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Phase 2a Sam > MICROBIOLOGY > Flashcards

MICROBIOLOGY Flashcards

1
Q

What is a pathogen?

A

An organism capable of causing disease

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2
Q

What is a commensal?

A

Organism which colonises a host but causes no disease

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3
Q

What is an opportunist pathogen?

A

Microbe that causes disease if host defences are compromised

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4
Q

What is virulence?

A

The degree to which a given organism is pathogenic

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5
Q

What are virulence factors?

A

factors are microbial factors that cause/modify disease

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6
Q

Define invasiveness

A

the capacity to penetrate mucosal surfaces to reach normally sterile sites

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7
Q

What is asymptomatic carriage?

A

When a pathogen is carried harmlessly

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8
Q

What are round bacteria called?

A

Coccus

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9
Q

What are rod bacteria called?

A

Bacillus

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10
Q

What colour do gram positive bacteria stain?

A

Purple

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11
Q

What colour do gram negative stain?

A

Red/pink

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12
Q

What type of organism would you stain with Ziehl-Neelsen?

A

Mycobacteria e.g., TB.

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13
Q

How would you carry out a gram stain?

A

ComeInAndStain

Apply primary stain - crystal violet (purple) - to heat fixed bacteria
Add iodine which binds to crystal violet and helps fix it to the cell wall
Decolourise with ethanol or acetone
Counterstain with safranin (pink)

  1. CRYSTAL VIOLET
  2. IODINE
  3. ACETONE/ETHANOL
  4. SAFRANIN (COUNTERSTAIN)
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14
Q

What are the differences between gram negative and positive bacteria?

A

Gram positive

  • Thick peptidoglycan layer
  • Single membrane - no outer lipid layer
  • No endotoxin - as no lipopolysaccharide

Gram negative

  • Inner and outer lipid membrane
  • Do have endotoxin, due to large lipopolysaccharide
  • thin peptidoglycan area
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15
Q

Describe the characteristic features of gram positive bacteria?

A
  1. Single membrane.
  2. Large peptidoglycan area.
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16
Q

Describe the characteristic features of gram negative bacteria?

A
  1. Double membrane.
  2. Small peptidoglycan area. (
  3. LPS (endotoxin area).
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17
Q

Between what temperatures and what pH range can bacteria grow?

A

Between -80 to +80°C. And from a pH of 4 to 9.

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18
Q

What are the 3 phases of bacterial growth?

A
  1. Lag phase.
  2. Exponential phase.
  3. Stationary phase
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19
Q

Give an example of a slow growing bacteria.

A

TB.

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20
Q

Give an example of a fast growing bacteria.

A

E.coli (Gram positive rod, anaerobic)

S.aureus. (gram positive Clusters Catalase +ve and coagulase +ve)

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21
Q

Give 2 functions of pili

A
  1. Help adhere to cell surfaces.
  2. Plasmid exchange
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22
Q

What is the primary function of flagelli?

A

Locomotion.

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23
Q

What is the primary function of the polysaccharide capsule?

A

Protection; prevents MAC or opsonisation molecules attacking.

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24
Q

What types of bacteria release endotoxin?

