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Year 5 Pathology > Microbiology > Flashcards

Microbiology Flashcards

1
Q

What are some examples of selective targets for antibiotics?

A
  • Peptidoglycan layer of cell wall
  • Inhibition of bacterial protein synthesis
  • DNA gyrase and other prokaryotic-specific enzymes
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2
Q

What are two types of antibiotics which inhibit bacterial cell wall synthesis?

A

1) Beta-lactam antibiotics

2) Glycopeptides

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3
Q

What are examples of beta-lactam antibiotics?

A
  • Penicillins
  • Cephalosporins
  • Carbapenems
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4
Q

What are examples of glycopeptide antibiotics?

A
  • Vancomycin

- Teicoplanin

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5
Q

What are the differences between gram-positive and gram-negative cell walls?

A

Gram positive bacteria have a thick peptidoglycan layer and no outer lipid membrane whilst Gram negative bacteria have a thin peptidoglycan layer and have an outer lipid membrane.

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6
Q

How do beta-lactams work?

A
  • Inactivate the enzymes that are involved in the terminal stages of cell wall synthesis (transpeptidases also known as penicillin binding proteins) – β-lactam is a structural analogue of the enzyme substrate
  • Bactericidal
  • Weakened cell wall results osmotic lysis of the bacterial cell
  • Active against rapidly-dividing bacteria
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7
Q

Which bacteria are beta-lactams ineffective against?

A

Bacteria which lack peptidoglycan cell walls:

  • mycoplasma
  • chlamydia
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8
Q

Which organisms can penicillin be effective against?

A

Gram positive organisms, Streptococci, Clostridia; broken down by an enzyme (β-lactamase) produced by S. aureus

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9
Q

Which organisms can amoxicillin be effective against?

A

Broad spectrum penicillin, extends coverage to Enterococci and Gram negative organisms ; broken down by β-lactamase produced by S. aureus and many Gram negative organisms

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10
Q

Which organisms can flucloxacillin be effective against?

A

Similar to penicillin although less active. Stable to β- lactamase produced by S. aureus.

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11
Q

Which organisms can piperacillin be effective against?

A

Similar to amoxicillin, extends coverage to Pseudomonas and other non-enteric Gram negatives; broken down by β-lactamase produced by S. aureus and many Gram negative organisms

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12
Q

Which organisms can clavulanic acid and tazobactam be effective against?

A

β-lactamase inhibitors. Protect penicillins from enzymatic breakdown and increase coverage to include S. aureus, Gram negatives and anaerobes

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13
Q

What are examples of cephalosporins?

A
  • Cefuroxime - stable to many β-lactamases produced by Gram negatives. Similar cover to co-amoxiclav but less active against anaerobes
  • Ceftriaxone - 3rd generation cephalosporin. Associated with C. difficile
  • Ceftazidime - anti-Pseudomonas
  • Extended spectrum beta-lactamase (ESBL) - producing organisms are resistant to all cephalosporins regardless of in vitro results
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14
Q

What are examples of extended spectrum beta-lactamase enzymes?

A

Meropenem
Imipenem
Ertapenem

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15
Q

What are key features of beta-lactams?

A
  • Non-toxic
  • Renally secreted
  • Short half life
  • Will not cross intact blood-brain barrier
  • Cross-allergenic (penicillins approx 10% cross-reactivity with cephalosporins or carbapenems)
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16
Q

Which organisms are carbapenem resistant?

A

Acinetobacter

Klebsiella

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17
Q

What is the mechanism of action of glycopeptides?

A

Glycopeptide antibiotics inhibit synthesis of the bacterial cell wall by binding to the dipeptide terminus D-Ala-D-Ala of peptidoglycan precursors, thereby sequestering the substrate from transpeptidation and transglycosylation reactions at the late extracellular stages of peptidoglycan cross-linking.

Inhibits transglycosidase
Stops transpeptidase binding

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18
Q

What are inhibitors of protein synthesis?

A
  • Aminoglycosides
  • Tetracyclines
  • Macrolides
  • Chloramphenicol
  • Oxazolidinones
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19
Q

How do aminoglycosides work?

A
  • Bind to amino-acyl site of the 30S ribosomal subunit
  • Prevent elongation of polypeptide chain
  • Cause misreading of codons along mRNA
  • Rapid, concentration-dependent bactericidal action
  • Require specific transport mechanisms to enter cells (accounts for some intrinsic R)
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20
Q

Why must aminoglycoside levels be monitored?

A

Ototoxic

Nephrotoxic

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21
Q

Which aminoglycosides are particularly affective against Ps aeruginosa?

A

Gentamicin

Tobramycin

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22
Q

How is the activity of aminoglycosides affected when combined with:

  • beta-lactams?
  • anaerobes?
A
  • Synergistic combination with beta-lactams

* No activity vs. anaerobes

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23
Q

Which bacteria are tetracyclines affective against?

A

Broad-spectrum agents with activity against intracellular pathogens (e.g. chlamydiae, rickettsiae & mycoplasmas) as well as most conventional bacteria - they are BACTERIOSTATIC

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24
Q

What are some limitations of tetracyclines?

A
  • Widespread resistance limits usefulness to certain defined situations
  • Do not give to children or pregnant women
  • Light-sensitive rash
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25
Q

What is the mechanism of action of tetracyclines?

A
  • Reversibly bind to the ribosomal 30S subunit

* Prevent binding of aminoacyl-tRNA to the ribosomal acceptor site, so inhibiting protein synthesis.

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26
Q

How do macrolides work?

A

They are bacteriostatic and bind to the 50S subunit of the ribosome - interferes with translocation and stimulate dissociation of the peptide-tRNA.

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27
Q

How does chloramphenicol work?

A

Bacteriostatic and has very broad anti-bacterial activity. It is RARELY USED. It binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation

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28
Q

Why is chloramphenicol rarely used?

A

Risk of aplastic anaemia (1/25,000 – 1/45,000 patients) and grey baby syndrome in neonates because of an inability to metabolise the drug

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29
Q

What is the mechanism of action of oxazolidinone (linezolid)?

A

Binds to the 23S component of the 50S subunit to prevent the formation of a functional 70S initiation complex (required for the translation process to occur).

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30
Q

Which bacteria are oxazolidinones (linezolid) effective against?

A

Highly active against Gram positive organisms, including MRSA and VRE. Not active against most Gram negatives.

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31
Q

When should oxazolidinones (linezolid) be used?

A

Is expensive, may cause thrombocytopoenia and should be used only with consultant Micro/ID approval

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32
Q

What are the inhibitors of DNA synthesis?

A

Quinolones

Nitroimidazoles

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33
Q

Give 3 examples of Quinolones

A

Ciprofloxacin
Levofloxacin
Moxifloxacin

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34
Q

Give 2 examples of Nitroimidazoles

A

Metronidazole

Tinidazole

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35
Q

How do fluoroquinolones work?

A

Act on alpha-subunit of DNA gyrase predominantly, but, together with other antibacterial actions, are essentially bactericidal

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36
Q

Which bacteria are fluoroquinolones effective against?

A
  • Broad antibacterial activity, especially vs Gram –ve organisms, including Pseudomonas aeruginosa
  • Newer agents (e.g. levofloxacin, moxifloxacin) - increase in activity vs G +ves and intracellular bacteria, e.g. Chlamydia spp
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37
Q

When are fluoroquinolones used?

A

Use for UTIs, pneumonia, atypical pneumonia & bacterial gastroenteritis

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38
Q

How do nitroimidazoles work?

A
  • Include the antimicrobial agents metronidazole & tinidazole
  • Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage
  • Rapidly bactericidal
  • Active against anaerobic bacteria and protozoa (e.g. Giardia)
  • Nitrofurans are related compounds: nitrofurantoin is useful for treating simple UTIs
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39
Q

Which antibiotics are inhibitors of RNA synthesis?

A

Rifamycins e.g. rifampicin & rifabutin

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40
Q

What is rifampicin’s mechanism of action?

A
  • Inhibits protein synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation
  • Bactericidal
  • Active against certain bacteria, including Mycobacteria & Chlamydiae
  • Monitor LFTs
  • Beware of interactions with other drugs that are metabolised in the liver (e.g oral contraceptives)
  • May turn urine (& contact lenses) orange
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41
Q

How does rifampicin bacterial resistance develop?

A
  • Except for short-term prophylaxis (vs. meningococcal infection) you should NEVER use as single agent because resistance develops rapidly
  • Resistance is due to chromosomal mutation.
  • This causes a single amino acid change in the ß subunit of RNA polymerase which then fails to bind Rifampicin.
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42
Q

Give 2 examples of cell membrane toxin antibiotics and their mechanism of action

A

Daptomycin – a cyclic lipopeptide with activity limited to G+ve pathogens. Recently licensed antibiotic likely to be used for treating MRSA and VRE

Colistin – a polymyxin antibiotic that is active against Gram negative organisms, including Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella. pneumoniae. It is not absorbed by mouth. It is nephrotoxic and should be reserved for use against multi-resistant organisms

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43
Q

What are the 2 inhibitors of folate metabolism?

A

Sulfonamides

Diaminopyramidines (e.g. trimethoprim)

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44
Q

How do sulphonamides and diaminopyrimidines work?

A
  • Act indirectly on DNA through interference with folic acid metabolism
  • Synergistic action between the two drug classes because they act on sequential stages in the same pathway
  • Sulphonamide resistance is common, but the combination of sulphamethoxazole+trimethoprim (Co-trimoxazole) is a valuable antimicrobial in certain situations (e.g. Treating Pneumocystis jiroveci pneumonia)
  • Trimethoprim is used for Rx community-acquired UTIs
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45
Q

What are the different mechanisms of resistance?

A 
• Chemical modification or inactivation of the antibiotic
• Modification or replacement of target
• Reduced antibiotic accumulation
1) Impaired uptake
2)Enhanced efflux
• Bypass antibiotic sensitive step
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46
Q

Which antibiotics cause difference mechanisms of resistance?

1) Inactivation
2) Altered Target
3) Reduced Accumulation
4) Bypass

A

1) Inactivation
ß Lactams
Aminoglycosides
Chloramphenicol

2) Altered Target
ß Lactams
Macrolides
Quinolones
Rifampicin
Chloramphenicol
Linezolid
Glycopeptides
3)Reduced Accumulation
Tetracyclines
ß Lactams
Aminoglycosides
Quinolones
Chloramphenicol

4)Bypass
Trimethoprim
Sulphonamides

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47
Q

How are beta-lactams inactivated?

A
  • ß Lactamases are a major mechanism of resistance to ß Lactam antibiotics in Staphylococcus aureus and Gram Negative Bacilli (Coliforms).
  • NOT the mechanism of resistance in penicillin resistant Pneumococci and MRSA.
  • Penicillin resistance not reported in Group A (S. pyogenes), B, C, or G ß haemolytic Streptococci.
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48
Q

How did MRSA become resistant?

A
  • mecA gene encodes a novel PBP (2a)
  • Low affinity for binding ß Lactams
  • Substitutes for the essential functions of high affinity PBPs at otherwise lethal concentrations of antibiotic
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49
Q

How did streptococcus pneumoniae develop penicillin resistance?

