Nosocomial infection and antibiotic resistance Flashcards

1
Q

What is an antibiotic?

A

an antimicrobial agent produced by a micro-organism that kills or inhibits other micro-organisms

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2
Q

What are most antibiotics produced by?

A

soil-dwelling fungi or bacteria

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3
Q

What is minimal inhibitory concentration?

A

lowest concentration of antibiotic required to inhibit growth

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4
Q

What is resistance?

A

when an antibiotic concentration required to inhibit growth is above the breakpoint (clinically-achievable conc.)

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5
Q

How does antibioic use contribute to resistance strains?

A

provides selective pressure for the acquisition and maintenance of resistance genes

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6
Q

Why are gram negative bacteria generally harder to treat/

A

harder to find antibiotics as outer membrane provides very good barrier of protection

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7
Q

What are the main gram negative ressitant bacterial pathogens?

A

pseudomonas aeruginosa; E.coli- ESBL and NDM-1; salmonella; acinetobacter baumanii; neisseria gonorrhoeae

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8
Q

What are the main gram positive resistant bacterial pathogens?

A

s. aureus; strep pneumo; c.diff; enterococcus; M.tb

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9
Q

What infections is pseudomonas involved in?

A

CF; burn wound infections

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10
Q

What infections is E.coli involved in?

A

GI; neonatal meningitis; septicaemia; UTI

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11
Q

What infections is salmonella involved in?

A

GI; typhoid

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12
Q

What infections is acinetobacter baumanii invovled in?

A

opportunistic- wounds; UTI; pneumonia

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13
Q

What is selective toxicity?

A

toxicity that selects for pathogens using the large number of different pathways in microbes vs mammals

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14
Q

What is the MOA of beta-lactams?

A

interfere with the synthesis of peptidoglycan by binding to and inhibiting penicillin binding proteins which are involved in the synthesis of peptidoglycan

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15
Q

What is hte MOA of tetracycline?

A

inhibits protein synthesis by binding to the 30S ribosomal subunit preventing the interaction of charged aminoacyl-tRNAs with the mRNA/ribosome complex preventing elongation of the peptide (bacteriostatic)

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16
Q

What is the MOA of chloramphenicol?

A

inhibits protein synthesis by binding to 50S ribosomal subunit and blocking peptidyl transfer step- bacteriostatic

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17
Q

What is the MOA of quinolones?

A

targets DNA gyrase in gram negs and topoisomeras IV in gram pos preventing DNA replication- bactericidal

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18
Q

What is the MOA of sulphonamides?

A

bacteriostatic by blocking folic acid metabolism- mimic PABA and compete for an enzyme that synthesises folic acid

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19
Q

Give examples of aminoglycosides?

A

gentamicin and streptomycin

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20
Q

What is the MOA of aminoglycosides?

A

target protein synthesis, RNA proofreading and case damage to cell membrnae

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21
Q

What type of infection are macrolides used to treat?

A

gram positive

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22
Q

What is the MOA of macrolides?

A

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

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23
Q

What are the 4 mechanisms of antibiotic resistance?

A

altered target site; inactivation of antibiotic; altered metabolism; decreased drug accumulation

24
Q

How can an altered target site arise in antibiotic resistance?

A

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

25
Q

How does MRSA use altered target site as a mechanism of resistance?

A

MRSA encodes an alternative PBP-PBP2a with low affinity for beta-lactams

26
Q

How does strep. pneumo use altered target site as a mechanism of resistance?

A

resistance to erythromycin by acquisition of the erm gene which encodes an enzyme which methylates the AB target site on the ribosome

27
Q

Give examples of inactivation of antibiotic as a method of resistance?

A

beta-lactamase production or chloramphenicol acetyl-transferase

28
Q

What is an example of an antibiotic that is created to avoid beta lactamase?

A

co-amoxiclav: amoxicillin plus clavulonic acid a beta lactamase inhibitor

29
Q

What is the function of beta-lactamase?

A

breaks a bond in the beta lactam ring of penicillin to disable tohe molecule

30
Q

Give an example of altered metabolism as a mechanism for resistance?

A

increased production of enzyme substrate can out-compete antibiotic inhibitor- e.g increased PABA confers resistance to sulphonamides or using other metabolic pathways reducing need for PABA

31
Q

What are the methods of decreased drug accumulation as a method of resistance?

A

reduced penetration of ABx into bacterial cell (permeability) and/or increased efflux so drug doesn’t reach required conc

32
Q

What are the sources of antibiotic resistance genes?

A

plasmids; transposons; naked DNA

33
Q

What is the problem with plasmids in antibiotic ressitance?

A

often carry multiple antibiotic resistance genes so selection for one maintains resistance to all

34
Q

What are transposons?

A

allow transfer of genes from plasmid to chromosome and vice versa

35
Q

What is naked DNA?

A

DNA from dead bacteria released into environment

36
Q

How can genes responsible for conferring abx resistance be shared between bacteria?

A

transformation; transduction and conjugation

37
Q

What is transformation?

A

uptake of extracellular DNA

38
Q

What is transduction?

A

phage-mediated transfer

39
Q

What is conjugation?

A

pilus-mediated DNA transfer

40
Q

How did vancomycin resistant S.aureus arise?

A

conjugal transfer of plasmid and transposition of the vanA operon from enterococcus faecalis

41
Q

How did vancomycin insensitive S.aureus arise?

A

spontaneous point mutations at multiple loci

42
Q

What are the 2 types of MRSA?

A

hospital acquired and community acquired

43
Q

What is the difference between hospital and community acquired MRSA?

A

HA- more resistance to oxacillin and CA- more virulent : evidence of selection pressures as people in hospital are sick so dont need high virulence but have high abx whereas CA-healthy so need high virulence

44
Q

Why did MRSA emerge and spread in hospital?

A

high selection pressure for resistance with lots of sick people prone to infection; indwelling medical deivces gives access to deep tissues —fitness costs of resistance outweighed by advantage of resistance and pressnce of large susceptible population

45
Q

Why does resistnace come at a price for bacteria?

A

more drug resistnace results in lower virulence

46
Q

What gene encodes beta-lactamase?

A

blaZ

47
Q

What represses the RNA transcription of blaZ?

A

Blal

48
Q

What causes the inactivation of Blal?

A

binding of penicillin to to BlaR1 which causes BlaR1 autocatalytic activation which cleaves Blal into inactive fragments

49
Q

What is often found on the same plasmid with the gene for beta-lactamase?

A

additional antimicrobial ressitance genes

50
Q

Why is it assumed that mecA was acquired from one of the several coagulase-negative staph species?

A

there is no homologue of mecA in MSSA

51
Q

How does resistance to quinolones arise?

A

stepqise acquisition of chromosomal mutations

52
Q

Which enzymes do quinolones act upon?

A

DNA gyrase; topoisomerase IV

53
Q

What are the new agents available with activity against drug-resistance staphylococci?

A

dalfopristin and linezolid; daptomycin

54
Q

What is the general MOA of dalfopristin and linezolid?

A

protein synthesis inhibitors

55
Q

What is the MOA of daptomycin?

A

damages the cytoplasmic mechanism

56
Q

What is the mortality rate of S.aureus bacteraemia?

A

20-40%