Infection Flashcards
Describe the principles of “an infection” and how an individual develops an infection
Infection - invasion of host’s tissue by microorganisms. Disease caused by replication of microorganism, toxins and host response.
How you get infected - contact, inhalation, ingestion, vertical transmission.
How do microorganisms cause disease and some disease determinants
How do they cause symptoms:
Virulence factors Exotoxins(cytolytic, AB toxins, superantigens, enzymes) and
Endotoxins
Host cellular damage - direct or because of host immune response.
Disease determinants:
virulence factors
inoculum size
antimicrobial resistance
Site
Co-morbidities
Describe the 4 exotoxins produced by gram positive bacteria
Exotoxins are secreted
Cytolytic - membrane damaging
AB toxins - 2 part - B binds to cell and delivers A to cytosol which is often an enzyme that interferes with cell function.
Super antigens - microbial proteins that bind both class II MHC molecules and T-cell receptors (causing activation of the T cell)
Enzymes - destroy tissue that bacteria is trying to invade
What are endotoxins gram neg
lipopolysaccharide-protein complexes
components of cell wall of Gram Negative Bacteria
liberated only on cell lysis or death of bacteria.
Mildly toxic and do not bind to specific receptors.
Cause host cell damage either directly or as a result of the immune response e.g. cytokine determinants storms/SEPSIS.
Describe how to identify that a patient has an infection including history, examination and investigations.
How to identify:
History - symptoms - focal or systemic, severity, duration, potential exposures
Examination - organ dysfunctions
Investigations - specific and supportive
Supportive:
Full blood count(eg neutrophilia means bacterial infection)
CRP(inflammation)
Liver and kidney function tests(to see if drugs can be given)
Imaging
Histopatholoy(look at sample under microscope)
Specific(to determine cause):
Bacteriology- Collect specimen(eg swab, fluids, tissues). Then microscopy, culture and sensitivity.
Use gram stain
Or can look at antigen detection, nuclei acid detection(PCR) or antibiotic susceptibility.
Virology - ELISA tests with antigens or antibodies in well or detecting viral nuclei acid (PCR).
Microorganisms broad categorisation
bacteria - prokaryotic
viruses
parasites(eukaryotic) - Protozoa(single celled) and helminths (multi-cellular)
Fungi (eukaryotic) - yeasts (single-celled) and molds (multicellular)
Key features of bacteria
Look at diagram on notion
All are prokaryotes- do not have nucleus
Gram positive or negative
Cocci or bacilli
Aerobes or anaerobes
Gram stain
Treated with a solution of crystal violet, the bacterial cells will stain purple.
then treated with a solvent - alcohol
gram-positive organisms retain the stain, whereas gram-negative species lose the stain, becoming colourless.
Addition of the counterstain safranin stains gram-negative bacteria pink.
Agar plates
Used for culture of bacteria
Resists digestion by bacterial enzymes
Enriched medium as the plate with the protein and blood provides nutrients for a number of common bacteria.
bacterial structure
Look at notion
Virus features
Consists of DNA or RNA
Surrounded by a protein coat
A virus may also have an envelope derived from the membrane of the host cell.
Viruses contain the genetic information necessary for replication but require the host’s cellular structures and enzymatic machinery to complete the process.
The fate of the host cell following viral infection ranges from rapid lysis and release of many progeny virions to gradual, prolonged release of viral particles.
virus structure
Look at notion
Gram positive and neg diff
Look at notion
thick, multi-layered, peptidoglycan cell wall
or
negative:
have cell wall with 2 membranes which are separated by the periplasmic layer containing peptidoglycan. This layer is thin and so more susceptible to damage. Outer membrane has LPS which has a lipid portion that is toxic(endotoxin). Antigenic so can identify species.
Virulence factors - Factors that enhance pathogenicity
– Host entry (e.g. polysaccharide capsule to protect from enzymes and hostile environments)
– Adherence to host cells (e.g. pili to prevent from being washed away by mucus)
– Invasiveness (e.g. enzymes such as collagenase to degrade extracellular matrix and have easier access to host cell surfaces)
– Iron sequestration (siderophores - capture iron from host for growth)
Ses 2
Understand and describe a model of infection - see notion for flowchart
For any patient you are examining – think:
1) Patient – age, gender, social status, health status, time of year, home, recent
travel.
2)Pathogen – virus, bacteria, fungus, parasite.
3) Mechanism of infection - contiguous (direct) spread, inoculation, haematogenous, ingestion, inhalation, vector, vertical transmission.
4) Process of the infection – attachment, interaction with host defences, host.
5) Management of the patient – history, examination, investigations, treatment (specific and supportive).
6)Patient outcomes – cure, disability, chronic infection or death.
To understand how to apply the model of infection to a specific illness
Example:
Cellulitis - severe inflammation of dermal and subcutaneous layers of the skin.
