infections ISU

Question 1

3 things that are necessary for infection to occur

Answer 1

source - where the micro-organism lives
susceptible person - with a way for micro-organism to enter the body
transmission - a way for the micro-organism to move to the susceptible person.

Question 2

name 3 types of transmission, what PPE is used to protect us, and example infections

Answer 2

contact. handwashing, gloves and aprons, MRSA, C.difficile

Droplet, eye protection,surgical masks, influenza + COVID-19

Aerosol, Eye protection, masks, MDR-TB, COVID-19

Question 3

5 moments of hand hygiene

Answer 3

1- before touching patient
2-before aseptic procedure
3-after body fluid exposure risk
4-after touching patient
5-after touching patient surroundings

Question 4

what are the problems of antimicrobial resistance?

Answer 4

• delay in appropriate antibiotic therapy
  -increased hospital length stay
  -alternative antibiotics need to be used that aren’t first line (may cause adverse effects)

Question 5

what are the causes of antimicrobial resistance?

Answer 5

• over prescribing of antibiotics
• patient non-compliance
• poor quality of antibiotics
  -antibiotics use in domestic animals
• poor hygiene + sanitisation
  -lack of new antibiotics being developed

Question 6

the importance of rapid diagnosis and antimicrobial susceptibility testing?

Answer 6

• organism identification can lead to more appropriate antibiotics treatment.
• improves the patient outcome
  -use of narrow spectrum antibiotic earlier and IV to oral step down earlier.

Question 7

what factors influence the behaviours of prescribers in antimicrobial use?

Answer 7

• lack of awareness of guidelines
  -time constraints
  -decision fatigue
• uncertain diagnosis
• pressure from patient

Question 8

what is the epidemiology of infectious disease

Answer 8

the study of how often diseases occur in different groups of people and why

Question 9

name different modes of pathogen transmission, role of patient host defence mechanisms to recommend and rationalise interventions that prevent infectious disease.

Answer 9

1-transmission between humans e.g. contact
2-environmental e.g. water
3- vectors e.g. animals
Host prevention:
- barrier immunity e.g. skin
-innate immunity e.g. inflammatory response.
-adaptive immunity e.g. specific antibody production.

interventions that prevent infectious disease:

• prophylaxis e.g. for malaria
• sanitisation of drinking water

Question 10

describe the spectrum of activity of antibiotics + microorganisms of interest

Answer 10

a system that shows how susceptible a microorganism is to the treatment of a specific antibiotic. For example the gram-negative bacteria E.coli is susceptible to amoxicillin/ clavulanate.

Question 11

discuss general steps involved in infection pathogenesis

Answer 11

colonisation - establish residence at site of infection
invasion - breach host barriers and gain access to deeper tissue
proliferation - multiply and spread within the host
dissemination - spread to other sites or other host

Question 12

describe the mechanism by which pathogens adhere to host cells, evade immune system and cause tissue damage

Answer 12

1 - adherence through Pili, adhesins or biofilms to allow bacteria to stick to surfaces of host cells.

2- immune evasion by antigenic variation, intracellular survival and inhibition of phagocytosis.

3- tissue damage by releasing toxins, inflammation and host cell death.

Question 13

what are the systemic effects of infection such as fever, sepsis, organ failure

Answer 13

1- fever elevated body temp above 38 in response to infection.
2-sepsis response to infection characterised by widespread inflammation and organ dysfunction
3-organ failure due to vasodilation of both arteries and veins when experiencing septic shock.

Question 14

what are the origins of clinical markers for infections e.g. fever, C-reactive protein, immunoglobulins

Answer 14

markers for a fever include temp greater than 38 or less than 36, HR greater than 90bpm, tachypnoea greater than 20bpm, WBC count greater than 12000/mm^3.

C-reactive protein is produced by the liver in response to inflammation.

immunoglobulins are different antibodies which can be detected in the blood plasma when the body is fighting infection.

Question 15

what is the importance of understanding pathophysiology of infection in diagnosing and management of complications?

Answer 15

We can ensure we don’t get a differential diagnosis and we are more accurate, allowing us to select the appropriate treatment to the right patient within the right timeframe. This ensures that we don’t get to the late stages of infection where organ failure or sepsis shock occur - leading to death.