A

Gram negative

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25
What types of bacteria release exotoxins?
Gram negative and positive
26
Describe endotoxins.
Endotoxin: component of the outer membrane of bacteria e.g. LPS in Gram negative bacteria Non Specfific, Heat stable
27
Describe exotoxins. What bacteria have them
**Proteins** secreted from gram positive and gram negative bacteria. They are specific, but heat labile.
28
What are endotoxins made from?
Lipopolysaccarides
29
What are plasmids?
Circular pieces of DNA that often carry genes for antibiotic resistance.
30
How does genetic variation arise in bacteria?
Mutation -Base substitution -Deletion -Insertion Gene transfer - Transformation e.g., via plasmid - Transduction e.g., via phage - Conjugation e.g., via sex pilus
31
What are the two first classifications of bacteria?
- Obligate intracellular bacteria (bacteria not grown in a lab) - Bacteria that may be cultured on Artificial media
32
What are obligate intracellular bacteria? Give examples
Bacteria that can only grow inside a host cell i.e. we cannot grow them on agar. e.g. - Rickettsia - Chlamydia - Coxiella ***RICKETTSIA***
33
How do you differentiate between different types of Rod/cocci bacteria?
Gram positive and gram negative
34
What is the way to differentiate within gram negative/positive bacteria?
Aerobic vs anaerobic
35
Give an example of a gram-positive aerobic cocci?
Staphylococcus and streptococcus.
36
What are the 3 types of streptococcus bacteria? Map their classifications
- Beta-haemolytic - Alpha-haemolytic - Non-haemolytic Streptococcus - Gram neg, Aerobic, Catalase negative
37
What is anaerobic gram-positive bacteria?
PEPTOSTREPTOCOCCUS
38
What are aerobic gram-negative bacilli bacteria?
Either lactose fermenting - E Coli - Klebsiella Or non fermenting - Salmonella -Shigella - Pseudomonas or *other* Vibrio Legionella
39
How would you describe the arrangement of staphylococci?
Clusters of cocci
40
How would you describe the arrangement of streptococci?
Chains of cocci.
41
What bacteria would be coagulase positive?
Staphylococci aureus differentiating S.Aures from other staphs is key, as S aureus is much more virulent, has coagulase/DNAase
42
What bacteria would be coagulase negative?
All others e.g. staphylococci epidermidis.
43
What is the normal environment of staphylococci?
Nose and skin
44
How is Staphylococci aureus spread?
Aerosol and touch - carriers and shedders
45
What are virulence factors for Staphylococci aureus?
- Pore-forming toxins e.g., haemolysin - Proteases e.g., exofoaltin - Toxic shock syndrome toxin - Protein A (surface protein which binds to antibodies in wrong orientation)
46
What drug would be used to treat staphylococci?
Flucloxacillin
47
What type of infection is S. epidermidis
opportunistic
48
What test could be done to distinguish between different streptococci? How does it work?
Blood agar haemolysis. The haemolysis test used hydrogen peroxide to test reaction with haemoglobin
49
What would you see on the agar plate in α haemolysis and give an example of a bacteria in this group. Give an example of this
α haemolysis is PARTIAL erythrocyte lysis; you see a green colour. Streptococcus pneumoniae falls in this group
50
What would you see on the agar plate in β haemolysis and give an example of a bacteria in this group?
β haemolysis is complete erythrocyte lysis; you see a clear area. Streptococcus pyogenes and streptococcus agalactiae fall in this group.
51
What would you see on the agar plate in γ haemolysis and give an example of a bacteria in this group. Give an example of this
γ haemolysis is when there is no haemolysis. Streptococcus bovis falls in this group.
52
What is are two examples of beta haemolytic strep infections?
S.agalactiae and S.pyogenes
53
Give examples of alpha haemolytic bacteria.
- S.pneumoniae - Viridans group streptococci
54
MISC - Give examples of aerobic gram-positive bacilli. Rods
- Listeria monocytogenes (can cause menigitis) - Bacillus anthracis
55
Give examples of anaerobic gram-positive bacilli
- C. tetani  Tetanus - C. botulinum Botulism - C. difficile antibiotic-associated diarrhea pseudomembranous colitis
56
Give examples of gram-negative bacilli: 2 lactose fermenting and 2 non lactose fermenting.
Are either Lactose Fermenting, eg - Escherichia (E Coli) - Klebsiella Or non-Lactose fermenting - Salmonella - Shigella Pseudomonas (oxidase +Ve)
57
What kind of bacteria is MacConkey agar used with?
Gram negative bacilli
58
What is MacConkey agar?
MacConkey agar contains **bile salts, lactose and pH indicator.** If an organism ferments lactose, lactic acid will be produced, and the agar will appear a red/pink colour.
59
Name 2 gram-negative bacilli that will give a positive result with MacConkey agar.
1. E.Coli. 2. Klebsiella pneumoniae
60
Does e-coli have an H antigen?
Yes, as it is motile
61
Key Gram Negative Bacteria: For E coli, give a) Lactose fermenting or not b) Associated infections c) Commensal Locations d) Sensible Antbx
Lactose fermenting UTIs, traveller’s diarrhoea, cholecystitis, cholangitis GI tract Co-amoxiclav Causes majoirty of UTIs
62
Does shigella have an H antigen?
No as it is not motile
63
Key Gram Negative Bacteria: For Shigella , give a) Lactose fermenting or not b) Associated infections c) Commensal Locations d) Sensible Antbx e)What are the symptoms of shigella infection?
It is non lactose fermenting, and oxidase negative Shigellosis (diarrhoea, fever), frequent pooing Small volume, pus and blood, prostrating cramps, pain in straining, fever. No commensal location, it comes from water Treat with Quinolones, Azithromycin
64
Does salmonella have an H antigen?
Yes as it is motile
65
Key Gram Negative Bacteria: For Salmonella , give a) Lactose fermenting or not b) Associated infections c) Commensal Locations d) Sensible Antbx e) Symptoms What infections are caused by salmonella? It is gram negative and non lactose fermenting and so appears white on Macconkey agar
Non lactose fermenting, oxidase negative. Salmonellosis (diarrhoea) Intestines (from raw meats, poultry, eggs Amoxicillin, Quinolones, - Gastroenteritis/enterocolitis e.g., food poisoning
66
What is nisseria? What 2 main disease does it cause, what anbx would you treat it with?
Gram negative Cocci It mainly causes gonorrhoea and meningitis Some species commensal, some pathogenic only Anbx treatment Cephalosporins, **Ceftriaxone**
67
Why are there pathogenic strains of e.coli?
Due to the acquisition of genes from other bacteria
68
Which type of e.coli would you associate with causing travellers diarrhoea?
Enterotoxigenic e.coli (ETEC). **Most common cause of travellers diarrhoea**
69
What are the symptoms of enteropathogenic e.coli infection?
Chronic watery diarrhoea
70
What are the symptoms of enterohaemorrhagic e.coli infection?
Bloody diarrhoea.
71
What are the symptoms of v.cholerae?
Huge volumes of watery stools (no blood or pus).
72
Why is v.cholerae so dangerous?
You're losing huge amounts of water which can result in hypovolemic shock and severe dehydration, this can lead to death.
73
Why is v.cholerae not killed if you have a fever?
It grows at 18 - 42°C.
74
Why would you need to be infected with a large amount of v.cholerae to show symptoms of the disease?
The optimum pH for v.cholerae growth is 8; alkaline. It is therefore very sensitive to the pH of the stomach.
75
What is the pathogenesis of cholera?
Cholera toxin - causes Gs subunit to be locked on uncontrolled cAMP production increase PKA Increased activity of CFTR channel Loss of Cl- and Na+ Water follows and massive H2O loss aka releases A toxin that deregulates ion transport in epithelial cells
76
Name the bacteria that can cause legionnaires disease?
Legionella.
77
Who might be susceptible to infection by legionella?
Immunocompromised individuals.
78
What type of bacteria are Neisseria?
Gram negative diplococci.
79
What are the two medically important species of neisseria?
N.meningitidis and N.gonorrhoeae.
80
How is N.meningitidis transmitted?
Aerosol transmission. High risk in colonised people e.g. university, Haj.
81
Describe the pathogenesis of N.meningitidis.
Crosses nasopharyngeal epithelium and enters blood stream. Can cause asymptomatic bacteraemia or septicaemia. If the bacteria crosses the BBB it can cause meningitis.
82
How can you detect chlamydia?
Serum antibodies or PCR.
83
Name the spirochaete that is responsible for causing lyme disease.
B.burgdorferi.
84
Name the spirochaete that is responsible for causing syphilis.
T.pallidum.
85
What is the ziehl-neelsen stain? What gives what colours?
- Used for mycobacteria which don't take up gram stain - Acid fast bacilli are red - Non-acid-fast bacilli are blue
86
What is the catalase test?
- Add h2o2 to bacteria to see for bubbling reaction - Bubbles= positive test
87
What is the catalase test used to distinguish between?
Streptococci and Staphylococci
88
Are Streptococci catalase negative or positive?
Negative
89
Are Staphylococci catalase negative or positive?
Positive
90
Are most gram-negative bacteria catalase negative or positive?
- Most are positive - E-coli and fungi are positive
91
What is the coagulase test? What does the coagulase enzyme do?
- An enzyme produced by s.aureus turns fibrinogen (soluble) into fibrin (insoluble) - Used to distinguish between s.aureus and other types of staphylococci
92
Is Staphylococci aureus positive or negative for the coagulase test?
Positive (clumping) due to formation of fibrin, **making solution cloudy**
93
What further test can be done for those streptococci in the β haemolysis group?
Serogrouping; detecting surface antigens. e.g., lancefield grouping.
94
What would you see on the agar plate in α haemolysis and give an example of a bacteria in this group.
α haemolysis is partial erythrocyte lysis; you see a green colour. Streptococcus pneumoniae falls in this group
95
