robins browne Flashcards
(79 cards)
1
Q
T/F: Pencillin V is often used instead of penicillin G because it has a wider spectrum of antibacterial activity
A
FALSE: V and G have same spectrum
but
V is taken orally (more acid stable)
2
Q
Bactericidal antimicrobial agents are preferred to bacteriostatic ones when:
A
the patient’s immune system cannot be relied upon to eradicate the infection
3
Q
T/F: semisynthetic penicillins were designed to be less toxic than penicillin G
A
FALSE:
penicillin G has little toxicity in hmans
4
Q
Why are Semisynthetic penicillins preferred to pencillin G
A
- ease of administration - oral
2. broader antimicrobial spectrum
5
Q
Alter pharmacological properties (3)
A
- change kinetics - distribution, toxicity, spectrum
2. extend patent and make money
6
Q
Tetracyclines
A
4 ring Naturally occuring 4 times a day, short half life Excreted n bile Doxycycline(modified): taken 1x, 2x per day
7
Q
Penicillin G
A
GP and GN cocci
Disadvantage: injected, dont know how much active drug is in the body
8
Q
Penicillin V
A
Phenoxy methyl group instead of benzyl group
Oral
9
Q
Ampicillin
A
Oral
Broader spectrum than PenV
GN rods
~amoxycillin
10
Q
Methicillin
A
Penicillin-resistant S.aureus
Injected
11
Q
Carbenecilin
A
Pseudomonas GN rod
Important hospital acquired pathogens
Not used -big dose intravenously
Ticarcilin used instead
12
Q
Sulphonamides
A
Target folic acid synthesis - don’t affect humans
13
Q
Cell Wall antimicrobial target
A
Act on peptidoglycan synthesis
Peptidoglycan = disaccharide of NAG and NAM
End glycine displaces terminal D alanine - catalysd by transpeptidases, endopeptidases, carboxylases = penicillin binding proteins
14
Q
Vancomycin
A
Used to treat MRSA
Resistance in Enterococci if a different terminus is made because vancomycin can’t bind to sugar
15
Q
VRE
A
When resistance to commensals transfers to other bacteria
16
Q
VISA
A
Vancomycin Intermediate Staph Aureus
Make more peptidoglycan making it difficult for vancomycin to diffuse through
17
Q
VRSA
A
Vancomycin resistant Staph aureus - very rare
18
Q
VSSA
A
Vancomycin susceptible staph aureus
19
Q
Suicide inhibitor
A
irreversible enzyme inhibition that occurs when an enzyme binds a substrate analogue and forms an irreversible complex
20
Q
Transpeptidases
A
Bacterial enzyme that cross links peptidoglycan to form cell walls
21
Q
Clavulanic Acid
A
Beta lactamase inhibitor
Combines with penicillin group antibiotics to overcome resistance
Beta lactamase binds to clavulanic acid’s beta lactam ring
Does not inhibit chromosomal B-lactamase (ONLY PLASMID ENCODED)
22
Q
Augmentin
A
Clavulanic acid + amoxycilin in equal parts
23
Q
Timetin
A
Ticarcillin and clavulanic acid
24
Q
Ticarcillin
A
Treatment of pseudomonas
Treats GN bacteria
Ability to prevent cross-linking of peptidoglycan during cell wall synthesis
25
Aminoglycosides
```
Inhibit protein synthesis
Against GN aerobes and anaerobic bacilli
e.g. streptomycin, gentamicin
Tobramycin: antipseudomonal
Gentamycin: used with penicilli
Need to be injected
```
26
Streptomycin
First cure for TB
Bactericidal
Binds to 30S subunit of ribosome -> codon misreading --> inhibition
Broad spectrum
27
Types of Streptomycin
Strep S: susceptible, WT
Strep R: resistant, grows in presence of high and low strep
Strep D: streptomycin corrects defect in ribosome
28
Antibacterial spectrum of beta-lactam antibiotics vary because:
Bacteria have different PBPs
Accessibility of antibiotic to PBPs varies
Susceptibility of antibiotic to B-lactamase varies
29
Mechanisms of Resistance
Inactivation: hydrolysis (b-lactams), covalent modification (aminoglycoside)
Altering target of drug action:
Modify target to less sensitive form (b-lactam), overproduce target (vancomycin)
Reduce access of drug to target:
Reduced entry into cell, increase efflux from cell (aminoglycosides)
Failure to activate inactive precursor of drug (metronidazole) - activated by bacterial metabolic enzymes
30
Aminoglycoside resistance
Acetylation
Modified outer membrane --> reduced entry
Efflux: drug comes into cell, cell pumps it back out
Ribosomal mutation leading to reduced binding (strD)
31
Metronidazole:
Treats bacterial and parasitic infections
Obligate anaerobes
Target = nitroreductase, not present in humans
32
Intrinsic resistance
```
Aerobes - metronidazole
enterococci - sulphonamides
bordatella - penicillin
cell wall impermeabililty - vancomycin
lack of target - mycoplasmas
Chromosomal resistance genes - pseudomonas and b-lactamase
