40. Bacterial Antibiotic Resistance Flashcards

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1
Q

In the US, … million antibiotic-resistant infections occur each year and more than … die

A
  • more than 2.8
  • 35,000
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2
Q

It is estimated that by 2050, antimicrobial resistance will kill … yearly globally - this is more than … and … combined

A
  • 10 million
  • cancer and diabetes
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3
Q

Define ‘anti-microbial’

A

a compound that kills or slows the growth of micro-organisms e.g bacteria, fungi, viruses, parasites

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4
Q

Define ‘antimicrobial-resistance’

A
  • the ability of micro-organisms to withstand the effects of an antimicrobial compound to which they were formerly susceptible
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5
Q

Define ‘antibiotic’

A
  • a compound that can kill or slow the growth of bacteria specifically
  • can be natural or synthetic
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6
Q

Years when antibiotics were first made

A
  • penicillin discovered in 1928 by Fleming
  • paper noted it’s ‘clinical potential’ in 1929
  • development of it 19-39 to 1940
  • production of penicillin 1941
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7
Q

Why is antimicrobial resistance being monitored?

A
  • serious and growing problem worldwide
  • looming crisis and major threat to public health
  • major clinical, public health and economic implications
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8
Q

How have the WHO addressed antimicrobial resistance?

A
  • declared it one of the top 10 global public health threats facing humanity
  • a paper published in the Lancet in 2022
  • estimated 4.95 million associated deaths in 2019m including 1.27 million attributable to bacterial AMR
  • 6 leading pathogens for deaths associated are E.Coli, then Staph, aureus, K. pneumoniae, Strep, pneumoniae, A. baumannii and Pseudomonas aeruginosa
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9
Q

Antimicrobial resistance is linked to more deaths that what 2 conditions?

A
  • HIV
  • malaria
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10
Q

Factors which contribute to the emergence and spread of AMR

A
  • excessive and prolonged use of antibiotics
  • over-the-counter availability of antibiotics
  • prolonged survival and treatment of patients with chronic diseases
  • antibioitcs in animal feeds
  • international travel and migration of pops - inc. medical tourism
  • international distribution of fresh produce
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11
Q

List 4 ways to combat AMR

A
  • preventing infections
  • surveillance of AMR
  • monitor use of antimicrobials
  • development of new antimicrobials
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12
Q

How to prevent infection in order to combat AMR?

A
  • promote infection control protocols
  • immunisation
  • safe food prep
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13
Q

How to surveillance antimicrobial resistance in order to combat AMR?

A
  • public health systems
  • epidemiological data
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14
Q

How to monitor use of antimicrobials in order to combat AMR?

A
  • monitor prescribing
  • prescribing adults
  • monitor food and agricultural industries
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15
Q

How to develop new antimicrobials in order to combat AMR?

A
  • incentives to drug development countries
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16
Q

What is the origin of antibiotic resistance?

A
  • ideally with complete course of antibiotics, all pathogens destroyed but a few persister cells might survive
  • if some resistant cells in infecting pop, they survive and grow without competition
  • if person feels better and stops the antibiotics, mutant cells have opportunity to express AMR, survive and grow along with persister cells without comp
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17
Q

List 4 mechanisms of resistance

A
  • intrinsic
  • acquired
  • cross
  • multi
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18
Q

What is intrinsic AMR?

A
  • innate property of bacterium in all strains
  • characteristic of organisms
  • entire species is resistant
  • e.g resistance of gram-neg to many beta lactams and vancomycin (too large to cross cell membranes)
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19
Q

What is acquired AMR resistance?

A
  • drug resistance is selected by antibiotic use
  • doesn’t affect entire species and will only be seen in some strains
  • can be by chromosomal mutation or horizontal gene transfer
  • for example penicillin resistance in Staph. aureus
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20
Q

What is cross resistance AMR?

A
  • resistance to one antibiotic leads to antibiotic resistance to another
  • often when antibiotics are in same class
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21
Q

What is multi-resistance AMR?

