Mircobiology Flashcards
1
Q
What is a pathogen?
A
An organism capable of causing disease
2
Q
What is a commensal?
A
Organism which colonises a host but causes no disease
3
Q
What is an opportunist pathogen?
A
Microbe that causes disease if host defences are compromised
4
Q
What is virulence?
A
The degree to which a given organism is pathogenic
5
Q
What is asymptomatic carriage?
A
When a pathogen is carried harmlessly
6
Q
What are round bacteria called?
A
Coccus
7
Q
What are rod bacteria called?
A
Bacillus
8
Q
What colour do gram positive bacteria stain?
A
Purple
9
Q
What colour do gram negative stain?
A
Red/pink
10
Q
What type of organism would you stain with Ziehl-Neelsen?
A
Mycobacteria e.g., TB.
11
Q
What are the differences between gram negative and positive bacteria?
A
- Gram negatives have endotoxin (lipopolysaccharide layer) can cause endotoxic shock
- Gram negatives have an outer membrane
- Gram negatives have a lipoprotein layer
12
Q
Describe the characteristic features of gram positive bacteria?
A
- Single membrane.
- Large peptidoglycan area.
13
Q
Describe the characteristic features of gram negative bacteria?
A
- Double membrane.
- Small peptidoglycan area. (
- LPS (endotoxin area).
14
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.
15
Q
What are the 3 phases of bacterial growth?
A
- Lag phase.
- Exponential phase.
- Stationary phase
16
Q
Give an example of a slow growing bacteria.
A
TB.
17
Q
Give an example of a fast growing bacteria.
A
E.coli and S.aureus.
18
Q
Give 2 functions of pili
A
- Help adhere to cell surfaces.
- Plasmid exchange
19
Q
What is the primary function of flagelli?
A
Locomotion.
20
Q
What is the primary function of the polysaccharide capsule?
A
Protection; prevents MAC or opsonisation molecules attacking.
21
Q
What types of bacteria release endotoxin?
A
Gram negative
22
Q
What types of bacteria release exotoxins?
A
Gram negative and positive
23
Q
Describe endotoxins.
A
Endotoxin (LPS) is an outer membrane component released when bacteria are damaged. They are less specific and are toxic to the host. They are heat stable
24
Q
Describe exotoxins.
A
Proteins secreted from gram positive and gram negative bacteria. They are specific and heat labile.
25
What are endotoxins made from?
Lipopolysaccarides
26
What are exotoxins made from?
Proteins
27
What are plasmids?
Circular pieces of DNA that often carry genes for antibiotic resistance.
28
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
29
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
30
What are some types of obligate intracellular bacteria?
- Rickettsia
- Chlamydia
- Coxiella
31
What is the first way to distinguish between Bacteria that may be cultured on Artificial media?
Whether they have a cell wall or not
32
How do you distinguish between cells with cell walls?
- Whether they grow as single cells or as filaments
33
What are the three different types of cells growing as single cells?
- Rods
- Cocci
- Spirochates
34
How do you differentiate between different types of Rod/cocci bacteria?
Gram positive and gram negative
35
What is the way to differentiate between gram negative/positive bacteria?
Aerobic vs anaerobic
36
Give an example of a gram-positive aerobic cocci?
Staphylococcus and streptococcus.
37
What are the 3 types of streptococcus bacteria?
- Beta-haemolytic
- Alpha-haemolytic
- Non-haemolytic
38
What is anaerobic gram-positive bacteria?
PEPTOSTREP-
TOCOCCUS
39
What are aerobic gram-negative cocci bacteria?
- Coliforms’
- VIBRIO
40
How would you describe the arrangement of staphylococci?
Clusters of cocci
41
How would you describe the arrangement of streptococci?
Chains of cocci.
42
What bacteria would be coagulase positive?
Staphylococci aureus
43
What bacteria would be coagulase negative?
All others e.g. staphylococci epidermidis.
44
What is the normal environment of staphylococci?
Nose and skin
45
How is Staphylococci aureus spread?
