Hospital acquired infection and antibiotic resistance Flashcards

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1
Q

Antibiotic

A

an antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms

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2
Q

Antimicrobial

A

chemical that selectively kills or inhibits microbes (bacteria, fungi, viruses)

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3
Q

What are antibiotics made from?

A

Natural, semi-synthetic and synthetic chemicals with antimicrobial activity

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4
Q

Bactericidal

A

kills bacteria

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5
Q

Bacteriostatic

A

stops bacteria growing

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6
Q

Antiseptic

A

chemical that kills or inhibits microbes

Usually used topically to prevent infection

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7
Q

After discovery of penicillin, many other antibiotics were identified but

A

progress has slowed dramatically in recent years

Routine use of penicillin provided selective pressure for acquisition and maintenance of resistance genes

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8
Q

Minimal inhibitory concentration (MIC)

A

lowest concentration of antibiotic required to inhibit growth

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9
Q

Misconceptions at the dawn of antibiotic era

A

Resistance against >1 class of antibiotics at same time wouldn’t occur.
Horizontal gene transfer wouldn’t occur.
Resistant organisms would be significantly less ‘fit’

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10
Q

Antibiotic resistance leads to increased mortality, morbidity and cost

A

Increased time to effective therapy.
Requirement for additional approaches – e.g. surgery.
Use of expensive therapy (newer drugs).
Use of more toxic drugs e.g. vancomycin.
Use of less effective ‘2nd choice’ antibiotics

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11
Q

Give 2 examples of Beta Lactams and their mode of action

A

Penicillin and Methicillin

Interfere with synthesis of peptidoglycan component of bacterial cell wall by binding to penicillin-binding proteins.

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12
Q

Name 5 gram negative antibiotic resistant bacteria

A
Pseudomonas aeruginosa
E. Coli (ESBL) and E. coli, Klebsiella spp (NDM-1) 
Salmonella spp. (MDR)
Acinetobacter baumannii (MDRAB)
Neisseria gonorrhoeae
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13
Q

Name 5 gram postive antibiotic resistant bacteria

A
Staphylococcus aureus (MRSA, VISA)
Streptococcus pneumoniae
Clostridium difficle
Enterococcus spp (VRE)
Mycobacterium tuberculosis (MDRTB, XDRTB)
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14
Q

Name 5 antibiotics used therapeutically

A
Aminoglycosides
Rifampicin
Vancomycin
Linezolid
Daptomycin
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15
Q

Aminoglycosides

A

Bactericidal
Target and corrupt protein synthesis leads to damage in cell membrane
Toxicity limits use

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16
Q

Rifampicin

A

Bactericidal
Targets RpoB subunit of RNA polymerase
Makes secretions (tears) red

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17
Q

Vancomycin

A

Bactericidal.
Targets Lipid II component of cell wall biosynthesis, and wall crosslinking via D-ala residues
Toxicity limits use

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18
Q

Linezolid

A

Bacteriostatic.
Inhibits initiation of protein synthesis by binding to 50S rRNA subunit.
Gram-positive spectrum of activity

19
Q

Daptomycin

A

Bactericidal.
Targets bacterial cell membrane.
Gram-positive spectrum of activity.
Toxicity limits dose

20
Q

The large number of differences between mammals and bacteria allow antibiotics to be

A

Selectively toxic

21
Q

4 Mechanisms of antibiotic resistance

A

Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation

22
Q

Antibiotic resistance: Altered target site

A

Acquisition of alternative gene or a gene that encodes a target-modifying enzyme

23
Q

Antibiotic resistance: Inactivation of antibiotic

A

Enzymatic degradation or alteration, rendering antibiotic ineffective

24
Q

Antibiotic resistance: Altered metabolism

A

Increased production of enzyme substrate can out-compete antibiotic inhibitor

25
Q

Antibiotic resistance: Decreased drug accumulation

A

Reduced penetration of antibiotic into bacterial cell (permeability) and/or increased efflux of antibiotic out of cell
Drug does not reach concentration required to be effective

26
Q

Example of bacteria where multiple resistance mechanisms exist

A

N. gonorrhoea

27
Q

Macrolides

A

Prevent protein synthesis

Used for Gram-positive and some Gram-negative infections.

28
Q

what do macrolides target?

A

Targets 50S ribosomal subunit preventing amino-acyl transfer and thus truncation of polypeptides

29
Q

Quinolones

A

Synthetic, broad spectrum, bactericidal.

30
Q

What do quinolones target?

A

Target DNA gyrase in Gm-ve

Target topoisomerase IV in Gm+ve

31
Q

Sources of antibiotic resistance?

A

Plasmids
Transposons
Naked DNA

32
Q

How are plasmids sources of antibiotic resistance?

A

extra-chromosomal circular DNA, often multiple copy. Often carry multiple AB resistant genes: selection for 1 maintains resistance to all

33
Q

How are transposons sources of antibiotic resistance?

A

Integrate into chromosomal DNA.

Allow transfer of genes from plasmid to chromosome and vice versa

34
Q

How is naked DNA a source of antibiotic resistance?

A

DNA from dead bacteria released into environment

35
Q

3 modes of spread of antibiotic resistance

A

Transformation
Transduction
Conjugation

36
Q

List 5 non-genetic mechanisms of resistance/ treatment failure to antibiotics

A
Biofilm: form large sticky masses
Intracellular location: hide inside cells 
Slow growth
Spores
Persisters: dormant
37
Q

List 5 other reasons for antibiotic treatment failure

A

Inappropriate choice for organism
Poor penetration of AB into target site
Inappropriate dose (half-life)
Inappropriate administration (oral vs IV)
Presence of AB resistance within commensal flora e.g. secretion of beta-lactamase

38
Q

Measuring resistance

A

Swabs streaked out onto diagnostic agar to identify causative organism.
Pathogen streaked over a plate and over-laid with AB-containing test strips or discs.
Also could do broth micro-dilution and PCR detection of resistance genes

39
Q

Hospitals provide… for antibiotic resistance

A

Strong selective pressure as lots of infected people receiving high doses of antibiotics

40
Q

List 7 risk factors for hospital acquired bacterial infections

A

High No. of ill people (some immunosuppressed)
Crowded wards
Presence of pathogens
Broken skin: surgical wound/IV catheter
Indwelling devices: intubation
AB therapy may suppress normal flora
Transmission by staff: contact with multiple patients

41
Q

In what respect do commensal organisms outcompete pathogens in health?

A

Adhesion
Metabolism
Growth
So pathogen can’t colonise at levels sufficient for infection

42
Q

How are commensal flora effected by antibiotics?

A

Commensal flora may be impaired

43
Q

List 4 strategies to address resistance

A

Strict prescribing
Reduce use of broad spectrum ABs
Combination therapy
Quick identification of infection caused by resistant strains

44
Q

Give 2 strategies to overcome resistance

A

Modification of existing ABs

Combinations of AB + inhibitor