What would you see on the agar plate in β haemolysis and give an example of a bacteria in this group? What bacteria would you see here
β haemolysis is complete erythrocyte lysis; you see a clear area. Streptococcus pyogenes and streptococcus agalactiae fall in this group.
96
What is the lancefield test
- Specific antibodies (A B, C) BOUND to set of latex beads - Bacteria added and mixed If bacteria have the antigen that corresponds to the antibody, the latex beads clump together === white dots If they do not, then the suspension will remain milky white
97
What is the optochin test? For what bacteria would you use it for
- Place an optochin-soaked disc and place on agar plate of bacteria - If there is growth around the disc then the bacteria are resistant and no growth around disc means bacteria are sensitive For gram postive Streptococcus, that are alpha haemolytic eg Streptococci Pneumoniae Optochin Sensitive or Viridans Strep - optochin Resistant
98
What bacteria are optochin resistant?
Viridans streptococci (infective endocarditis) and other alpha haemolytic streptococci
99
What bacteria are optochin sensitive?
Streptococcus pneumoniae (causes lobar pneumonia and meningitis)
100
What is the oxidase test? For what bacteria would you use it for
- Test to see if microorganism **contains a cytochrome oxidase** - All bacteria that are oxidase positive are aerobic - Bacteria that are oxidase negative may be aerobic or anaerobic Gram negative Bacilli, that are non lactose fermenting (MC agar =white)
101
What are the colour changes for the oxidase test?
- Oxidase positive: Blue - Oxidase negative: No colour change
102
Name some oxidase positive bacteria?
- Pseudonomas - V. cholerae - Campylobacter e.g., C. jejuni - Helicobacter
103
Why does MacConkey agar only grow gram negative bacteria?
Bile salts inhibit the growth of gram positive bacilli
104
What will happen to the MacConkey agar if lactose fermenting bacilli are present?
- Lactose fermenting produce acid - This will turn indicator on agar red
105
Name some lactose fermenting bacilli?
- E. COLI - KLEBSIELLA PNEUMONIAE (typical organism that causes biliary infection) - ENTEROBACTER SPP.
106
Name some non-lactose fermenting bacilli?
- Salmonella spp. - Shigella spp. Psuedomonas They appear white/transparent
107
What is XLD agar used for?
To differentiate between Shigella and Salmonella Gram -ve bacilli, Non lactose fermenting, oxidase -ve test
108
What colour does Shigella go on XLD?
White spots on dark red
109
What colour does Salmonella go on XLD?
Black spots on bright pink
110
What shape are most gram-positive bacteria?
Round (cocci)
111
What shape are most gram-negative bacteria?
Rod (bacilli)
112
Which Lancefield groups are associated with tonsilitis and skin infection?
A , C and G.
113
Which Lancefield groups are associated with neonatal sepsis and meningitis?
B.
114
Which Lancefield groups are associated with UTI's?
D. *(Enterococci)*
115
Describe CLED agar and explain why it might be used. What bacteria is it good for diagnosing?
Cysteine Lactose electrolyte deficient Used to differentiate microorganisms in urine Also allows the classification of lactose fermenting (yellow) and non-lactose fermenting (blue) of gram-negative bacilli Good for culturing E.coli - LACTOSE FERMENTING yellow and Salmonella and shigella as blue
116
What agar is used to culutre TB?
Lowenstein-Jensen agar
117
What type of agar is often used to culture Neisseria bacteria?
Gonoccoccus agar
118
Describe chocolate agar and explain why it might be used.
Chocolate agar is blood agar that has been heated so as to release nutrients. Chocolate agar is often used for growing fastidious bacteria. (A fastidious organism is any organism that has complex or particular nutritional requirements. In other words, a fastidious organism will only grow when specific nutrients are included in its medium) eg H.Influenzae
119
What bacteria would be assciated with theses infections, and have the commensal location of nasal passages and skin? Impetigo, boils, cellulitis, endocarditis, toxic shock syndrome Nasal passages + skin
Staphyl. Aureus. Clusters Coagulase +ve
120
Key Gram positive bacteria: Outline bacterium Group A Strep (Strep pyogenes) (beta haemoyltic) a) Associated infections b) Commensal Location c) Sensible Antbx
Cellulitis, tonsillitis, impetigo, scarlet fever, pharyngitis Resp tract Amoxicillin (any penicillins) Throat + skin infections
121
Key Gram postive bacteria: What antibiotic would you give to treat MRSA?
A big gun, like Gentamicin, Vancomycin
122
What is Sabouraud's agar used for?
Used to culture fungi.
123
Describe mycobacteria.
- **Aerobic.** - Non-motile. - Non spore forming. - Bacilli.
124
What are the 3 classes of mycobacteria of medical importance and give an example of each
- MTB (Mycobacterium Tuberculosis) Complex - *M. tuberculosis* (Tuberculosis) - Non-Tuberculosis Mycobacterium - *M. kansasii* (chronic lung infection) - Non-cultivable - *M. leprae* (leprosy)
125
What is the cell wall of Mycobacteria like? How is it classified in terms of gram staing?
The cell wall is very thick and has a high lipid content. Sit within the gram-positive family
126
What do you use to stain mycobacteria? b) What can be used to aid the visualisation of mycobacteria?
- Do not stain with normal method therefore known as Ziehl-Neelsen/Acid fast Positive - Composition of cell wall makes it impervious to staining - High lipid content with mycolic acids in cell wall b) Fluorochrome stain augmentation
127
Are mycobacteria a) Aerboic or anaerobic b) Spore forming c) Motile
Aerobic No No
128
What is the significance of the waxy cell wall of mycobacteria?
- Difficult to target with antibacterial agents - Survive inside macrophages, even in low pH environments
129
Why is it hard to use therapeutic antibodies against mycobacteria?
- Slow reproduction - one of the targets for antibacterials is their fast reproduction time (Some as short as 20 minutes whereas mycobacteria can reach 20 hours) - Slow growth in humans - gradual onset of disease - Slow growth in culture - difficult to diagnose - Slow response to treatment
130
How could you detect whether an individual has had previous exposure to TB?
1. Tuberculin skin test (mantoux). 2. Interferon gamma release assays.
131
Name some sterile sites in the body.
1. Urinary tract. 2. CSF. 3. Pleural fluid. 4. Peritoneal cavity. 5. Blood. 6. Lower respiratory tract.
132
Where in the body would you find normal flora (commensals)?
1. Mouth. 2. Skin. 3. Vagina. 4. Urethra. 5. Large intestine.
133
What is a virus?
an infective agent that typically consists of a nucleic acid molecule in a protein coat, and is able to multiply only within the living cells of a host.
134
Which viruses are Non-enveloped?
- Adenovirus - Parvovirus
135
What viruses are enveloped?
- Influenza - HIV
136
Describe the process of viral replication?
1. Attachment to receptor on host cell 2. Cell entry- uncoating of virion within the cell 3. Host cell interaction and replication- migration of genome to cell nucleus, transcription to mRNA using host material 4. Assembly of new virion 5. Release of new virus partciles
137
How are new virus particles released?
1. Burts out resulting in cell death e.g., rhinovirus 2. Budding/exocytosis e.g., HIV and influenza
138
What diagnostic tests are used for identifying viruses?
- PCR - identifies viral genetic material - Serology - identifies if there is immunological memory of a particular virus (e.g. IgG is used to detect long-term memory) - Histopathology - identifies features of viral infection - Viral cultures, with light microscopy - Electron Microscopy
139
Outline how Serology works
- Serology - identifies if there is immunological memory of a particular virus (e.g. IgG is used to detect long-term memory)
140
Outline some pros and cons of PCR testing
Pros Very fast Cheap Can test for multiple viruses at the same time, by using a mix of primers Very sensitive - (if you have it, a PCR will almost definitely give a positive result) Cons Need to suspect viruses before hand Risk of giving false positive
141
What colour swabs do you use for diagnosing viruses and bacteria?
**Green viral swab** and **black charcoal swab** for bacteria
142
How do viruses cause disease?
1. Direct destruction of host cells e.g., poliovirus lysis of neurons 2. Modification of host cell e.g., rotavirus atrophies villi and flattens epithelial cells 3. "Over reactivity" of immune system e.g., hepatitis B 4. Damage through cell proliferation e.g., HPV which causes cervical cancer 5. Evasion of host defences e.g., Herpesviridae, Measels, HIV
143
What are protozoa?
One celled animals” Single cell with nucleus (Eukarytoic) >30,000 species
144
What are the 5 types of protoza?
1. Flagellates 2. Microsporidia 3. Sporozoa 4. Amoebae 5. Cilliates
145
What is African Trypanosomiasis? (flagellates) How is it transmitted
- Human African Trypanosomiasis (or sleeping sickness) - endemic in Africa. Spread by the bite of an infected tetse fly
146
How is American Trypanosomiasis transmitted?
- Spread through contact with faeces of triatomine “kissing” bug Also through blood, vertically and eating contaminated food
147
What is the main type of Malaria? What two types can incubate for up to a year?
1. Plasmodium falciparum (most severe disease) 2. Plasmodium ovale 3. Plasmodium vivax Others: 4. Plasmodium malariae 5. Plasmodium knowlesi
148
What two types of malaria can persist in humans long-term without proper treatment? What do they stay dormant as, and what can you give to prevent this?
P. ovale and P. vivax - These two species can **persist in the liver as hypnozoites.** To prevent relapses, patients with Plasmodium vivax or Plasmodium ovale infection should be given a **14- day course of primaquine**, which will treat the hypnozoite forms
149
How is malaria transmitted?
By bite of the female anopheles mosquito
150
