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Antimicrobial resistance mechanisms Flashcards

1
Q

Define susceptibility

A

Organism is inhibited by the usually achievable concentrations of antimicrobial agent when the dosage recommended to treat at site of infection is used

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2
Q

Define susceptible dose dependent

A

Susceptibility depends on the dosage regimen used - to achieve levels that are clinically effective, there must be greater antimicrobial exposure than achieved with the dose used to determine the breakpoints

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3
Q

Define “intermediate” resistance

A

Response rates/zone size/MICs are lower than for susceptible isolates

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4
Q

Define resistance

A

Organism is not inhibited by the usually achievable concentrations of the agent with normal dosage schedules or fall into the range in which a specific known resistance mechanism is likely

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5
Q

Define MDR

A

Acquired non-susceptibility to ≥ 1 agent in ≥3 antimicrobial categories

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6
Q

Define XDR

A

Acquired non-susceptibility ≥ 1 agent in all but 2 or less antimicrobial categories

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7
Q

Name mechanisms of genetic variability of bacteria

A

Intracellular
Intercellular

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8
Q

What intracellular mechanisms can result in genetic variability of bacteria?

A

Homologous recombination
Mutations

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9
Q

What intercellular mechanisms can result in genetic variability in bacteria?

A

Bacterial
- transformation
- transduction
- transposition
- conjugation

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10
Q

Explain bacterial transformation

A

Bacterial lysis -> uptake of free segments of naked bacterial DNA from surroundings through the cell membrane -> combination of new DNA with pre-existing DNA -> degradation of unused DNA -> expression of new genes

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11
Q

Give examples of bacteria that often undergo transformation

A

Neisseria
Haemophilus influenza B
Strep pneumo

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12
Q

Which enzyme prevents bacterial transformation and how does it do this?

A

Deoxyribonucleases as they break down free DNA

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13
Q

Explain bacterial conjugation

A

Transfer of plasmids by a bridge like connection between two bacteria
Example: F+ bacteria connect with F- bacteria via the sex pills -> a single strand of plasmid DNA is transferred from F+ bacteria to F- bacteria -> 2 F+ bacteria

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14
Q

What is F factor?

A

Fertility factor - a bacterial plasmid that enables transfer of genetic material between bacteria

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15
Q

What are Hfr cells?

A

High frequency recombination cells - bacteria with a conjugative plasmid integrated into their chromosomal DNA

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16
Q

Explain bacterial transduction

A

The process of gene transfer between bacteria via bacteriophages

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17
Q

What is the difference between a prophage and a lytic phage?

A

Lytic phage - bacteria is destroyed
Prophage - bacteria integrates the phage DNA into its genome

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18
Q

Differentiate generalised vs specialised transduction

A

Generalised - any portion of the bacterial genome is transferred
Specialized - a specific portion of the bacterial genome is transferred

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19
Q

Explain generalised transduction

A

Bacteriophage attaches itself to the bacterial cell wall and injects its DNA into the bacterium -> cleavage of bacterial DNA and replication of viral DNA -> formation of new bacteriophages with phage capsids containing fragments of bacterial DNA -> lysis of bacterium -> release of new bacteriophages

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20
Q

Explain specialised transduction

A

Bacteriophage infects bacteria -> viral DNA incorporated into bacterial DNA at specific location but remains inactive -> when activated the viral DNA is replicated -> viral DNA and flanking bacterial DNA excised from the bacterial genome -> excised DNA is incorporated into new bacteriophage capsids -> lysis of bacterium -> release of new bacteriophages

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21
Q

Give examples of toxins that have their genes transferred via specialised transduction

A

Erythrogenic
Cholera
Diphtheria
Shiga
Botulinum

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22
Q

Explain bacterial transposition

A

Exchange of genetic information via transposons within the genome or between genomes of various bacteria

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23
Q

Define beta lactamases

A

Enzymes that inactivate beta lactam antibiotics by splitting the amide bond of the beta lactam ring

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24
Q

What gene encodes for beta lactamases?

A

Bla genes

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25
Q

How are beta lactamases classified?

A

Ambler classification (molecular)
Bush-Jacobi-Medeiros (functional)

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26
Q

What is the active site of class A, C and D?

A

Serine

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27
Q

What is the active site of class B?

A

Metallo-beta-lactamases (zinc)

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28
Q

Which enzymes are class A?

A

Penicillinases
- Broad spectrum
- Extended spectrum
- Carbapenemases

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29
Q

Which enzymes are class B?

A

Carbapenemases

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30
Q

Which enzymes are class C?

A

Cephalosporinases

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31
Q

Which enzymes are class D?

A

Oxacillinases
- Broad spectrum
- Extended spectrum
- Carbapenemases

32
Q

Which classes do carbapenemases fall under?

A

A, B and D

33
Q

What are the substrates of the broad spectrum penicillinases?

A

Benzylpenicillin
Aminopenicillins
Carboxypenicillins
Ureidopenicillins
Narrow spectrum cephalosporins

34
Q

What are the substrates of the extended spectrum penicillinases?

A

Broad spectrum penicillinases
PLUS
Oxymino-beta-lactams
Aztreonam

35
Q

What are the oxymino-beta-lactams?