Patient - children, elderly and immunocompromised.
Pathogen - Group A streptococcus, Staphylococcus aureus and Haemophilus influenza type B
Mechanism -break in skin so pathogens invade subcutaneous layers
Management- antibiotics
Patient outcomes- cure or septic shock
Thrush
Patient - Most HIV-positive individuals oral candidiasis, which often spreads to the oesophagus(AIDS).
Pathogen - yeast Candida albicans - normal body flora of skin, mouth, vagina and intestines
Mechanism - competing bacterial flora eliminated so yeast over grows
Management - nystatin or clotrimazole.
Patient outcomes
Identify microbes commonly found on the skin and other body sites
The skin
Staphylococcus aureus Staphylococcus epidermidis Streptococcus pyogenes Candida albicans
The mouth and nasopharynx
Streptococcus mutans Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenza type B.
The gastrointestinal tract
E. Coli
Urogenital tract - Lactobacillus
Describe how microbes, normally present as commensals (part of the microbiome) can cause disease / infections in certain situations and give
examples.
Normal flora is displaced from its normal location to sterile
location:
Breaching the skin integrity eg skin loss, surgery, IV lines
Fecal-oral route - Foodborne infection
Fecal-perineal-urethral route - Urinary tract infection (women)
Poor dental hygiene
Normal flora overgrows and becomes pathogenic
when host becomes immuno-compromised:
Diabetes o AIDS o Malignant diseases o Chemotherapy (mucositis)
When normal flora in mucosal surfaces is depleted by antibiotic therapy:
Intestine -> severe colitis (Clostridium difficile)
Vagina -> thrush (Candida albicans)
Describe the different innate barriers to infection, including physical,
physiological, chemical and biological
1) Physical barriers – skin, mucous membranes(mouth, RT, GI tract, UT) and bronchial cilia
2) Physiological barriers – diarrhoea, vomiting(hepatitis, meningitis), coughing(pneumonia) and sneezing(sinusitis).
3) Chemical barriers – low pH and antimicrobial molecules eg IgA - tears, saliva, mucous
membrane
lysozyme - sebum, perspiration,
urine
mucus
β-defensins - epithelium
gastric acid
4) Biological barriers – normal flora in strategic locations - benefits:
synthesise vitamins (e.g. K, B12) immune maturation
Compete with pathogens for
attachment sites and ressources Produce antimicrobial chemicals
Describe how these different barriers work together to maximise the response against microbes
Recognize the different interventions that affect integrity of the innate
barriers
Normal flora is displaced from its normal location to sterile location
• Breaching the skin integrity - Skin loss (burns), Surgery, IV lines, Skin diseases, Injection drug users
• Fecal-oral route - Foodborne infection. Fecal-perineal-urethral route - Urinary tract infection esp women.
Poor dental hygiene - o Gingivitis
Normal flora overgrows and becomes pathogenic when host becomes immuno-compromised:
o Diabetes o AIDS o Malignant diseases o Chemotherapy (mucositis)
When normal flora in mucosal surfaces is depleted by antibiotic therapy:
o Intestine -> severe colitis (Clostridium difficile)
o Vagina -> thrush (Candida albicans)
Understand the risk of infection associated with these interventions
State name and function of the second line of defence, including the role of phagocytes and chemicals.
3 phagocytes
4 cells of innate IS
2 chemicals
1) Phagocytes - intracellular killing by O2 dependant pathway(mostly):
macrophages - Present in all organs, Ingest and destroy microbes (Phagocytosis), Present microbial antigens to T cells (adaptive immunity), Produce cytokines/chemokines
monocytes - In blood, Recruited at infection site and differentiate into macrophages
neutrophils - in blood, Increased during infection, Recruited by chemokines to the site of infection, Ingest and destroy pyogenic bacteria - Staph. aureus and Strep. pyogenes
2) Other key cells of the innate immune system
Basophils (mast cells) - Early actors of inflammation (vasomodulation), Important in allergic responses
Eosinophils - Defence against multi-cellular parasites (worms)
Natural killer cells - Kill all abnormal host cells
Dendritic cells - Present microbial antigens to T cells (acquired immunity)
3) Chemicals – complement system and cytokines
Describe how pathogens are recognised by cells of the innate immune
system
PAMPs – pathogen associated molecular patterns - and include carbohydrates, lipids, proteins and nucleic acids, e.g. peptidoglycan (a component of bacterial cell walls), lipopolysaccharide (a lipid/carbohydrate moiety found in bacterial cell membranes), ß-glucan (found in fungal cell walls) or dsRNA (some viruses).
PRRs – pathogen recognition receptors – they are proteins that span the phagocyte membrane and they essentially bind
Opsonisation of microbes enhances the interaction between the phagocyte and the microbe. Opsonins are proteins that bind to and coat the surface of the microbe. These are produced by various components of the immune system.