A
  • Penicillin resistance is the result of stepwise mutations in PBP genes
  • Lower level resistance can be overcome by increasing penicillin dose
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50
Q

Describe extended spectrum ß Lactamases (ESBL-based) resistance

A

ESBLs can enzymatically break down cephalosporins (cefotaxime, ceftazidime, cefuroxime) and penicillins but, not carbapenems

Flucloxacillin is a member of the penicillin class, but is RESISTANT to beta-lactamase

Tazobactam is a beta-lactamase inhibitor which is given along with piperacillin, but which is not itself an antibiotic
 
More common in E. coli and Klebsiella

Treatment failures reported with beta lactam and beta lactamase inhibitor combinations – augmentin/tazocin

Aminoglycoside used in combinations
 
New beta-lactamases are spreading MDR instead of just the ESBL-component of resistance (big problem)

If something is erythromycin-resistant, be careful about giving clindamycin (may make the bacteria MDR)

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51
Q

How do altered targets in bacteria result in macrolide resistance?

A

Adenine-N6 methyltransferase modifies 23S rRNA –> reduces binding of MLS antibiotics and results in resistance
Encoded by erm (erythromycin ribosome methylation) genes.

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52
Q

What are some example of mis-use of antimicrobial agents is common?

A
  • No infection present
  • Selection of incorrect drug
  • Inadequate or excessive dose
  • Inappropriate duration of therapy
  • Expensive agent used when cheaper is available
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53
Q

What are some side effects of antibiotics?

A
  • GI upset
  • Fever & rash
  • Renal dysfunction
  • Acute anaphylaxis
  • Hepatitis
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54
Q

How many hospitalised patients experience adverse effects to antimicrobials?

A

Approximately 5% of hospitalised patients given an antimicrobial experience an adverse event

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55
Q

If a patient experiences a non-severe reaction e.g. rash, what does this mean?

A

For patients with non-severe reactions (such as rash) a related antibiotic class may be considered. (e.g. cephalosporins in penicillin allergy)

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56
Q

What does CHAOS stand for in terms of antimicrobial selection?

A 
CHOICE of the correct antimicrobial depends upon the
HOST characteristics 
ANTIMICROBIAL
susceptibilities of the
ORGANISM itself and also the
SITE of the infection
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57
Q

What does the choice of drug depend on?

A

Pharmacokinetics
• Absorption
• Distribution
• Elimination

Route of administration
• I.v. for serious infection or if patient not absorbing p.o.
• I.v. if need to access deep site or CNS

Dosage
• Age
• Renal/ hepatic function
• Drug monitoring

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58
Q

What are some factors which impact host characteristics?

A 
Age
Allergy
Renal function
Genetics
Hepatic function
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59
Q

If it is necessary to treat a patient on an empirical basis, which antibiotic may be used?

A

Use a broad-spectrum agent that is likely to cover the organisms.
Collect specimens for culture prior to starting antibiotics
The empirical cover may then be changed to a more specific/narrow spectrum agent on the basis of the culture results

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60
Q

Why is broad spectrum a good initial option for nosocomial pneumonia ?

A
  • Appropriate initial antibiotic therapy is associated with higher survival rates, shorter hospital stays and lower healthcare costs
  • Broad spectrum antibiotics are an optimal initial choice for nosocomial pneumonia and severe sepsis
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61
Q

What are some preliminary identification techniques of the infecting organism?

A

Gram stain:
• CSF
• Joint aspirate
• Pus

Rapid antigen detection:
• Immunofluorescence
• PCR

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62
Q

What factors could affect the local concentration of the antimicrobial at the side?

A
  • pH at the infection site
  • Lipid-solubility of the drug
  • Ability to penetrate the blood- brain barrier (CNS infections)
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63
Q

What are signs of infection which would warrant antimicrobial usage?

A

Is there evidence of a systemic response, e.g.
•Fever
•Raised CRP
• High WBC count (neutrophils +++) or very low WBC count

Also consider:
•Duration of symptoms
•Underlying risk factors
•Likely source of infection
•Exclude other pro-inflammatory medical disease
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64
Q

Which route would you use for each type of infection?

A

i.v. Serious (or deep-seated) infection

p.o. Usually easy, but avoid if poor GI function or vomiting
Different classes of antimicrobial have different oral bioavailabilities

i.m. Not an option for long-term use Avoid if bleeding tendency or drug is
locally irritant

Topical Limited application and may cause local sensitisation

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65
Q 
What is the recommended length of ABs courses for these particular infections?
N. meningitidis meningitis 
Acute osteomyelitis (adult)
Bacterial endocarditis
Gp A Streptococcal pharyngitis 
Simple cystitis (in women)
A

N. meningitidis meningitis
7 days

Acute osteomyelitis (adult)
6 weeks

Bacterial endocarditis
4-6 weeks

Gp A Streptococcal pharyngitis
10 days

Simple cystitis (in women)
3 days
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66
Q

How common are hospital acquired infections in the UK?

A

4 million in Europe
~8%
May be around 25% in developing nations

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67
Q

What are some of the economical impacts of hospital acquired infections?

A

~£1 billion a year

15-30% are preventable

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68
Q

What is the most common syndrome of hospital acquired infections?

A

Hospital acquired pneumonia (~25%)

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69
Q

What type of bacteria is C. difficile?

A

Gram-positive spore-forming anaerobe

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70
Q

Where do C. difficile spores germinate?

A

In the gut - transmissible and can contaminate environment and persist for long periods of time

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71
Q

What are the different types of C. difficile?

A

– Toxinotype III/BI/NAP1/027
– Pro-inflammatory – causes inflammation
– Cytotoxic – cell damage
– Enterotoxic – damage to the gut

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72
Q

How are C. difficile patients affected?

A

Mild diarrhoea → severe colitis – dehydration, pseudomembranous colitis, perforation

Attack rates higher in – older
– debilitated
– antibiotic-treated

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73
Q

How can C. difficile be treated pharmacologically?

A

Fidaxomicin

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74
Q

What is Fidaxomicin?

A
  • Macrocyclic antibiotic

- Non-inferior to vancomycin for response to treatment and lower recurrence

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75
Q

What are some non-drug approaches to C. difficile?

A

Faecal transfer: microbiome. fresh faeces, healthy donor

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76
Q

What percentage of hospital acquired infections do MRSA bacteraemia and C. difficile make up?

A

15%

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77
Q

Why do catheters cause high rates of UTIs?

A

Colonised very rapidly - 60% within 96hrs

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78
Q

What are some of the resistance mechanisms gram negative bacteria possess?

A

– Chromosomal
– Plasmid-mediated

E. coli < Klebsiella < Enterobacter

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79
Q

What are some contributors to surgical site infections?

A
  • Wound environment
  • Host defence
  • Pathogens
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80
Q

What factors can be changes to reduce the risk of surgical site infection?

A
  • Do not remove hair routinely to reduce risk of surgical site infection
  • Antibiotic prophylaxis - clean surgery involving. placement of prosthesis or implant, clean-contaminated surgery
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81
Q

Gram-positive, purple and bacteria in clusters refers to which bacteria?

A

Staphylococcus aureus

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82
Q

How can MRSA blood stream infection arise?

A

Normally preceded by colonisation

Skin breach: skin disease, chronic disease, invasive procedure, device

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83
Q

What are the key strategies for infection control?

A

Improving infection control activities (improving transmission) –> measuring –> analysing (data management) –> feedback and altering practice

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84
Q

Which bacteria arise in the different parts of the hospital environment?

A

Environmental hygiene e.g. C. difficile, Norovirus, Acinetobacter outbreaks

Environmental sources Legionella- cooling towers Aspergillus- building works

Negative pressure
isolation: TB, Chickenpox, RSV

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85
Q

What are the four routes of entry of pathogen?

A

a) Haematogenous spread
b) Direct implantation - via instrumentation
c) Local extension - secondary to established infections
d) PNS into CNS

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86
Q

What is the difference between meningitis and meningoencephalitis?

A

Meningitis: inflammatory process of meninges and CSF

Meningoencephalitis: inflammation of meninges and brain parenchyma

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87
Q

How can neurological damage by meningitis occur?

A

Direct bacterial toxicity

Indirect inflammatory process and cytokine release and oedema

Shock, seizures, and cerebral hypo-perfusion

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88
Q

Which are the most common organisms that cause acute meningitis?

A 
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae
Listeria monocytogenes 
Group B Streptococcus
Escherichia coli
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89
Q

Describe the clinical presentation of N meningitidis

A

Infectious cause of childhood death in all countries.

Transmission is person-to-person, from asymptomatic carriers.

Pathogenic strains are found in only 1% of carriers.

Cause infections in less than 10 days.

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90
Q

Describe the clinical presentation of meningococcal meningitis

A

A nonblanching rash (petechial or purpuric) develops in 80% of children.
A maculopapular rash remains in 13% of children, and no rash occurs in 7%.

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91
Q

What is the clinical spectrum in septicaemia?

A

1) Capillary leak - albumin and other plasma proteins leads to hypovolaemia
2) Coagulopathy - leads to bleeding and thrombosis
3) Metabolic derangement - particularly acidosis
4) Myocardial failure

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92
Q

What would chronic meningitis look like on the CT scan?

A

CT scan - tuberculous meningitis – enhancement in the basal cistern and meninges, with dilatation of the ventricles

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93
Q

Describe the pathophysiology of chronic tuberculous meningitis

A

Incidence: 544 per 100,000 population in Africa.

More common in patients who are immunosuppressed.

Mortality was 5.5 deaths per 100,000 persons.

Involves the meninges and basal cisterns of the brain and spinal cord.

Can result in tuberculous granulomas, tuberculous abscesses, or cerebritis.

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94
Q

What is aseptic meningitis?

A

Aseptic meningitis is the most common infection of the CNS.

Patients with aseptic meningitis have headache, stiff neck, and photophobia.

A nonspecific rash can accompany these symptoms.

Enteroviruses (e.g. Coxsackievirus group B and echoviruses) are responsible for 80-90% cases in which a causative organism of aseptic meningitis is identified.

It most frequently occurs in children younger than 1 year.

The clinical course of aseptic meningitis is self-limited and resolves in 1-2 weeks.

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95
Q

How can transmission of encephalitis occur?

A

Mosquitoes
Lice
Ticks

Various viridae from Togavirus, Flavivirus, and Bunyavirus families. West Nile virus is becoming the leading cause of encephalitis.

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96
Q

List the main bacteria causes of infectious encephalitis

A

Bacterial encephalitis
- Listeria monocytogenes

Amoebic encephalitis
- Naegleria fowleri
- Habitat – warm water
- Acanthamoeba species, and Balamuthia mandrillaris,
brain abscess, aseptic or chronic meningitis

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97
Q

Describe toxoplasmosis as a cause of infectious encephalitis

A

An obligate intracellular protozoal parasite, Toxoplasma gondii. Via the oral, transplacental route or organ transplantation. Severe infection in immunocompromised patients.

Affected organs include the gray and white matter of the brain, retinas, alveolar lining of the lungs, heart and skeletal muscle.