Question 16

summarise the innate immune system

Answer 16

• non - specific
  -defence against entry of microorganisms via physical barriers and secretions
  -when penetrated mediated by phagocytic cells e.g. macrophages, neutrophils, and NK cells. creates inflammatory response via release of histamines. NK cells kill recognisable cells using chemicals that damage cell membranes.
• Also has an alternate pathway gets activated after opsonization of pathogen (complement)

Question 17

summarise the adaptive immune system

Answer 17

• specific and memory
• antigen on APC is recognised by lymphocytes via B cell and T cell receptors.
• proliferation of lymphocytes that recognise the antigen.
  -by MHC molecule/ MHC complex.
  -production of specific antibodies.
• first exposure is B-cells that produce antibodies.
  -secondary response T-memory cells form plasma cells more quickly.
  -key cells are T helper cells that release cytokines and cytotoxic T cells that target virus infected cells.

Question 18

how does the immune system respond to viral infection

Answer 18

1- extracellular phase: either acts as opsonin’s for macrophages or is bound to pre existing antibodies to prevent entry to target cells.
2- if not effective macrophages present antigen fragments on surface + secrete cytokines which stimulates NK and Thelper cells but also makes interferons.
3- helper t cells bind to antigen on macrophage which activates them causing release of cytokines to stimulate B lymphocytes (plasma cells to make antibodies) and cytotoxic T lymphocytes.
4 - production of more antibodies via plasma cells after B lymphocyte activation.
5-cytotoxic T cells recognise MHC I complex and cause infected host cell to undergo apoptosis.

In some cases infected host cells withdraw MHC complex from surface which is recognised by NK cells - leading to apoptosis of infected cell.

Question 19

how does the immune system respond to bacterial infection

Answer 19

• extracellular response - inflammation
• complement is activated acting as opsonins to activate phagocytosis.
  -degranulation of mast cells release histamine and chemo attractants.
  -complement cascade ends with formation of membrane attack complex.
  Other innate response:
  -phagocytes are activated and macrophages begin to ingest.
  -antibodies + complement/opsonins coat to help with identification.
• enhances phagocytosis.

Question 20

what are the functions of specific immune cells in the innate immune response

Answer 20

neutrophils - first to site + increase inflammation response + recruit other cells to site
macrophages - clean up dead neutrophils and responsible for phagocytosis.
Basophils,mast cells,eosinophils - when activated release histamine and leukotrienes to help inflammatory response.
NK cells - recognise infected viral cells and cause apoptosis

Question 21

describe the role of infection agents and the immune system in pneumonia

Answer 21

Can be caused by both bacteria and viruses

• changes in airway direction trap pathogens.
  -epiglottis and cough reflex protect lower airways
  -ciliated epithelium propels mucous upwards towards the mouth
• at site of alveoli T-cell mediated immunity, humoral immunity and inflammatory responses occur to defend lower respiratory tract infections.
  -macrophages and neutrophils inactivate the bacteria and compliment and antibodies produced help with opsonisation.

Question 22

How is CAP diagnosed and classified in terms of severity

Answer 22

• patient history
  -increase in CRP + WCC through blood tests
  -patient observations e.g. BP, temp, HR, resp rate, and O2 saturation.
  -chest x-ray

Usually caused by step or influenza viruses

severity based on CRB-65(primary) or CURB-65(hospital) score. One point for each of the following: confusion, Urea>7mmol/L, resp rate >30/min,BP less than 90 systolic and less than 60 diastolic, and over the age of 65.

CRB-65 severity :
0 = low
1-2 = intermediate
3-4 = high

CURB-65 severity :
0-1 = low
2 = intermediate
> 3 = high.

Question 23

How is HAP diagnosed and classified in term of severity

Answer 23

diagnosed through chest x-ray + either fever or WCC plus any of the following:
- increased resp/ secretions , SOB, cough, new confusion.

not deemed severe unless symptoms such as: new confusion, resp rate >30/min, bilateral on chest x-ray, sepsis , multi organ dysfunction , new resp failure, require critical care.