Aerosol and touch
- carriers and shedders
46
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)
47
What drug would be used to treat staphylococci?
Flucloxacillin
48
What type of infection is S. epidermidis
opportunistic
49
What is the main virulence factor of s.epiermidis
Can form biofilms
50
What test could be done to distinguish between different streptococci?
Blood agar haemolysis.
51
What further test can be done for those streptococci in the β haemolysis group?
Serogrouping; detecting surface antigens. e.g., lancefield grouping.
52
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
53
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.
54
What would you see on the agar plate in γ haemolysis and give an example of a bacteria in this group.
γ haemolysis is when there is no haemolysis. Streptococcus bovis falls in this group.
55
What is are two examples of beta haemolytic strep infections?
S.agalactiae and S.pyogenes
56
What are the virulence factors of S.pyogenes?
Exported factors
- Streptokinase (breaks down clots)
Toxins
- Streptolysins
- Erythrogenic toxin
Surface factors
- capsule
- M protien
57
What infections do s-agalactiae usually cause?
Neonatal
58
Name some infections caused by S.pyogenes?
Respiratory
- Tonsillitis & pharyngitis
- Otitis media
Skin and Soft tissue
- Wound infections
- Impetigo
- cellulitis
- puerperal fever
Scarlet fever
- SPeA and M type
Complications
- rheumatic fever
- glomerulonephritis
59
Give examples of alpha haemolytic bacteria.
- S.pneumoniae
- Viridans group streptococci
60
Give examples of aerobic gram-positive bacilli.
- Listeria monocytogenes
- Bacillus anthracis
- Corynebacterium diphtheriae
61
Give examples of anaerobic gram-positive bacilli
- C. tetani
Tetanus
- C. botulinum
Botulism
- C. difficile
antibiotic-associated diarrhea
pseudomembranous colitis
62
Give examples of gram-negative bacilli.
Shigella, salmonella, E.coli etc.
63
What kind of bacteria is MacConkey agar used with?
Gram negative bacilli
64
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.
65
Name 2 gram-negative bacilli that will give a positive result with MacConkey agar.
1. E.Coli.
2. Klebsiella pneumoniae
66
What antigen do the flagella contain?
H
67
What antigen does the LPS contain?
O (somatic)
68
Does e-coli have an H antigen?
Yes, as it is motile
69
What infections are caused by e-coli?
i) Wound infections (surgical)
(ii) UTIs (cystitis; 75-80% of ♀ UTIs - faecal source or sexual activity;
catheterisation - the most common type of nosocomial infection)
(iii) Gastroenteritis
(iv) Travellers’ diarrhoea
(v) Bacteraemia (sometimes leading to sepsis syndrome)
(vi) Meningitis (infants) - rare in UK
70
Does shigella have an H antigen?
No as it is not motile
71
What are the symptoms of shigella infection?
Frequent passage of stools (>30/day)
Small volume, pus and blood, prostrating cramps, pain in straining, fever.
Self-limiting (in adults)
Pathology like EIEC but with the addition of Shiga toxin
72
Does salmonella have an H antigen?
Yes as it is motile
73
What infections are caused by salmonella?
- Gastroenteritis/enterocolitis e.g., food poisoning
- Enteric fever - typhoid/paratyphoid fever from drinking poor water quality
- Bacteraemia (uncommon)
74
Why are there pathogenic strains of e.coli?
Due to the acquisition of genes from other bacteria
75
Which type of e.coli would you associate with causing travellers diarrhoea?
Enterotoxigenic e.coli (ETEC).
76
What are the symptoms of enteropathogenic e.coli infection?
Chronic watery diarrhoea
77
What are the symptoms of enterohaemorrhagic e.coli infection?
Bloody diarrhoea.
78
What are the symptoms of v.cholerae?
Huge volumes of watery stools (no blood or pus).
79
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.
80
Why is v.cholerae not killed if you have a fever?
It grows at 18 - 42°C.
81
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.
82
Name the bacteria that can cause legionnaires disease?
Legionella.
83
Who might be susceptible to infection by legionella?