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98
Q

Describe the pathophysiology of brain abscess

A

Pathophysiology: otitis media/mastoiditis/paranasal sinuses/endocarditis/haematogenously

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99
Q

List the organisms which cause brain abscesses

A

Streptococci (both aerobic and anaerobic)

Staphylococci,

Gram-negative organisms (particularly in neonates)

Mycobacterium tuberculosis

Fungi

Parasites

Actinomyces and Nocardia species

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100
Q

What are the risk factors for spinal infections?

A 
Advanced age
Intravenous drug use
Long-term systemic steroids
Diabetes mellitus
Organ transplantation
Malnutrition
Cancer
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101
Q

Which is the best scan for seeing parenchymal abnormalities such as abscesses and infarctions?

A

MRI is superior to CT scanning in detecting parenchymal abnormalities such as abscesses and infarctions.

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102
Q

What are the limitations of diagnostics in CSF infections?

A

MRI oedema pattern and moderate mass effect cannot be differentiated from tumor or stroke or vasculitis in some patients.
Infections in early stages and serological tests.
Amount of CSF.
PCR techniques.
Methods to detect amoebic infections.
Availability of good laboratory technique.

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103
Q

What is the generic therapy to treat meningitis?

A

Ceftriaxone 2g IV bd

If >50yrs or immunocompromised add: Amoxicillin 2g iv 4hourly

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104
Q

What is the generic therapy to treat meningo-encephalitis?

A

Aciclovir 10mg/kg iv tds

Ceftriaxone 2g iv bd

If >50yrs or immunocompromised add:
Amoxicillin 2g iv 4hourly

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105
Q

What are fungi?

A
  1. Eukaryotic organisms with chitinous cell walls and ergosterol containing plasma membranes
  2. Small protein packages containing genetic material; some also contain enzymes
  3. Single-celled organisms with prokaryotic cells
  4. Single-celled eukaryotes that are either free living or parasitic
  5. An organism that lives on or in an organism of another species and benefits by deriving nutrients at the other’s expense
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106
Q

What are the differences between yeast and mould fungi?

A

Yeasts – single celled, reproduce by budding

Moulds – multicellular hyphae, grow by branching and extension

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107
Q

Give three example of yeast fungi and mould fungi

A

Yeasts – single celled, reproduce by budding
– Candida
– Cryptococcus
– Histoplasma (dimorphic)

Moulds – multicellular hyphae, grow by branching and extension
– Dermatophytes
– Aspergillus
– Agents of mucormycoses

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108
Q

Which is the commonest cause of fungal infections in human?

A

Candida spp

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109
Q

What are the clinical manifestations of Candida spp?

A

> 150 Candida spp., but < 10 are human pathogens

Clinical manifestations
– Acute, subacute, chronic, episodic
– Superficial or systemic/invasive

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110
Q

List examples of superficialities Candida infections

A

Oral thrush

Candida oesophagitis

Vulvovaginitis

Cutaneous
– Localised or generalised

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111
Q

What is the treatment of superficial Candida infections?

A

Topical
– Oral thrush: nystatin
– Vulvovaginitis: cotrimazole
– Localised cutaneous: cotrimazole

Oral
– Vulvovaginitis: fluconazole
– Oesophagitis: fluconazole

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112
Q

What are the risk factors for Candidaemia?

A

– Malignancies, esp haematological
– Burns patients
– Complicated post-op courses (eg Tx or GIT Sx)
– Long lines

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113
Q

What is the management of Candidaemia?

A 
• Look for source and signs of dissemination
– Imaging
– Serology for beta-D-glucan
– ECHO
– Fundoscopy

• Antifungals for at least 2/52 (from date of first –ve BC)
– Echinocandin eg anidulafungin (whilst a/w identification and susceptibilities)

  • BC every 48 hours
  • REMOVE ANY LINES/PROSTHETIC MATERIAL
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113
Q

What is the management of Candidaemia?

A 
• Look for source and signs of dissemination
– Imaging
– Serology for beta-D-glucan
– ECHO
– Fundoscopy

• Antifungals for at least 2/52 (from date of first –ve BC)
– Echinocandin eg anidulafungin (whilst a/w identification and susceptibilities)

  • BC every 48 hours
  • REMOVE ANY LINES/PROSTHETIC MATERIAL
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114
Q

What are examples of invasive Candida infections?

A 
• Candidaemia
• CNS
– Dissemination, trauma, Sx
• Rx: Ambisome/voriconazole • Endocarditis
– Abnormal valves/prosthetic valves, long lines, IVDU
• Rx: Ambisome/voriconazole, Sx
• Urinary tract
– Vulvovaginits, catheters
• Rx: Fluconazole
• Bone and joint
– Dissemination. Trauma
• Rx: Ambisome/voriconazle, Sx
• Intra-abdominal
– Peritoneal dialysis, Sx, perforation
• Rx: Echinocandin/Fluconazole
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115
Q

What is cryptococcosis?

A

• Encapsulated yeast
– Serotypes A&D = C neoformans
(immunodeficient)
– Serotypes B&C = C gattii (immunocompetent)

  • Transmission by inhalation of aerosolised organisms
  • Chronic, subacute to acute pulmonary, meningitic or systemic disease
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116
Q

Which animal is cryptococcus associated with?

A

Pigeons

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117
Q

Describe the lifecycle of Cryptococcus

A

Bird/eucalyptus –> spores –> inhalation –> lodging in alveoli –> dissemination to central nervous system

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118
Q

What are risk factors for Cryptococcus?

A

• Impaired T-cell immunity
– E.g patients with HIV, who have reduced CD4 helper T-cell numbers (typically
less than 200/ml)

• Patients taking T-cell immunosuppressants for solid organ transplant also have a 6% lifetime risk

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119
Q

What is C gattii?

A
  • Causes a meningitis in apparently immunocompetent individuals in tropical latitudes esp. SE Asia and Australia
  • High incidence of space-occupying lesions in brain and lung
  • Increased resistance to amphotericin B clinically
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120
Q

What type of ink is used for a cryptococcal stain?

A

India

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121
Q

How is Cryptococcal diagnosed?

A
  • Typical clinical history/features -Immunosuppressed host
  • Imaging
  • India ink staining of CSF
  • Serum/CSF cryptococcal Ag (CRAG)
  • Can culture from blood/body fluids
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122
Q

How is Crytococcal managed?

A

• Induction:
– Amphotericin B + flucytosine (at least 2/52)

• Consolidation:
– High dose fluconazole (at least 8/52)

• Maintenance:
– Low dose fluconazole (at least 1 year)

• Repeat LP for pressure management

• Pulmonary disease:
– If mild, fluconazole alone

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123
Q

Describe the different types of Aspergillosis infection

A

• A mould with worldwide distribution

– Mycotoxicosis - ingestion of contaminated foods

– Allergy and sequelae - presence of conidia/transient growth of the organism in body orifices

– Colonization - in preformed cavities and debilitated tissues

– Invasive, inflammatory, granulomatous, necrotizing disease of lungs, and other organs

– Systemic and fatal disseminated disease

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124
Q

How is Aspergillus diagnosed?

A
  • Imaging
  • Sputum/BAL – MC&S, Ag testing
  • Aspergillus Abs (precipitans)
  • Galactomannan
  • Bx – histology, MC&S
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125
Q

How is Aspergillus managed?

A
  • Voriconazole
  • Ambisome
  • Duration based on host/radiological/mycological factors
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126
Q

What is Pneumocystis jiroveci?

A
  • Fungal infection which causes pneumonia
  • Ubiquitous in the environment and distributed worldwide
  • Lacks ergosterol in it’s cell wall

Acquisition by airborne route
– Pneumonia
– Extrapulmonary disease = rare

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127
Q

What are the risk factors for Pneumocystis jiroveci?

A

– Immunodeficiency
– Immunosuppressive drugs
– Debilitated infants
– Severe proteinnmalnutrition

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128
Q

How is Pneumocystis jiroveci diagnosed?

A

– Microscopy
– PCR
– Beta-D-glucan

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129
Q

How is Pneumocystis jiroveci managed?

A

– High dose cotrimoxazole 2-3/52
– Alternatives: atovaquone, clindamycin + primaquine
– Steroids if hypoxia present

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130
Q

Why might antifungals targeting the cell membrane not work in Pneumocystis jiroveci?

A

It lacks ergosterol in it’s cell wall

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131
Q

What is Mucormycoses?

A
  • Clinical syndrome caused by a number of fungal species belonging to the order Mucorales eg Rhizopus, Rhizomucor, Mucor
  • Inoculation via inhalation of spores or primary cutaneous inoculation
  • Favours immunosuppressed/diabetic patients
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132
Q

What are the clinical features of Mucormycoses?

A

• Rhinocerebral => CNS
– Cellulitis of the orbit and face progress with discharge of black pus from the palate and
nose
– Retro-orbital extension produces proptosis, chemosis, ophthalmoplegias and blindness
– As the brain is involved, there are decreasing levels of consciousness

  • Pulmonary
  • Cutaneous
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133
Q

How is Mucormycoses diagnosed?

A

Isolation from tissue Bx

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134
Q

How is Mucormycoses managed?

A

– Ambisome/Posaconazole – Sx

– Rx guided by response

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135
Q

What are dermatophytes?

A
  • A group of fungi capable of invading dead keratin of skin, hair and nails
  • Classified by site infected e.g tinea capitis
  • Spread via contact with desquamated skin scales
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136
Q

What are the risk factors for dermatophytes?

A

– Moisture
– Deficiencies in cell-mediated immunity
– Genetic predisposition

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137
Q

List the different dermatophytes and the site of infection

A

Foot -> tinea pedis
Scalp -> tinea capitis
Groin -> tinea cruris
Abdomen -> tinea corporis

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138
Q

What types of rashes can you get with dermatophytes?

A

Trichophyton rubrum

Tonsuurans

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139
Q

Which organisms can cause onchomycosis?

A

Trichophyton spp
Epidermophyton spp
Microsporum spp

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140
Q

What is tinea/pityriasis versicolour?

A

Tinea versicolor is skin infection with Malassezia furfur that manifests as multiple asymptomatic hypo pigmented scaly patches

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141
Q

How can a diagnosis of fungal infection be made?

A

Skin scrapings, nail specimens and plucked hairs

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142
Q

How can pityriasis versicolour be managed?

A

Topical e.g. clotrimazole, ketoconazole

Oral e.g. griseofulvin, terbinafine, itraconazole

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143
Q

List the most associated side effects which occur with antifungals

A

Azoles –> abnormal LFTs
Polyenes –> nephrotoxicity
Pyrimidine analogues –> blood disorders
Echinocandins –> relatively innocuous

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144
Q

What are the different targets of anti fungal therapy?

A

Cell membrane
Fungi use principally ergosterol instead of cholesterol

DNA Synthesis
Some compounds may be selectively activated by fungi, arresting DNA synthesis

Cell Wall
Unlike mammalian cells, fungi have a cell wall

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145
Q

List the different types of cell membrane active antifungals

A

Polyene antibiotics

  • Amphotericin B, lipid formulations
  • Nystatin (topical)

Azole antifungals

  • Ketoconazole
  • Itraconazole
  • Fluconazole
  • Voriconazole
  • Miconazole, clotrimazole (and other topicals)
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146
Q

Describe the function of azoles

A

• In fungi, the cytochrome P450-enzyme lanosterol 14-a demethylase is responsible for the conversion of lanosterol to ergosterol

• Azoles bind to lanosterol 14a-demethylase inhibiting the production of ergosterol
– Some cross-reactivity is seen with mammalian cytochrome p450 enzymes

  • Drug Interactions
  • Impairment of steroidneogenesis (ketoconazole, itraconazole)
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147
Q

How do polyenes like amphotericin B work?

