mechanism of antimicrobial resistance Flashcards
basis of resistance:
1. —
2. Antimicrobial agents kill susceptible organisms, resistant ones survive ‘survival of the fittest’
3. Susceptible organisms may become resistant by –
4. Some bacteria inherently resistant – may be selected by —
5. Resistant bacteria can — resistance
6. Bacteria — multiple resistances to unrelated antibiotics e.g. MRSA
natural selection
mutation
antimicrobial therapy
transfer
accumalate
factors contributing to resistance:
— use
* — of antimicrobials over the counter
* — use of antimicrobials
* Patient — e.g. TB
* — dosing
* — penetration to body sites
* In other sectors (agriculture, food, veterinary medicine)
Inadequate infection — procedures
—- in healthcare and children facilities
Increased –
antimicrobial
availability
unnecessary
non compliance
Sub-therapeutic
low
control
overcrowding
travel
emergence of antimicrobial resistance:
1- resistance — transfer which can be done by —
2- then — will occur by which we will have — bacteria turned into — bacteria
gene
by: Transformation
Conjugation Transposition
Transduction
mutation
susceptible to new resistant
genetic exchange process:
Bacteria have – processes by which they can transfer genetic information between cells/species
1. —
– – fragments / — taken up – by bacterial cells
– Sometimes integrated into – genome ( — )
– stably – and—
2- — :
– — transfer between bacterial cells
– Can occur between different bacterial—
– Plasmids denature in – cell and a — transfers from the donor cell into the recipient cell where the — strand is synthesised
3- —- :
– Between bacteria via — with a —
– – infect the bacterial cell, — the host DNA and use host cell systems to replicate —
4- —- :
— = DNA sequences
that can ‘—’ within the bacterial — and from the — to —
within the same cell. — genetic element
- simplest form is —- that carry the — required for their own transposition
( — ) and are flanked on either side with – repeats.
-transposition facilitates rapid— of antibiotic resistance genes among different bacterial
species
4
transformation
dna + plasmid
directly
hist
recombination
maintained n inherited
conjugation
plasmid
species
donor
single strand
complementary
transduction
infection
bacteriophage
phag
degrades
phag dna
transposition
jump
genome
and from genome to plasmid
mobile
insertion sequences
enzyme
transposes
inverted
dissemination
acquired resistance to antimicrobial:
Mutations on the —
— acquired resistance
What proteins/enzymes are encoded
from the genome (chromosome or
plasmids) that give bacteria the
capability to resist being killed by
antibiotics?
( a — is a piece of genetic material which can easily be transmitted from one bacterium to another. )
c/some
plasmid
plasmid
mechanism of resistance:
1. — of agent before it reaches its target e.g. – enzymes
2. Agent prevented from reaching its — due to — changes or —
3. Target altered so it no longer – the antimicrobial (— modification)
4. Bacterium acquires an alternative — by-passing the site of action
(Can have a number of different mechanisms in one bacterium)
inactivation
inactivating enzyme
target
permeability or drug efflux
recognises
biding site
alt metabolic pathway
1- inactivating enzyme:
Bacteria produce enzymes that – or— agent
1. — produced by — ( by which active pencilin will become inactive peniclloate)
2. —-modifying enzymes add — groups to the antibiotic altering its — and interferes with its — .
destroy or alter
b lactamases
gram+ve and -ve which can be plasmid or c./some
amino glycoside
chemical
structure
transport
- b-lactamase enzymes cleave the –
in — and — drugs
-Produced by many types of bacteria - e.g., Most — can produce b-lactamase that destroys penicillin
-Extended spectrum beta-lactamases (ESBLs): - Produced by some — mainly —
- Destroy many beta-lactam antibiotics (eg penicillin,—– generation cephalosporins)
- — are beta-lactams that cannot be destroyed by ESBLs
-Carbapenemase-producing Enterobacterales (CPE)
b lactam ring
penicillin n cephalosporin
staphlyococci
-ve
enterobactealses
1,2,3rd generation
carbapenems
2- agent cant reach target due to impaired permeability (Remember, for an antibiotic to kill/inhibit a bacteria, it must be able to get in, usually via porins/transport proteins)
* If permeability is impaired, the agent cannot— as well
* Changes in – (Gram- – ) or —-
* Can make it harder for some antibiotics to —
e.g. — resistance and –
penetrate
outer membrane porins in gram -ve
cell membrane transport protein
gain entry
gentamicin resistance and P. aeruginosa
AGENT CANNOT REACH TARGET DUE TO —-
But what if the antibiotic does get in? What can the bug do then to defend itself?