Question 24

how are acute ineffective exacerbations of COPD diagnosed and classified in terms of severity

Answer 24

-history of COPD, worsening of symptoms and trigger identification. Symptoms inculde: SOB, increased cough, changes in sputum production, icreased fatigue.

Question 25

summarise antibiotic treatment for CAP

Answer 25

Low severity treatment (duration 5 days):
non-pen allergy = amoxicillin (PO) 500mg TDS
pen allergy = Doxycycline (PO) 200mg STAT, 100mg OD or Clarithromycin (PO) 500mg BD.

moderate ( duration 5 days):
non-pen allergy = amoxicillin (PO) 500mg-1000mg TDS + Clarithromycin (PO) 500mg BD.
Doxycycline (PO) 200mg STAT, 100mg OD
or Clarithromycin (PO) 500mg BD

High severity:
non-pen allergy = co-amoxiclav (PO/IV), PO 625mg TDS, IV 1.2g TDS + clarithromycin 500mg BD (PO)

pen allergy = Levofloxacin (PO/IV) 500mg BD

Question 26

summarise antibiotic treatment for HAP

Answer 26

non - severe (5 days):
non-pen allergy: Co-amoxiclav (PO) 625mg TDS.
Pen allergy: Doxycycline (PO) 200mg STAT, 100mg OD
or Co-trimoxazole (PO) 960mg BD
or Levofloxacin (PO) 500mg OD-BD

Severe (5 days):
non-pen allergy: Tazocin (IV) 4.5g TDS
non severe pen allergy: Meropenem (IV) 1g TDS
severe pen allergy: Levofloxacin (IV) 500mg OD-BD

Question 27

summarise antibiotic treatment for IECOPD

Answer 27

non-severe (5 days):
- non - pen allergic: Amoxicillin (PO) 500mg TDS
- pen allergic:Doxycycline (PO) 200mg STAT, 100mg OD
- or clarithromycin (PO) 500mg BD

IV antibiotic choices:
-amoxicillin 500mg-1g TDS
-co-amoxiclav 1.2g TDS
-clarithromycin 500mg BD
-co-trimoxazole 960mg BD
-Tazocin 4.5g TDS

All patients should also recieve a 5 day course of oral prednisolone 30mg OD

Question 28

difference in therapeutic approach of narrow v broad - spectrum antibiotics.

Answer 28

-broad is used to target many types of bacteria caused by an unidentified microorganism or infection from multiple bacteria.
-narrow is effective against a limmited number of bacteria and used when the microorganism has been identified to minimise the disruption of natural flora.

Question 29

how to determine level of antibacterial drug activity + measure effectiveness

Answer 29

2 ways:

1) Minimal inhibitory conc (MIC) lowest conc of drug that prevents visible growth of the pathogen (indicates bacterial drug resistance).
2) Minimum bacterialcidal conc (MBC) - lowest conc of drug that kills pathogen.

Bacteriostatic = MBC/MIC ratio > 4

Bacteriocidal = MBC/MIC < 4

Question 30

contrast bacterialcidal and bacterialstatic effects and their properties from the dilution susceptibility tests.

Answer 30

• Broth of agar showing lowest conc with no more growth of pathogen will be MIC.
• Broth of agar with lowest conc that doesn’t support any of the microbes growth will be MBC.
• Both conc can now be used to calculate the MBC/MIC ratio to see if the drug is bacterialcidal or bacteriostatic.

Question 31

1) idetntify subclasses of penicillins
2) explain their MoA
3) main adverse effects

Answer 31

1)
i) Natural penicillins e.g. Penicillin G and V (narrow spectrum)
ii) Antistaphyloccal penicillins e.g. Flucloxacillin.
iii) Aminopenicillins e.g. Ampicillin or Amoxicillin (broad-spectrum)
iv) Antipseudomonal penicillins e.g. piperacillin or ticarcillin (extended broad - spectrum)

2) Inhibitors of cell wall synthesis:
Block the formation of peptide bridges in peptidoglycan chains and have bacterialcidal effect by binding and blocking transpeptidases (PBP) . Resistant bacterial can produce b-lactamase to inactivate the beta lactam ring. To overcome this beta-lactamase inhibitors can be combined with the drug such as clavulanic acid with amoxicillin to make co-amoxiclav.

