week 1 Flashcards
1
Q
define antibiotics?
A
chemical products of microbes that inhibit or kill other organisms
2
Q
what is antimicrobial agents? Give examples
A
it is a umbrella term of agent that kills a wide rang of different things. Antibacterial, antifungal and antiviral
3
Q
what are the different types of antimicrobial agents?
A
antibiotics, synthetic compounds with similar affects or semi synthetic compounds
4
Q
what are semisyntheti compounds?
A
are modified versions of antibiotics.
They have different antimicrobial activity/spectrum, pharmacological properties or toxicity
5
Q
what is Bacteristatic and what does it affect?
A
it inhibits bacterial growth –> stops the growth of bacteria and therefore allows the human immune system to destroy the bacteria.
It is a protein synthesis inhibitor
6
Q
what is bacteriacidal? What does it affect?
A
it kills the bacterial and affect cell wall-active agent
7
Q
what is minimum inhibitory concentration MIC?
A
Minimum concentration of antibiotic at which visible growth is inhibited
8
Q
can someantibiotic act as both bacteristatic and bacteriacidal? Explain
A
yes at low concentration the antibiotic can be bacteristatic but then at high become bacteriacidal
9
Q
what is Synergism?
A
the activity of 2 antimcrobials together is greater than activity given seperately
10
Q
What is antagonism?
A
when one agent diminishes the activity of another?
11
Q
what is Indifference in terms of antibiotics?
A
the addition of antibiotic have no affect on the other antibiotic activity
12
Q
what is the treatment of streptococcal endocarditis? What type of interaction is it?
A
β-lactam/aminoglycoside combination therapy
Synergism interaction
13
Q
what are antibacterial target types ?
A
molecules, structures and enzymes?
14
Q
what are structures?
A
things bigger than molecules
15
Q
what are the two types of selective toxicity?
A
Tackle a Target not present in human host but in the bacteria
Tackle a Target significantly different in the bacteria compared to the human host
16
Q
what are the main 5 antibacterial targets?
A
Cell wall Protein synthesis DNA synthesis RNA synthesis Plasma membrane
17
Q
what is bacterial cell wall made up of?
A
peptidoglycan
18
Q
do animals have cell wall?
A
no
19
Q
what type of bacteria have cell wall?
A
both gram positive and gram negative bacteria have cell walls
20
Q
what is peptidoglycan made up of?
A
Polymer of glucose-derivatives, N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG)
21
Q
why is antibiotics targeting cell walls so effective?
A
all bacteria have cell wall while humans do not
22
Q
why do bacteria need cell wall?
A
Need cell wall for protection and is constantly remolding –> essential for their life
23
Q
what are the 2 classes of cell wall inhibitors?
A
B lactams and Glycopeptides
24
Q
what is the most common type of B lactams?
A
penicillin
25
what was the first true B lactam antibiotics?
Benzylpenicillin ( Penicillin G)
26
what do all B lactam antibiotics contain in their structure?
B lactam ring
27
what does B lactam ring contain?
Four-membered ring structure (C-C-C-N)
| Structural analogue of D-alanyl-D-alanine
28
how do B lactam antibiotics work?
They intefere with penicillin binding proteins. These are Transpeptidases enzymes that are invovled in peptideoglycan cross linking ( cell walls)
29
what is the first oral B lactam?
phenoxymethyl penicillin (penicillin V).
30
what was the first antibiotic to be active against the family of Enterobacteriaceae?
Ampicillin
31
what two B lactam can only be given parenterally?
Benzylpenicillin and ampicillin
32
what does parental dosage mean?
are intended for administration as an injection or infusion
33
what is the oral equivilant of Ampicillin ?
amoxycillin
34
what is Meticillin ?
anti-staphylococcal penicillin.
35
what is key about the structure of meticillin?
it has a side chain that prevents the hydrolysis of the drug by staphylococcal b-lactamase
36
what two drugs have replaced meticillin?
cloxacillin and flucloxacillin
37
what are the 4 main key antibiotics underneath B lactam antibiotics?
Penicillins
Cephalosporins
Carbapenems
Monobactams
38
give me examples of penicillin and what is the most common type? What type of spectrum does it have?
Benzylpenicillin,
amoxicillin --> most common
flucloxacillin
Relatively narrow spectrum
39
give me examples of Cephalosporins and what is the most common type? Does it cover gram negative bacteria?
Cefuroxime--> common
ceftazidime
Broad spectrum
covers gram negative bacteria
40
give me examples of Carbapenems?
Meropenem, imipenem
| Extremely broad spectrum
41
what type of antibiotics is used when allergic to penicillin? give example of this type of antibiotic? what Type of bacteria is it active too?
Monobactams
type of monovactams is: Aztreonam
Gram-negative activity only
42
give me examples of glycopeptides antibiotics?