A
  • Polyene antibiotic
  • Fermentation product of Streptomyces nodusus
  • Binds sterols in fungal cell membrane
  • Creates transmembrane channel and electrolyte leakage
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148
Q

Which fungi are polyenes not effective against?

A

Aspergillus terreus

Scedosporium spp

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149
Q

How does nephrotoxicity occur in polyenes?

A

• Most significant delayed toxicity

• Renovascular and tubular mechanisms
– Vascular-decrease in renal blood flow leading to drop in GFR, azotemia
– Tubular-distal tubular ischemia, wasting of potassium, sodium, and magnesium

• Enhanced in patients who are volume depleted or who are on concomitant nephrotoxic agents

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150
Q

What are alternatives to amphotericin B which are less nephrotoxic?

A

1) Liposomal amphotericin B
2) Amphotericin B colloidal dispersion
3) Amphotericin B lipid complex

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151
Q

Which antifungals target the cell wall?

A

Echinocandins - Caspofungin acetate (Cancidas)

152
Q

Describe how echinocandins target fungus

A
  • Cyclic lipopeptide antibiotics that interfere with fungal cell wall synthesis by inhibition of ß-(1,3) D-glucan synthase
  • Loss of cell wall glucan results in osmotic fragility

• Spectrum:
– Candida species including non-albicans isolates resistant to fluconazole
– Aspergillus spp. but not activity against other moulds (Fusarium, Zygomycosis)
– No coverage of Cryptococcus neoformans

153
Q

Which antifungals target DNA/RNA synthesis?

A

Pyrimidine analogues

- Flucytosine

154
Q

How does flucytosine work? What are some issues with its use?

A 
• Restricted spectrum of activity
• Acquired Resistance
– result of monotherapy – rapid onset
• Due to:
– Decreased uptake (permease activity)
– Altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity)
155
Q

What are the uses of flucytosine?

A

Used in candida and cryptococcosis infections in combination with Ambisome/fluconazole

156
Q

What is the herd immunity threshold?

A

HIT = 1 -1/R0

Percentage of fully immune individuals required to stop the spread of disease

157
Q

How does an attenuated virus cause memory cell production?

A

T cell response

158
Q

What is an inactivated vaccine?

A

Whole microorganism destroyed by heat, chemicals, radiation or antibiotics (e.g. Influenza, cholera, polio)

159
Q

What are the advantages and disadvantages of inactivated vaccines?

A

Advantages:
• Stable
• Constituents clearly defined
• Unable to cause the infection

Disadvantages
• Need several doses
• Local reactions common
• Adjuvant needed
• Shorter lasting immunity
160
Q

What are examples of attenuated vaccines?

A

Live organisms modified to be less virulent

161
Q

What are examples of attenuated vaccines?

A

Measles
Mumps
Rubella
Yellow fever

162
Q

What is a toxoid vaccine?

A

Inactivated toxic components

163
Q

Gives examples of toxoid vaccines

A

Tetanus

Diphtheria

164
Q

What is an example of a subunit vaccine?

A

Protein component of the microorganisms or synthetic virus like particles. Lacking viral genetic material and unable to replicate.

165
Q

What are examples of subunit vaccines?

A

Hepatits B

HPV

166
Q

What is a conjugate vaccine?

A

Poorly immunogenic antigens paired with a protein that is highly immunogenic (adjuvant).

167
Q

What are examples of conjugate vaccines?

A

Haemophilus influenzae type B

168
Q

What is an example of a heterotypic vaccine?

A

Pathogens that infect other animals but do not cause disease or cause mild disease in humans

169
Q

What is an example of a heterotypic vaccine?

A

BCG

170
Q

What is a viral-vectored vaccine?

A

Use a modified virus (e.g. adenovirus) to deliver genetic code for an antigen.

171
Q

What are examples of viral-vectored vaccines?

A

Ebola

Janssen and AZ COVID vaccines

172
Q

What is a nucleic acid vaccine?

A

Use DNA/RNA from the pathogen.

173
Q

What are examples of nucleic acid vaccines?

A

Pfizer

Moderna

174
Q

What are prerequisites for vaccination programmes success?

A
  • No animal reservoir
  • Antigenically stable pathogen with only one (or small number of) strains
  • No latent reservoir of infection and no integration of pathogen genetic material into host genome
  • Vaccine must induce a lasting and effective immune response
  • High coverage required for very contagious pathogens
175
Q

What are side effects of vaccines?

A
  • Adenoviral vectored vaccines
  • VITT
  • 14.2 per million doses
  • CLS
  • Pfizer
  • Lymphadenopathy
  • Myocarditis
176
Q

Which screening tools can be used to prevent post-natal infections in neonates?

A

Hep B
HIV
Syphilis

177
Q

What is the TORCH screen in neonates?

A

‘TORCH’ screen:

Toxoplasmosis
Other – syphilis; HIV; hepatitis B/C
Rubella
Cytomegalovirus (CMV)
Herpes simplex virus (HSV)
178
Q

How may congenital toxoplasmosis present?

A

May be asymptomatic at birth – 60% but may still go on to suffer long term sequelae
Deafness, low IQ, microcephaly

40% symptomatic at birth
Choroidoretinitis
Microcephaly/hydrocephalus
Intracranial calcifications
Seizures
Hepatosplenomegaly/jaundice
179
Q

What are some long term effects of congenital rubella syndrome?

A

Effect on foetus – dependent on time of infection
Mechanism – mitotic arrest of cells; angiopathy; growth inhibitor effect
Eyes: cataracts; microphthalmia; glaucoma; retinopathy
Cardiovascular syndrome: PDA; ASD/VSD
Ears: deafness
Brain: microcephaly; meningoencephalitis; developmental delay
Other: growth retardation; bone disease; hepatosplenomegaly; thrombocytopenia; rash

180
Q

How long is the ‘neonatal period’?

A

Definition varies
First 4-6 weeks of life

If born early (premature)
Neonatal period longer and is adjusted for expected birth date

181
Q

Why is there an increased risk of neonatal infection in prematurity?

A

Less maternal IgG
NICU care
Exposure to microorganisms; colonisation and infection

182
Q

Which organisms commonly affect neonates?

A

Group B streptococci
E. coli
Listeria monocytogenes

183
Q

Describe some features of group B streptococci

A

Gram positive coccus
Catalase negative
Beta-haemolytic
Lancefield Group B

In neonates:
Bacteraemia
Meningitis
Disseminated infection e.g. joint infections

184
Q

List the typical infections caused by E. coli in neonates

A

Gram negative rod

In neonates:
Bacteraemia
Meningitis
UTI

185
Q

What are the maternal risk factors for early onset sepsis?

A 
PROM/prem. Labour
Fever
Foetal distress
Meconium staining
Previous history
186
Q

What are some risk factors in the baby which increase the risk of early onset sepsis?

A 
Birth asphyxia
Resp. distress
Low BP
Acidosis
Hypoglycaemia
Neutropenia
Rash
Hepatosplenomegaly
Jaundice
187
Q

What is the treatment of early onset neonatal sepsis?

A

Supportive management:

Ventilation
Circulation
Nutrition
Antibiotics: e.g. benzylpenicillin & gentamicin

188
Q

What are some causes of late onset sepsis?

A 
Coagulase negative Staphylococci (CoNS)
Group B streptococci
E. coli
Listeria monocytogenes
S. aureus
Enterococcus sp.
Gram negatives – Klebsiella spp. /Enterobacter spp. /Pseudomonas aeruginosa/Citrobacter koseri
Candida species
189
Q

How is late onset sepsis treated?

A

NICU-Example of antibiotics for late onset sepsis:

1st line: cefotaxime & vancomycin
2nd line: meropenem

Community acquired late onset neonatal infections: cefotaxime, amoxicillin +/-gentamicin

190
Q

Describe streptococcus pneumoniae infection

A

Leading cause of morbidity and mortality esp. in <2yrs
Gram positive diplococcus – alpha haemolytic streptococcus
Meningitis, bacteraemia, pneumonia
>90 capsular serotypes
Increasing penicillin resistance

191
Q

What are the causative organisms of meningitis in each age group?

A

<3/12: N. meningitidis; S. pneumoniae; (H. influenzae (Hib) if unvaccinated); GBS; E. coli; Listeria sp.

3/12 - 5 years:N. meningitidis; S. pneumoniae; (Hib if unvaccinated)

> 6 years: N. meningitidis; S. pneumoniae

192
Q

Describe the typical presentation of mycoplasma pneumoniae

A

Acquired by droplet transmission person to person.
Epidemics occur every 3-4 years. Occurs in school age children and young adults.
Incubation period 2-3 weeks

Many asymptomatic
Classically presents:
Fever
Headache
Myalgia
Pharyngitis
Dry cough
193
Q

What are some extra pulmonary manifestations of mycoplasma pneumoniae?

A

Haemolysis
IgM antibodies to the I antigen on erythrocyte
Cold agglutinins in 60% patients

Neurological (1% cases)
Encephalitis most common
Aseptic meningitis, peripheral neuropathy, transverse myelitis, cerebellar ataxia
Aetiology unknown ?antibodies cross react with galactocerebroside

Cardiac

Polyarthralgia, myalgia, arthritis

Otitis media and bullous myringitis

194
Q

What are the major pathogens which cause infection at a surgical site?

A

Staph.aureus (MSSA and MRSA)
E.coli
Pseudomonas aeruginosa

195
Q

What is the pathogenesis of a surgical site infection?

A

If surgical site is contaminated with > 10 5 microorganisms per gram of tissue, risk of SSI is increased.
The dose of contaminating bacteria required to cause infection is much lower if there is foreign material present e.g. silk suture

196
Q

What are the three levels of surgical site infection?

A

Superficial incisional- affect skin and subcutaneous tissue

Deep incisional- affect fascial and muscle layers

Organ/space infection- any part of anatomy other than incision

197
Q

How is MRSA treated after surgical site infection?

A

IV linezolid

198
Q

What is a big risk factor of surgical site infection?

A

Age - linear increase in age
ASA score of 3 or more
Diabetes – association with post-op hyperglycaemia
Malnutrition
Low serum albumin
Radiotherapy and steroid use
Rheumatoid arthiritis - DMARDs for 4 weeks before and 8 weeks post-op
Obesity - adipose is poorly vascularised
Smoking - nicotine delays primary wound healing

199
Q

What is the most powerful independent risk factor for SSI following cardiothoracic surgery?

A

S.aureus is carried in the nares of 20-30%

200
Q

What is the epidemiology of septic arthritis?

A

Incidence is 2-10 cases per 100,000
In patients with RA incidence is 28-38 per 100,000 population.
Mortality is 7-15%
Morbidity is 50%

201
Q

What is the pathogenesis of septic arthritis?

A

Organisms adhere to the synovial membrane, bacterial proliferation in the synovial fluid with generation of host inflammatory response.
Joint damage leads to exposure of host derived proteins such as fibronectin to which bacteria adhere

202
Q

What are the risk factors of septic arthritis?