3)
Question penicillin allergy before treatment:
Mild = rash, breathing or swallowing difficulties
Severe = anaphylaxis and death
Penicillins have cross-reactivity with all beta - lactams
GI distress
CNS toxicity

Question 32

name the beta-lactam subgroups

Answer 32

penicillins e.g. amoxicillin
cephalosporins e.g. cefotaxime
carbapenems e.g. Imipenem
monobactams e.g. Aztreonam

Question 33

Difference between B-lactams and glycopeptides e.g. Vancomycin

Answer 33

B-lactams bind to transpeptidases for the inhibition of the cell wall. Whereas glycopeptides such as vancomycin bind to the amino acids linked to NAM in the peptidoglycan to stop cell wall synthesis.

B-lactams can cover both gram + / -ve. Whereas glycopeptides only cover gram +ve.

Question 34

which antibiotics target 30s ribosomes to cause inhibition of protein synthesis?

Answer 34

Aminoglycosides e.g. gentamycin (disrupt protein elongation in translation/mRNA misreading) - used for aerobic gram -ve. Bactericidal effect.

Tetracyclines e.g. Doxycycline (Block access of tRNA to ribosome site A). Broad spectrum and has bacteriostatic effect.

Question 35

which antibiotics target the 50s subunit of ribosomes to inhibit protein synthesis?

Answer 35

Macrolides e.g. Erythromycin. Prevent translocation step and have bacteriostatic effect. Mostly broad spec.

Lincosamides e.g. clindamycin. Prevent translocation step + bacteriostatic.

Oxazolidinones e.g. Linezolid. Interfere with translation initiation assembly. Bacteriostatic and used against gram +ve

Chloramphenicol - block attachment of tRNA to ribosome site A causing bacteriostatic effect. Broad spectrum.

Question 36

which antibiotics target metabolic pathways acting as antimetabolites?

Answer 36

Sulfonamides - compete with PABA as a substrate for the enzyme dihydropteroate synthase so folic acid cannot be produced to produce purines in DNA. Has bacteriostatic effect.

Trimethoprim - competes with Dihydrofolate reductase (DHFR) to stop production of folic acid and DNA. Bacteriostatic effect.

Question 37

how do sulphonamides mimic the structure of PABA to inhibit the enzyme dihydropteroate synthetase?

Answer 37

1 - free para amino group for H-bond.
2-para-substituted phenyl ring for VDW’s interactions.
3-sulphanomide for ionic bond
4- both sulphonamide and amino group must be attached directly to aromatic ring.
5- R2 group is the only site that can be varied which will affect PK.

Question 38

how does trimethoprim mimic the general structure of dihydrofolic acid to compete for the binding sites of dihydrofolate reductase?

Question 39

SAR of penicillins

Answer 39

1- beta - lactam ring is essential
2- COO- essential to bind to NH3+ of Lys on transpeptidase.
3-bicyclic system is important
4-acylamino side chains are essential.
5-sulphur is usual
6- cis stereochemistry of bicyclic ring is important.

Question 40

name some issues with penicillins and how they can be overcome

Answer 40

1 - acid - resistant penicillins - influence of acyl side chain can open up lactam ring. Solution introduce EWG to acyl side chain

2- broad spectrum penicillins - limited breadth of activity. Inability to reach outer surface of cell membrane due to hydrophobic barrier in gram -ve bacteria. Solution addition of hydrophilic group attached to carbon at side chain

3- some bacteria express beta lactamases which open up the lactam ring making the antibiotic not effective. Solution adding a bulking group to act as a steric shield or the use of beta lactamase inhibitors

Question 41

difference in structure of cephalosporins v penicillins?

Answer 41

• variations of 7-acylamino side chain
• variation of 3 - acetoxymethyl side chain
  -extra substitution at C7

Question 42

what antibacterial agents inhibit nucleic acid transcription/replication?

Answer 42

Fluroquinolones (end in floxacin) for DNA
Rifamycincs for RNA e.g. Rifampin

Question 43

what antibiotics generate free radicals?