Vancomycin --> more common
| teicoplanin
43
how does glycopeptides work?
Inhibit binding of transpeptidases and thus peptideoglycan cross-linking
44
what type of bacteria can glycopeptides be active against?
only active against gram positive bacteria.
| Because it cannot penetrate the outer membrane porins of gram negative bacteria
45
what is Ribonucleoprotein complexes main up of?
2/3rds RNA and 1/3rd protein
46
what is mRNa made up of?
50s (large) subunit and 30s (small) subuinte that combine to form the 70s initation complex
47
give example of Aminoglycosides
Aminoglycosides
| Examples are: Gentamicin, amikacin
48
how does Aminoglycosides work?
Bind to 30S ribosomal subunit
49
what is the severe side affect of gentamicin?
it is a nephrotoxic
50
what is nephrotoxicity?
it is toxic to the kidneys
51
give examples of Macrolides, Lincosamides, Streptogramins (MLS)
Erythromycin, --> most common type
| clarithromycin (macrolides)
52
what is alternative option to erthromycin?
clindamycin--> less side affects
53
how does MLS antibiotics work?
Bind to 50S ribosomal subunit1
Blockage of exit tunnel
Inhibit protein elongation --> prevent the addition of more peptides
54
give examples of tetracyclines?
tetracylcine and deoxytetracycline
55
how does tetracyclines work?
bind to 30s and prevent the translation of tRNA with rRNA
56
give examples of Oxazolidinones?
Linezolid
57
how does Linezolid work?
Inhibits initiation of protein synthesis
Binds to 50S ribosomal subunit
Inhibits assembly of initiation complex
May also bind to 70S subunit
58
what antibiotic prevents folic acid production?
Trimethoprim and sulfonamides
59
together what are Trimethoprim and sulfonamides called?
co-trimoxazole
60
why is folic acid inhibited by antibiotics?
it is a precusor for purin synthesis
61
what is Trimethoprim?
Dihydrofolate reductase
62
what does Sulfonamides directly inhibit and why?
Dihydropteroate synthetase because it is the enzyme catalyses the first step in folic acid synthesis.
63
how do bacteria synthesise folic acid?
from para-aminobenzoic acid
64
what is trimethoprim mainly used for?
used mainly for UTI's
65
are together Trimethoprim and sulfonamides together effective against bacterial infection?
in vitro they are but not in real life --> no longer really used
66
why is sulphonamides rarely used?
It is highly toxic and become highly resistant
67
when is co-trimoxazole used?
treatment of some protozoal infections and, increasingly, to treat resistant bacterial infections
68
how does Quinolones and fluoroquinolones work?
Inhibit one or more of two related enzymes:
DNA gyrase and topoisomerase IV
Involved in remodelling of DNA during DNA replication
69
give me examples of Quinolones and fluoroquinolones
Nalidixic acid, ciprofloxacin, levofloxacin
70
give me a example of RNA synthesis inhibitors?
Rifampicin
71
how does Rifampicin work?
RNA polymerase inhibitor
| which prevents the synthesis of RNA
72
what type of antibiotic is Colistin ?
it is a plasma membrane agent that affect gram negative bacteria
73
what line is colistin used in?
last option as it is very toxic
74
what type of antibiotic affects plasma membrane of gram positive bacteria?
Daptomycin
75
how does Daptomycin?
destruction of cell membrane
76
what is the most common problem with B lactam antibiotics?
people are allergic to them
77
common adverse affects of antibiotics?
Nausea, vomiting, headache, skin rashes etc.
| Allergic reactions
78
how do bacteria become resistant?
through evolution are bacteria that are resistant to antibiotics and in right enviroment grow and spread
79
what type of infections can be caused by antibiotic infection? secondary?
Fungal infection --> oral or vaginal thrush
80
give example of funcal infection that can be caused by antibiotics?
Superficial and invasive candidiasis
81
what is the adverse effects of Aminoglycosides?
Can cause renal impairment if accumulated so need to be stopped --> reversible
however can cause irrevesible otoxicity
82
what is otoxiticy?
toxic to the ear --> specifically the cochlea or auditory nerve
83
what percentage off people have a general rash due to B lactam?
1-10%
84
what percentage of people have anaphylatic shock due to B lactam?
0.01%
85
what type of antibiotic is Linezolid? what is its adverse afect?
it is a protein synthesis inhibitor and can cause bone marow depression if used for long time
86
what can happen if intollerant to B lactam?
Nausea, diarrhoea, headache etc.
87
what occurs in minor allergic reaction to B lactam?
skin rash
88
what occurs in severe allergic reaction to B lactam?
Anaphylaxis, urticaria, angio-oedema, bronchospasm, severe skin reaction (Stevens-Johnson syndrome)
89
what type of antibiotics are safe to use when someone ahs non-severe penicillin allergy
carbapenems
| cephalosporins
90
what type of antibiotic is safe to use with any pencillin allergy?
aztreonam
91
explain the structure of aztreonam?
it is a Monobactam with a single ring rather than a double ring
92
what is the most common cause of antibiotic associated diarrhoea?
