Core Microbiology - Antibiotic Resistance (2) Flashcards

1
Q

Antibiotic era

A

Time since widespread availability of antibiotics to treat infection

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2
Q

Post-Antibiotic era

A

Time after widespread antibiotic resistance has reduced the availability of antibiotics to treat infection

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3
Q

Organisms resistant to antibiotics

A
  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Vancomycin/glycopeptide-resistant enterococci (VRE/GRE)
  • Extended-spectrum B-lactamase-producing Enterobacteriaceae (ESBL)
  • NDM-1 producing Gram-negative bacilli
  • Multi-drug resistant tuberculosis (MDR-TB)
  • Extremely-drug resistant tuberculosis (XDR-TB)
  • Enterobacteriaceae resistant to amoxicillin, ciprofloxacin, gentamicin, carbapenems
  • Pseudomonas resistant to ceftazidime, carbapenems
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4
Q

Resistance effecting empiric therapy

A
  • Risk of under-treatment

- Risk of excessively broad-spectrum treatment (can lead to resistance)

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5
Q

Resistance effecting targeted therapy

A

Requires use of alternatives

  • Expensive
  • Last line
  • Toxic
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6
Q

Examples of expensive alternative antibiotics

A
  • Linezolid
  • Tigecycline
  • Daptomycin vs flucloxacillin (MRSA)
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7
Q

Examples of last line alternative antibiotics

A

Meropenem vs ciprofloxacin (multi-resistant Enterobacteriaceae)

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8
Q

Examples of toxic alternative antibiotics

A

Colistin vs meropenem for NDM-1 producers

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9
Q

Reasons for sensitivity testing

A
  • Enable transition from empiric > targeted therapy
  • Explain treatment failures
  • Provide alternative antibiotics (if treatment fails/adverse effects)
  • Provide alternative oral antibiotics with IV no longer required
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10
Q

Limitations of sensitivity testing

A
  • Organism tested may not be cause of infection
  • Correlation between antimicrobial sensitivity and clinical response is not absolute
  • Clinical resistance in vivo
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11
Q

Example of clinical resistance in vivo

A

AmpC B-lactamase genes in eneterobacteriaceae

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12
Q

Resistance mechanisms

A
  1. No target
  2. Reduced permability
  3. Altered target
  4. Over-expression of target
  5. Enzyme degradation
  6. Efflux pump
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13
Q

No target

A

No effect (trying to use antibacterial agent to treat fungi/viruses)

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14
Q

Reduced permeability

A

Drug cannot enter

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15
Q

Examples of reduced permeability

A
  • Gram-negative bacilli have an outer membrane that is impermeable to vancomycin
  • Uptake of aminoglycosides (gentamicin), requires O2 dependent active transport mechanism - only aerobic organisms
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16
Q

Target alteration examples

A
  • MRSA altered penicillin-binding protein (PBP2’ MecA gene) doesn’t bind B-lactams (Flucloxacillin)
  • VRE alterted peptide sequence in gram +ve peptideoglycan reduces beinding of vancomycin
  • Mutations in dhr in gram -ve bacilli means trimethoprim cannot bind
17
Q

Over-expression of target

A

Effect diluted

18
Q

Enzymatic degradation

A

Drug destroyed

19
Q

Enzymatic degradation examples

A
  • B-lactamases (Penicillins and cephalosporins)
  • Aminoglycoside modifying enzymes (gentamicin)
  • Chloramphenical acetyltransferase (cholramphenicol)
20
Q

Drug efflux

A

Drug expelled

21
Q

Examples of drug efflux

A

Multiple antibiotics (gram -ve organisms, antifungal triazoles and candida)

22
Q

Resistance mechanisms often encoded by a single gene

A

Antibiotic-modifying enzymes and altered antibiotic targets

23
Q

Resistance genes encoded in plasmids

A

Transmitted between species by conjugation

24
Q

Horizontal transfer of resistance

A

Enabled by transposons and integrons, transfered plasmid > plasmid/plasmid > chromosome, contain ‘cassettes’ mutiple resistance genes

25
Q

Vertical transfer of resistance

A

Bacterial cell-division

26
Q

Consequences of antibiotic exposure

A
  • Sensitive strains exposed to antibiotics at sub-lethal concentrations
  • Chance of survival enhance by development of resistance
  • Resistant strain out-compete sensitive strains
  • Resistance perpetuated by vertical transfer