Answer 43

nitroimidazoles and nitrofurantoin - both contain nitro group. Reduction of nitro group causes toxic metabolites to be released which damage bacterial DNA

Question 44

how do fluoroquinolones cause inhibition of DNA synthesis?

Answer 44

• Targets Topoisomerases
• DNA gyrase in gram -ve and topoisomerase IV (human) target gram +ve
• fluoroquinolones inhibit DNA gyrase and topoisomerase IV making DNA inaccessible –> blocking bacterial DNA replication –> cell death.

Question 45

how do Rifamycins/Rifampicin inhibit RNA synthesis

Answer 45

• inhibit the initiation step of DNA transcription
• blocks activity of RNA polymerase.

Question 46

Identify the therapeutic agents for tuberculosis

Answer 46

Initial treatment (2months):
R - Rifampicin
I - isoniazid
P - pyrazinamide
E - ethambutol
continuation phase (4months):
R - Rifampicin
I - Isoniazid

Retreatment:
Initial = RIPE + streptomycin (2 months)
Continuation = RI + Ethambutol (5months)

Question 47

differences between intrinsic and acquired antibiotic resistance.

Answer 47

intrinsic - common with bacterial species. Where bacteria are resistant naturally to an antibiotic usually due to lack of drug target or cell wall being impermeable to the drug.

acquired - not uniform within a species. When there is a change or gene gain caused by mutations, vertical transfer, or horizontal transfer.

Question 48

differences between vertical and horizontal transfer of drug resistance

Answer 48

Vertical:
-DNA from parent to offspring (chromosome and plasmids)
-asexual reproduction

Horizontal:
- genetic material transmission to unrelated bacteria.
- plasmid is copied and transferred to recipient cell.

Question 49

describe the mechanism of transformation, transduction, conjugation within the horizontal transfer of drug resistance.

Answer 49

1- transformation: bacterial cell taking up DNA from environment from dead donor cells that released DNA.

2 - transduction: transfer of DNA via bacteriophages, no direct contact between bacteria.

3- conjugation: transfer of DNA via sex pili/cell to cell contact from a conjugation tube.

Question 50

explain different antibiotic resistance mechanisms in bacteria.

Answer 50

1 - alteration of drug target site such as mutations in enzymes.

2- drug inactivation from bacteria producing enzymes that break down antibiotics e.g. beta lactamases. Or transfer of unusual chemical groups to the antibiotic - making the drug ineffective.

3- Limit drug uptake either due to differences in hydrophobicity of the outer membrane. Or mutations in genes that alter the bacteria’s porins.

4- Drug efflux actively transporting toxic substances out of the plasma membrane.

Question 51

compare virus- and host-targeting antiviral approaches. Pros vs cons?

Answer 51

Virus target:

e.g. Sofosbuvir (HCV)-nucleotide inhibitor. Inhibition of viral polymerase.
Adv = selective toxicity to the virus so reduced toxicity to host cells.
Disadv = risk of drug resistance.

Cell-host target:

e.g. Maraviroc (HIV) - targets human CCR5 protein (blocks viral entry)
adv = reduced risk of drug resistance + broad - spec effects.
disadv = reduced specificity (Higher risk S/E)

Question 52

outline main MOA and targets of different classes of antiviral drugs related to the life cycle of a virus.

Answer 52

Virus attachment inhibitors (HIV) - prevent proteins in the virus binding to receptors on the surface of the cell.

Viral penetration/fusion inhibitors (HIV) - Enfuvirtide mimics HIV-1 fusion machinery, binding to gp41 and preventing HIV envelope fusion with the cell membrane.

Viral uncoating inhibitors (Influenza) - blocking of M2 proton channel stops the virus from uncoating. M2 blockers are Amantadine and Rimantadine.

Viral polymerase inhibitors (nucleotide inhibitors and non-nucleoside inhibitors) - stops viral replication.

Viral protease inhibitors - stop protein synthesis by binding to viral proteases stronger than the natural substrate + can block active sites.

Viral release inhibition (influenza) - neuraminidase inhibitors are analogues of sialic acid and compete for binding site preventing release of viral progenies.

Question 53

difference between nucleoside/nucleotide and non-nucleoside antiviral agents?

