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CP - JL > Core Microbiology - Part 1 > Flashcards

Core Microbiology - Part 1 Flashcards

1
Q

What do bacteriostatic antibiotics do

A

inhibit bacterial growth e.g. protein synthesis inhibitors

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2
Q

What is MIC

A

The minimum concentration of an antibiotic at which VISIBLE growth is inhibited

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3
Q

What is synergism?

A

Activity of two microbial together is greater than seperately e.g. B lactams/aminoglycosides for streptococcal endocarditis

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4
Q

What is selective toxicity?

A

choosing targets that are not present or are significantly different to the human host

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5
Q

Antibiotic targets

A

Call wall, DNA synthesis, RNA synthesis, plasma membrane, protein synthesis

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6
Q

Major component of cell wall

A

Peptidoglycan

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7
Q

Peptidoglycan structure

A

NAM cross linked by NAG

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8
Q

Why is the cell wall a good antibiotic target?

A

Not present in humans

Constantly remodelled

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9
Q

What are the 2 cell wall synthesis inhibitor groups

A

B-lactams

Glycopeptides

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10
Q

What are the B-Lactam antibitoics

A

Contain the B-lactam ring (C-C-C-N)

Target cell wall synthesis

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11
Q

What is the B-lactam ring a structural analogue of?

A

The D-alanyl D-alanine residue that hang of N

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12
Q

How do B-lactam antibitoics word

A

Interferes with function of penicillin binding proteins as trans peptidase enzymes are involved in the cross linking of peptidoglycan

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13
Q

4 group of beta lactam antibiotics

A

Penicillins - narrow
Carbapenems - broad
Cephalosporins - v broad
Monobactams - gram -ve activity only

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14
Q

What are glycopeptides

A

Large molecules that bind directly to terminal D-alanylD-alanine on NAM
Inhibit transpeptidases and peptidoglycan crosslinking
They inhibit cell wall synthesis

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15
Q

What do glycopeptides act on

A

gram +ve activity only as unable to penetrate the second outer layer in gram -ve bacteria

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16
Q

What ribosomes are used in bacteria protein synthesis

A

70S (have 50S and 30S subunits)

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17
Q

Name the groups of protein synthesis inhibitors

A 
Aminoglycosides
Macrolides, Lincosamids, Streptogramins (MLS)
Tetracyclines
Oxazolidunones
Mupirocin and Fusidic Acid
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18
Q

How do aminoglycosides work

A

bind to 30S subunit

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19
Q

How do MLS work

A

bind to 50S subunit –> blocks exit tunnel of ribosome preventing protein elongations

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20
Q

How do Tetracylines work

A

Bind to 30S sub unit

Interferes with tRNA and rRNA binding hence prevents RNA translation

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21
Q

How to oxazolidinone work

A

Bind to 50S subunit –> inhibit assembly of the initiation complex!