When should you think of malaria as a cause of disease?
fever and recent travel
151
How would you diagnose malaria? What do thick and thin films show
A blood flim by using light microscopy Thick - Sensitive but low resolution - Only does the person have malaria = yes or no Thin film - helps identify different species
152
What is the main symptom of malaria?
Fever
153
What are some other symptoms of malaria?
Chills Headache Myalgia Fatigue Diarrhoea Vomiting Abdo pain
154
What are some Haemolysis specific signs of malaria?
Anaemia Jaundice Hepatosplenomegaly ‘Black Water Fever’- Hb passes into urine
155
Malaria life cycle - Outline first human liver stage
- 1️⃣ Mosquito takes a blood meal, injecting the indiviual with sporozoites (infected for of the Plamsodium) - 2️⃣ Sporozoites travel in the blood and infect liver cells (hepatocytes) - 3️⃣ Hepatocytes mature and develop into *Shizonts* - 4️⃣ Schizonts eventually bursts and releases *Merozoites* into the blood
156
Malaria life cycle - Outline second human blood stage
- 5️⃣ Merozoites infect RBCs - 6️⃣ Once within the RBC, plasmodium become *Trophozoites* - 7️⃣ 🅰️ Trophozoite develop into *Schizonts*, which ruptures and reinfects RBC with merizoites - this cycle continues as the disease develops - 7️⃣ 🅱️ Some Trophozoites differentiate into *sexual stage gametocytes* - ✳️ At this stage, as RBCs rupture, the individual develops cyclical fever and haemolytic clinical manifestations, such as anaemia, jaundice (bilirubinaemia), haemoglobinuria
157
Malaria life cycle - Outline second human blood stage
- 8️⃣ Another mosquito takes a blood meal from this infected individual will ingest *gametocytes* - 9️⃣ Gametocytes mature into an *oocyst* - 🔟 Oocysts ruptures and release *sporozoites* - 🔟+ 1️⃣ Sporozoites are injected into the blood of a different individual - cycle.
158
Describe the pathogenesis of p.falciparum?
Causes complicated malaria happnes in 3 stages - 1️⃣ Cytoadherence Infected RBCs present membrane proteins that bind to microvascular endothelial cells in vessels - 2️⃣ Rosetting Infected RBCs also adhere to non-infected RBCs, causing small vessels to become obstructed by clumbs of RBCs - this causes hypoxia. - 3️⃣ Sequestration Microinfarcts form in major organs (brain, heart, lungs, liver, kidney) where they are able to mature and evade the immune system.
159
Malaria complications - Outline what happens in a)cerebal malaria b) Renal failure c) Acute respiratory distress syndrome ARDS
Cytoadherence in the brain; vessel occlusion causes hypoglycaemia or haemorrhage. Vascular occlusion of the kidneys causes dehydration, hypotension, haemoglobinuria, haemolysis Vascular occlusion of the lungs causes anaemia, lactic acidosis and increased vascular permeability.
160
What genetic conditions can give immunity to malaria?
Someone with sickle cell anaemia or thalassaemias.
161
Can immunity to malaria be acquired?
Recurrent infection can lead to someone being 'semi-immune'. Antibodies could be transferred by maternal transmission.
162
What is the treatment for malaria?
Chloroquine.
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What is the treatment for severe malaria?
IV artesunate
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What are the symptoms of complicated malaria?
- Cerebral - ARDS/Pulmonary oedema - Renal failure - Sepsis - Bleeding/Anaemia
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What do viruses need to do in order to be successful?
Need rapid cell entry Free viruses in the blood stream are easily neutralised
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What is in the cell mediated response that viruses elicit?
Interferons from Th (CD4+ ) or Cytotoxic T lymphocytes have direct antiviral action CTL can kill infected cells NK cells and macrophages are involved in antibody-dependent cellular cytotoxicity (ADCC) killing Interferons induces anti viral proteins for bystander cells
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Viral evasion: How does influenza virus evade detection?
they change the coat antigen, and coat themselves in a lipid bilayer acquired from they infected host cell Haemagglutinin HA and Neuraminidase NA
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What are the two thibngs that changes of coat antigens result in?
Antigenic Drift - spontaneous mutations, occur gradually giving minor changes in HA (haemagglutinin) and NA (neuraminidase). Epidemics. Antigenic Shift - sudden emergence of new subtype different to that of preceding virus. Pandemics. That’s why the flu vaccine changes each year
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What are the 4 main ways that antibiotics work?
Where they work: Disrupting: 1. Cell wall synthesis 2. Nucleic acid synthesis 3. Protein synthesis 4. Folate synthesis
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What is a bacteriostatic antibiotic?
Bacteriostatic Prevent the growth of bacteria; defined as a ratio of Minimum Bactericidal Concentration (MBC) : Minimum Inhibitory Concentration (MIC) of > 4 Includes antibiotics that: - Inhibit protein synthesis - Inhibit DNA replication - Inhibit metabolism Useful in disease where its the bacteria exotoxin that's causing the symptoms as they reduce toxin production.
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What is a bacteriocidal antibiotic? Give an example How does it work?
Will kill the bacteria; kills 99.9% in 18-24 hours Includes antibiotics that: - Inhibit cell wall synthesis Useful in cases of poor drug penetration due to poor blood supply (endocarditis); difficult to treat infections or when we need to eradicate infections quickly (meningitis).
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What does the MBC:MIB ratio tell us? ****test****
The Minimum Bactericidal Concentration (MBC) is the lowest concentration of an antibacterial agent required to **kill** a bacterium over a fixed time (18 hours or 24 hours), under a specific set of conditions. The Minimum Inhibitory Concentration (MIC) is defined as the lowest concentration of an antimicrobial ingredient or agent that is bacteriostatic (prevents the visible **growth** of bacteria). **Antibacterial agents are usually regarded as bactericidal if the MBC is no more than four times the MIC.**
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Antibiotics that inhibit cell wall: How do B-lactam antibiotics work?
- ○ disrupt peptidoglycan production ○ by binding covalently and irreversibly to the Penicillin Binding Proteins ○ cell wall is disrupted and lysis occurs ○ results in a hypo-osmotic or iso-osmotic environment ○ Active only against rapidly multiplying organisms Baso, cause lysis by messing up peptidoglycan production - Won't affect human cells is bactericidal
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Name some B-lactam antibiotics categories (3) , with some key examples
- Penicillin (any of the cillins) eg Penicillin V Penicillin G (Benzyl penicillin) Flucloxacillin Amoxicillin / Ampicillin Pipericillin - Cephalosporin eg Cefuroxime Cefotaxime Ceftriaxone - Carbapenems eg Meropenem
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Antibiotics that inhibit the cell wall - How do we administer Glycopeptides? When do we use them? Give some examples of them
IV only Only work on Gram positive: - MRSA - Penicillin allergy Examples Vancomycin - For MRSA Teicoplanin
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What type of bacteria are B-lactams more effective at treating?
- Gram positive as they only have one cell layer. Whereas gram-negative bacteria have an additional LPS layer which reduces the penetration - Penicillin poorly penetrate mammalian cells so ineffective at treating intracellular pathogens Differences in the spectrum and activity of β-lactam antibiotics are due to their relative affinity for different PBPs.
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Antibiotics that inhibit DNA synthesis: Name some, and what they target. When would we use quinolines?
Rifampicin - Targets RNA polymerase Metronidazole - KEY ONE Fluoroquinolones - target both DNA Gyrase and DNA topoisomerase Quinolines are more effective against GRAM NEGATIVE than positive, use then and in - Penicillin allergy - UTIs - intra-abdominal infections
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Antibiotics that work by inhibiting protein synthesis - Name the 2 name categories, that work on 30S subunit and with examples
Aminoglycosides eg Gentamicin Tetracyclines eg Doxycycline
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Antibiotics that work by inhibiting protein synthesis - Name the 2 name categories, that work on 50S subunit and with examples
Lincosamides eg Clindamycin Macrolides eg Clarithromycin
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How do sulphonamides and trimethoprim work?
- Inhibit folic acid metabolism - Bacteria turn PABA to folate - Inhibit PABA turning into folate - Folate is needed for synthesis Adenine and thymine in DNA - Humans don't synthesise folic acid so safe to use, but don't give to pregnant women!!
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What are the two major determinants of antibacterial effects?
1. Concentration (number of binding sites taken up) 2. Time (that the antibiotic remains on the binding sites)
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What is MIC?
MIC - lowest conc THAT IS BACTERIOSTATIC (lowest amount required to prevent visible growth of bacteria)
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What is time dependant killing?
Key parameter is the time that the serum concentration remains above MIC during the dosing interval
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What antibiotics rely on time dependant killing?
- beta-lactams (penicillins, cephalosporins, carbapenems, monobactams), - clindamycin, - macrolides - oxazolidinones