A

Rheumatoid arthritis, osteoarthritis, crystal induced arthritis
Joint prosthesis
Intravenous drug abuse
Diabetes, chronic renal disease, chronic liver disease
Immunosuppression- steroids
Trauma- intra-articular injection, penetrating injury

203
Q

What are the host factors which affect the pathogenesis of septic arthritis?

A

Leucocyte derived proteases and cytokines can lead to cartilage degradation and bone loss.

Raised intra-articular pressure can hamper capillary blood flow and lead to cartilage and bone ischaemia and necrosis.

Genetic deletion of macrophage –derived cytokines (lymphotoxin α, TNFα, interleukin 1 receptor) reduces host protection in S.aureus sepsis in animal models

204
Q

Which bacterial factors affect the pathogenesis of septic arthritis?

A

S.aureus has receptors such as fibronectin binding protein that recognise selected host proteins.
Kingella kingae synovial adherence is via bacterial pili

Some strains produce the cytotoxin PVL ( Panton-Valentine Leucocidin) which have been associated with fulminant infections.

205
Q

What are the causative organisms of septic arthritis?

A 
Staph. aureus  46%
Coagulase negative staphylococci 4%
Streptococci  22%
Streptococcus pyogenes
Streptococcus pneumoniae
Streptococcus agalactiae
Gram negative organisms 
E.coli 
Haemophilus influezae
Neisseria gonorrhoeae
Salmonella	
Rare- Lyme, brucellosis, mycobacteria, fungi
206
Q

What are the clinical features of septic arthritis?

A

1-2 week history of red, painful, swollen restricted joint
Monoarticular in 90%
Knee is involved in 50%

Patients with rheumatoid arthritis may show more subtle signs of joint infection

207
Q

Which investigations would you do on someone with septic arthritis?

A

Blood culture before antibiotics
Synovial fluid aspiration for microscopy and culture
ESR, CRP
Traditionally a synovial count> 50,000 cells/mm3 used to suggest septic arthritis
(Negative culture result does not exclude septic arthritis)

208
Q

Which imaging is used in septic arthritis?

A

X-rays- soft tissue oedema
US - confirm effusion and guide needle aspiration
CT - erosive bone change, periarticular soft tissue extension
MRI - joint effusion, articular cartilage destruction, abscess, contiguous osteomyelitis

209
Q

What is the management of septic arthritis?

A

IV Cephalosporin or Flucloxacillin - may need to add vancomycin if at high risk of MRSA (up to 6 weeks)

Drainage- arthoscopic washout

210
Q

Describe the features of vertebral osteomyelitis

A

Acute haematogenous
Exogenous - after disc surgery
- implant associated

211
Q

What are the causative organisms of vertebral osteomyelitis?

A

S.aureus - 48.3%
CNS - 6.7%
GNR - 23.1%
Strep - 43.1%

212
Q

Where is vertebral osteomyelitis localised?

A

cervical - 10.6%
cervico-thoraco - 0.4%
lumbar - 43.1%

213
Q

What are the symptoms of vertebral osteomyelitis?

A

Back pain 86%
Fever 60%
Neurological impairment 34%

214
Q

What are the clinical features of chronic osteomyelitis?

A

Pain
Brodies abscess
Sinus tract

215
Q

How is chronic osteomyelitis treated?

A

Radical debridement down to living bone - remove sequestra, and remove infected bone and soft tissue

1) Lautenbach technique
2) Papineau technique (complete excision)

216
Q

What are signs and symptoms of post prosthetic joint infections?

A

Pain
Patient complains that the joint was ‘never right’
Early failure
Sinus tract

217
Q

What are the causative organisms of prosthetic joint infection/?

A 
Gram positive cocci
-coagulase negative staphylococci
-staphylococus aureus
Streptococci sp
Enterococci sp

Aerobic gram negative bacilli
Enterobacteriaceae
Pseudomonas aeruginosa

Anaerobes
Polymicrobial
Culture negative
Fungi

218
Q

What are the intraoperative microbiological sampling techniques used for prosthetic joint infections?

A

Tissue specimens from at least 5 sites around the implant

Histopathology – infection defined as >5 neutrophils per high power field

If 3 or more specimens yield identical organisms, this is highly predictive of infection (sensitivity 65%, specificity 99%)

219
Q

What is the difference between an uncomplicated and complicated urinary infection?

A

Complicated - UTI + functional or structural abnormality

Uncomplicated - infection in structurally and neurologically normal urinary tract

220
Q

What is the most common UTI-causing organism?

A

E. coli

221
Q

Which serotypes of E.coli are the cause of most UTIs?

A

O1, O2, O4, O6, O7, O8, O75, O150, O18ab - different virulence factors

222
Q

Apart from E. coli, what are other organisms that can cause UTI?

A
  • Proteus mirabilis
  • Klebsiella aerogenes
  • Staphylococcus saprophyticus
  • Staphylococcus epidermis

Higher prevalence when there is a structural abnormality

223
Q

Why is UTI more common in females?

A

Shorter urethra and more proximity to warm moist vulvar and perianal areas - can colonise the vaginal Introits and the periurethral area

224
Q

What are the extra renal and infrarenal causes of obstruction which increase the risk of UTI?

A
  • Extrarenal - valves, stenosis or bands, calculi, BPH

- Intrarenal - nephrocalcinosis, uric acid neophropathy, PKD, hypokalaemia nephropathy, renal lesions of sickle cell

225
Q

What are causes of neurogenic malfunction of the kidneys?

A
  • Poliomyelitis
  • Tabes dorsaliis
  • Diabetic neuropathy
  • Spinal cord injuries
226
Q

How can kidney infection of the haematogenous route cause UTI?

A

Kidney site of abscesses in patients with staph. aureus (rarely gram negative bacilli)

227
Q

What is the difference between symptoms of UTI in children under 2 and over 2 years old?

A

Under 2: failure to thrive, vomiting, fever

Over 2: frequency, dysuria, abdominal or flank pain

228
Q

How would you investigated complicated UTI?

A

Renal USS

IV urography

229
Q

What are some methods that can be used to collect a sample of urine for testing?

A
  • MSU
  • Catheterisation
  • Suprapubic aspiration
230
Q

What information would the following results give you?

1) White cells pyuria
2) Squamous epithelial cells

A

1) White cells pyuria - infection

2) Squamous epithelial cells - contamination

231
Q

What colour changes would you see when examining urine cultures for E. coli and enterococcus?

A

E.coli - pink

Enterococcus - blue

232
Q

How could you treat UTI in the following groups of patients?

  • Female
  • Pregnant/breastfeeding female
  • Male
  • Pyelonephritis
  • Catheter-associated
A
  • Female: cefalexin, nitrofurantoin
  • Pregnant/breastfeeding female: cefalexin, co-amoxiclav
  • Male - cefalexin, ciprofloxacin
  • Pyelonephritis - co-amoxiclav +/-gentamicin (IV)
  • Catheter-associated: gentamicin, amikacin
233
Q

How long would you treat uncomplicated UTI compared to complicated or those with more than 7 days of symptoms?

A

Uncomplicated: 3 days

Complicated: 7 days

233
Q

Which fungal infection are common in catheter caused UTIs?

A

Candida UTIs

Fluconazole treatment

234
Q

What is the difference between endogenous and exogenous viral infections?

A

‘Endogenous’
Latent viruses that reactivate in absence of immune system
Acquired in past prior to immune suppression e.g. Varicella Zoster

‘Exogenous’
Viruses acquired from environment
increased severity in immunosuppressed e.g. Influenza, SARS-CoV-2

235
Q

What is the difference between direct and indirect detection of viruses?

A

Indirect detection: response of the immune system to the virus
These tests are useful to see if you have ever had the infection

Direct detection: fragments of the actual virus
Viral proteins (lateral flow/antigen tests)
Viral genetic material (the virus genetic material present with patient sample
Polymerase chain reaction

236
Q

What information do IgG and IgM levels give us?

A

+++ IgM indicate Active or Resolving infection
+++ IgG indicates past infection > 6 weeks ago

Antibody levels ↓↓↓ reduced in Immunosuppressed

237
Q

What are the diagnostic protocols in immunosuppressed individuals with viral infections?

A

Serological screening - antigens and antibodies for HBV

Monitoring/prophylaxis - PCR

238
Q

List the relative risk of opportunistic viral infection from the highest risk to the lowest

A

Allogeneic stem cell transplant

Advanced HIV infection (CD4 dep)

Solid organ transplant

Various monoclonal antibody therapies

Cytotoxic chemotherapy

DMARDs and steroids

239
Q

What are the issues with herpes simplex types 1 and 2?

A

Increased frequency

Increased severity /risk of dissemination

More organs can be involved (pneumonitis, eosophagitis, hepatitis); NB: not enceph!

Increased risk of acyclovir resistance

240
Q

How can herpes simplex types 1 and 2 be managed?

A

HIV/AIDS
CD4 <200

Prophylaxis
Test for HSV IgG
Bone marrow
1 month (until engraftment)
Solid organ
3-6 months
And if treated for rejection
241
Q

What are the clinical manifestations of varicella zoster (VZV)?

A 
Varicella (chicken-pox)
Pneumonitis
Encephalitis
Hepatitis
Purpura fulminans in neonate

Zoster (shingles)
Multi-dermatomal / disseminated
Often a late presenting immunosuppression

242
Q

How can varicella zoster (VZV) be managed?

A

Prevention: prophylaxis, PEP, vaccination

Treatment:
Varicella
Anti-viral for 7-10 days
IV until no new lesions; PO until all crusted

Zoster
Anti-viral (IV if disseminated) + analgesia
If Ramsay-Hunt: add steroids
If HZO: add topical steroids

243
Q

What is the pathophysiology of post-transplant lymphoproliferative disease (PTLD)?

A

Latently infected B cells – polyclonal activation
Predisposes to lymphoma
Suspicion on rising EBV viral load (> 105 c/ml) and CT scan
Confirmation with biopsy of lymph nodes

244
Q

What are the potential complications of Epstein Barr Virus?

A

Oncogenesis
B cell latency, high turn-over
T-cells monitor/control this

B-cell lymphomas

PTLD (post-transplant lympho-proliferative disorder)

245
Q

How can Epstein Barr Virus be managed?

A

Monitor EBV levels

Ix for lymphoma as needed

Rx: ?Rituximab

Rx: reduce immunosuppression

246
Q

What are the complications of cytomegalovirus?

A 
HIV/AIDS: CD4 <50
Ocular (retinitis)
Polyradiculopathy
Pneumonitis
GI tract

SOT
Allograft disease
GI tract (i.e. renal)

247
Q

How can cytomegalovirus be managed?

A

Prophylaxis (i.e. lung transplant)

Pre-emptive treatment (i.e. renal transplant / HSCT)

Treat if disease (HIV/AIDS)

Rx: Ganciclovir / Valganciclovir

Ganciclovir (IV): bone marrow suppression
Valganciclovir: oral
Foscarnet (IV) (nephrotoxicity)
Cidofovir (nephrotoxicity)
IVIg (with another drug for pneumonitis)
248
Q

How can CMV be prevented post-translate?