```
33
Acquired resistance
Transformation e.g. pneumococcus, commensal bacteria are source of most antibiotic resistance genes
Transduction: e.g. s.epidermidis
Conjugation: Via plasmid
34
DILUTION METHOD
GOLD STANDARD
MIC: lowest concentration that inhibits growth (last clear well)
MBC: lowest concentration that killed bacteria
35
Diffusion tests
e.g. Disc susceptibility
zone diameter = MIC, but individual to antibiotics
e.g. E test strip
Can read MIC directly off the strip where zone of inhibition intersects E strip (very reliable)
36
Latex agglutination
Cross-linking of latex particles
e.g. Rickettsia
Sample mixed with latex beads coated with antibodies - if antigen is present, it will react with antibodies causing latex beads to clump
Very specific
37
Solid phase assay
Solid phase - antigen of interest - known antibody - label
38
Capture assay
Solid phase - capture antibody - antigen of interest - specific antibody to antigen of interest - label
39
Intact Cell Mass Spectrometry
Uses whole bacteria
Detects unique biomarkers or patterns
e.g. MRSA
40
Matrix-assisted laser dsorption/ionization (MALDI-TOF)
Soft ionization technique used in mass spec
Analyses biomolecules and large organc molecules which are fragile and fragment when ionized by more conventional methods
41
Media types:
Selective: TCBS - vibrios, DCA-salmonella
Indicator: MAC - lactose fermenters
Enriched: haemophilus
Enrichment: Selenite broth
42
Immunoblot/western blot
1. separate proteins by electrophoresis
2. transfer
3. add patient's serum
4. add 2nd Ab to reveal bound Ab
Good for HIV testing
43
Sensitivity:
Measures false neg:
| true pos/total patients with disease x 100
44
Specificity:
Measures false positives:
| True neg/total patients with disease x 100
45
Bayes' theorem
Predictive value = true pos/true pos + false pos x 100
46
Recent or past infection?
Rising titre
| If IgM is present that means recent exposure as it is the early antibody produced
47
Pseudomonas
```
GN
Motile
Aerobes or facultative anaerobes
Non fermenting, non-sporing
Widespread
Low nutritional requirements
```
48
pseudomonas epidemiology
```
Widespread in moist environments
Colonize skin, muscous membranes, GIT
Leading nosocomial pathogen
Problem in CF patients
Spread by hands and fomites
Strains are intrinsically resistant to many antibiotics and weak disinfectants
```
49
Pseudomonas diseases
Superficial:
skin - wound infection, otitis externa
eye - keratitis, corneal ulcer
Deep:
pulmonary - nosocomial pneumonia, chronic infection in CF patients
UTI, osteomyelitis, septicaemia
50
Pseudomonas: adhesion and invasion
Weakly adheres to intact epithelium via flagella, pili, LPS
| Biofilm after adherence
51
Pseudomonas spread and multiplication
Flagella
Exoenzymes
Exotoxin A - inhibits phagocytosis
52
Pseudomonas + CF
Defect in CFTR --> abnormal ion transport, thickened mucus and impaired mucociliary function
53
Pseudomonas tissue damage
T3SS protein: Exoenzymes S,T,U, Y interfere with phagocytosis and enhance cytokine production
Exotoxin A: blocks protein synthesis, identical to diphteheria toxin but does not cause diphtheria because B subunit binds to diff tissue
Phospholipase: damages cell membranes, degrades surfactant
54
T/F: Beta-lactam and glycopeptide antibiotics act on the same target in bacteria and have similar mechanisms of action
FALSE:
Both inhibit cross-linking of peptide side chains during peptidoglycan synthesis BUT act on diff targets
Vancomycin - binds D-ala-D-ala
Beta-lactam inhibit penicillin binding proteins which catalyse cross-linking
55
T/F:
The selective toxicity of some antimicrobial agents depends upon the capacity of specific microbial enzymes to activate them
TRUE
56
The general antimicrobial action of metronidazole is best described as:
Attacking obligate anaerobic micro-organisms
57
T/F:
Clavulanic acid inhibits the action of certain beta-lactamases because its beta-lactam ring is resistant to their hydrolytic activity
TRUE:
| Beta-lacamases bind to clavulanic acid but cannot hydrolyse it --> INHIBITED
58
T/F:
In an antibiotic susceptibility test, the diameter of the zone around an antibiotic-containing disc gives an indication of the bactericidal activity of the antibiotic.
false: clear zone due to growth inhibition, directly related to MIC
59
Which of the following determinants does NOT influence whether a particular penicillin or cephalosporin will act upon a Gram-negative bacillus?