A
  • resistance to several antibiotics via independent mechanisms
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22
Q

Staphylococcus aureus has acquired resistance to …

A
  • penicillin
  • erythromycin
  • methicillin
  • cephalosporins
  • vancomycin
  • linezolid
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23
Q

Types of horizontal gene transfer

A
  • transformation
  • transduction
  • conjugation
24
Q

How does mutation lead to acquired resistance?

A
  • chromosomal mutation resulting in genetically-altered bacterial population
  • alteration of DNA within cell
  • evolutionary advantage
25
Q

Explain spontaneous mutation leading to AMR

A
  • antibiotic doesn’t kill the spontaneously mutated AMR pathogen
  • it’s then selected so vertical transmission of AMR in future
26
Q

How does transformation pass on acquired AMR?

A
  • DNA taken up into bacterial cell from environment
  • DNA taken up encodes new genes and may include genes to confer antibiotic resistance
27
Q

How does transduction pass on AMR?

A
  • DNA transmitted via viruses
  • certain viruses able to infect bacteria
  • DNA picked up by viruses and passed from one bacterial cell to another
28
Q

Key difference in transformation and transduction

A
  • in transformation, lysis of donor cell releases DNA to be taken up by bacterial cell
  • in transduction, virus injection and chromosome disruption so donor DNA-containing viruses attach to bacterial cell
29
Q

Conjugation to transfer AMR

A
  • occurs via pili
  • donor cell containing conjugative plasmid and recipient cell that doesn’t
  • only donor cells have pili
  • cells drawn together for transfer of DNA - in plasmid form (small DNA rings)
  • resistance genes often on plasmids, plasmids able to be transmitted between bacteria
30
Q

Bacteria use 3 main mechanisms to become resistant to antibiotics. List them

A
  • modification of antibiotic/inactivating antibiotic
  • modification of target
  • sequestering antibiotic from target/preventing drug from reaching target
31
Q

A bacteria’s mechanism of AMR is modification of antibiotic. List 5 ways it could do this

A
  • antibiotic hydrolysis
  • antibiotic modification
  • membrane modification
  • target modification
  • metabolic pathway alteration
32
Q

How does antibiotic hydrolysis work?

A
  • beta-lactamase break the structure of antibiotics like penicillin
  • production of enzymes to degrade/inactivate antibiotic
33
Q

How does antibiotic modification work?

A
  • chemical groups or modifiers inactivate an antibiotic like streptomycin
  • production of enzymes to degrade/inactivate antibiotics
34
Q

How does membrane modification work?

A
  • cell membrane pumps out antibiotic like tetracycline
  • reduced uptake into cell/removal of antibiotic from cell
35
Q

How does target modification work?

A
  • cell targets such as ribosomes change structure so antibiotics like streptomycin can’t bind
  • structural alteration to drug target
36
Q

How does metabolic pathway alteration work?

A
  • alternate pathway used to bypass an antibiotic-blocked metabolic pathway
  • such as for sulfa drugs
  • contingency measures to avoid drug toxicity
37
Q

How does amoxicillin work?

A
  • penicillin family of antibiotics (beta-lactam antibiotics, bacteriocidal)
  • inhibits synthesis of bacterial peptidoglycan cell wall
  • prevents formation of rigid cross-linked cell wall structure
  • weakened cell wall leads to cell rupture
38
Q

How does amoxicillin actually stop the cell wall of bacteria forming?

A
  • beta-lactam antibiotics block the cross linking of peptidoglycan units
  • as they inhibit transpeptidases which enable peptide bond formation
39
Q

Gram-negative bacteria are intrinsically resistant to … due to …

A
  • early penicillins
  • lack of permeability through outer membrane, multidrug efflux pumps, beta-lactamases encoded on chromosome
40
Q

How do staph aureus have acquired resistance to penicillins?