Immunocompromised individuals.
84
What type of bacteria are Neisseria?
Gram negative diplococci.
85
What are the two medically important species of neisseria?
N.meningitidis and N.gonorrhoeae.
86
How is N.meningitidis transmitted?
Aerosol transmission. High risk in colonised people e.g. university, Haj.
87
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.
88
What are the virulence determinants of N.meningitidis?
STI - rectal, vaginal or oral inflammation.
89
Describe bacteroides.
Opportunistic, obligate anaerobes.
90
Can you grow chlamydia on agar?
No, chlamydia is an obligate intracellular parasite
91
How can you detect chlamydia?
Serum antibodies or PCR.
92
Name the spirochaete that is responsible for causing lyme disease.
B.burgdorferi.
93
Name the spirochaete that is responsible for causing syphilis.
T.pallidum.
94
What is the ziehl-neelsen stain?
- Used for mycobacteria which don't take up gram stain
- Acid fast bacilli are blue
- Non-acid-fast bacilli are red
95
What is the catalase test?
- Add h2o2 to bacteria to see for bubbling reaction
- Bubbles= positive test
96
What is the catalase test used to distinguish between?
Streptococci and Staphylococci
97
Are Streptococci catalase negative or positive?
Negative
98
Are Staphylococci catalase negative or positive?
Positive
99
Are most gram-negative bacteria catalase negative or positive?
- Most are positive
- E-coli and fungi are positive
100
What is the coagulase test?
- An enzyme produced by s.aureus turns fibrinogen (soluble) into fibrin (insoluble)
- Used to distinguish between s.aureus and other types of staphylococci
101
Is Staphylococci aureus positive or negative for the coagulative test?
Positive (clumping) due to formation of fibrin
102
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
- Viridians group streptococci
103
What is the Haemolysis test?
- The ability of bacteria to break down red blood cells
-It requires the expression of haemolysin
- Very useful for deciding between streptococci
104
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.
- Staphylococcus aureus and listeria monocytogenes also beta-haemolytic
105
What further test can be done for those streptococci in the β haemolysis group?
Serogrouping; detecting surface antigens. e.g., lancefield grouping.
106
What is the optochin test?
- 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
107
What bacteria are optochin resistant?
Viridans streptococci (infective endocarditis) and other alpha haemolytic streptococci
108
What bacteria are optochin sensitive?
Streptococcus pneumoniae (causes lobar pneumonia and meningitis)
109
What is the oxidase test?
- 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
110
What are the colour changes for the oxidase test?
- Oxidase positive: Blue
- Oxidase negative: No colour change
111
Name some oxidase positive bacteria?
- P. aeruginosa
- V. cholerae
- Campylobacter e.g., C. jejuni
- Helicobacter
112
What is MacConkey agar?
- Only grows gram negative bacilli
- Good at determining between lactose-fermenting and not
113
Why does MacConkey agar only grow gram negative bacteria?
Bile salts inhibit the growth of gram positive bacilli
114
What will happen to the MacConkey agar if lactose fermenting bacilli are present?
- Lactose fermenting produce acid
- This will turn indicator on agar red
115
Name some lactose fermenting bacilli?
- E. COLI
- KLEBSIELLA PNEUMONIAE (typical organism that causes
biliary infection)
- ENTEROBACTER SPP.
116
Name some non-lactose fermenting bacilli?
- Salmonella spp.
- Shigella spp.
They appear white/transparent
117
What is XLD agar used for?
To differentiate between Shigella and Salmonella
118
What colour does Shigella go on XLD?
White spots on dark red
119
What colour does Salmonella go on XLD?
Black spots on bright pink
120
What shape are most gram-positive bacteria?
Round (cocci)
121
What shape are most gram-negative bacteria?
Rod (bacilli)
122
Which Lancefield groups are associated with tonsilitis and skin infection?
A , C and G.
123
Which Lancefield groups are associated with neonatal sepsis and meningitis?
B.
124
Which Lancefield groups are associated with UTI's?
D.
125
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.
