxis Immunoglobulin replacement for cvid, bruton's, hyper IgA Management of resp function Avoid exposure to radiation
Phagocytes deficiency presentation and management
Ulcers Osteomyelitis Deep abcesses Staphylococcal Invasive aspergillus Inflam proba.
Prophylactic Suregry Interferon-g (CGD) Steroids (CGD) Stem cell transplant
SCID presentation
Failure to thrive Long term Atb therapy Deep abcesses Low lymphocyte Viral and fungal infections
Management of SCID
No live vaccine Irradiated cmv- blood Aggressive treatment for infections Prevention of infection Bone marrow/ stem cells Gene therapy