A

CMV viral load twice weekly, treat if virus reactivates until suppressed (pre-emptive therapy)

Valganciclovir prophylaxis for 100 days

249
Q

What is JC Virus: John Cunningham?

A

JC virus is a polyomavirus

Progressive multifocal leukoencephalopathy

Effective antiretroviral therapy has drastically reduced PML incidence in HIV+ve patient

PML can be seen in other types of immunosuppressed
humanised monoclonal antibodies

Natalizumab (for treatment of multiple sclerosis)

250
Q

What is progressive multifocal leukoencephalopathy (PML)?

A

Cognitive disturbance, personality change, motor deficits other focal neurological signs

Demyelination of white matter
→neurological deficits

Diagnosis: MRI and PCR on CSF

251
Q

What is BK virus?

A

Polyomavirus
Double stranded DNA
BK cystitis post SCT
BK nephropathy post Renal Tx

252
Q

How can respiratory viruses in immunocompromised individuals be treated?

A

Increased risk of complications (pneumonitis) and high mortality associated particularly with:

Influenza A and B
Parainfluenza 1, 2, 3 and 4
Respiratory Syncytial Virus (RSV) Adenovirus
SARS-CoV-2

Influenza A and B →Oseltamivir (oral drug) for 5 days

Resistance/severe/immunosuppressed →zanamivir (inhalation or IV)

SARS-CoV-2
Sotrovimab or Casirivimab/imdevimab

253
Q

How can the different hepatitis viruses be treated?

A

Hep A: more severe, vaccinate

Hep B: re-activation, vaccinate/prophylaxis

Hep C: ?increased fibrosis, Rx direct-acting antiviral

Hep E: chronic infection, reduce immunosuppression

254
Q

How can hep B re-emerge in those immunocompromised?

A

Reactivation ↑ B-cell depleting therapies (i.e Rituximab)
IL-6 inhibitor COVID also a risk

Prevention:
Nucleoside (lamivudine), nucleotide (tenofovir, entecavir)
Prophylaxis

255
Q

What are the hepatitis B serological markers of disease and markers of immunity?

A

Markers of disease:
sAg+
Circulating virus

cAb+ (IgM)
Acute immune response

eAg+
Circulating virus

Markers of immunity:

sAb+
Generated from:
sAg (virus)
sAg (vaccine)

cAb+ (IgG/total)
Generated from cAg (virus)
Prior infection

eAb+
Generated from eAg (virus)

256
Q

Define gastroenteritis

A

A rapid onset diarrheal illness, lasting less than 2 weeks with diarrhoea (loose and unformed stool) three or more times a day or at least 200 g of stool which is either viral or bacterial in aetiology

257
Q

What is the difference between small and large bowel diarrhoea?

A

Small bowel diarrhea- often watery, associated with crampy abdominal pain and of large volume with bloating and gas. Accompanying fever and blood or inflammatory cells in the stool are rare.

Large bowel diarrhea –small volume painful stool which occur often with blood, mucus and inflammatory cells found in the stools and an accompanying fever.

258
Q

Define diarrhoea

A

Loose or watery stools passed at least three times in 24 hours which can be acute, chronic or persistent
Acute-lasting less than 14 days often due to either viral or bacterial pathogens
Persistent- between 14-29 days
Chronic- lasting greater than 30 days, may be due to parasites and non-infectious aetiology should be excluded

259
Q

What is the mechanism of cholera toxin causing secretory diarrhoea?

A

cAMP: opens Cl channel at apical membrane of enterocytes

Efflux of Cl to lumen: loss of H2O and electrolytes

260
Q

How do superantigens cause secretory diarrhoea?

A

Superantigens bind directly to T-cell receptors and MHC molecules;

outside the peptide binding site

> > massive cytokine production by CD4 cells ie systemic toxicity and suppression of adaptive response

261
Q

What is the difference between inflammatory diarrhoea vs enteric fever in gastroenteritis?

A

Host responses in bacteraemia:

Inflammatory (exudative) diarrhoea Vs Enteric fever; interstitial inflammation

262
Q

What are the extra-intestinal manifestations of gastroenteritis?

A

Aortitis, osteomyelitis, deep tissue infection
- Salmonella, Yersinia

Haemolytic aneamia
- Campylobacter, Yersinia

Glomerulonephritis
- Shigella, Campylobacter, Yersinia

Hemolytic uremic syndrome
- STEC, Shigella dysenteriae serotype 1

Erythema nodosum
- Yersinia, Campylobacter, Salmonella, Shigella

Reactive arthritis
- Salmonella, Shigella, Campylobacter, Yersinia, rarely Giardia, and Cyclospora cayetanensis

Meningitis
- Listeria, Salmonella (infants ≤3months of age are at high risk)

263
Q

What is staph food poisoning?

A

Staphylococcus aureus

1/3 population chronic carriers, 1/3 transient

Spread by skin lesions on food handlers

Catalase, coagulase positive Gram positive coccus

Appears in tetrads, clusters on Gram stain

Golden colonies on blood agar

Produces enterotoxin, an exotoxin that can act as a superantigen in the GI tract, releasing IL1 and IL2 –> prominent vomiting and diarrhoea

264
Q

What is an example of a Gram positive rods which is spore forming and causes food poisoning?

A

Bacillus cereus : food poisoning

Spores germinate in reheated fried rice

Heat labile diarrhoeal toxin - food is not cooked to a high enough temperature

Watery non bloody diarrhoea; self limited
Rare cause of bacteraemia in vulnerable population
Can cause cerebral abscesses

265
Q

Give three examples of gram positive anaerobes and their clinical manifestations

A

Clostridium botulinum : botulism
Source : canned or vacuum packed food (honey / infants)
Ingestion of preformed toxin (inactivated by cooking)
Blocks Ach release from peripheral nerve synapses
Treatment with antitoxin

Clostridium pefringens : food poisoning
Source : reheated food (meat)
Normal flora of colon but not small bowel, where the enterotoxin acts (superantigen)
Incubation 8-16hrs
Watery diarrhoea, cramps,little vomiting lasting 24hrs

Clostiridium difficile : Pseudomembranous colitis

266
Q

Describe some clinical features of pseudomembranous colitis

A

It is not an invasive disease and non-toxin producing strains do not often cause disease but can colonise the gut and asymptomatic shedders of spores can continue to act as a reservoir for infection

267
Q

What are the two types of toxin produced by clostridium difficile?

A

C.difficle produces two toxins; Toxin A, an enterotoxin and Toxin B, a cytotoxin

Toxin A causes inflammation with intestinal fluid secretion and damage to the mucosa

Toxin B, more potent than toxin A acts as a virulence factor
3%, 30% of hospitalised patients
Antibiotic related colitis (any but.. mainly cephalosporins, cipro and clindamycin)

268
Q

How is Clostridium difficile treated?

A

Vancomycin

Stop other antibiotics where possible

269
Q

Describe the features of Listeria monocytogenes gastroenteritis

A

Outbreaks of febrile gastroenteritis

ß haemolytic, aesculin positive with tumbling motility

Source : refrigerated food (“cold enhancement”) i.e. unpasteurised dairy, vegetables

270
Q

Describe the clinical features of Listeria monocytogenes in gastroenteritis

A

Grows at 4 ºC GI watery diarrhoea, cramps, headache, fever, little vomiting

Perinatal infection, immunocompromised patients

271
Q

How is Listeria monocytogenes gastroenteritis treated?

A

Amoxicillin

272
Q

What are the different enterobacteriacae which cause gastroenteritis?

A

Facultative anaerobes, glucose/lactose fermenters (LF),
oxidase negative

1) E.coli: traveller’s diarrhoea, faeces, enterotoxins
2) EnteropathogenicE. coli(EPEC) pathogenic, infantile diarrhoea
3) EnteroinvasiveE. coli(EIEC) invasive, dysentery
4) EnterohemorrhagicE. coli(EHEC, also called Shiga toxin-producingE. colior STEC)
5) O157:H7 EHEC: shiga- like verocytotoxin causes HUS

AVOID ANTIBIOTICS

273
Q

Where do enterotoxins produced by E.coli act in gastroenteritis?

A
  • Heat labile stimulates adenyl cyclase and cAMP
  • Heat stable stimulates guanylate cyclase
  • Act on the jejeunum, ileum not on colon
274
Q

Name some features of Salmonellae gastroenteritis

A

Non lactose fermenters, H2S producers, TSI agar, XLD agar, selenite F broth

Antigens:

  • cell wall O (groups A-I)
  • flagellar H
  • capsular Vi (virulence, antiphagocytic)

Many species :

  • S. typhi (and paratyphi)
  • S.enteritidis
  • S.cholerasuis
275
Q

Name some features of S.enteritidis in gastroenteritis

A

Enterocolitis
Transmitted from poultry, eggs, meat
Invasion of epi- and sub-epithelial, tissue of small and large bowel
Bacteraemia infrequent <5%
Diarrhea resolves in 4-7 days with abdominal pain
Nausea, vomiting and fever resolves in 48 to 72 hours
Usually self limiting and does not require treatment for immune-competent patients aged between 12-50 years of age
Stool positivity

276
Q

Name some features of S.typhi in gastroenteritis

A

Typhoid (enteric) fever transmitted only by humans multiplies in Payer’s patches, spreads ERS bacteraemia, 3% carriers

Slow onset, fever and constipation, splenomegaly, rose spots, anaemia, leucopaenia, bradycardia, haemorrhage and perforation

Blood culture positive 40-80%

Stool culture positivity is 30-40%

Bone marrow may have additional yield >90% in more complicated cases or if unresponsive to treatment and can remain positive for >5 days after antibiotic initiation

277
Q

List some features of gastroenteritis caused by Shigellae

A

Non lactose fermenters, non H2S producers, non motile

Antigens: cell wall O antigens, polysaccharide (groups A-D): S.sonnei, S.dysenteriae, S.flexneri (MSM)

The most effective enteric pathogen (low ID 10-100)
No animal reservoir
No carrier state

  • Dysentery
  • Invading cells of mucosa of distal ileum and colon
  • Producing enterotoxin (Shiga toxin)
  • Abdominal pain 70-93% and watery diarrhoea 30-40% which proceeds to bloody diarrhoea 35-55%
  • Fever 30-40% of patients
  • Vomiting 35%
  • Disease is self-limiting to about seven days
  • Antibiotic choice should be based on patient demographics and likely local resistance profile
278
Q

Name some features of Vibrios bacteria and the three types which cause gastroenteritis

A

Curved, comma shaped, late lactose fermenters, oxidase positive

1) Vibrio cholerae (the causative agent of cholera)
2) Vibrio parahaemolyticus
3) Vibrio vulnificus can cause diarrhoea, but has been isolated from the blood and tissues of septic patients (especially those with liver disease)

279
Q

How is Vibrios-caused gastroenteritis treated?