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22
Q

Name the DNA Synthesis INhibitors

A

Trimethoprim and Sulphonamides

Quinolone and fluoroquinlones

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23
Q

What is folate acid a precursor to

A

Purine synthesis

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24
Q

How does trimethoprim work

A

Dihydrofolate reductase inhibior

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25
How does sulphonamides work
Dihydropteroate synthetase inhbitor | But toxicity and resistance
26
What do fluorquinolones and quinolones act via
DNA gyrase andn topoisomerase IV | These are involved in the remodelling of the DNA
27
How do RNA synthesis inhibitors work?
RNA polymerase inhibitor --> Prevent the synthesis of mRNA | Rifampicin
28
Name the 2 plasma membrane agents
Collision (gram -Ve activity only) - fairly toxic | Daptomycin (Gram +ve activity only)
29
How does daptomycin work
Cyclic lipo-peptides | Lipphilic tail enters the cell membrane
30
Main adverse effects of aminoglycosides
Reversible renal impairment Irreversible Ototoxicity TDM indicated
31
Main adverse affects ofo B-lactams
Allergic reactions | Steven Johnson syndrome is a severe skin reaction
32
Main adverse effects of Linezolid
Bone marrow depression
33
What is safe to use with a mild penicillin allergy
Cephalosporins and carbapenems
34
What is safe to use with any penicillin allergy
Aztreonam but be careful if allergic to ceftazidime due to similar side chains
35
What is the % of C.diff in normal flora
20%
36
What are the four common precipitating factors before C.Diff
Co-amoxiclav Cephalosprins Ciprofloxacin Clindamycin
37
What do we use to treat CSF infections
Beta lactase --> good availability in the presence of inflammation Amino glycosides and vancomycin have poor availability
38
What do we use to treat Urine infections
Trimmethoprim and beta lactams have good availabiility | MLS have poor availability
39
What does concentration dependent mean
Determinant of bacterial killing is the factor by which the concentration exceeds the MIC Inhibit intermittently to achieve high peaks
40
What does time dependent mean
Main determinant of killing is the amount of time the antibiotic concentration exceeds the MIC Administer frequently to maintain high levels
41
Why use combination therapy?
Increases efficacy Provide broad spectrum Reduce resistance
42
What is the post antibiotic era1
the term used to describe the time after widespread antibiotic resistance
43
What is RMSA resistant to
Penicillin | Penicillinase conveys the resistance
44
What is CPE
Carbapenemase producing eneterbactericaea
45
What are enterebacteriaceae resistant to
amoxicillin, ciprofloxacin, gentamicin, carbapenems
46
what are ESBL
Extended spectrum beta lactamase producing enterebactericaeae
47
What is sensitivity testing used for
Allows for the transition from empiric to targeted antibiotics Basic principle to measure zone of inhibition of antibiotic Liquid media provides more accurate measure of MIC
48
What do we have determine about the MIC in sensitivity testing
If the MIC is above a predetermined breakpoint level i.e. high enough to kill the organism and sustained in the body for long enough using practicable dosing regimes
49
Limitation of sensitivity testing
Correlation between antimicrobial sensitivity and clinical response is not absolute Certain organisms are clinically resistant despite being effective invitro
50
What resistance gene is expressed in vivo in response to beta lactam antibitoics in eneterbactericaea infections
Amp-C Beta lactamase gene in enterobactericaea
51
Resistance mechanisms
``` No target Reduced permeability Altered target Over expression of target Enzyme degradation of antibiotic Efflux pump to expel the drug ```
52
What infection do we suspect after surgery if still not getting better despite broad spectrum antibiotics
Candida
53
What is vancomycin impermeable to?
The outer layer on gram -ve bacteria
54
What is the uptake of aminoglycosides dependent on?
An oxygen dependent active transport (hence doesn't work on anaerobes)
55
Why is MRSA resistant to penicillin
Altered penicillin binding protein (encoded for by the MecA gene)
56
Why is VRE resistant to vancomycin
Altered peptide sequence in gram +ve bacteria D-ala D-ala to D-ala D-lac Reduces vancomycin binding 1000 fold
57
What degrades pencillins and cephalosporins
B-lactamases (produced by ESBLs and NDM-1)
58
How do efflux pumps convert resistance?
Drug expelled before antibiotic can interact with the target | Occurs with multiple antibiotics especially in gram -ves
59
What are resistance genes coded in
Plasmids
60
What enables the horizontal transfer of resistance
Transposons and intergrons
61
How to avoid problems with antibiotics
Only use when necessary Use most narrow spectrum available Use combination therapy if indicated be willing to consult books and expert sources for information
62
Acute viral infections
mumps, hep A, influenza, measles
63