126
What is CLED agar used for?
It is used to differentiate micro-organisms in urine and can classify lactose fermenters and non-lactose fermenters.
127
What is Sabouraud's agar used for?
Used to culture fungi.
128
Describe mycobacteria.
- Aerobic.
- Non-motile.
- Non spore forming.
- Bacilli.
129
Give an example of mycobacteria.
Give an example of mycobacteria.
130
Give an example of mycobacteria.
The cell wall is very thick and has a high lipid content.
131
Why is it hard to use therapeutic antibodies against mycobacteria?
Mycobacteria grow very slowly and so treatment with antibodies is difficult. (This also makes them hard to culture).
132
How could you detect whether an individual has had previous exposure to TB?
1. Tuberculin skin test (mantoux).
2. Interferon gamma release assays.
133
Name 6 sterile sites in the body.
1. Urinary tract.
2. CSF.
3. Pleural fluid.
4. Peritoneal cavity.
5. Blood.
6. Lower respiratory tract.
134
Where in the body would you find normal flora (commensals)?
1. Mouth.
2. Skin.
3. Vagina.
4. Urethra.
5. Large intestine.
135
What is a virus?
An infectious, obligate intracellular parasite comprising genetic material surrounded by a protein coat
136
What are the different shapes of viruses?
- Helical
- Icosahedral
- Complex
137
Which viruses are Non-enveloped?
- Adenovirus
- Parvovirus
138
What viruses are enveloped?
- Influenza
- HIV
139
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
140
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. REPLICATION -- may localise in nucleus, cytoplasm or both, production of progeny viral nucleic acid and proteins.
5. Assembly of new virion
6. Release of new virus particles
141
How are new virus particles released?
1. Burts out resulting in cell death e.g., rhinovirus
2. Budding/exocytosis e.g., HIV and influenza
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
Name some Sporozoa
- Cryptosporidiosis
- Toxoplasmosis
144
What are protozoa?
One celled animals”
Single cell with nucleus
(Eukarytoic)
>30,000 species
145
What is Leishmaniasis?
- Leishmaniasis is a disease that causes a range of clinical pictures, as there are many species that affect humans.
146
What are the 5 types of protoza?
1. Flagellates
2. Microsporidia
3. Sporozoa
4. Amoebae
5. Cilliates
147
What is African Trypanosomiasis? (flagellates)
- Human African Trypanosomiasis (or sleeping sickness) is a disease that unsurprisingly is endemic in Africa.
- specices Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. T.B.gambiense is endemic in West Africa (as is Gambia), and T.B.rhodesiense South East
148
How is African Trypanosomiasis transmitted?
- The trypanosomes are transmitted via the bite of an infected Tsetse fly and can cause a chancre (large red sore) at the site of the bite.
149
How is American Trypanosomiasis transmitted?
- Spread through contact with faeces of triatomine “kissing” bug
Also through blood, vertically and eating contaminated food
150
What are the symptoms of American trypanosomiasis?
- Two phases, both can be asymptomatic or life-threatening
- Acutely patients can get flu-like symptoms, lymphadenopathy and a Romaña sign (swollen eyelid where triatomine faeces rubbed into the eye!
151
How is leishmaniasis transmitted? (flagellates)
- It is acquired through the bite of an infected sandfly.
152
What is amoebiasis?
- Microsporidia
- Poor sanitary conditions/tropical countries
MSM (men who have sex with men) at risk
- Entaemoeba histolytica can live in the colon asymptomatically, but also can invade the colon and consume red blood cells
153
How do viruses evade the immune system?
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
154
What are the 5 types of malaria?
1. Plasmodium falciparum (most severe disease)
2. Plasmodium ovale
3. Plasmodium vivax
4. Plasmodium malariae
5. Plasmodium knowlesi
155
How is malaria transmitted?
By bite of the female anopheles mosquito
156
When should you think of malaria as a cause of disease?
fever and recent travel
157
How would you diagnose malaria?
A blood flim by using light microscopy
158
What is the main symptom of malaria?