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What is concentration dependant killing?
- Key parameter is how high the concentration is above MIC
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What antibiotics rely on concentration dependant killing?
- aminoglycosides - quinolones
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What are things to consider when deciding on what antibiotics should be given and how they should be administered?
Pharmakinetics - Absorbtion (how should I give it orally/IV) - Distribution: which antibiotics will penetrate the site, what is the PH of the site, is the antibiotic lipid soluble - Metabolism/elimination: what is the half-life, what dosage interval and duration
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What mechanisms can make bacteria resistant to antibiotics
- Change the antibiotic target - Destroy antibiotic - Prevent antibiotic access - Remove antibiotics from bacteria
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Define what changing the antibiotic target means and name some bacteria that have done this
Bacteria change the molecular configuration of the antibiotic binding site or masks it - Flucloxacillin (or methicillin) is no longer **able to bind PBP** of Staphylococci – **MRSA** - **Wall components change in enterococci** and reduce **vancomycin** binding – *Vancomycin Resistant Enterococci* - **Rifampicin** activity is reduced by **changes to RNA polymerase in MTB** ===> *Become multidrug resistant TB* (MDR-TB)
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Define what destroying antibiotic means and name some bacteria that have done this
- The antibiotic is destroyed or inactivated e.g. - Beta-lactam ring of Penicillins and cephalosporins hydrolysed by bacterial enzyme ‘Beta lactamase’ now unable to bind PBP
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Define what preventing antibiotic access means and name some bacteria that have done this
- modify the bacterial membrane porin channel size, numbers and selectivity e.g. - Pseudomonas aeruginosa against imipenem, - Gram-negative bacteria against aminoglycosides
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Define what removing antibiotics from bacteria means and name some bacteria that have done this
- Proteins in bacterial membranes pump the antibiotic out the cell. - S. aureus or S. pneumoniae resistance to fluoroquinolones -
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What is intrinsic resistance?
- Bacteria that have a natural resistance to an antibiotic - All subpopulations will be equally resistance
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Give some examples of bacteria that have intrinsic resistance.
- Aerobic bacteria are unable to reduce metronidazole to its active form - Vancomycin cannot penetrate the outer membrane of gram-negative bacteria - Penicillin's struggle more against Gram Negative Bacteria as they have less peptidoglycan to target and have to get through an outer membrane in order to get at it. They are better suited to Gram positive bacteria -
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What has acquired resistance?
- A bacterium which was previously susceptible obtains the ability to resist the activity of a particular antibiotic - Only certain strains or subpopulations of a species will be resistant.
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What are the two ways that bacteria develop resistance?
- Spontaneous gene mutation - Horizontal gene transfer
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What are the 3 ways in which a horizontal gene transfer can occur, in order for bacteria to **Develop** resistance?
Conjugation Transduction Transformation
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Types of Horizontal Gene transfer - What is conjugation?
Sharing the DNA on Plasmids via Pilus, aka "Bacterial Sex"
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Types of Horizontal Gene transfer - What is transduction?
insertion of DNA from one bacterium is transferred to another bacterium via a **Bacteriophage** (viruses that infect bacteria)
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Types of Horizontal Gene transfer - What is Transformation? Where have we seen it?
When some bacteria can take up free DNA from the environment and incorporate it into their one chromosome. Seen how foregin DNA from S. Mitis to S. Pneumoniae , which leads to Penicillin Resistance
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What are the 4 main ways that antibiotics work?
Where they work: Disrupting: 1. Cell wall synthesis 2. Nucleic acid synthesis 3. Protein synthesis 4. Folate synthesis
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What does the MBC:MIC ratio tell us?
The Minimum Bactericidal Concentration (MBC) is the lowest concentration of an antibacterial agent required to **kill** a bacterium over a fixed time (18 hours or 24 hours), under a specific set of conditions. The Minimum Inhibitory Concentration (MIC) is defined as the lowest concentration of an antimicrobial ingredient or agent that is bacteriostatic (prevents the visible **growth** of bacteria). **Antibacterial agents are usually regarded as bactericidal if the MBC is no more than four times the MIC.** (Because at relatively lower times of dosing (<4 Times) they can still Kill bacteria/be bactericidal
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Resistant gram-positive bacteria: How has VRE developed resistance?
VRE vancomycin-resistant enterococci - Plasmid mediated acquisition of gene That alters the sequence of amino acid on peptide chain ====> This means Vancomycin cant bind to Enterococci Has been Promoted by cephalosporin use
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Resistant gram-positive bacteria: How has MRSA become resistant?
MRSA Methicillin-resistant Staphylococcus aureus **Has acquired Staphylococcal cassette chromosome mec (SCCmec)** - confers resistance to all β-lactam antibiotics in addition to methicillin (= flucloxacillin)
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Resistant gram negative bacteria: How have ESBL developed resistance?
A B-lactamase enzyme , that has gone under **Further mutation** Known as extended spectrum beta lactamase (ESBL) enzymes - extended antimicrobial resistance These hydrolyse **oxyimino side chains of cephalosporins** cefotaxime, ceftriaxone, and ceftazidime and monobactams: aztreonam
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When are cephalosporins good to use?
- Good for people with penicillin allergy - Work against some resistant bacteria - Get into different parts of the body e.g., meningitis
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What is a mechanism by which Gram negative strains confer resistance?
They produce β-lactamase enzymes which hydrolyse penicillins. (they break the beta lactim ring in the penicllin)
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How can we combat gram negative resistant bacteria that produce beta lactamase?
Design drugs that utilise agents that inhibit β-lactamase e.g. Co-Amoxiclav = Amoxicillian + Clavulanate. Clavulanate inhibits the β-lactamase.
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What is AmpC-β-lactamase? Where would you find it?
A cephalosporinase enzyme; **encoded on the chromosomes the Enterobacteriaceae;** It is b-lactamase inhibitor resistant! It mediates resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and beta-lactamase inhibitor-beta-lactam combinations.
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What Kind of antibiotic should you give if you need to combat bacteria with lots b-lactamases or cephalosporinases?
Carbapenems such as **Meropenem** ===> They are highly resistant to degradation by b-lactamases or cephalosporinases. treat infections due to *ESBL or AmpC -producing organisms* of the Enterobacteriacae family. (Known as the last resort)
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What bacteria do B-lactam antibiotics work most effectively against
Gram-positive bacteria as they have a thick peptidoglycan layer - this is what Penicillin targets. Gram negative bacteria, therefore, already have some intrinsic resistance to Penicillin as they only have a thin peptidoglycan layer, in-between an inner and outer membrane
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What antibiotic would be used for S.aureus and A, C, G strep?
Flucloxacillin - think skin A, C, G strep you can also use PO penicillin or IV Benzylpenicillin
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What antibiotic would be used for S. pneumoniae
PO amoxicillin IV benzylpenicillin
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When would you use a glycopeptide?
- Vancomycin and teicoplanin **only use with gram-positive bacteria** - They target the cell wall, so use with B-lactam bacteria - Used when patient has **penicillin allergy, and with MRSA**
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When would you use clarithromycin and erythromycin (macrolides which inhibit protein synthesis)
- Gram positives S.aureus and beta haemolytic strep and atypical pneumonia - Use with penicillin allergy - Use with severe pneumonia
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When would you use lincosamides- protein synthesis
- Clindamycin - Use in cellulitis - Use in necrotising fasciitis Turns off nasty toxins made by gram-positive bacteria
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What group of antibiotics would you use commonly against: - Use against gram negatives and staphs - Use for UTIs - Use for infective endocarditis
Aminoglycosides (protein synthesis, 30s unit) - Gentamicin IV only
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Use of what antibiotic group has been associated with - Use for gram negatives - Use for UTIs - Use for intra-abdominal infectionshas been How does it work?