Acute viral infections have what type of genetic material
DNA
64
Chronic viral infections have what type of genetic material
RNA
65
Chronic latent viral infections
HSV, cytomegalovirus
66
Chronic persistent viral infections
HIV, Hep B, Hep C
67
Structure of cirus
Nucleic Acid Protein Coat With or without envelope They are obligate intracellular parasties
68
What are LTR
Long terminal repeats essential for incorporating virus into the genome
69
Virus replication
Attachment, cell entry, uncaring, early proteins produced and viral enzymes, replication, late transcription/translation produces structural enzymes, virus assembly, virus release
70
Polymerases in eukrayotes and DNA viruses
DNA to DNA | DNA to RNa
71
polymerases in RNA viruses
RNA to RNA
72
Polymerases in retroviruses
RNA to DNA
73
What is Azidothymidine (AZT)
Anti-cancer drug also inhibits HIV replication | NRTI - inhibits reverse transcriptase
74
2 types of NRTIS
``` Pyrimidine analogus (zidoviduine and lamivudine) Purine analogues (abacavir and tenofovir) ```
75
Why ae NRTIs also effective against HBV
as it also contains the reverse transcriptase enzymes
76
What are protease inhibitors
Act as aspartate protease inhibitor in HIV
77
What does ritonavir do?
Helps boost the level of other protease inhibitors
78
Newer HIV drugs
Fusion inhibitors --> stop viruses fusing with membrane (enfuvritide) Chemokine receptor agonists (prevent HIV entering the cell) e.g. Maraviroc (CCR-5)
79
What is HAART
Highly active retroviral treatment
80
What does HAART consist of
2 NRTI's and 1 NNRTI or Protease inhibitor
81
When do we give HAART
When CD4 count start to fall and taken life long | But problems with liver toxicity
82
What mutation results in lamivudine resistance
M184V mutation
83
What can cure people with HIV
CCR5 delta 32 allelle!
84
Treatment of Hep C
Interferons and ribvirin
85
2 type of fungi
Moulds/filamentous or yeast
86
How do moulds/filmentous divide
By spores - have hairy micellium
87
How do yeasts divide
by budding - produce buttery colonies
88
What type of fungi cause disease in humans
only micro
89
Cryptococcus and candida are what type of fungi
yeast
90
athletes foot is what type of fungi
filamentous
91
Where is ergosterol found
fungal cell membranes
92
what does ergosterol do?
Regulates membrane permeability --> required for normal growth and function of cells
93
What are B-1,3, glucans
Large polymers of UDP glucose not in human cells | Forms fibrous netweorks on the inner surface of cell walls
94
What synthesizes B-1,3 glucans
B-1,3,-glucan synthase
95
What are the 4 anti fungal classes
Polyenes Allyamines Azoles Echinocandins
96
How do polyenes work
Associate with ergosterol -- > form pore-like aggregates in cell membrane Loss of membrane integrity and leakage of potassium causing cell death
97
Range of amphotericin B
Most fungi of medical importance
98
Problems of amphotericin B
Allergic reactions and nephrotoxicity! hence made lipid associated amphotericin B to reduce nephotoxicity!
99
Amphotericin B administration
Paraenterally
100
Nyastin Use
Superifical infections --> oral/vanginal candidiasis as too toxic for systemic use
101
How do allyamines work
Inhibit squalene epoxidase preventing ergosterol synthesis
102
Allyamines adverse effects
Liver toxicity they are broad spectrum though
103
Allyamines use
Dermatophyte infections --> topical or systemic for tinea captious and onychomycosis
104
How do azoles work
Lanesterole demethylase inhibitos
105
Types of azoles
Imidazole - 2 nitrogen atoms, toxic so rarely used | Triazoles - 3 nitrogen atoms, less toxic
106
Activity of azoles
Essestially broad for fungi
107
What does fluconazole now have activity against
aspergillus
108
Adverse affects of azoles
Hepatotoxicity | Drug interaction --> inhibits cytochrome P450 enzymes
109
Use of imidazoles
Superficial infections and candidiases
110
Triazole uses
Systemic infections Aspergilliosis Candidiasis (fluconazole)
111
How do echinocandins work
B-1,3, glucan synthase inhibitos cause abnromal cell wall
112
What do echinocandins work on
Aspergillum and candida BUT misses mouulds and cryptooccus | Has minimal side effects
113
Use of echinocandins
Systemic infections
114
What is 5-fluorocytosine
A synthetic analogue of cytosine
115
How does 5-flurocytosine enter fungal cells
Using cytosine premise enzyme
116
How foes 5-fluorocytosine work
Converted to 5-fluorouracil and 5-fluorodeoxyuridine monophosphate Inhibits RNA/protein syntehss and DNA synthesis
117
5-fluorocytosine spectrum of activity
Candida and cryptococcus
118
Adverse effects of 5-fluorocytosine
Bone marrow suppression --> 5-fluorouracil is an anticancer drug
119
Treatment of cryptoccus
Amphotericin B and 5-flurorcytosine
120
How does griseofulvin work
Inhibits fungal mitosis | Treats dermatophytes with mental adverse effects
121
Use of griseofulvin
Treats dermatophyte infections in children that require systemic treatment
122
What drugs require TDM
Itraconazole 5-fluorocytosine Voriconazole

CP - JL (14 decks)

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