Fever
159
What are some other symptoms of malaria?
Chills
Headache
Myalgia
Fatigue
Diarrhoea
Vomiting
Abdo pain
160
What are some signs of malaria?
Anaemia
Jaundice
Hepatosplenomegaly
‘Black Water Fever’
161
Describe the pathogenesis of p.falciparum?
Unique cerebral malaria, fatal infection. Parasites mature in RBC's, RBC's collect in small vessels and cause blockage of cerebro-microvasculature = hypoxia
162
What genetic conditions can give immunity to malaria?
Someone with sickle cell anaemia or thalassaemias.
163
Can immunity to malaria be acquired?
Recurrent infection can lead to someone being 'semi-immune'. Antibodies could be transferred by maternal transmission.
164
What is the treatment for malaria?
Chloroquine.
165
What is the treatment of complicated malaria
166
What are the symptoms of complicated malaria?
- Cerebral
- ARDS/Pulmonary oedema
- Renal failure
- Sepsis
- Bleeding/Anaemia
167
What are the 4 stages of pathogenesis?
1. exposure (contact),
2. adhesion (colonization),
3. invasion,
4. infection
168
What is an antibiotic?
- A molecule that works by binding to a target site on a bacteria
- Points of biochemical reaction crucial to the survival of the bacterium
- The crucial binding site will vary with different antibiotic classes
169
What are the two modes of action of an antibiotic?
- Slow the growth of bacteria (bacteriostatic) kills 90% in 18-24 hours: antibiotics that inhibit protein synthesis
- Destroy bacteria (bactericidal) kills 99.9% in 18-24hrs: antibiotics that inhibit cell wall synthesis
170
How do polymyxins and polyenes work?
- Binds to cell membrane and alters its structure
- Makes the cell membrane more permeable
- Water will move into the cell via osmosis
Note polyenes can be used for fungal infections
171
How do B-lactam and glycopeptides antibiotics work?
- They are bactericidal
- They inhibit cell wall synthesis by binding to proteins which inhibit synthesis of peptidoglycan
- Active only against rapidly dividing organisms
- Won't affect human cells
172
Name some B-lactam antibiotics
- Penicillin
- Cephalosporin
- Carbapenems
- Monobactams
173
Name a glycopeptide
Bacitracin
Vancomycin
174
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
175
How do quinolines and nalidixic acid antibiotics work?
- They inhibit RNA/DNA synthesis
- They are bacteriostatic
176
Name a quinoline
Rifamiacin
177
Name a Quinoline/nalidixic acid
Rifamycin (inhibits RNA polymerase)
178
How do Erythromycin and Chloramphenicol work?
- They inhibit protein synthesis
- They do this by targeting the 50s subunit of ribosome
179
How do Tetracyclines and aminoglycosides work
- They inhibit protein synthesis
- They do this by targeting the 30s subunit of ribosome
- Protein can still be alive but they can't do anything (bacteriostatic)
180
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
181
How much antibiotic do you need?
- The drug not only needs to attach to its binding site but must also occupy an adequate number of sites (concentration)
- To work effectively the antibiotic should remain at the binding site for a sufficient period of time in order for the metabolic process to be inhibited (time)
182
What are the two major determinants of antibacterial effects?
1. Concentration
2. Time (that the antibiotic remains on the binding sites)
183
What is MIC?
Minimum inhibitory concentration (the minimum amount of an antibiotic needed to have the desired effect
184
What is time dependant killing?
Key parameter is the time that the serum concentration remains above MIC during the dosing interval
185
What antibiotics rely on time dependant killing?
- beta-lactams (penicillins, cephalosporins, carbapenems, monobactams),
- clindamycin,
- macrolides
- oxazolidinones
186
What is concentration dependant killing?
- Key parameter is how high the concentration is above MIC
187
What antibiotics rely on concentration dependant killing?