A

Cefotaxime
Ceftazadime
Ceftriaxone

36
Q

What are the substrates of the carbapenemase penicillinases?

A

Extended spectrum penicillinases
PLUS
Cephamycins
Carbapenems

37
Q

Give examples of the genes involved in broad spectrum penicillinases

A

PC1
TEM-1
SHV-1

38
Q

Which bacteria is associated with the PC1 gene?

A

Staph aureus

39
Q

Which bacteria are associated with the TEM-1 and SHV-1 genes?

A

E.coli
Klein
Gram -ve’s

40
Q

Give examples of the genes involved in extended spectrum penicillinases

A

TEM-derived
SHV-derived
CTX-M-derived
PER-1
VEB-1
VEB-2
GES-1
GES-2
IBC-2

41
Q

Which bacteria are associated with the TEM, SHV and CTX-M derived genes?

A

Enterobacteriaceae

42
Q

Which extended spectrum beta lactase genes are associated with pseudomonas aeruginosa?

A

PER-1
VEB-1
VEB-2
GES-1
GES-2
IBC-2

43
Q

Give examples of the genes involved in carbapenemase penicillinases

A

KPC-1
KPC-2
KPC-3
NMC
IMI
SME family

44
Q

Which carbapenemase genes are associated with klebs pneumonia?

A

KPC-1
KPC-2
KPC-3

45
Q

Give examples of genes associated with the metal lo-beta-lactamases

A

NDM-1
IMP
VIM
GIM
SPM
SIM

46
Q

Give examples of cephalosporinase enzymes

A

AmpC-type enzymes

47
Q

What are the substrates of the cephalosporinases?

A

Extended spectrum
PLUS
Cephamycins

48
Q

What is level of antibiotic resistance mediated by beta lactamases determined by?

A
  1. Rate of hydrolysis
  2. Affinity for antibiotic
  3. Amount of beta lactamase produced by the bacterial cell
  4. Susceptibility of the target protein to the antibiotic
  5. Rate of diffusion of the antibiotic into the bacterial cell
49
Q

Is the bla gene inducible?

50
Q

What is the bla gene carried on?

A

Small plasmids
Transposons

51
Q

Where is the penicillinase enzyme excreted?

A

Extracellularly

52
Q

How does penicillinase work

A

Hydrolysis of penicillin compounds into inactive penicilloic acid

53
Q

What is the laboratory marker for an ESBL?

A

GNB that shows CTX resistance

54
Q

How does TEM allow narrower spectrum enzymes to attack oxymino-beta-lactams?

A

Amino acid substitutions around active site of the enzyme to change configuration and allow access to oxymora-beta-lactam substrates

55
Q

Amino acid substitutions via TEM at which positions produce the ESBL phenotype?

A

104
164
238
240

56
Q

How many TEM-type enzymes are there?

57
Q

What does SHV stand for?

A

Sulfhydryl Reagent Variable

58
Q

How many SHV-type enzymes are there?

59
Q

What are the most common positions for amino acid substitutions via SHV?

60
Q

What does CTX-M stand for?

A

Cefotaxime Munich

61
Q

Which beta lactamase inhibitor works more on CTX-M beta lactamases?

A

Tazobactam > clavulanic acid

62
Q

How many CTX-M enzymes are there?

63
Q

Which bacteria are oxacillinases mostly described in?

A

Pseudomonas aeruginosa

64
Q

What does IRT stand for?

A

Inhibitor resistance TEM

65
Q

How many inhibitor resistant beta lactamases are there?

66
Q

What is the laboratory marker of AmpCs?

A

Resistance to cefoxitin

67
Q

What are the 3 categories of AmpCs?

A
  1. Inducible resistance
  2. Non-inducible resistance
  3. Plasmid mediated resistance
68
Q

What are the AmpC organisms?

A

ESCAPPE MAYHEM
Enterobacter
Serratia marcescens
Citrobacter freundii
Acinetobacter baumannii
Pseudomonas aeruginosa
Providencia stuartii
E.coli/albertii

Morganella morganii
Aeromonas
Yersinia enterocolitica
Hafnia alvei
Edwardsiella
Many others

69
Q

Explain the mechanisms of AmpCs

A

Beta lactams produce cell wall degradation products -> NAG and NAM compete with UDP-n-acteyl-muramic acid peptides to bind to AmpR -> disabled AmpR -> decreased AmpC transcription regulation -> increased AmpC enzyme production

70
Q

What is AmpR?

A

Negative regulatory protein that reduces AmpC beta lactamase expression

71
Q

What is AmpD?

A

Protein responsible for cleavage of residues off cell wall degradation products to reduce their binding to AmpR and allow them to be recycled back into the cell wall synthesis pathway

72
Q

What is AmpG?

A

AmpG transports oligopeptides involved in peptidoglycan recycling into the cytoplasm

73
Q

In which AmpC regulatory gene do mutations most often occur?

A

AmpD > AmpR > AmpG

74
Q

What are the potent AmpC producers?

A

HECK-YES
Hafnia alvei
Enterobacter cloacae
Citrobacter freundii
Klebsiella aerogenes
Yersinia enterocolitica

Bacteriology (4 decks)

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