Antimicrobial resistance Flashcards
Antimicrobial resistance
occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines making infections harder to treat and increasing the risk of disease spread, severe illness and death.
Clinical deployment of new antibiotics has quickly been followed by the evolution of bacteria able to resist their effects
Mechanisms of AMR can be classed as (2)
intrinsic or extrinsic mechanisms
Intrinsic mechanisms of AMR
organism that lacks the target for an antimicrobial or the target that is present is structurally different.
e.g., all gram positives are resistant to aztreonam as they lack the corresponding target
Examples of acquired resistance
- Efflux pumps- remove the active substance before it can cause damage
- Limiting the uptake of drug- remove receptors/ channels
- Modification of target- make it so the antibiotic can’t bind
- Inactivation of a drug- e.g. secreting acid to denature medicine
- Bypassing the targeted process- e.g., alternative metabolic route
How do cells acquire resistance?
- Transfer of resistant genes
- mutation
- selection due to antibiotic pressure
- growth conditions- biofilms
5 major groups of efflux pump
All cells have efflux pumps
- ABC- uses ATP
- MFS- uses proton motor force
- SMR- antiporter
- RND
- MATE
How are beta-lactam medications overcame?
Drug uptake limitation- decrease the number of porins
Drug target modification- gram positive alterations to PBPs
Drug inactivation- B lactamases
Mechanisms to overcome aminoglycosides
Drug uptake limitation- change cell wall polarity
Drug target modification- ribosomal mutation/ methylation
Explain how selection pressure leads to acquired AMR
- Group of microbes are given antibiotic
- If that concentration is sublethal then resistant or persistor cells will remain
- The resistant cells remain with less competition from other less resistant strains
- The selected strains multiply and now a greater proportion of the cells in a population are resistant.
- If the process is repeated then successive generations will get progressively more resistant.
Dose response curve
Describes the response by an organism to a stimulus. In this case how many organisms are killed by the use of an antimicrobial.
There is often a sharp downturn, signifying the minimum inhibitory concentration, where cells start to die
Minimum inhibitory concentration
The minimum concentration required to kill cells in a population.
An increase in concentration will result in a proportionately greater decrease in cell survivors while on the curve of this point.
Persistor cell
cell that is typically identical to the rest of the population but is metabolically different (e.g., growing slower as they have lack of nutrients or are slightly damaged). This difference makes them less susceptible- not truly resistant.
Multidrug resistant bacteria
bacteria that are resistant to more than one kind of medication
- e.g.,
- MRSA (gram +ve coccus)
- C.difficile (gram +ve)
- E.coli (intrinsic and acquired - gram -ve rods)
- Pseudomonas aeruginosa
This is a global problem
What has led to increasing rates of antimicrobial resistance
- Presence of antibiotics where they’re not required/ used successfully
- Increased use of antibiotics
- Prescriptions taken incorrectly
- Sold without medical supervision
- Prophylactic use before surgery
- Antibiotics used for viral infection
- Spread of resistant microbes in hospitals due to lack of hygiene
- Patients who do not complete course
- Antibiotics in animal feed
What are the 2 ways of managing resistance
Infecrion prevention and control
Antimicrobial usage
Infection prevention and control for managing infection
- Minimises the transmission of organisms with succesful antimicrobial resistance
- Avoidance of infection and exposure to resistant organisms is key (e.g., increase vaccination rates)
- We paradoxically expose our most vulnerable patients to our highest risk practice (hospital)
Controlling antimicrobial usage in managing resistance
Antimicrobial exposure exerts a selective pressure to enable organisms with inherent or acquired resistance to proliferate
Any reduction in antimicrobial usage will reduce risk of resistance
The ‘easy win’ is appropriate usage. Do this by:
- Reduce broad spectrum antibiotic use
- Reduce treatment duration
- Reduce antibiotics when no infection is present
What is antimicrobial stewardship
“set of co-ordinated strategies to improve the use of antimicrobial medications with the goal of enhancing patient health outcomes, reducing antimicrobial resistance and decreasing unnecessary costs”
When changing behaviours around antibiotic use you can either _____ or _____ them
Enable
restrict
Changing behaviours on antimicrobial perscribing- enabling
give people the appropriate knowledge to use antibiotics correctly
Providing feedback improves effectiveness
Enhanced sustainability of intervention
Better professional acceptance
Changing behaviours around prescribing antibiotics- restiction
“you’re not allowed to use these tools”
+ve -provides a wuick win
-ve -negative professional culture through breakdown in trust and communication
delays in 1st dose administration
Management of sepsis
Aggresive inititation of broad spectrum antibiotics at first if suspected
send for blood tests, imaging and diagnosis to confirm sepsis and specific pathogen
Once you know the specific causative agent switch to narrow spectrum antibiotics
Stop antibiotics if it doesnt work
Benefits of switching to oral antibiotics rather than IV antibiotics
- Reduction in the liklihood of developing hospital acquired bacteraemia
- Patient is more likley to receive oral antibiotics at the correct time and miss fewer doses
- Reduction in risk of adverse reactions
- Reduces patient discomfort and enables improved mobility and the possibility of earlier discharge from the hospital
- Saves medical and nursing times
- A reduction in treatment costs
How might you determine whether to prescribe antibiotics or not?
use the FEVER/pain scale to determine
How do you calculate surviving fraction
divide the CFU (for given conc)/ by CFU for the control
CFU= colony forming unit