TYPE OF CROSS-LINKING OF PEPTIDES IN PEPTIDOGLYCAN
60
T/F:
A serological diagnosis of infection, i.e., the demonstration of a specific antibody response, is only used to confirm the diagnosis made by culturing the causative organism
FALSE: SEROLOGY CAN BE USED TO MAKE A DIAGNOSIS
e. g. 1. causative organism can't be cultured - syphlis, HIV
2. Infectious agent no longer present e.g. rheumatic fever
3. culture may not be definitive - salmonella
61
T/F:Capture” assays for specific IgM antibodies (i.e. assays which first separate total IgM from other immunoglobulins in patients' sera) are more sensitive than assays which directly detect IgM antibodies bound to the antigen of interest
TRUE:Assays with anti -Igm antibodies may have other other immunoglobulin classes which interfere with anti-IgM binding
62
T/F: Western blot can be used to detect antibodies to a specific protein in a mixture of different proteins
TRUE:
| proteins are separated by gel electrophoresis, transferred to filter and incubated with test serum
63
T/F:Enriched media are liquid media that are used to enhance the growth of some bacteria at the expense of others
FALSE:
Enriched: added nutrients
Enrichment: enhance growth at expense of other bacteria e.g. Salmonella - E.coli
64
Enzyme immunoassay (EIA) and Western blot (immunoblot) are used in conjunction for the serological diagnosis of infection with HIV. This is because:
EIA is more sensitive than Western blot, but Western blot is more specific than EIA
65
Specificity/sensitivity
According to Bayes’ theorem if a test has a 1% false-positive rate and the frequency of true-positives in the population being tested is 0.1%, then only 1 of 11 positive tests will be a true positive
66
T/F:
Pseudomonas aeruginosa produces a large variety of exoenzymes and exotoxins which contribute to its virulence, including one with an identical mechanism of action to diphtheria toxin
TRUE
67
T/F:When growing in biofilms, Pseudomonas aeruginosa exhibits a specific phenotype
TRUE: biofilms - non-motile, mucoid, more adherent, less invasive, rough, slower growing, more resistant to antibiotics
68
Which of the following antibiotic-resistant, opportunistic pathogens is LEAST likely to cause an outbreak of hospital acquired infections?
Staph epidermidis: Does not usually spread between patients
69
E.Coli subtypes
```
Serotype - O and H antigens
Multilocus sequence typing: housekeeping genes, not based on virulence factors
Phage type: useful in outbreaks
Pulsotype: RFLP
Pathotype: virulence determinants
```
70
ETEC
Watery diarrhoea
Traveller's
Adhere to small intestine by type 1 and 4 pili
Adhesin: Colonization factor antigen
HEAT labile toxin: high immunogenicity, resembles cholera toxin
heat stable toxin: resembles guanylin, low immunogenicity, 3 disulfide bonds (strong and heat stable)
71
EPEC
Bfp forms loose attachment with microvilli (plasmid mediated)
A/E (chromosomal)
T3SS injects Tir, Tir binds intimin --> close attachment
LEE pathogenicity island: T3SS, Tir, Intimin, Effector proteins (cytoskeletal rearrangement and pedestal formation)
72
EHEC
```
Foodborne
Have A/E but no bfp
Shiga toxin encoded by lysogenic phage
Noninvasive
Shiga toxin = A2B5
Adhesins: intimin, Efa1
Toxins: Shiga, EspB, haemolysin Ehx, serine protease EspP
```
73
EHEC pathogenesis
Bacteria ingested in food/water
Attach to intestinal mucosa
Produce Shiga toxins
Damage small blood vessels supplying gut, kidney
HUS: fragmented red cells, very few and large platelets
74
T/F:Commensal strains of E. coli that cause opportunistic, extraintestinal infections often possess virulence determinants which facilitate their survival in tissues.
TRUE
75
T/F:Although very different in structure, both the heat-stable and heat-labile enterotoxins of ETEC act by increasing production of cyclic nucleotides within intestinal epithelial cells and interfering with the transport of Na+ and Cl- ions across these cells.
TRUE:
ST--> gcyclase --> increase in cGMP
LT--> a cyclase --> cAMP
cGMP and cAMP block transport of Na+ and Cl- ions across absorptive epithelial cells
76
T/F:Shiga toxin is produced by enteroinvasive E. coli and Shigella species, where it is phage-encoded and leads to the production of the haemolytic uraemic syndrome (HUS).
FALSE: Shiga toxin is produced by EHEC and Shigella dysenteriae (stx1 only,not phage ncoded))
77
T/F: All major pathotypes of diarrhoeagenic E. coli can be diagnosed by PCR
TRUE
78
T/F: Apart from typical strains of enterohaemorrhagic E. coli (EHEC), which other pathotype of E. coli may occasionally produce Shiga toxin and, as a consequence, cause outbreaks of haemorrhagic colitis and the haemolytic uraemic syndrome?
enteroaggregative E.coli
79
Dukoral® is an oral cholera vaccine comprising heat-killed cells of Vibrio cholerae and recombinant B-subunit of cholera toxin. Infection with which of the following pathotypes of E. coli is most likely to be prevented by people who take this vaccine?
ETEC
