CD 06 Flashcards
How does resistance develop?
- Innately resistant
2. (be acquired) due to a genetic mutation
Why bacterial ACQUIRED resistance develop so quickly?
Due to the unique properties of bacterial replication:
Vertical Transmission: Reproduce quickly-Parents to daughter to daughter Known as Vertical transmission
Horizontal Transmission: Extra-chromosomal DNA (plasmids) facilitates the spread of AMR(anti-microbial resistance) called Horizontal transmission, within and between bacterial species (through conjugation, transformation, transduction)
What happens with Bacterial Plasmids during AMR?
readily transferred from one bacteria to another bacterial plasmid
What is Metabolic burden to a bacteria ?
Plasmid because when plasmid is not present it raplicate faster On the other hand but it lost selective pressure
A single plasmid may contain how many resistance genes ?
> 1 resistance genes
How bacteria achieve intrinsic (innate) resistance against antibiotics?
1) Drug target is not present
2) Drug can’t cross the OM of a gram
negative cell
3) Or the bacteria may naturally have efflux pumps which remove the drug
How bacteria can achieve Acquired Resistance Based on DRUG accumulation mechanism?
Through stopping drug accumulation by following
1) by Decrease entry (influx)
- Reduce the number of pores
- Change the type of pore
- Impair pore function
2) by Increased exit (efflux)
- Genes for efflux pumps can be encoded on plasmids and cause acquired AMR as bacteria gain new efflux pumps
- Mutations can also increase the expression of pumps
How bacteria can Acquired Resistance - based on The Target?
Acquired Resistance: 1) the target
• Replace the target – via gene transfer with one that has low affinity for the drug
• Modification of the target – via mutation of the binding site while retaining function
• Protection of the target – dislodge drug or compete with drug for target
• Overproduce the target – via mutation to to retain function
How bacteria Acquired Resistance: based on The DRUG?
- Inactivates/breaks down the drug
* Changes/modifies the drug
Bacterial Resistance develops can be slower by
Drugs with MULTIPLE mechanisms of action
Increasing the concentration of drugs can be effective however Can we just give more drugs???
It depends on drugs mechanisms of action
With some types of resistance increasing the concentration can be effective.
What social factors impact on the development of drug resistance?
Misuse/Overuse of antibiotics
• OTC supply of antibiotics
• Incorrect prescribing (viral infections)
• Empirical use of antibiotics
• Prophylactic use (disease hower agyi medicine khawa).
• Increased use of broad spectrum antibiotics
• Use of antibiotics in animal feeds
• Not taking the entire course of antibiotics????????
One factor which can develop drug resistance?
Antibiotic use in animal
Long course of antibiotics are causing drug resistance ?
Long courses are more associated with resistance (more likely to get missed doses and sub therapeutic levels)
Common misconception
Not taking the entire course of antibiotics?
m
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Antimicrobial stewardship
How fast resistance develops can be regulated by cautious use of antibiotics in appropriate situations
Which bacteria is ~ 100% resistance to b-lactams, >50% vancomycin resistant (VRE), gut organism?
Enterococcus faecium (E)
Which bacteria is Methicillin resistant (MRSA), now also VRSA, skin organism, commonly infects i.v. lines and other devices?
Staphylococcus aureus (S)
Which bacteria cause Hospital infections, and MDR
Enterobacter species (E)
Gut organisms,which cause blood infections, and carbapenem resistant (CRKP)
Klebsiella pneumoniae (K) & E.coli
Which bacteria is harmful for Aquatic, cystic fibrosis (lung damage)
Pseudomonas aeruginosa (P)
Do fungi become multi drug resistant (MDR)?
Yes, but is not such a big problem as with bacteria
Why not?
- bacterial replication rate is much faster
- bacteria can transfer resistance on plasmids
- bacterial replication has more mutations as a result can change in DNA sequence.
What is the proportion of high mortality and morbidity by Invasive Candida infections
(~35%), as well as higher health-care costs and prolonged length of hospitalization
Does Candida are becoming MDR?
-yes.
With azole, polyenes, and flucytosine
-Little resistance with amphotericin B as well.
What we can do to stop or limit AMR?
Modified old drugs
Novel drugs (include herbal), new targets
Improved hygiene
Alternative therapies
The proportion of infections of invasive candida?
(35%) as well as High morbidity and mortality. as well as higher health care costs and prolonged length of hospitalization