Answer 53

nucleoside/nucleotide mimic and compete with natural nucleotides to bind to enzyme active site. Whereas non -nucleotides do not resemble natural nucleotides and bind to the allosteric site.

• n/n are incorporated into the growing nucleic acid chain. Non - N is not incorporated into nucleic acid chain.
• n/n terminate polymerase elongation and are needed to be activated by viral kinases to the triphosphate form. Whereas non - n causes enzyme structure rearrangements that inhibit function also they don’t require activation steps.

Question 54

what are the principles of microbial identification?

Answer 54

rapidly + accurately identify pathogens responsible for infection.

excludes incorrect diagnosis, best possible therapeutic option is given, antimicrobial susceptibility testing

Question 55

contrast different types of microbial tests to identify microorganisms

Answer 55

Rapid tests + immunoassays - Identifies antigen-antibody binding usually identified by rate of colour formation due to enzymes

Microscopy - staining plus use of electron microscope

Culture - use of different media and growth requirements to grow desired organisms.

Biochemical tests - uses growth requirements and enzymatic activities using biochemical kits.

Molecular testing - PCR, allows the growth of desired DNA/RNA with high purity and yield.

Question 56

explain biology of PCR

Answer 56

1 - Denaturation: two strands of DNA are separated by heating breaking H bonds.
2- Annealing - rapid process where primers bind to specific target sequence when cooling.
3- Extension - reaction heated to optimum temp for DNA polymerase so efficient DNA synthesis.

Question 57

why is PCR relevant in microbial diagnosis?

Answer 57

Primers and PCR are designed to amplify a portion of the microorganisms specific genome. Nucleic acids can then be loaded into agarose gel and visualised via electrophoresis. Expected molecular weight of the microbe helps to identify presence within the specimen.

Question 58

what are the symptoms of sepsis and how is it diagnosed?

Answer 58

sweats, disorientation, shivering, high HR, extreme pain, SOB

Diagnosing:
- history check related to symptoms and risk factors
-tests e.g. chest x-ray, CT scan, urine sample, sputum, faeces sample, bloods
- full examination: capillary refill time, skin, dehydration.
-observations: temp (feverlike), HR, RR > 30, BP

Question 59

what are the symptoms of meningitis and how is it diagnosed?

Answer 59

symptoms: fever, nausea, muscle pain, lethargy, chill, sore throat, stiff neck, unusual skin colour, non -blanching rash.

Diagnosing:
-History of patient symptoms, risk factors, rule out differential diagnosis
-physical examination - temp, HR, BP, conscious level, photosensitivity, non-blanching rash.
-diagnostic tests e.g. LP, CT scan of head, Blood tests

Question 60

What is the most appropriate antimicrobial regimens to treat sepsis?

Answer 60

Unknown source + renal function >20mls/min:

amoxicillin (IV) 1g TDS + gentamycin 5mg/kg
pen allergy: Levofloxacin(IV) 500mg BD + gentamycin (IV) 5mg/kg

Unknown source + renal function <20mls/min:
Tazosin (IV) 4.5g BD + clarithromycin (IV) 500mg BD

If chest source:
<48h treat like severe CAP
>48h treat like HAP

Question 61

What is the most appropriate antimicrobial regimens to treat meningitis?

Answer 61

Non pen allergy:
Ceftriaxone (IV) 2g OD
Pen allergy:
Chloramphenicol (IV) 25m/kg every 6 hours

If pen resistance suspected add:
Vancomycin (IV) 15-20mg/kg
or
Rifampicin (PO) 600mg BD

If viral encephalitis suspected add:
Acyclovir (IV) 10mg/kg TDS

Question 62

bacteria groups likely to be associated with different infection sites

Answer 62

Brain -bacterial meningitis
Lungs - pneumonia
reproductive system - STDs e.g. chlamydia, gonorrhea, syphilis

Question 63

recommend simple, effective and economical approach to minor illness

Question 64

what are common antibiotics used for minor illness

Answer 64

acute sore throat - if not resolved within a week - non pen allergy: Phenooxymethlypenicillin 500mg QDS
pen allergy: Clarithromycin 500mg BD

acute otitis externa - acetic acid 2% 1 spray TDS for 7 days