QUINOLONES **Target Nucleic acid synthesis** - Ciprofloxacin
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When would co-amoxiclav be used?
- Use for aspiration pneumonia, severe CAP and more resistant UTIs
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When would meropenem be used?
- They are broad and active against resistant strains - Use for sickest patients, resistant gram negatives e.g. MRSA and for immunocompromised
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What are retroviruses?
- Retroviruses are enveloped viruses. - Viral genetic material is RNA which is copied into DNA by reverse transcription and incorporated into the host cell to allow gene transcription.
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What is lentivirus?
Lentivirus represents a genus of slow viruses with long incubation period
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Fungi are eukarytoic - what does this mean? Whats in their cell wall? How do they get their nutrients?
Eukaryotic means they have a nuclear membrane They have a chitinous cell wall They are heterotrophic - they get nutrients from what they are living from.
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How do fungi move?
By means of growth of spore release
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Outline how a) Yeasts b) Moulds spread What is dimorphic fungi?
Yeasts are small single celled **organisms that divide by budding** Moulds form **multicellular hyphae and spores** Dimorphic fungi - fungi that can exist as either yeast or moulds - can switch in between
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Why won't most fungi harm humans?
Fungi have an inability to grow at 37 degrees (body temperature) - Fungi also cannot evade the adaptive/innate immune response
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Key fungal infections - what is Pneumocystis? When would you get it?
A type of pneunomia - often in people with healthy lungs Source of opportunistic infection, causing infections of people with weak immune systems eg HIV/AIDS (30-40% of PCP) ,
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Key fungal infections - what is Candidiasis? When would you get it?
Known as thrush - common in children's mouth (yellow tongue) and vaginal thrush eg caused by candida albicans
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What enzyme is used to integrate HIV DNA into the host cell?
Reverse transcriptase
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HIV: (Human Immunodeficiency Virus) What does it lead to?
Complications of HIV lead to Aquired Immundeficiency Syndrome AIDS
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Name some risk factors for getting HIV/AIDS. What age group makes up for 50% of all new infections worldwide?
Men who have sex with men, IVDU, Commercial sex workers Age group 50% all new infections occur worldwide: 19-24yo
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Where would you most likely find HIV1? HIV2? What were they both derived from?
HIV1 - more common, and seen in US and worldwide Chimpanzee-dreived Simian Immunodeficiency Viruses (SIVcpz) - thought to have been transmitted the 1950s HIV2 - alot Rarer, seen in Western Africa and Southern Asia Sooty Mangabey-derived Simian Immunodeficiency Viruses (SIVmp)
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HIV affects CD4+ cells. (this includes T Helper Cells, Macrophages and Dendritic Cells). CD4 + molecule helps immune cells communicate, How does HIV get into them?
HIV attaches a CD4 cell via BOTH gp120 protein and a co receptor CXCR4 - In T Cells CCR5 - In T cells, macrophages, monocytes, dendritic cells People with mutations to co proteins can be protected from HIV
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What type of Virus is HIV? What does reverse transcriptase do?
A single stranded RNA retrovirus The Virus injects a single strand of RNA into the cell. Retrovirus - needs reverse transcriptase enzyme to transcribe a piece of complimentary proviral DNA,
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When in the cell, what does HIV virus do?
Uses reverse transcriptase enzyme to transcribe a piece of complimentary proviral DNA, to make a double strand with the original RNA strand. This double stranded DNA then pops itself into the DNA of the cell (via integrase enzyme.) , ready to be transcribed into another virus cell, when the old immune cell becomes activated and starts trying to transcribe proteins for the immune response. (sneaky)
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How does HIV attach and enter a cell?
- GP120 on HIV virus binds to CD4 - This induces a conformational change in GP120 - This enables co-receptor binding - This results in membrane fusion between virus and CD4 cells
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How does HIV go from entering the body to infecting loads of cells at the lymph node? What does this lead to?
1. Enters, say, through Genito urinal mucosa 2. Macrophage recognise virus as forgein and phagocytose it, and then present HIV antigens on its surface 3. Antigen presenting macrophage present HIV virus to a reservoir of immune cells T cells at lymph node. 4. HIV virus can infect all these cells, leading to a massive spike of HIV in the blood, leading to flu like symptoms
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What is viral tropism?
The host cell preference that different strains of HIV cells in the body want to target due to mutations. **It is determined by the virus's ability to interact with the cell's receptors, which determine the cell type that the virus can infect**
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HIV infection - How long is the acute phase? What happens after this? How long is the chronic phase and what happens here?
12 weeks, After this the immune system will launch a counterattack and the number of normal T cells will begin to rise again. The chronic phase then starts, lasting from 2 - 10 years, as the virus slowly increases and T cell number slowly start to decrease
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HIV infection: What do patients with 200-500 T cell/mm^3 present with?
Swollen lymph nodes Hairy leukoplakia (white patch tongue) Oral Candidiasis (Yeast infection in mouth)
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What do patients with <200 T cell/mm^3 present with?
Persistent fever, fatigue, Weight loss and diarrhoea AIDS defining conditions appear eg Recurrent bacterial pneumonia Pneumocystis pneumonia Fungal infections
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What are the percentages of the different modes of transmissions of HIV?
75% Sexual contact the rest IV drug abuse Mother to child (via placenta or breast milk) Accidental needlestick injury and error in blood transfusion are least likely.
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What tests can you do for HIV. What is recommend as the first test?
Antibody tests (look for antibodies against HIV) Antibody/Antigen (Look for virus directly and also antibodies RNA tests - (look for viral RNA) DNA tests -( look for Copies of the viral RNA) Antibody/antigen test is recommended first
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If your first test for HIV is postive (Antibody/antigen test), what tests should you do next?
Antibody test, and RNA tests
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Once it has been diagnosed,how can we go about treating HIV?
With HAART drugs **(Hight active Anti-retroviral inhibitors)** ==> It usually consist of 3+ antiretroviral drugs, that suppress viral replication, eg *Nucleoside reveres transcriptase inhibitor*
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what Anbtx should you use to traet MRSA?
Vancomycin
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What are common bacterial causes of meningitis in a) Neonates b) In infants
a) E coli, Group B strep, Listeria Monocytogenes b) Neisseria Meningitidis, haemophilus Influenzae, Strep Pneumoniae
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What are common bacterial cuases of meningitis in c) Young adults d) In the elderly
c) Neisseria meningitidis, Strep Pneumoniae d) Neisseria meningitidis, Strep Pneumoniae, Listeria Monocytogenes
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What are the two most common causes of Meningitis? Are they gram negative or positive?
N.meningitidis + S.pneumoniae = diplococci N. Meningitidis= Negative S. Pneumoniae = Positive
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Name some viral causes of Meningitis
mumps virus, echo virus, coxsackie virus, herpes simplex virus, poliovirus
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What antibiotic group to we tend to give instead of penicillins to those with a penicillin allergy?
Macrolides, eg Clarithromycin, and Erythromycin (these inhibit protein synthesis)
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What antbx do we often give to treat Meningitis?
Bacterial: start antibiotics before tests come back if suspected **Cephalosporins: IV cefotaxime/ IV ceftriaxone** If over 50/immunocompromised add IV amoxicillin to cover listeria Meningococcal septicaemia: immediate IM benzylpenicillin in community/ IV cefotaxime in hospital Viral: supportive treatment, self-limiting in 4-10 days, acyclovir for HSV meningitis
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What is the main bacterium responsible for most UTIs? What would be some sensible antbx to use to treat it?
Escherichia Coli - *Gram Negative Bacilli, non lactose fermenting* Use Co amoxiclav, or Trimethoprim, *(that inhibits folate synthesis)*
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What antbx would you use to treat chlamydia?