- aminoglycosides
- quinolones
188
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
189
What mechanisms can make bacteria resistant to antibiotics
- Change the antibiotic target
- Destroy antibiotic
- Prevent antibiotic access
- Remove antibiotics from bacteria
190
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 – VRE
- Rifampicin activity is reduced by changes to RNA polymerase in MTB – MDR-TB
191
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
- Staphylococci produce ‘penicillinase’ so penicillin but not flucloxacillin inactivated
- Gram-negative bacteria phosphorylate and acetylate aminoglycosides (gentamicin)
192
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
193
Define what removing antibiotics from bacteria means and name some bacteria that have done this
- Proteins in bacterial membranes act as export or efflux pumps - so the level of antibiotics is reduced
- S. aureus or S. pneumoniae resistance to fluoroquinolones
- Enterobacteriacae resistance to tetracyclines
194
What is intrinsic resistance?
- Bacteria that have a natural resistance to an antibiotic
- All subpopulations will be equally resistance
195
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
196
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.
197
What are the two ways that bacteria develop resistance?
- Spontaneous gene mutation
- Horizontal gene transfer
198
Name some resistant gram-positive bacteria.
MRSA
Methicillin-resistant Staphylococcus aureus
-Bacteriophage mediated acquisition of Staphylococcal cassette chromosome mec (SCCmec)
- confers resistance to all β-lactam antibiotics in addition to methicillin (= flucloxacillin)
VRE
vancomycin-resistant enterococci
- Plasmid mediated acquisition of gene encoding altered amino acid on peptide chain preventing vancomycin binding
Promoted by cephalosporin use
199
What bacteria do B-lactam antibiotics work most effectively against
Gram-positive bacteria as they have a thick cell wall
200
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
201
What antibiotic would be used for S.aureus and A, C, G strep?
Flucloxacillin
A, C, G strep you can also use PO penicillin or IV Benzylpenicillin
202
What antibiotic would be used for S. pneumoniae
PO amoxicillin
IV benzylpenicillin
203
When would you use a glycopeptide?
- Vancomycin and teicoplanin only used with gram-positive bacteria
- Used with B-lactam bacteria
- Used when patient has penicillin allergy
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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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When would you use aminoglycosides (protein synthesis)?
- Gentamicin IV only
- Use against gram negatives and staphs
- Use for UTIs
- Use for infective endocarditis
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When would you use quinolones?
- Ciprofloxacin
- Use for gram negatives
- Use for UTIs
- Use for intra-abdominal infections
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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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Where did HIV come from?
- HIV-1 arose from transmission of SIV cpz from chimpanzees to humans sometime pre-1950.
- HIV 2 (SIV sm) from the sooty mangabey
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What are the 3 types of HIV?
M (main) O (outlying) N (new)
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How is the M (main) group of HIVS separated
Into clades A-D, F-H, J-K.
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What clade of HIV is most common in Europe and USA?
Clade B
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What clade of HIV is most common in West and Central Africa?
Clade A
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What clade of HIV is most common in West and Southern Africa?
Clade C
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What cells are affected in HIV?
- HIV results in the death of CD4+ T lymphocytes
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What are the two main ways CD4 cells are affected in HIV?
- Replicating within CD4 T cells leads to their death. However, only a tiny minority <1% of CD4 T cells are ever infected.
- Uncontrolled activation of CD4 T cells. Activated CD4 T cells are by design, destined to undergo activation induced cell death.
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What are some other ways cells are affected in HIV?
Other processes contribute including bystander cell death (e.g., infected macrophage causes death of infected CD4 T cells), Thymus atrophy (preventing thymic maturation of T cells), loss of bone marrow progenitors and fibrosis of lymph node
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How does HIV lead to AIDS?
Given their central role in coordinating adaptive immune responses, it follows that their depletion by HIV infection leads to an Acquired Immune deficiency.
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What are the 9 stages of HIV replication?
1. Attachment
2. Entry
3. Uncoating
4. Reverse transcription (error prone so genomic variability)
5. Genome integration
6. Transcription of viral RNA
7. Splicing of mRNA and translation into proteins
8. Assembly of new virions
9. Budding
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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
- Once it's attached uses chemokine receptors CCR5 and CXCR4
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What are 4 main problems that surround HIV treatment?
