Antibiotic Resistance Flashcards

1
Q

What does the breakpoint refer to in regards to AB resistance?

A

The breakpoint is the concentration of AB that is clinically achievable in most tissues. If any bacteria require more AB than that, we consider the bacteria to be resistant.

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2
Q

What is the minimal inhibitory concentration (MIC)?

A

The minimal inhibitory concentration (MIC) is the lowest concentration of AB require to inhibit growth.

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3
Q

Antibiotic resistance evidences how natural selection works. What are the 4 distinct mechanisms used to achieve AB resistance?

A

Altered target site.
Inactivation of the antibiotic.
Altered metabolism.
Decreased drug accumulation.

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4
Q

How can a target site be altered?

A

It can arise via the acquisition of an alternative gene or a gene that encodes a target modifying enzyme. The erm gene encodes an enzyme that methylates the AB target site in the 50S ribosomal subunit allows streptococcus pneumoniae to become resistant to erythromycin.

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5
Q

How does inactivation of an antibiotic occur?

A

Enzymatic degradation or alteration renders the antibiotic ineffective. Examples include beta-lactamase (bla) and chloramphenicol acetyl-transferase (cat). ESBL and NDM-1 are examples of broad-spectrum beta-lactamases (can degrade a wide range of beta-lactams, including newest).

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6
Q

How does a bacteria altering its metabolism help it become resistant to ABs?

A

Increased production of enzyme-substrate can out-compete the antibiotic inhibitor. For example, Sulphonamides mimic PABA and compete for an enzyme that synthesizes folic acid, and increased production of PABA counteracts this.
Alternatively, bacteria can switch to other metabolic pathways, in this example reducing the requirement for PABA.

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7
Q

How can a bacteria decrease the accumulation of an antibiotic within itself?

A

Cell membrane proteins can become less permeable to ABs or increase the efflux of ABs. This stops the drug from reaching the concentration required to become effective.

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8
Q

What are some sources of antibiotic resistance?

A

Plasmids.
Transposons.
Naked DNA.

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9
Q

What are the three main ways in which bacteria can share DNA?

A

Transformation - uptake of extracellular DNA
Transduction - bacteriophages (type of virus) infect a bacteria, take up their DNA and then when infecting another bacteria deposit some of this DNA.
Conjugation - pilus on bacteria can share DNA between two bacteria.

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10
Q

How long has AB resistance been around for?

A

AB resistance has been around for a long time, there is evidence of bacteria from 30,000 years ago that had antibiotic resistance.

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11
Q

What are biofilms?

A

Biofilms matrix enclosed communities of bacteria which are highly drug-tolerant.

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12
Q

How may the location of a bacteria prevent an AB from working?

A

Some persist in human cells, which makes them hard for antibiotics to access.

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13
Q

Why may slow growth prevent an AB from working?

A

This means that they aren’t using many processes to replicate, making it hard for an antibiotic to inhibit them.

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14
Q

What are spores?

A

Spores encapsulate a bacteria, providing strong protection against heat, antiseptics and antiobiotics.

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15
Q

What are persisters?

A

Dormant organisms that don’t use the processes inhibited by ABs and thus are not inhibited by them.

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16
Q

What are some other reasons for an AB failing?

A

Inappropriate choice for organism - some antibiotics only work versus GP bacteria
Poor penetration of AB into target site
Inappropriate dose (half-life)
Inappropriate administration (oral vs IV)
Presence of AB resistance with commensal flora, the bacteria we live with, e.g. secretion of beta-lactamase

17
Q

Why may strong antibiotics increase your chance of developing a dangerous infection?

A

AB therapy can impair commensal flora, stopping competitive inhibition of dangerous bacterial growth.

18
Q

How can we combat AB resistance on a chemical level?

A

Combinations of antibiotics and inhibitors of e.g. beta-lactamase such as Augmentin can be used.
However, this is a reactive approach in response to emergence of resistance.

19
Q

How can prescribing strategies help prevent AB resistance?

A

We can temporarily withdraw certain classes of ABs so that there is no longer a selection pressure for AB resistance to that class of antibiotic, leading to a general decline in prevalence of bacteria with the gene for that AB resistance.