Name and describe important opsonins
complement proteins - C3b, C4b.
antibodies - IgG, IgM
acute phase proteins - C-reactive protein (CRP), mannose-binding lectin (MBL).
Describe how a clinical evaluation of the innate immune response helps
to identify the presence of infection, and in particular that of acute
inflammation and acute infection.
As examples describe the role and evaluation
of neutrophils and C-reactive protein.
Neutrophilia = bacterial infection
Raised CRP - opsonise that inc phagocytosis - indicates inflammation
Ses 3
Sepsis definition
Sepsis is characterised by a life-threatening organ dysfunction due to a dysregulated host response to infection.
Sepsis effect on organs in ABCDE
Airways - no specific effect
Breathing/Respiratory: Raised respiratory rate (tachypnoea). Fluids and proteins leaking into interstitial tissues lead to lung oedema and decreased lung compliance.
Circulation: Hypovalemia (due to vasodilation and increased capillary leakage) so low blood pressure.
This would result in tachycardia.
End-organ damage (kidneys, liver, and brain)
Disability/CNS: As a result of reduced blood flow to the brain,
patients can present with confusion, drowsiness, slurred speech, agitation, anxiety,
and reduced level of consciousness.
Exposure / Pyrexial (hypothalamic response to infection) BUT remember hypothermia for
elderly.
Renal: As a result of reduced blood transfusion to the kidneys, there is reduction in
urine output.
Sepsis risk factors
• Very young (< 1 year old).
• Elderly (>75 years) or very frail. • Pregnant, post partum (within last 6 weeks).
• Patients with impaired immune system
Sepsis screening
A patient should be screened for sepsis when:
• a clinician or carer is worried
• the NEWS2 score is 5 or more
Scores to:
Resp rate
O2 sat
Systolic BP
Pulse rate
Consciousness
Temp
• the patient is at risk of neutropenia
• there’s evidence of organ dysfunction e.g. lactate 2mmol/l or above
Treatment for amber flag
Amber - (NEWS2 5 or 6 or 1-4 with one of lactate >2mmol, chemotherapy in last 6 weeks, organ failure, deteriorating):
Send bloods
Senior clinical review within 1 hr
Antimicrobials and escalation plan in 3 hrs
Red flag - sepsis 6
NEWS 2 more than 7
Sepsis 6 within the hour
- Senior help
- Give O2 to inc O2 sat
- Send bloods - culture and FBC
- IV antibiotics - consider likely organisms, penetration, patient factors. Source control - drain abscess.
- Consider IV fluids - correct hypovalemia
- Monitor - urine output, are they deteriorating
Consider critical care if patient continues to deteriorate. Continue reviewing patients
daily.
Understand the mechanism by which micro-organisms trigger the
inflammatory cascade
Micro-organisms trigger inflammatory responses via special methods in the following processes:
Gaining entry into the host (e.g. via respiratory, GI, urogenital, skin)
Adherence to host cells (e.g. via cell surface adhesion molecules,
fimbriae/pili)
Invasive into host cells / mucosal surfaces (e.g. via enzymes such as
collagenase and hyaluronidase)
This would then result in inflammation (either pyogenic or granulomatous)!
Understand the relevance of HIV in a global and UK context
many millions of people living with HIV.
Substantially fewer deaths due to HIV in the UK. Biggest burden of HIV infections in Africa.
Describe the principles of HIV structure, replication notion for structure
HIV is a single stranded RNA retrovirus.
Attachment to cells is accomplished via the gp120 portion of the envelope gene product on the HIV surface, which preferentially binds to the CD4 molecule.
The virus infects helper T cells, lymphocytes, monocytes, and dendritic cells, which produce this glycoprotein on their surface.
Replication - The ssRNA is converted to dsDNA and incorporated into the cell’s genome.
Apply the infection model to a patient with HIV and acquired
immunodeficiency syndrome (AIDS)
Describe the principles of infection transmission and prevention with
regard to HIV.
Transmission - Contact of infected bodily fluids with mucosal tissue / blood / broken skin eg sexual contact, blood transfusion, contaminated needles, vertical transmission to fetus during delivery.
Affected by - viral load
Prevention - Condom use, use of clean new needles, treatment during pregnancy, screening,
Post-exposure prophylaxis (PEP), Pre-exposure prophylaxis (PrEP), Male circumcision
Treatment notion
Anti-retroviral drugs (ARVs) ensure undetectable viral load and allowing CD4 count to recover. They work by:
Targeting binding - CCR5 so entry inhibitor
Target enzymes responsible for incorporation of viral DNA into host - integrase inhibitor.