C.difficile
93
what does C.difficile produce?
toxin A and B
94
What happens that allows C.difficile to cause sickness?
be the destruction of normal colonisation resistance ( normal bacteria)
95
what accounts for C.diff clinical features and transmissibility?
spore production
| enterotoxin
96
what strain of C.diff is of cause severe cases?
Hypervirulent strain 027
97
what 4 antibiotics are most common cause of C.diff?
Co-amoxiclav (amoxicilin-clavulanate) --> B lactam
Cephalosporins --> B lactam
Ciprofloxacin --> inhibit DNA synthesis
Clindamycin --> MLs antibiotics
98
what are less common causes of C.diff?
Benzylpenicillin, aminoglycosides, glycopeptides
| Piperacillin-tazobactam (despite broad-spectrum)
99
what are the stages of antibiotic use?
emperic therapy
target therapy
susceptibility guided therapy
100
what is emperic therapy based on?
predicted susceptibility of likely pathogens
| likely antimicrobial properties
101
what information is available at the time of emperic therapy?
organ system involved
| exogenous or endogenous infection is likely pathogen
102
what information is available at the time of target therapy?
infection organism
| likely antimicrobial susceptibility
103
what is target therapy based on?
predicted susceptibility of infected organisms
| local antimicrobial policies
104
what is susceptibility guided therapy based on?
susceptibility testing results
105
what should be done when first treating a person with antibiotics? start smart
Only start antibiotics if there is clinical evidence of bacterial infection
Use local guidelines
Document indication, duration or review date
Obtain cultures first
Use single dose antibiotics for surgical prophylaxis
106
what should be done when treating a person after 48 hours? focus
Stop antibiotics if there is no evidence of infection
Switch antibiotics from intravenous to oral
Change antibiotics – ideally to a narrower spectrum – or broader if required
Continue and review again at 72 hours
Outpatient Parenteral Antibiotic Therapy (OPAT)
107
what is Flucloxacillin used for?
Staphylococcus aureus (not MRSA
108
what is Benzylpenicillin used for?
Streptococcus pyogenes
109
what is Cephalosporins used for ? Avoid which age group?
Gram-negative bacilli
| avoid elderly
110
Metronidazole used for?
anaerobes
111
Vancomycin used for?
Gram-positives (MRSA)
112
Colistin used for?
last option for multi-resistant Gram-negatives
113
To treat infections in CSf what antibiotics have good avialability?
β-lactams
| Good availability in presence of inflammation
114
To treat infections in CSf what antibiotics have poor avialability?
Aminoglycosides and vancomycin
115
to treat infections that are in the urine what antibiotics have good avialability?
Trimethoprim and β-lactams
116
to treat infections that are in the urine what antibiotics have poor avialability?
MLS antibiotics
117
what is needed to be considered in terms of Pharmacodynamic ?
time and concentration dependent
118
reasons for combination therapy?
To reduce resistance
To increase efficacy
Synergistic combination may improve outcome
β-lactam/aminoglycoside in streptococcal endocarditis
To provide adequately broad spectrum
119
what does Antibiotic era mean?
Term used to describe the time since the widespread availability of antibiotics to treat infection
120
what does post antibiotic era mean?
term used when there is widespread antibiotic resistance that has reduced the availability for antibiotics to treat infections
121
What does MRSA stand for?
Meticillin-resistant Staphylococcus aureus
122
what antibiotics is enterococci resistant to?
Vancomycin/glycopeptide
123
what is Enterobacteriaceae resistant to?
amoxicillin, ciprofloxacin, gentamicin, carbapenems
124
what is Pseudomonas resistant to?
ceftazidime, carbapenems
125
how does antibiotic resistance affect emperic therapy?
risk of under treatment as the antibiotic has no affect or the need to use overal broad spectrum antibiotics that can cause resistance
126
how does antibiotic resistance affect target therapy?
may have to use alternative treatment that is: toxic, last line or expensive
127
why is sensitive testing important?
1) transmision from emperic to target therapy
2) Shows whether or not antibiotic is working and therefore if a alternative antibiotic should work.
3) explain why antibiotic is failing
4) Also shows alternative oral antibiotics when IV no longe required
128
what does MDR-TB) stand for?
Multi-drug resistant tuburculosis
129
what does XDR-TB stand for?
Extremely-drug resistant tuberculosis
130
what does ESBL stand for?
Extended-spectrum β-lactamase-producing Enterobacteriaceae
131
In terms of abx sensitivity testing what is meant by a 'breakpoint level'?
The breakpoint level is a known value. Its the concentration of that abx which can feasibly be available in the body
132
what are the basic principle of sensitive testing?