1. Mainly transmitted by sexual intercourse and so people don't like to talk about it - taboo.
2. Period of latency means someone may infect others unwittingly.
3. HIV leads to a weakened immune system and so there is increased risk of infection.
4. HIV mutates a lot and so drug treatment is difficult.
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What enzyme copies HIV RNA into DNA?
Reverse transcriptase.
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Why are mutations common in HIV?
HIV is a retrovirus and replicates via reverse transcription. This process is prone to errors and mutations.
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What part of HIV enters the host cell following attachment?
The viral caspid, enzymes and nucleic acids.
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Briefly describe the mechanism of HIV replication.
1. GP160 binds to CD4 receptors.
2. Viral caspid, enzymes and nucleic acids are uncoated and released into the cell.
3. RNA is converted into DNA using reverse transcriptase.
4. Viral DNA is integrated into cellular DNA by intergrase.
5. Viral DNA is transcribed into viral proteins.
6. Splicing.
7. New HIV cells 'bud' from CD4.
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Name 4 enzymes involved in HIV replication.
1. Reverse transcriptase.
2. Integrase.
3. RNA polymerase.
4. Proteases
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Which enzyme is responsible for integrating HIV DNA into cellular DNA?
Integrase.
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Why might macrophages also be infected by HIV?
Macrophages also have CD4 and CCR5 receptors.
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Describe what happens when someone is initially infected with HIV.
HIV enters via mucosa.
Macrophages ingest HIV and presents an epitope of HIV to a T cell. HIV then infects the T cell. Infection spills into the blood stream - viraemia
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HIV leads to immune dysfunction, how are the immune system cells affected?
1. CD4 cells are excessively and inappropriately activated.
2. There is impaired IL-2 production.
3. There is a decrease in the number and function of CD4 cells.
4. B cells produce fewer specific Ab's.
5. There are fewer NK cells, neutrophils and macrophages.
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If a HIV test comes back as negative in a high risk individual why should a second HIV test be done?
A second test should be done after the window period: the window period is the time between exposure to HIV infection and the point when the test will give an accurate result. During this time a person can be infected with HIV and be very infectious but still test HIV negative.
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HIV: what is the 'window period'?
The time between potential exposure to HIV infection and the point when the test will give an accurate result. During this time a person can be infected with HIV and be very infectious but still test HIV negative.
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HIV RNA can be detected using RT-PCR. What is this useful for?
It can quantify the amount of HIV RNA in the blood and so can indicate disease progression and how well the individual is responding to antiretroviral therapy.
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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.
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What are the 3 stages of the HIV epidemic?
1. Nascent; <5% prevalence in risk groups.
2. Concentrated; >5% prevalence in one or more risk groups.
3. Generalised; >5% prevalence in the general population.
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How can the impact of HIV be reduced?
1. Behaviour change; education, condom use, needle exchange.
2. Know your status; testing.
3. Specific interventions; PMTCT, PEP, VMCC, PrEP etc.
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How can sexual transmission of HIV be reduced?
Condom use!
Voluntary medical male circumcision.
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How can transmission of HIV among IV drug users be reduced?
Harm reduction measures e.g. needle exchange.
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What are the problems with trying to ensure everyone living with HIV has access to antiretroviral treatments?
1. Lack of awareness.
2. Understaffed clinics.
3. Medication needs monitoring.
4. Cost.
5. Adherence.
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What are the 4 main phases in the natural history of HIV?
1. Acute primary infection.
2. Asymptomatic phase.
3. Early symptomatic HIV.
4. AIDS.
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What are the 4 main phases in the natural history of HIV?
1. Acute primary infection.
2. Asymptomatic phase.
3. Early symptomatic HIV.
4. AIDS.
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What happens in the acute primary infection phase of HIV?
There is a transient fall in CD4+ count followed by a gradual rise. There is also an acute rise in viral load
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What signs and symptoms might you see when someone is in the acute primary infection phase of HIV?
