Core Microbiology - Antibiotic Resistance (2) Flashcards Preview

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Flashcards in Core Microbiology - Antibiotic Resistance (2) Deck (26):
1

Antibiotic era

Time since widespread availability of antibiotics to treat infection

2

Post-Antibiotic era

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

3

Organisms resistant to antibiotics

- 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

4

Resistance effecting empiric therapy

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

5

Resistance effecting targeted therapy

Requires use of alternatives
- Expensive
- Last line
- Toxic

6

Examples of expensive alternative antibiotics

- Linezolid
- Tigecycline
- Daptomycin vs flucloxacillin (MRSA)

7

Examples of last line alternative antibiotics

Meropenem vs ciprofloxacin (multi-resistant Enterobacteriaceae)

8

Examples of toxic alternative antibiotics

Colistin vs meropenem for NDM-1 producers

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Reasons for sensitivity testing

- 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

10

Limitations of sensitivity testing

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

11

Example of clinical resistance in vivo

AmpC B-lactamase genes in eneterobacteriaceae

12

Resistance mechanisms

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

13

No target

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

14

Reduced permeability

Drug cannot enter

15

Examples of reduced permeability

- 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

16

Target alteration examples

- 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

Over-expression of target

Effect diluted

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Enzymatic degradation

Drug destroyed

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Enzymatic degradation examples

- B-lactamases (Penicillins and cephalosporins)
- Aminoglycoside modifying enzymes (gentamicin)
- Chloramphenical acetyltransferase (cholramphenicol)

20

Drug efflux

Drug expelled

21

Examples of drug efflux

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

22

Resistance mechanisms often encoded by a single gene

Antibiotic-modifying enzymes and altered antibiotic targets

23

Resistance genes encoded in plasmids

Transmitted between species by conjugation

24

Horizontal transfer of resistance

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

25

Vertical transfer of resistance

Bacterial cell-division

26

Consequences of antibiotic exposure

- 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

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