1)Culture of micro-organism in the presence of antimicrobial agent -->Solid or liquid media
2)Determine whether MIC is above a predetermined “breakpoint” level --> High enough to kill the organism
Sustained in the body for long enough using practicable dosing regimens
133
what are the steps in disck susceptible testing?
1) “Clinical interpretation
2) Read and interpret results
3) Incubate
4) Add antibiotics
5) Add organism
134
what are the steps in Liquid media - microtitre plate susceptibility testing?
1) Add antibiotic
2) . Add organism
3) Incubate
4) Read MIC
5) Compare with breakpoint
6) Interpret result
135
what are the limitations of sensitive testing?
1) Certain organisms are “clinically resistant” to antimicrobial agents even where in vitro testing indicates susceptibility
2) The infection may not be caused by the organism that has been tested
3) The correlation between antimicrobial sensitivity and clinical response is not absolute
136
what are the 6 ways that a bacteria can become antibiotic resistance?
```
No target – no effect
Reduced permeability – drug can’t get in
Altered target – no effect
Over-expression of target – effect diluted
Enzymatic degradation – drug destroyed
Efflux pump – drug expelled
```
137
give examples of bacteria that have become antibiotic resistnace by reducing permeability?
Vancomycin:Gram-negative bacilli -->Gram-negatives have an outer membrane that is impermeable to vancomycin
Gentamicin:anaerobic organisms -->Uptake of aminoglycosides requires an O2 dependent active transport mechanism
138
how does MRSA become resistant to B lactams?
target alteration --> Altered penicillin-binding protein (PBP2’, encoded by MecA gene) does not bind β-lactams
139
how does Vancomycin-resistant Enterococcus become resistant to vancomycin?
Altered peptide sequence in Gram-positive peptideoglycan (D-ala D-ala --> D-ala D-lac)
Reduces binding of vancomycin 1000-fold
140
how does Gram-negative bacilli become resistant to Trimethoprim?
Mutations in dhr (dihydrofolate reductase gene)
141
give examples of enzyme degredation?
Penicillins and cephalosporins: β-lactamases (including ESBLs and NDM-1)
Gentamicin: aminoglycoside modifying enzymes
Chloramphenicol: chloramphenicol acetyltransferase (CAT)
142
give examples of drug efflux?
Multiple antibiotics, specially in Gram-negative organisms
| Antifungal triazoles and Candida spp.
143
by how many genes is resistant mechenism coded by?
usually just by a single gene
144
give example of antibiotic modified enzymes that are encoded by a single gene? What antibiotics are they resistant to?
Β-lactamases (including ESBL -->Resistant to Penicillins, cephalosporins
Aminoglycoside-modiying enzymes --> resistant to Gentamicin
145
is it one feature or number of features that make a organism resistant to antibiotic?
usually a number of features
146
where is resistant gene encoded?
in plasmids--> circular strand of transferred within species and less commonly between species, mainly by conjugation
147
Which 2 structures enable horizontal transmission of resistance genes?
transposons and integrons
148
What is meant by a cassette and transponsons and integrons?
transponsons and integrons are dna sequences designed to be transferred from plasmid to plasmid and/or from plasmid to chromosomes - they often contain a cassette with multiple resistance genes
149
what is Vertical transfer of resistance?
Chromosomal or plasmid-borne resistance genes transferred to daughter cells on bacterial cell-division
150
describe the steps for horizontal transfer?
1) gene on plasmid 2) gene may stay on plasmid and/or integrate into the chromosome 3) plasmid transferred between organisms by conjugation
151
describe the steps for verticle transfer?
1) gene on plasmid 2) gene may stay on plasmid and/or integrate into chromosome 3) 'new' organism has abx resistance 4) abx resistance transferred on cell division
152
what is the consequence of antibiotic exposure?
1) sensitive strains exposed to abx at sub lethal conditions eg. clinical and agricultural 2) Chance of survival will be enhanced by development of resistance (spontaneous mutation, aquisition of resistance genes) 3) Resistant strain will out compete sensitive strains 4) Resistance perpetuated by vertical transfer 5) Mixtures of sensitive and resistant strains (eg. normal gut flora) exposed to abx - resistant strains have a survival advantage and will become the dominant colonising strains, subsequent endogenous infection more likely to be caused by resistant strains
153
what happens when sensitive and resistant strains are exposed to antibiotics?
Resistant strains will have survival advantage and will become the dominant colonising strains
Subsequent endogenous infection more likely to be caused by resistant strains
154
give example of sensitive and resistant strains in hospital?
normal flora when exposed to antibiotics
155
how do you avoid antibiotic resistance?
Never use an antibiotic unless absolutely necessary
Always use the most “narrow-spectrum” agent available
Use combination therapy if indicated
Be willing to consult expert information sources