Abrupt onset of non-specific symptoms e.g. fever, rash. Weight loss, lethargy and depression can also occur.
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What happens in the asymptomatic phase of HIV?
There is a progressive loss of CD4+ cells. This is the latent phase and can last for years.
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What signs and symptoms might you see when someone is in the asymptomatic phase of HIV?
This phase is the latent phase and so you will rarely see symptoms. However, you might sometimes see enlarged lymph nodes.
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What is the CD4+ count when someone is diagnosed with having AIDS?
CD4+ <200
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Name 3 types of people who are likely to rapidly progress and develop AIDS.
1. Elderly people.
2. Children.
3. People with a high viral load.
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Name 2 markers that are used for monitoring HIV.
1. CD4+ count.
2. HIV RNA copies (viral load).
- These markers are important in determining prognosis.
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Name 3 respiratory diseases associated with HIV.
1. Bacterial (pneumococcal) pneumonia.
2. TB.
3. Pneumocystis pneumonia (PCP).
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What are the characteristic signs of pneumocystis pneumonia (PCP)?
Decreased CD4+ count.
Decreased O2 sats on exertion.
Decreased exercise tolerance.
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Name 3 CNS diseases associated with HIV.
1. Mass lesions e.g. primary CNS lymphoma, cerebral toxoplasmosis.
2. Meningitis e.g. pneumococcal, cryptococcal.
3. Opthalmic lesions e.g. CMV, toxoplasmosis, choroidal tuberculosis etc.
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What does HAART stand for?
Highly active anti-retroviral treatment.
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What is HAART? What does it aim to do?
Anti-retroviral treatment where 3 drugs are taken together.
The aim is to reduce viral load and increase CD4+ count. Good compliance = good prognosis.
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Where in the cell can HIV drugs target?
1. Reverse transcriptase inhibitors.
2. Protease inhibitors.
3. Fusion inhibitors.
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What is the UNAIDS goal by 2020?
90/90/90
- 90% diagnosed.
- 90% on anti-retroviral treatment.
- 90% viral suppression, undetectable viral load
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What behaviour modifications can be done in order to prevent HIV transmission?
Sex education, reduce frequency of changing sexual partners, reduce high risk sexual practices, consistent condom use!
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How would you define a 'late diagnosis' of HIV?
CD4+ count < 350.
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Why is it bad to diagnose HIV late?
A late diagnosis is associated with a 10 fold increase in risk of death in the first year after diagnosis.
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Name 5 AIDS defining conditions.
1. Oesophageal candidiasis.
2. TB.
3. PCP (pneumocystis jirovecii pneumonia).
4. Recurrent bacterial pneumonia.
5. Kaposi's carcinoma.
6. Hodgkins and Non-Hodgkin's lymphoma.
7. HIV dementia.
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What are routes of HIV transmission?
- Unprotected sexual contact
- IV drug use
- Transfusion of untested blood
- Mother to child transmission (breastmilk and in utero)
- Contaminated surgical equipment
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Why does the immune response fail to get rid of HIV?
- Neutralising antibodies take months to be made and are behind the mutations of HIV
- CD4+ cells are targeted first so it's harder for immune system to produce antibodies
- CD8+ cells are effective at first but stop working due to immune exhaustion
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why does the body take so long to produce an antibody response?
- HIV only contains a few cell membrane spikes to target
- The spikes are glycosylated which makes it difficult for antibodies to bind
- Key parts of viral envelope are hidden until binding
- The virus can evolve quickly
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Why can excessive immune response be bad for the progression of HIV?
- It can favour viral replication
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What are two markers used to monitor HIV infection?
1. CD4 count
2. HIV viral load
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If a patient has a fever, rash and non-specific symptoms what should you ask?
- Ask about their sexual history
- Think of HIV seroconversion
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When should you consider performing a HIV test on a patient?
When faced with a common problem in:
- In an unexpected patient
- That is recuring
- That has no clear underlying cause
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What is the most common type of opportunist infection?
PCP
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What is the most common treatment for Pneumocystis pneumonia (pcp)?
Co-trimoxazole