Those that effect **PROTEIN SYNTHESIS** Doxyclicne (a tetracycline) Azithromycin (a Macrolide)
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What antibiotic would you use to treat Neisseria Gonorrhoea? Is this bacterium gram positive or negative, rod or bacilli?
ceftriaxone = **A CEPHLASPORIN** **(its a gram negative diplococci)**
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What is the most common form of viral meningitis? What would cause it and how would you treat it?
-Enteroviruses (echoviruses, Coxsackieviruses, polioviruses)- most common -Mumps in countries without routine childhood immunisation There is no specific antiviral therapy -Supportive: analgesics, antipyretics, hydration
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What are the two main drugs given to treat drug-susceptible pulomonary TB?
rifampicin, isoniazid - BOTH ACT ON NUCLEIC ACID SYNTHESIS
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What disease can viridains strep cause? What drug would you give?
Endocarditis. Treat with Penicillin and supplement with Gentamicin if needed
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What is the empirical treatment for cellultis?
Empirical treatment for cellulitis (before the organism is confirmed) would usually be with flucloxacillin to cover S aureus which is also a common cause Clarithromycin as an oral alternative for those with Beta lactam / penicillin allergy. Vancomycin is an IV alternative for that can also be used if allergic to beta lactam antibiotics.
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What is the empirical treatment for an UTI, while you await for the results
Either Nitrofurantoin or Trimethoprim can be used first line as empirical treatment * Note that the local STH guidance is slightly different from national guidance -higher rates of trimethoprim resistance among UTI pathogens in the local community STH serves make this option less appropriate.*
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Why is urinalysis for protein and blood performed at all antenatal visits?
TO screen for Preeclampsia, not for UTIs
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Why is it important to collect urine from asymptomatic pregnant women?
In pregnancy, asymptomatic bacteriuria is present in around 4-7% of women. Left untreated, there is a high risk of ascending infection, with pyelonephritis and subsequent risk of miscarriage. ***To screen for this, mid stream urine samples are collected in antenatal clinics, irrespective of urinalysis.***
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What are some associated conditions caused by S.pyogenes? Outline its classification
Wound infections - cause cellulitis Tonsilitis and Pharyngitis Otitis media Impetigo Scarlet Fever Can lead to Rheumatic Fever *Gram positive, catalase negative, Beta haemolytic on Blood agar, Group A on Lancefield*
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Where is Streptococcus pneumoniae often found as a commensal organism? map its classification
In the oropharynx in roughly 30% of the population Is a gram positive, Alpha Haemolytic, optochin sensitive
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What are the associated conditions caused by S.pneumoniae?
Pneumonia Otitis media Sinusitis Meningitis
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What are the associated conditions caused by viridans group strep? map classification
Dental caries and abscesses Infective endocarditis Deep organ abscesses Postive, Coccus, Catalse negative, and Alpha haemolytic, optochin resistant
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What is the purpose of bacteria possessing the coagulase enzyme?
This means that they can clot the blood plasma around the bacteria to attempt to protect themselves from phagocytosis An enzymes produced by staph aureus turns fibrinogen (soluble) into insolubale fibrin - clot, cloudy, fibrin clumping
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What are the associated conditions caused by Staphylococcus aureus? Map classification
Wound infections Abscesses Impetigo Septicaemia Osteomyelitis Pneumonia Endocarditis Toxins could also cause toxic shock syndrome and food poisoning Staphylococcus aureus - Gram Positive, catalase positive, and coagulase positive - quite virulent
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Where are the likely sites of infection for S.epidermidis? Map classification
Prostheses Catheters Mainly affects immunocompromised individuals Gram positive, Catalase positive, and coagulase negative
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What are the associated infections caused by E.coli? map classification
1. Wound infections (surgical) 2. UTIs (cystitis; ~80% of female UTIs - faecal source or sexual activity; catheterisation - most common nosocomial infection) 3. Gastroenteritis 4. Traveller's diarrhoea 5. Bacteriemia 6. Meningitis (infants) - rare in the UK Gram negative, bacilli, Lactose fermenting
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What is special about shigella? map its classification
It is acid tolerant and so it will not be destroyed by gastric acid Gram negative bacilli, non lactose fermenting, oxidase negative and White spots on dark red XLD agar
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How is shigella spread?
Via person to person contact Via contaminated food and water
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What is the pathogenesis of Salmonella infection?
Invasion of gut epithelium (SI) Transcytoses to basolateral membrane Enters submucosal Macrophages; survive and replicate within the macrophage. Systemic infection due to dissemination within macrophages: serovar Typhi Gram negative bacilli, non lactose fermenting, oxidase negative, Black on Pink XLD agar
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What kind of bacteria is Klebsiella pneumonia?
Environmental - not gut It is an opportunistic pathogen and so will infect immunocompromised subjects Anaerobic gram negative bacilli, Lactose fermenting *(along with E.Coli)*
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What kind of patients get infected with Klebsiella?
It is an opportunistic pathogen so will infect immunocompromised patients Including: Neonates Elderly Immunocompromised
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What are the associated infections caused by Klebsiella pneumonia?
UTIs Pneumonia Surgical wound infection Sepsis
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What is Haemophilus influenzae?
Exclusively human parasite opportunistic infection Fastidious - requires chocolate agar to culture non-motile
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Where is Haemophilus influenzae often found on the body?
Nasopharyngeal carriage in 25-80% of the population
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What is the major associated condition caused by Bordetella pertussis?
Whooping Cough (pertussis) Caused by the Pertussis toxin
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Is helicobacter spread?
No - it is not spread but exists in the gastric mucus of roughly 50% of the global population Therefore only a fraction of people develop disease
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What composes a granuloma?
Infected macrophage in the centre Other recruited Macrophages aggregated together (aggregates of epithelioid histocytes) Surrounded by Lymphocytes (T and B cells)
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What is the function of a granuloma? What is a problem with this?
It will wall off the bacteria However this can create a niche for the bacteria to enter latency and survive
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What cell type is responsible for walling off the granuloma?
Fibroblasts
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What conditions can make granulomas unstable and at risk of rupture?
CD4 depletion caused by HIV TNFa depletion caused by therapies against RA or organ transplant
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What are some characteristics of a virus?
Grow inside living cells - replicate inside host machinery Possess only one type of nucleic acid - DNA OR RNA (not both) No cell wall - Have a protein coat (capsid) or membrane lipid evenlope Inert outside of host cell Protein receptors on virus surface to allow for attachment to susceptible host cells
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How do viruses cause disease?
Direct destruction of host cells Modification of host cells Over reactivity of the immune system Damage through cell proliferation Evasion of Host defenses
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Give examples of diseases caused by flagellates?
Human African Trypanosomiasis (sleeping sickness) American Trypanosomiasis (Chagas disease) Leishmaniasis Trichomoniasis Giardiasis
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Why do patients with malaria experience high fever spikes every 48 hours?
Due to the replication of the merozoites in the RBCs taking 48 hours at which point the RBC ruptures leading to an inflammatory response
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What are the scenarios where you would carry out an HIV test?
- Clinician indicate diagnoses - clinical indications of immunosuppressive disease - Routine screening in high prevalence locations - Antenatal screening - Screening in high risk groups - Patient initiated request for testing
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What conditions would indicate that an HIV test may be needed?
- Unexplained lymphadenopathy - Unexplained weight loss or diarrhoea, night sweats of PUO - Oral or esophageal candidiasis or hairy leukoplakia - Flu like illness, rash, meningitis - Unexplained blood dyscrasias