* It can pump it back out, so that it does not – or reach its — .
* New — synthesised to facilitate
removal – drug pumped out of cell
e.g. — resistance or —
resistance in Gram-negative bacteria.
- we can also produce altered porins that prevent entry of drugs
drug efflux ( active transport of drug from cell)
accumulate or reach target
proteins
tetracycline or quilones
3- target modification :
* Antimicrobial agent does not bind as well due to a modification at the — of the target
* Altered penicillin binding protein (PBP2a) and
MRSA: PBP2a has – affinity for penicillin
* MCR-1 gene in — which encodes an enzyme which alters the – for—
4- metabolic bypass:
* Described for — and —
* These antibiotics inhibit enzymes involved in— synthesis
* Bacteria can activate new — for production of —
* Synthesis of — nucleotides can continue despite the presence of these agents
biding site
lower
e coli
outer membrane binding site for colisitin
sulphonamides and trimethoprim
tetrahydrafolate synthesis
new metabolic pathways for tetrahydrofolate
purine
1- multiple mode of resistance to b lactam antimicrobial agents:
1- — aka don’t let it in
2- — aka change the goal post
3—— aka inactivating enyzme
2- problems causes by antimicrobial resistance:
* More — antimicrobial choice: some
infections untreatable
* — lost with inappropriate treatment =
patient — and —
* Increased – stay = increased –
* Increased antibiotic use = more —
* More — , less – , more –
drugs may be required
drug exclusion
drug evasion
drug elimination
more limited
time lost
morbidity and mortality
increase cost
more resistance
more toxic less effective more expensive
key prevention strategies:
prevent infection:
1. —
2. Good – care
(IV lines, urinarycatheters)
- Don’t put them inunless indicated
- Get them out when
no longer required
diagnosis n treat infection:
1. Use diagnosis
diagnosis wisely
2. Ask for help(clinicalmicrobiology, ID)
use antimicrobial wisely:
. Antimicrobial
stewardship
2. Use — to inform
prevent transmission:
1. – diagnosis of antimicrobial resistance and infection
2. Infection prevention &
control
- start —- then —
day 1 start — :
1. Start antibiotics only if there is clinical evidence of —-
- If there is evidence of bacterial infection, prescribe in
accordance with your local antibiotic guidelines andappropriately for the individual patient (see notes below)
2. Obtain appropriate — before starting antibiotics
3. Document in both the drug — and medical— :
- Treatment indication
- Drug name, dose, frequency and route
- Treatment duration (or review date)
4. Ensure antibiotics are given within — of prescription
- Within — for severe sepsis or neutropenic sepsis
day 2 for — :
At — after starting antibiotics, make
an Antimicrobial Prescribing Decision
- Review the clinical diagnosis
- Review laboratory/radiology results
- Choose one of the five options below
- D o c u m e n t this decision( then u’ll have th option to stop switch change continue or OPAT )
- info:
When deciding on the most appropriate antibiotic(s) to prescribe, consider the following factors:
- History of drug allergy (document allergy type: minor (rash only) or major (anaphylaxis,
angioedema))
- Recent culture results (e.g. is patient colonised with a multiple-resistant bacteria?)
- R e c e n t antibiotic t r e a t m e n t
- Potential drug interactions
- Potential adverse effects (e.g. C. difficile infection is more likely with broad spectrum antibiotics)
- Some antibiotics are considered unsafe in pregnancy or young children
- Dose adjustment may be required for renal or hepatic failure
Consider removal of any foreign body/indwelling device, drainage of pus, or other surgical intervention
vaccination
catheter
local data
rapid
smart then focus
bacterial infection
cultures
drug chart n medical notes
four hours
1 hour
focus
24-48 hours
summary:
Effective antibiotics are available and fall into three general categories according to —
* Selection of resistant bacteria, arising by mutation and genetic transfer, is driven by —
* Mechanisms of resistance include — of antibiotics, prevention of – , — pumps or —- of antibiotic target
* Prevention strategies aimed at prevention of infection, improved diagnosis, appropriate use and prevention of transmission
mode of action
antibiotic exposire
inactivation
prevention
efflux
modification