A

Doxycycline

280
Q

Name the features of the three types of Vibrios gastroenteritis

1) Vibrio cholerae
2) Vibrio parahaemolyticus
3) Vibrio vulnificus

A

1) Vibrio cholerae: O1 group: epidemics, biotypes El Tor, Cholerae and serotypes Ogawa, Inaba, Hikojima
Non O1 group: sporadic or non pathogens
Transmitted by contamination of water and food from human faeces (shellfish, oysters, shrimp)
Colonisation of small bowel and secretion of enterotoxin with A and B subunit, causing persistent stimulation of adenylate cyclase
Causes massive diarrhoea (rice water stool) without inflammatory cells
Treat the losses

2) Vibrio parahaemolyticus
Ingestion of raw or undercooked seafood (ie oysters),
Major cause of diarrhoea in Japan..or when cruising in the Carribean.. ,
Self limited for 3 days
Cholerae : grows in salty 8.5% NaCl

3) Vibrio vulnificus
Cellulitis in shellfish handlers
Fatal septicaemia with D+V in HIV patients

281
Q

Describe the features of Campylobacter gastroenteritis

A 
Curved, comma or S shaped
Microaerophilic
C.jejuni at 42 ºC
Oxidase pos ,motile
Transmitted via contaminated food and water with animal faeces

? Enterotoxin (watery diarrhoea) ? Invasion (+/- blood)

Loose stools 10 times a day

Self-limiting - TREAT WITH MACROLIDE IF IMMUNOCOMPROMISED (Treat with erythromycin or cipro if in the first 4-5 days)

GBS syndrome, reactive arthritis, Reiter’s

282
Q

Describe features of Yersinia enterocolitica infection

A
  • Non lactose fermenter, prefers 4ºC “cold enrichment”
  • Transmitted via food contaminated with domestic animals excreta
  • enterocolitis
  • mesenteric adenitis
  • associated with reactive arthritis , Reiter’s
283
Q

Describe features of Mycobacteria (M.Tuberculosis, M.Avium Intracellulare) infection in gastroenteritis

A
  • Will appear as Gram variable

- Consider TB

284
Q

List the types of Protozoa organisms which can cause gastroenteritis

A

1) Entamoeba histolytica:

284
Q

List the types of Protozoa organisms which can cause gastroenteritis

A

1) Entamoeba histolytica
2) Giardia lamblia
3) Cryptosporidium parvum

285
Q

List the features of Entamoeba histolytica gastroenteritis

A

Motile trophozoite in diarrhoea

Non motile cyst in nondiarrhoeal illness

Killed by boiling, removed by water filters

4 nuclei

No animal reservoir

Ileum&raquo_space; colonize cecum, colon&raquo_space; “flask shaped” ulcer

Chronic : wt loss,+/- diarrhoea

Liver abscess

286
Q

How is Entamoeba histolytica treated?

A

Metronidazole + paromomycin in luminal disease

287
Q

Name the features of Giardia lamblia

A
  • Trophozoite “pear shaped”
  • 2 nuclei
  • 4 flagellas and a suction disk
  • Ingestion of cyst from fecally contaminated water, food
  • Excystation at duodenum tropho attaches
  • No invasion
  • Malabsorption of protein and fat –> foul smelling non-bloody diarrhoea, cramps, no fever, flatulence
288
Q

How can Giardia lamblia be diagnosed and treated?

A

Diagnosis : stool micro, ELISA, “string test”

Treatment :metronidazole

289
Q

List some features of Cryptosporidium parvum infection

A

Infects the jejunum

Severe diarrhoea in the immunocomromised

Oocysts seen in stool by modified Kinyoun acid fast stain

Treatment : reconstitution of immune system

290
Q

List the viral causes of gastroenteritis and some of their features

A 
1) Norovirus: GII.4 currently predominant strain, faeco-oral route from person to person
Low ID (18-1000 viral particles)
Environmental resilience (0-60 ºC)
No long term immunity
Incubation period is 24-48 hours
Shedding in the stool as long as 4 weeks/months in immunocompromised 
2) Rotavirus
dsRNA “wheel like”
Symptoms 3-8 days and occurs in children aged 6m-2yrs
Occasionally in elderly
Often year round in tropical climates and in the winter months in temperate areas
Vomiting is less common
Replicates in mucosa of small intestine
Secretory diarrhoea, no inflammation
Watery diarrhoea 
6yrs - most have antibodies
Natural infection twice = lifelong immunity 
Economic burden worldwide
3) Adenovirus
Types 40, 41 cause non bloody diarrhoea  <2yrs of age
Any type in immunocompromised
Diagnosis: stool EM, antigen detection, PCR
Poliovirus
Enteroviruses (coxsackie, ECHO)
Hepatitis A
Transmitted via  faecal-oral route
291
Q

List the vaccines which are given to prevent certain types of gastroenteritis

A 
Cholera: serogroups O1(Inaba , Ogawa, biotypes El Tor  and classical), O139
Inactivated, whole cell, contains all above + B subunit of toxin (PO)
Live attenuated (PO) not recommended

Campylobacter : military, infants, traveller, candidate vaccines exist..

ETEC: inactivated and live vaccines in trials

Salmonella typhi: Vi capsular PS (IM) and (PO)live

Rotavirus
Rotarix : live attenuated human strain monovalent, 2(PO) doses
Rotateq : pentavalent, 3 (PO) doses, one bovine and four human strains
Rotashield and intussusception (8-20 weeks)
Given at 6-12w

292
Q

List the organisms which cause gastroenteritis that come under notifiable diseases

A

1) Campylobacter
2) Clostridium sp
3) Listeria monocytogenes
4) Vibrio
5) Yersinia

293
Q

Which viruses have pandemic potential?

A
  • Influenza
  • SARS-CoV-2
  • Nipah
  • West Nile Virus
  • Dengue
  • Zika
294
Q

Which animal is the natural reservoir of influenza A viruses?

A

Ducks

295
Q

Which influenza protein is essential to host cofactors that support influence polymerase activity?

A

ANP32 proteins

296
Q

Which mutation leads to influenza polymerase adapting to utilize shorter mammalian ANP32 homologues?

A

Polymerase adaptation to mammals can be achieved by a single amino acid change in PB2 E627K

297
Q

What is an example of antigenic shift in influenza which leads to increased capacity for replication in human cells?

A

H1N1 Human Adapted

H2N2 Avian virus

298
Q

How does the avian mutation of influenza penetrate the respiratory system in humans?

A

1) Transmission requires incoming virus to penetrate mucus and infect epithelial cells
2) Incompatibility of avian-origin influenza virus with human respiratory tract

3) Avian influenza HA must adapt for transmission in humans by acquiring affinity for human receptors –> Neu5Ac binds to Gal at a2,6 instead of a2,3
- entry is pH sensitive

299
Q

How do neuraminidase inhibitors work at treating influenza?

A

Influenza A viruses mediate binding to cell surface sialic acid receptors via the haemagglutinin (HA) glycoprotein, with the neuraminidase (NA) glycoprotein being responsible for cleaving the receptor to allow virus release. Blocking it stops viral release.

300
Q

What are examples of neuraminidase inhibitors?

A

Oseltamivir (Tamiflu)

Zanamivir (Relenza)

301
Q

Name an example of a new anti-influenza antiviral drug which targets polymerase

A

Baloxavir inhibits the PA endonuclease

302
Q

Which influenza vaccines are in use in the UK?

A

Inactivated vaccine
Split or subunit- HA rich
Given to those at risk
Short term strain specific immunity mediated by antibody to HA head

Live attenuated vaccine
Cold adapted virus limited to urt
Given to children
Broader more cross reactive immunity including cellular response

303
Q

What are nidovirales?

A

A nested set of mRNAs from one large genome

304
Q

Where does COVID bind to on cells?

A

SARS and SARS CoV2 bind to cells via ACE 2

305
Q

Which drugs can be used to treat COVID?

A

Dexamethasone
Monoclonal antibodies: Regeneron, Sotrovimab
Small molecule antivirals:
Molnupiravir: targets polymerase, nucleoside analgue
Paxlovid: targets protease

306
Q

What do the mRNA COVID vaccines encode:

A

Encode stabilised spike

307
Q

What is hepatitis A virus?

A

Picornaviridae, genus hepatovirus
Single-stranded, positive sense RNA genome
Quasi-enveloped virions
Faeco-oral versus blood-borne transmission
Incubation period of 15-50 days

308
Q

How is Hepatitis A diagnosed?

A

Acute infection: IgM reactive; unlikely if bilirubin level <30umol/L

Past infection: IgM nonreactive, IgG reactive

309
Q

When is hepatitis A infectious?

A

Two weeks before onset of first symptoms and until one week after the onset of jaundice

310
Q

Describe the structure of hepatitis B virus

A

The family Hepadnaviridae
Double-strained DNA with reverse transcriptase
Enveloped virions
10 genotypes (A-J) with distinctive geographic distribution
Blood-borne transmission: horizontal & vertical
Incubation period of 40-160 days

311
Q

What is the most important antibody/marker predicting the risk of HBV vertical transmission?

A

HBeAg as the most important risk predictor for vertical transmission

312
Q

Define what chronic hepatitis B infection is

A

Persistence of HBsAg for 6 months or more after acute HBV infection

313
Q

What are the complications of chronic HBV infection?

A
  • Cirrhosis: 8-20% untreated CHB in 5 years;
  • Hepatocellular carcinoma: the annual risk of 2-5% among CHB cirrhotic patients; affected by host (e.g. alcohol abuse) and viral factors (e.g. high HBV viral load & qHBsAg)
314
Q

How is HBV serology interpreted?

A 
HBsAg: infection
HBsAb: immunity through either immunisation or past infection
HBcAb: exposure
IgM: acute infection
HbeAg: replication activity
HBeAB
315
Q

Describe the structure of hepatitis D (delta) virus

A

Single-stranded, circular RNA genome

A defective virus that relies on HBV for propagation

Blood-borne transmission
Incubation period: 3-6 weeks

316
Q

What is the structure of hepatitis C virus?

A

The family Flaviviridae, genus Hepacivirus

Single-stranded, positive sense RNA genome

Blood borne transmission
Incubation period: 2-6 weeks

317
Q

What are the treatment options for hepatitis (direct-acting antivirals)?

A

Revolutionised the treatment for acute/chronic HCV infection
Any HCV cases should be considered

8 or 12 weeks
Sustained virological response (SVR) at week 12

Pan-genotypic regimen
Single-tablet regimen

Drug-drug interaction

318
Q

Describe the structure of hepatitis E virus

A

The family Hepeviridae, genus Orthohepevirus; species A strains (8 genotypoes) infect humans
G1 & G2: obligate human pathogens
G3 & G4: zoonotic; pigs & wild boar are natural hosts

Single-stranded, positive sense RNA genome
Quasi-enveloped HEV

Faeco-oral versus blood-borne transmission
Incubation period: 15-60 days

319
Q

Describe the antiviral therapy

A
  • Reverse transcription
  • Transcription and translation
  • Release (cell lysis)
320
Q

How are the human herpesviruses classified?

A

1) Alpha: HSV-1, HSV-2, VZV
2) Beta: CMV, HHV-6, HHV-7
3) Gamma: EBV, HHV-8

321
Q

What are the differences between alpha, beta and gamma human herpes viruses?

A

Alpha: rapid growth, latency in sensory ganglia
Beta: slow growth restricted host range
Gamma: oncogenic

322
Q

Describe how human varicella zoster virus manifests in immunocompetent and immunocompromised patients

A

Immunocompetent: dermatomal distribution, post-herpetic neuralgia

Immunocompromised: multidermatomal or disseminated infection

323
Q

Define the term ‘prodrug’

A

A prodrug is an inactive precursor of a drug, that is metabolized into the active form within the body.