A
  • plasmid-borne beta-lactamase
  • modification of mecA gene encoding PBP2a - reduced binding of beta-lactams (methicillin resistance)
41
Q

Which mechanism of AMR do these fall into?
- lack of permeability through membrane
- multidrug efflux pumps
- beta-lactamases encoded on chromosome
- plasmid-borne beta-lactamase
- modification of mecA gene encoding PBP2a - reduced binding to beta-lactams

A
  • sequestering from target
  • sequestering from target
  • modification of antibiotic
  • modifcation of antibiotic
  • modification of target
42
Q

Role of Beta-lactamases

A
  • modified penicillin binding proteins
  • bind to beta-lactam ring and hydrolyse it
43
Q

What can inhibit beta-lactamases?

A
  • clavalanic acid
  • augmentin (Co-amoxiclav) = amoxicillin + clavulanic acid
44
Q

How does horizontal gene transfer occur in NDM-1 for AMR?

A
  • carbapenems are potent beta-lactams (last line antibiotics vs penicillin resistant gram-negs)
  • NDM-1 can break down the carbapenem ring
  • gene encoding NDM-1 is present on a plasmid - can be transferred between bacteria including E.Coli and Klebsiella etc
45
Q

How has NDM-1 spread from first cases in UK?

A
  • many of first cases in UK from patients visiting India for medical care
  • dental care one of the most common reasons for healthcare-related international travel
  • by 2015, NDM-1 in over 70 countries
46
Q

Dentists issue around …% of all antibiotic prescriptions in NHS primary care and … % of the NHS total

A
  • 10.8
  • 5%
47
Q

… million antibiotic prescriptions dispensed by pahrmacists for dental prescription in 2017

A

2.9

48
Q

Treatment of odontogenic infections (with AMR in mind)

A
  • usually require dental treatment
  • done via removal of the source of infection
  • antibiotics should only be prescribed if necessary as adjunct
  • odontogenic infections are polymicrobial and in biofilms - more resistant to antibiotics
49
Q

Why is there increased antimicrobial resistance in biofilms?

A
  • slow penetration of antibiotics and can be complete failure/de-activated before it can diffuse through like beta-lactamase
  • resistant phenotype like persisters. some bacteria can differentiate into protected phenotypic state
  • altered microenvironment - microscale gradients can antagonise antibiotics like oxygen, pH - in zones of nutrient depletion or waste product accumulation, antibiotic action may be antagonised
50
Q

AMR mechanisms in oral biofilm

A
  • modification of antibiotic - reaction with ECM
  • modification of target - slow growth
  • reduced intracellular concentration - exclusion by matrix, up-regulation of efflux pumps
51
Q

Treatment steps of bacterial dental infection

A
  • local measures
  • drain pus if present
  • tooth extraction
  • access and drain through root canals
  • soft tissue pus drain by incision
  • debride infected periodontal pockets
  • irrigate/debride infected operculum
52
Q

What guidance is followed for what to prescribe?

A
  • BNF
  • SDCEP Drug Prescribing in Dentistry
  • FGDP (UK) Antimicrobial Prescribing for GDPs
53
Q

What antibiotics are prescribed by dentists?

A
  • amoxicillin
  • phenoxymethylpenicillin
  • metronidazole
54
Q

Explain antimicrobial stewardship

A
  • appropriate, safe and discriminate use of antimicrobials
  • systematic effort to educate and persuade prescribers of antimicrobials to follow evidence-based prescribing in order
  • to stem antibiotic overuse and antiobiotic resistance
55
Q

How to avoid over-prescribing?

A
  • follow uo-to-date prescribing guidance
  • prioritise local measures
  • ensure suitable length to appointments
  • informed consent for treatment - options, risks, benefits
  • communication regarding risks of over-prescribing
56
Q

How can dentists be responsible prescribers?

A
  • justify prescribing
  • follow guidance
  • communicate with patient regarding prescription
  • prescribing audits completed
  • prescribing monitored
57
Q

How to increase public awareness of antimicrobial resistance?

A
  • toolkit to support antimicrobial stewardship
  • ongoing training of staff and CPD
  • communication with patients
  • patient education
  • information for patients and posters for dental practice waiting rooms