Antibiotics and Antimicrobial Resistance Flashcards
What is antimicrobial stewardship
Coordinated interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose, duration of therapy, and route of administration.
What questions should you ask when deciding to use antimicrobials
Is there good evidence of a bacterial infection?
What diagnostics will you employ that help decision-making?
When are cultures (and sensitivity used) used?
If you make the choice to use what drives your final choice of antibiotic?
What is critically important antibiotic (CIA)
Last line resorts for human medicines - very bad if any resistance builds up
What are the different ‘lines’ of antibiotics
Primary (1st line)
Secondary (2nd line)
Tertiary (3rd line)
Restricted
Which line of antibiotics should you reach for first, and how to approach using the other lines
Primary
To use secondary - justify why didn’t use primary
To use tertiary - need C&S and justification
Why are some antibiotics restricted in animals
Critical in human medicine
Give some examples of primary (1st line) antibiotics (x6)
Penicillins
1st generation cephalosporins
Amoxy/clav
Tetracyclines
TMPS (Trimethoprim/sulfonamide)
Lincosamides
Give some examples of broad (x1) and narrow (x2) spectrum secondary (2nd line) antibiotics
Broad
- Chloramphenicol
Narrow
- Aminoglycosides
- Metronidazole
- Macrolides
Name 2 secondary (2nd line) antibiotics which are critically important
Fluoroquinolones
Cefovecin
Name some tertiary (3rd line) antibiotics
3rd and 4th gen cephalosporins
Rifampicin
Fosfomycin
Name the steps in the 7-point plan for the responsible use of antimicrobials
- Work with clients to avoid the need for antimicrobials
- Avoid inappropriate use
- Choose the right drug for the right bug
- Monitor antimicrobial sensitivity - C&S
- Minimise use
- Record and justify deviations from protocols
- Report suspected treatment failure to the VMD
Name 4 ways to work with clients to avoid the need for antimicrobials (step 1 in the 7-point plan)
Regular health checks
Use symptomatic relief or topical treatment where appropriate
Isolate infected animals where possible
Keep animals healthy - vaccinations, good diet, good practices
Name 4 ways to avoid inappropriate use of antibiotics (step 2 in the 7-point plan)
Avoid using them when not needed - viral infections
Restrict use to animals who are unwell or at risk
Advise clients on correct use
Avoid underdosing
Name 3 ways to choose the right drug for the right bug (step 3 in the 7-point plan)
Identify target organisms
Use narrow-spectrum where possible
Understand how antimicrobials work and their pharmacodynamic properties
Name 2 ways to monitor antimicrobial sensitivity (step 4 in the 7-point plan)
Culture and sensitivity where you can
If C&S is not possible - empirical antibiotic therapy
Name 3 ways to minimise use of antimicrobials (step 5 in the 7-point plan)
Use only when necessary
Assess use and develop protocols
Use alongside aseptic techniques and guidelines
Name 2 ways to record and justify deviations from protocols (step 6 in the 7-point plan)
Justify choice - especially when using secondary or tertiary line antimicrobials
Keep accurate records
Why do we report suspected treatment failure to the VMD (step 7 in the 7-point plan)
It may be the first indicator of resistance
What does PROTECT ME stand for
Prescribe only when necessary
Reduce prophylaxis
Offer other options
Treat effectively
Employ narrow spectrum
Culture appropriately
Taylor practice policy
Monitor
Educate others
What 6 factors can influence choice of antimicrobials
Principals of treatment
Cost/client
Food producing animals
Empirical selection
Pharmacodynamic considerations
Other factors - risk of drug class
Name the 2 spectrums of antibiotics
Narrow spectrum - targets a narrow group of bacteria (gram +ve or -ve)
Broad spectrum - targets gram +ve and -ve bacteria, will have more impact on other bacteria in the host so more likely to cause a bad reaction
What is the difference between bacteriocidal and bacteriostatic antibiotics and give examples
Bacteriocidal - Kills the organism e.g. penicillin, cephalosporins
Bacteriostatic - temporarily inhibit the growth of an organism (reversible if removed) e.g. tetracyclines, chloramphenicol
If a patient is immunocompromised, should you use bacteriocidal or bacteriostatic antibiotics
Bacteriocidal
Bacteriostatic require the hosts immune system to remove the bacteria, so if immunocompromised this is not ideal
What does MIC stand for and what is its definition
MIC = minimum inhibitory concentration
The concentration required at the site of infection to achieve bacterial inhibition
What does MBC stand for and what is its definition
MBC = minimum bactericidal concentration
The concentration required at the site of infection to kill the bacteria
Name the 7 main targets of action for antibiotics
Cell wall targeting
Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of cell membrane function
Disruption of DNA structure
Inhibition of DNA dependent RNA polymerase
Interfering with other pathways
Why is peptidoglycan a good target for antimicrobials
It is unique to bacterial cell walls
Name the 4 groups of antibiotics which target the cell wall
Beta lactams
Peptide antibiotics
Bacitracin
Teixobactin
How do beta lactams target the cell wall and give some examples
Inhibit the transpeptidase penicillin-binding protein (PBP) which stops peptide links from forming in the cell wall
Examples:
- Penicillins
- Cephalosporins
How do peptide antibiotics target the cell wall and give some examples
Directly interact with the cell wall D-Ala-D-Ala section which prevents the synthesis of the NAG/MAM polymers
Examples:
- Vancomycin - CIA protected
Give some examples of antibiotics which work by inhibiting protein synthesis
Aminoglycosides
Tetracyclines
Clindamycin
How do antibiotics commonly inhibit protein synthesis