324
Q

Which antiviral drugs are used for treatment of HSV and VZV?

A

1st line:

1) Aciclovir (po/iv)
2) Valaciclovir (prodrug of acyclovir - high bioavailability)

2nd line:

1) Famciclovir: Foscarnet or cidofovir for ACV-resistant virus
2) Ganciclovir

Interfere with viral DNA synthesis

325
Q

Describe the mechanism of action of acyclovir

A

Elongation of the DNA chain is impossible because acyclovir lacks the 3’ hydroxyl group necessary for the insertion of an additional nucleotide

326
Q

Describe the selective activity of guanosine analogues

A
  • Monophosphorylated by viral thymidine kinase (TK) and then further phosphorylation by cellular kinases to ACV-PPP (active form)
  • Affinity for herpesvirus DNA polymerase is 10- to 30-fold higher than for cellular (host) DNA polymerase for ACV-PPP
  • Selective activity means reduced drug toxicity
  • Susceptibility: HSV-1 > HSV-2&raquo_space; VZV
  • VZV 10x less sensitive so higher doses required
327
Q

If you suspect HSV encephalitis, what must be your immediate treatment?

A

On clinical suspicion:

Start empiric treatment immediately with iv ACV 10mg/kg tds without waiting for test results

If confirmed, treat for 14 - 21 days

328
Q

Where does CMV reside in latent infection?

A

Blood monocytes and dendritic cells

329
Q

Which antiviral drugs can be used to treat CMV?

A
  • Ganciclovir
  • Valganciclovir
  • Foscarnet
  • Cidofovir
  • Letermovir
330
Q

What are the indications of ganciclovir use?

A

CMV disease in immunocompromised

331
Q

How is CMV pneumonitis treated?

A

Ganciclovir and IVIG

332
Q

What are the side effects of ganciclovir?

A
  • Bone marrow toxicity (leukopenia, thrombocytopenia, anaemia, pancytopenia)
  • Renal and hepatic toxicity
  • Bone marrow suppression: neutropenia
333
Q

Describe the mechanism of action of Foscarnet and its indications

A

Non-competitive inhibitor of viral DNA polymerase

Indications: CMV, HSV, (some activity against VZV, EBV, HHV6)

334
Q

What are the side effects of Foscarnet?

A

Nephrotoxic

335
Q

What is the mechanism of action and indications of Cidofovir?

A

Nucleotide (cytidine) analogue - competitive inhibitor of viral DNA synthesis

Indications: third line CMV in immunocompromised

336
Q

How are the nephrotoxic side effects of Cidofovir accounted for?

A

Require hydration and probenicid

337
Q

Describe the mechanism of action of Maribavir and its indications

A 
Effective in vitro against CMV and EBV
Directly inhibits viral kinase (UL97)
Effective in vitro against GCV-resistant CMV strains
Relatively well tolerated
Mainly GI side effects
338
Q

Describe the mechanism of action of Letermovir and its indications

A

CMV DNA terminase inhibitor

Remains active against GCV-resistant strains
Mainly GI side effects
Drug interactions with immunosuppressants (eg cyclosporine, tacrolimus, sirolimus) - need to monitor drug levels of the above

339
Q

Describe the aetiology of Epstein-Barr virus (EBV)

A

Salivary transmission, infection common in childhood, usually minimally symptomatic and self-limiting
Classical cause of infectious mononucleosis
Lifelong infection - continuous low grade viral replication in B lymphocytes kept in check by cellular immune system (immunosurveillance)
Associated with lymphoproliferative disease in the immunocompromised

340
Q

What is post-transplant lymphoproliferative disease associated with?

A

EBV

Breakdown of immunosurveillance –> latently infected B cells –> polyclonal expansion

341
Q

How is post-transplant lymphoproliferative disease diagnosed?

A

EBV viral load in blood (>105 c/ml), biopsy

342
Q

How is post-transplant lymphoproliferative disease diagnosed?

A

Reduce immunosuppression (regression in < 50%)

Anti-CD20 monoclonal Ab therapy (B cell marker) – rituximab

343
Q

What is the mechanism of action of Peramivir?

A

Neuraminidase inhibitor

H275Y mutation –> avoid use with oseltamivir resistance

344
Q

What is the mechanism of action of Baloxavir?

A

Inhibitor of endonuclease activity of the RNA polymerase complex required for viral gene transcription

345
Q

What are the side effects of Baloxavir?

A

Diarrhoea

Bronchitis

346
Q

What is dual therapy for flu?

A
  • Favipravir: a viral RNA polymerase inhibitor prodrug

- Oseltamivir

347
Q

What is the mechanism of action of Ribavirin?

A

Guanosine analogue
Inhibits viral RNA synthesis
Clinical efficacy for RSV is unclear

348
Q

What is the mechanism of action of Palivizumab?

A

Monoclonal antibody against RSV

Indication: prevention of serious lower respiratory tract disease caused by RSV in infants

349
Q

What is the mechanism of action of Nirsevimab?

A

Extended half life mAb

Requires single IM injection to provide protection for the whole winter

350
Q

Which antiviral medications can be used to treat SARS CoV-2?

A
  • Remdesevir: broad spectrum adenosine nucleotide prodrug. iv.
  • Molnupiravir: broad spectrum induces viral RNA mutagenesis
  • Paxlovid: protease inhibitor nirmatrelvir (administered together with low dose ritonavir to increase drug t1/2)
351
Q

Which monoclonal antibodies can be used to treat SARS-COV2?

A
  • Ronapreve

- Sotrovimab

352
Q

What are the immunomodulators of SARS COV-2?

A

Tocilizumab: IL-6 receptor antagonist

Sarilumab: IL-6 receptor antagonist

Anakinra: IL-1 receptor antagonist

353
Q

What is the BK virus?

A

Part of Polyomavirus family (related to JC virus)
Primary BK virus infection in childhood with minimal symptoms, but subsequent lifelong carriage in kidneys and urinary tract

  • BMT - haemorrhagic cystitis
  • Renal transplant - BK nephritis, ureteric stenosis
354
Q

Which drug can be used to treat BK haemorrhagic cystitis?

A

Cidofovir

355
Q

What is the lipid-conjugated oral prodrug of cidofovir?

A

Brincidofovir
100mg twice a week
Less toxicity – mainly diarrhoea and mild transaminitis
Not licensed in UK
Main potential is for treatment of adenovirus and of BK virus disease in the immunocompromised

356
Q

Where do HSV drug resistant mutations usually occur?

A

Mutations usually in viral thymidine kinase (95%), and rarely in the viral DNA polymerase (5%)

357
Q

Where do CMV drug resistant mutations usually occur?

A

CMV genetic mutations:
In protein kinase gene (UL97) - most common
In the DNA polymerase gene (UL54) – rare
UL56 terminase gene (letermovir)

2nd line: foscarnet or cidofovir

358
Q

Name some typical features of S. pneumoniae infection?

A 
Gram +ve Streptococcus
30-50% of CAP
Acute onset
Severe pneumonia
Fever, rigors
Lobar consolidation
Almost always penicillin sensitive
359
Q

What are the main organisms in community acquired pneumonia?

A 
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Staphylococcus aureus
Klebsiella pneumoniae
360
Q

What are the most common pathogens which cause community acquired pneumonia?

A

0-1 mths- E.coli, GBS, Listeria
1-6mths- Chlamydia trachomatis, S. aureus, RSV
6mths-5yrs- Mycoplasma, Influenza
16-30yrs-M pneumoniae, S. pneumoniae

361
Q

Which organisms come. under typical and atypical pneumonia?

A 
Typical 85%
S. pneumoniae
H. influenzae
Atypical 15%
Legionella
Mycoplasma- epidemics 4-6 yrs
Coxiella burnetii (Q fever)-worldwide, farm animals, hepatitis
Chlamydia psittaci (Psittacosis)-exposure to birds, splenomegaly, rash, haemolytic anaemia
362
Q

What is the CURB-65 score?

A 
CURB-65 score
Confusion
Urea >7 mmol/l
RR >30
BP <90 systolic <60 
diastolic
>65 years

Score 2 = consider admitting
Score 2-5 = manage as severe

363
Q

What would you see on a Petri dish for haemophilia influenzae?

A

Gram negative cocco-baccelli

364
Q

In which individuals is H. influenzae more common in?

A

More common with pre-existing lung disease

May produce β-lactamase

365
Q

What are some specific features of Legionella pneumophilia?

A 
Inhalation of infected water droplets
Environmental outbreaks
Associated with confusion, abdo pain, diarrhoea
Lymphopenia, hyponatremia
Dx by antigen in urine/serum
Sensitive to macrolides
Can cause multi-organ failure
Requires special culture: buffered charcoal yeast extract
366
Q

List some features of atypical pneumonia

A

Pneumonia caused by organisms without a cell wall
Mycoplasma
Legionella
Chlamydia
Coxiella
Cell-wall active antibiotics e.g. penicillins don’t work
Need agents that work on protein synthesis
Macrolides (clarithromycin / erythromycin)
Tetracyclines (doxycycline)
Extrapulmonary features – e.g. hepatitis; low sodium

367
Q

Which class of antibiotics is Legionella, Coxiella and Chlamydia sensitive to?

A

Macrolides

368
Q

What is the typical appearance of tuberculosis on CXR?

A

Classically upper lobe cavitation (Auramine stain + ZN staiin)

369
Q

Which organisms typically cause hospital acquired pneumonia?

A 
Staphylococcus aureus		19%
Enterobacteriales			31%
Pseudomonas spp			17%
Acinetobacter baumannii	 	 6%
Fungi (Candida sp.)		 	 7%
370
Q

What are some typical features of pneumocystis jirovecii?

A 
Protozoan
Ubiquitous in environment
Insidious onset
Dry cough, weight loss, SOB, malaise
CXR “bat’s wing”
Dx Immunofluorescence on BAL
Rx Septrin (Co-trimoxazole)
Prophylaxis Septrin
371
Q

What are the different features of Aspergillus fumigatus respiratory infection?

A 
Allergic bronchopulmonary aspergillosis
Chronic wheeze, eosinophilia
Bronchiectasis
Aspergilloma
Fungal ball often in pre-existing cavity
May cause haemoptysis
Invasive aspergillosis
Immunocompromised
Rx Amphotericin B
372
Q

Which urine antigen tests are available to check for LRTIs?

A

S. pneumoniae
Legionella pneumophila

(In severe CAP)

373
Q

Which organisms causing LRTI are difficult to culture?

A

Chlamydia

Legionella

374
Q

How is CAP treated?

A

Mild-moderate:
Amoxicillin
Or erthromycin / clarithromycin

Moderate-severe:
Needing hospital admission: co-amoxiclav AND clarithromycin

Allergic: Cefuroxime AND clarithromycin

375
Q

How is HAP treated?

A

First line: Ceftazidime/Ciprofloxacin +/- vancomycin

Second line/ITU: Piperacillin/tazobactam AND vancomycin

Specific therapy:
MRSA: Vancomycin.

Pseudomonas: Piperacillin/tazobactam or Ciprofloxacin +/- gentamicin

Year 5 Pathology (5 decks)

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