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What are some recognised risk factors for HIV?
Heterosexual and homosexual sex (men to women and men to men) IVDU Multiple sexual parteners Rape Vertical transmission
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What type of virus is HIV?
Retrovirus
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What are the HIV associated neoplasms?
- Lymphoma - Caused by EBV - Cervical neoplasia - Caused by HPV - Kaposi's sarcoma - Caused by human Herpesvirus 8 - Hepatocellular Carcinoma - Caused by Hepatitis B/C
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What is the marker for AIDS?
CD4 count less than 200/ul
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When are antibacterial agents regarded as bactericidal?
Antibacterial agents are usually regarded as bactericidal if the **MBC is no more than four times the MIC.** *(Because at relatively lower times of dosing (<4 Times) they can still Kill bacteria/be bactericidal*
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Name 2 Gram-Positive resistant strains of clinical importance
MRSA - Methicillin (Flucloxacillin) resistant Staphylococcus Aureus VRE - Vancomycin resistant enterococci
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How does VRE have antibiotic resistance?
Vancomycin resistant enterococci Have acquired an mutation amino acid change via plasmid acquisition, that prevents vancomycin binding to bacteria - has been promoted by cephalosporin use
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How can we combat drugs that have beta lactamases?
Design drugs that utilise agents that inhibit beta lactamase Co-amoxiclav - Amoxicillin and Clavulanate Clavulanate inhibits the beta lactamase
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What are the 2 main classes of antibiotics that inhibit bacterial cell walls?
Beta Lactams Glycopeptides
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What compound do beta lactam antibiotics target?
Peptidoglycan
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What is the mechanism of action of beta lactam antibiotics?
Disrupt peptidoglycan production by: 1. Binding covalently and irreversibly to the penicillin-binding proteins (PBPs) particularly transpeptidase 2. Cell wall synthesis is disrupted and cell lysis occurs as peptidoglycan crosslinking can not occur → Active only against rapidly multiplying organisms.
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What are carbapenems?
Antibiotics designed to overcome the actions of beta lactamases and cephalosporinases Therefore these are the most broad specturm antibiotics and used as a last resort
303
What are CREs? Give examples of them
Carbapenem resistant enterobacteriaceae: Pseudomonas aeruginosa Escherichia coli Klebsiella pneumoniae
304
Give examples of some Glycopeptides
Vancomycin Teicoplanin
305
What is the route of administration for glycopeptides?
IV only
306
What types of antibiotics will inhibit protein synthesis? Give an example for each
Aminoglycosides - Gentamicin (30s) Tetracyclines - Doxycycline (30s) Lincosamides - Clindamycin (50S) Macrolides - Clarithromycin/ Erythromycin (50s) Chloramphenicol
307
What are endogenous infections?
Infections caused by the patients own flora
308
What common procedures often cause endogenous infections?
Surgery Catheterisation Cannulisation
309
When can chickenpox infection be serious?
- Immunocompromised patients - Patients who have had transplants - Adults - Pregnant people - Smokers - Infants
310
What symptoms would a varciella zoster virus show?
SHINGLES, and a red painful rash confined to a single dermatome
311
What is the treatment for VZV infection?
Acyclovir
312
What disease is Epstein Barr Virus known to cause? How would you diagnose it?
Infectious Mononucleoisis **(Glandular fever)** Need to do a blood test, will see atypical lymphocytes
313
What importnat differential for EBV glandular fever do you need to rule out when testing for it? What would serology show for acute and past infections of EBV?
unlike alot of viral illness, EBV can leads to white/yellowish purulent lining over tonsils -- So you also need to a black charcoal swab to **exclude S. Pyogenes**, an imporatnt differential cause IgM - EBV+ve - Acute IgG EBV +ve - chronic/past infection
314
Where do Quinolones act?
DNA topoisomers
315
Where does Rifampicin act?
RNA polymerase
316
Where do Penicillins, Cephalosporins and Carbapenems act?
Inhibit peptidoglycan cross linking
317
Where do Glycopeptides (vancomycin) act?
Inhibit peptidoglycan Synthesis
318
What are the Gram positive anaerobes and how do you remember them?
CLAP: Clostridium Lactobacillus Actinomyces Propionbacterium
319
How do you remember the atypical penumonia
Legions of Psittaci MCQs Legionella pneumophilia a Chlamydia psittaci Mycoplasma pneumoniae Chlamydophila pneumoniae Q fever (coxiella)
320
What is the first line option for treating cellulitis?
Flucloxacillin
321
What is the first lie option for treating UTIs?
Nitrofurantoin Trimethoprim
322
What is the first line treatment for treating chest infections?
Amoxicillin
323
What is the first line treatment for treating tonsilitis?
Phenoxymethylpenicillin
324
Name 5 groups of people who are at high risk of HIV infection.
1. Homosexual men. 2. Heterosexual women. 3. Sex workers. 4. IV drug users. 5. Truck drivers.
325
Name 4 diseases that haemophilus influenzae can cause.
1. Meningitis. 2. Otitis media. 3. Pharyngitis. 4. Exacerbations of COPD.
326
Name a bacteria that can cause cholecystitis What antbx would you use against it?
Bacteria that can cause this - EECK Enterococci +ve Cocci E Coli - Gram -ve Rod Clostdrium +ve Rod Klebsiella -ve Rod - Antibiotics IV - Cefuroxime and Metronidazole
327
What is the first line treatment for meningitis?
Cephalosporins - IV Cefotaxime, of Ceftriaxone
328
Give examples of macrolide antibiotics?
Clarithromycin Erythromycin
329
Give examples of tetracycline antibiotics
Doxycycline
330
Give examples of aminoglycoside antibiotics?
Gentamicin Streptomycin
331
What drugs inhibit folate acid synthesis?
Trimethoprim Sulphonamides Sulphamethoxazole *Trimethoprim and Suulfamethoxazole = Co Trimoxazole*
332
Why should you not give a pregnant women trimethoprim?
Because it will inhibit folate acid synthesis which is required for neural tube closure and therefore could cause the child to have spina bifida or anencephaly
333
What is Co-trimoxazole?
Combination therapy of: Trimethoprim + Sulphamethoxazole
334
What antibiotics would be used to treat atypical bacterial pneumonia?
Staph Aureus - Flucoxacillin, or cefuroxime MRSA - vancomycin Klebsiella Pneumoniae Co amoxiclav P.Aerruginosa Tazocin
335
What is the main source of bacteria to cause a UTI?
Normal intestinal bacteria contaminate the urethral opening via faeces Usually E.coli
336
How may a UTI Present?
Dysuria (pain, stinging or burning when passing urine) Suprapubic pain or discomfort Frequency Urgency Incontinence Confusion is commonly the only symptom in older more frail patients
337
What are the main causes of UTIs?
E.coli (most common) Klebsiella Enterococcus Pseudomonas S. saprophyticus Candida albicans
338
What are the antibiotics of choice for UTIs?
Trimethoprim Nitrofurantoin
339
When would Nitrofurantoin be avoided?
Third trimester as it is linked with haemolytic anaemia of the newborn
340
When would Trimethoprim be avoided?
Generally safe in pregnancy but avoided in the first trimester as it can affect folic acid metabolism and synthesis.
341
What is Cellulitis?
An infection of the skin and soft tissues underneath.
342
What are the most common causes of cellulitis?
Staphylococcus aureus and Streptococcus pyogenes are the most common causative organisms in cellulitis Group C strep - S. dysgalactiae
343
What is the antibiotic of choice to treat cellulitis? What are some alternatives that could be used?
Choice treatment: Flucloxacillin. Clarithromycin Clindamycin Co-amoxiclav
344
key bacteria - outline the classification of Pseudomonas. Aeruginosa, what it can typically cause and anbtx it can be treated with.
Gram negative Bacilli, Postive on the oxidase test Pneumonia Tazocin, Gentamicin, Quinolones
345
What type of agar is often used to culture Neisseria bacteria?
Gonoccoccus agar
346
Outline some pros and cons of PCR testing
Pros Very fast Cheap Can test for multiple viruses at the same time, by using a mix of primers Very sensitive - (if you have it, a PCR will almost definitely give a positive result) Cons Need to suspect viruses before hand Risk of giving false positive
347
What symptoms would a varciella zoster virus show?
SHINGLES, and a red painful rash confined to a single dermatome
348
What disease is Epstein Barr Virus known to cause? How would you diagnose it?
Infectious Mononucleoisis **(Glandular fever)** Need to do a blood test, will see atypical lymphocytes
349
Recap - what colour does a) Salmonella B) shigella Show up as on XLD agar?
Salmonella - **BLACK colononies** on Pink/red agar Shigella - **WHITE COLONIES** on red agar.
350
Side effects of TB medication - Give some side effects of Rifampicin
Haematuria
351
Side effects of TB medication - Give some side effects of Isoniazid
Peripheral Neuropahty,
352
Side effects of TB medication - Give some side effects of Pyrazinamide
Hepatitis, Also gout
353
Side effects of TB medication - Give some side effects of Ethambutol
– Eye problems e.g. uveitis
354
How long should you give each of the TB medications for?
Note RI = 2 months, PE = 6 months
355
What prophylactic medication can be given to those at a very high risk of TB? aka family member who has with TB
one off dose of ciprofloxacin
356
name some aids defining illness?
pneumocystis jirovecii Cyptomegalovirus infection of any organ other than liver, spleen or glands

Phase 2a Sam (18 decks)

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