Target ribosomes and bind specific proteins meaning proteins cannot be synthesised
Give an example of an antibiotic which targets RNA synthesis
Rifampicin
How do Sulphonamides/Trimethoprim (TMPS) affect the DNA
Competitive inhibitors of the enzyme dihydropteroate synthetase
Inhibits the synthesis of dihydrofolate which is required for DNA synthesis
How do Quinolones and Novobiocin affect the DNA
Bind to and stop DNA gyros
Inhibits supercoiling of the chromosome
Disrupts DNA-associated processes
How do nitroimidazoles affect the DNA
The reduction products of this group are reactive with DNA which damaged the DNA
Causes DNA strands to break
What conditions do aminoglycosides not work well in and why
Anaerobic conditions
They require aerobic respiration to enter the cell
What conditions do nitroimidazoles require
Anaerobic conditions
They need to be reduced by anaerobic bacteria to be metabolised into their active form
Give 2 examples of aminoglycosides
Streptomycin
Neomycin
Give 2 examples of tetracyclines
Oxytetracycline
Doxycycline
Name 3 reasons you may use a combination of antibiotics
- Treating mixed bacterial infections
- Achieving synergistic antimicrobial activity against resistant strains
- To reduce risk or overcome bacterial resistance
Why might you use a combination of penicillins and aminoglycosides
Penicillins have good anaerobic coverage
Aminoglycosides have a good effect on gram negatives
What action do B-lactams have which is useful when using other antibiotics
Facilitate movement of other drugs through the damages cell wall => the microbe
What action does Clavulanic acid have which aids penicillin
Prevents B-lactamase destruction of penicillin
Name 5 reasons that antibiotic treatment can fail
- Unjustified therapy - a viral infection
- Poor selection
- Wrong dose/ regimen
- Suppressed host response
- Resistance
Name 3 ways resistance to antimicrobials can be assessed
- Liquid culture MIC minimum inhibitory concentration) determination
- Disk diffusion (Kirby-Bauer) - diameter of zone inhibition for a genus os matched to a breakpoint for MIC
- Detection of known resistance genes or mutations
By which value is resistance defined
Clinical breakpoint values
How are clinical breakpoints related to MIC
If MIC is less than X, then it is scored as sensitive
If MIC is more than X, the scored as resistant
Why are you at risk of bacterial resistance if you are below the MIC
The susceptible bacteria may survive but grow slower / less well compared to the resistant.
So the resistant bacteria slowly take over.
What is the MSC and what does it mean
MSC= minimum selective concentration
It is the concentration at which there is no therapeutic effect but there is still a selective advantage to being resistant or susceptible.
Why is a long MSC window bad
Can lead to increased resistance
Define intrinsic resistance
An innate ability to resist the activity of a particular antimicrobial agent through inherent structural or functional characteristics which allow a tolerance of the drug
Define acquired resistance
When a microorganism obtains the ability to resist the activity of a drug.
Can be a mutation or new gene acquisition.
Give 3 examples of intrinsic resistance
- Poor permeability due to the outer membrane
- Target different to the other genera
- Lack the target e.g. mycoplasma have no cell wall so any drugs targeting cell wall will not affect them
Give 3 ways in which a bacteria can have acquired resistance
- Gene mutation
- Gene acquisition
- Co-resistance
Give an example of a compound which leads to “degradation” of an antibiotic
B-lactamases
Which bacteria type are B-lactamases found commonly in
Staphylococci
Name an antibiotic which is resistance to B-lactamase
Methicillin
How does “efflux” work as an acquired mechanism
Efflux systems pump solutes out of a cell
Allow bacteria to regulate their internal environment by removing toxic substances (including antibiotics)
Which group of bacteria have the drug efflux mechanism
Gram negative
Name the 3 major mechanisms of resistance that work against B-lactams
Cleavage of B-lactams by B-lactamases
Extended Spectrum Beta-Lactamase (ESBL’s)
Altered penicillin-binding proteins (PBP)
Name the 3 major mechanisms of resistance that work against aminoglycosides
Efflux
Enzymatic modification
Ribosomal mutations
Name the 3 major mechanisms of resistance that work against quinolones
Target mutations
Efflux
Modification
Name the 2 major mechanisms of resistance that work against glycopeptides
Altered cell wall peptides
Efflux
Name the major mechanism of resistance that work against tetracyclines
Efflux
Name the major mechanism of resistance that work against rifamycins
Altered mutated RNA polymerase
Name the major mechanism of resistance that work against pleuromutilins
Mutations in the 23S rRNA genes
ribosomal proteins preventing binding to target
Name 3 factors which increase the risk of resistance selection
Underdosing
Length of selective level
Presence of resistant bacteria to select
What does MDR, XDR and PDR stand for
MDR = multiple drug resistance
XDR = extensive drug resistance
PDR = Pan drug resistance (no usable options)
What is the mode of action of B-lactam antibiotics
Inhibition of cell-wall synthesis
What is the mode of action of Aminoglycoside antibiotics
Inhibition of protein synthesis
What is the mode of action of quinolones antibiotics
Inhibition of DNA gyros and supercoiling
What is the mode of action of glycopeptide antibiotics
Inhibition of cell wall synthesis
What is the mode of action of tetracycline antibiotics
Inhibition of translation
What is the mode of action of rifamycin antibiotics
inhibition of transcription
What is the mode of action of oxazolidinone antibiotics
Inhibition of formation of 70S ribosomal complex
What is the mode of action of pleuromutilin antibiotics
Inhibition of the of formation of 50S ribosomal complex