Target reverse transcriptase competitively or non - NNRTI or NRTI
Prevent larger proteins breaking down into smaller proteins in viral life cycle - protease inhibitor
Virus mutates frequently so multiple drugs to resist resistance.
Who should be tested
Resp: bacterial pneumonia / TB • Neuro: meningitis/dementia • Derm: Severe psoriasis
Gastro: Chronic diarrhoea
Cancer
HIV testing
Testing - a) serology – detects both antigens (viral proteins) and antibodies to HIV in the blood, b) PCR – detects the viral nucleic acid and c) rapid testing – usually picks up the antibodies to HIV in either blood or saliva.
Ses 4
Antimicrobial classes
Antibacterial, antifungal, antiviral &
antiprotozoal agents
Anti bacterial classes - 4 (not mechanism of action)
Bactericidal or bacteriostatic
Spectrum – ‘broad’ v. ‘narrow’
Target site (mechanism of action)
Chemical structure (antibacterial class)
How to choose an antibiotic
Cause
Active
Site eg cross blood brain barrier
Right formulation
Half life - dosing
Interaction with other drugs
Toxicity - eg aminoglycosides are nephrotoxic
Monitoring - therapeutic window
different ways to measure antibiotic activity
Disc Sensitivity/Diffusion Testing – putting the organism on the agar plate and putting ‘paper discs’ containing antibiotics and reading the zone of clearance.
Minimum Inhibitory Concentration (MIC) – The first concentration of antibiotic that inhibits the growth of bacteria. Done via: broth microdilution OR E-test strip.
3 Types of antibiotic resistance:
Intrinsic - The antibiotic does not target the specific characteristics of the bacteria, therefore, unable to gain access to bacteria
Acquired - via chromosomal gene mutation/horizontal gene transfer (via plasmids). 3 ways:
Enzymatic destruction of antibiotics
Enzymatic alteration or mutations of bacterial target sites
Overexpression of efflux pumps (multi drug resistance)
Adapted: if there are a sub-therapeutic levels of antibiotics, this only causes a mild stress response to the bacteria – hence it will respond by becoming resistant to the antibiotic
Classes of antibacterials and their mechanism of action
Cell wall synthesis
Beta - lactams
Protein synthesis
Tetracycline, aminoglycosides, macrolides
Cell membrane function
Polymixins
Nucleic acid synthesis
Quinolones, Trimethoprim
Beta lactams + glycopeptides
Penicillins eg penicillin(streptococci), amoxicillin(some gram -ve)
Cephalosporins - broad spectrum but not anaerobes. Gives C.difficile infection. Eg Ceftriaxone (crosses blood-brain).
Carbapenems - broad spectrum eg imipenem. Penicillin allergy. G -ve + G+ve + anaerobes.
Glycopeptides
Vancomycin - G +ve, C.difficile oral otherwise IV.
Narrow therapeutic window.
Protein synthesis
Tetracycline (30s ribosome subunit) & doxycycline - oral, g+ve, broad. Treats protozoa, chlamydia, atypical pneumonia.
Not to children <12 years/pregnant women (causes staining of developing teeth).
Aminoglycosides - gentamicin, g-ve, nephrotoxic
Macrolides (50s) - erythromycin, g+ve
Nucleic acid synthesis
Quinolones - ciprofloxacin, Inhibit DNA gyrase, Very active against Gram negs.
Risk of tendinitis and rupture, aortic dissection, central nervous system effects and C.difficile infection.
Trimethoprim & sulphonamides - Inhibitors of folic acid synthesis, treat UTI.
Co-trimoxazole – Used to treat Pneumocystis jirovecii, Has activity against MRSA
Rifampicin - inhibits RNA polymerase
Antifungals
Azoles (active against yeasts, molds)
• Inhibit cell-membrane synthesis
• Fluconazole used to treat Candida
Polyenes (nystatin and amphotericin)
• Inhibit cell membrane function • Amphotericin for IV treatment of systemic + severe fungal
infections (e.g. aspergillus)
Nyastin for topical treatment of Candida
Antivirals
Aciclovir • When phosphorylated inhibits viral DNA polymerase
Herpes simplex – genital herpes, encephalitis
Varicella zoster – chicken pox & shingles
Oseltamivir (‘Tamiflu’) • Inhibits viral neuraminidase • Influenza A & B
Metronidazole + Nitrofurantoin
anti-bacterial (anaerobes) and anti-protozoal
Protozoal:
1. Amoebae (dysentery & systemic)
2. Giardia (diarrhoea)
3. Trichomonas (vaginitis)
SHOULD NOT TAKE THIS WITH ALCOHOL - like disulfiram
Nitrofurantoin - Mixed between preventing protein synthesis and DNA/RNA synthesis.
Antimicrobial stewardship
Do not start antibiotics in absence of clinical evidence of bacterial infection
antibiotic resistance.
