Chemotherapeutic Antibiotics: Gene Transfer (DONE) Flashcards
Bacterial resistance- intrinsic and extrinsic
Intrinsic: natural property of a bacterium, impermeability barrier, efflux, enzymatic inactivation
Acquired: can be transferred between bacteria, decreased uptake/permeability, efflux, enzymatic inactivation, duplication and overproduction of targets, modification of target site, bypass of a metabolic pathway/enzyme
Conjugation
Mechanism of DNA exchange mediated by plasmid- some plasmids can mediate their own transfer, or mediate the transfer of other plasmids/part of chromosomal DNA
Requires a physical contact between donor and recipient cells: initiated by the sex pilus, cytoplasmic bridge
Steps of conjugation
Donor cell attaches to a recipient cell with its pilus, the pilus draws the cells together
The cells contact one another
One strand of plasmid DNA transfers to the recipient
The recipient synthesizes a complementary strand to become an F+ cell, the donor synthesizes a complementary strand, restoring its complete plasmid
Transposon
Mobile genetic elements
Transposable elements are defined as specific DNA segments that can repeatedly insert into one or more sites in one or more genomes
Self replicating unit
Transposons can move from one location to another location on the bacterial chromosome/plasmid- transposition
Transposon use site specific sequences
Transposition
Can create insertion mutation by physically disrupting a sequence encoding for a specific gene
Can create polar mutation by insertion into an operon (a set of genes transcribed by a single promoter)
Block gene expression downstream from the site of insertion
Transformation
Bacteria take up free DNA from the environment
Competent bacteria (ability to take a large macromolecule through the cell wall and cytoplasmic membrane)
Natural competence can be expressed during stage of cell division
Artificial competence: introduction of recombinant DNA molecules into bacteria (electroporation; heat shock)
Transduction
Bacteriophage (bacterial viruses) mediated gene transfer of genetic material from a host cell to a recipient
During viral replication, a small piece of host chromosome can be incorporated into phage capsids
When phage are released, they can infect new hosts and inject their genetic material, including that of the original host
The phage DNA (including host cell DNA) can then integrate the recipient chromosome and be expressed in their new host
Phage genome that are capable of incorporating into the bacterial chromosome are called prophage
Policy for the use of antimicrobial agents
30% of antibiotic use in secondary care is inappropriate
Optimising antibiotic use should ensure best treatment of infected patients, reduce direct risk to patients from adverse effects, reduce indirect risk to patients from the spread of antibiotic resistance, provide cost savings
Antimicrobial care bundle
The care bundle consists of the following elements, which should all be performed every time an antimicrobial is prescribed on the regular side of the medication chart:
Use of antimicrobial stickers, clear indication on chart and in notes, documentation of stop or review date on chart, consistency with health board guidelines, allergy status
Initiating antimicrobials (start smart)
Do not start in the absence of evidence of bacterial infection
Use guidelines to initiate prompt, effective treatment
Obtain cultures first
Prescribe single dose antibiotics for surgical prophylaxis, where they have been shown to be effective
Follow BNF good prescribing practice guidance
Reviewing antimicrobials
Review the clinical diagnosis and the continuing need for antibiotic by 48 hours and make a clear plan of action: stop, switch IV to oral, change, continue
Check latest microbiology results electronically
It is essential that the review and subsequent decision is clearly documented in the medical notes
Start Smart steps
Take history of relevant allergies
Initiate prompt effective antibiotic treatment
Comply with health board guidelines
Document clinical indication and dose on antibiotic sticker
Include review/stop date or duration
Ensure relevant microbiological specimens taken
Advantages of switching from IV to oral
Reduced risk of line infection
Reduced risk of thrombophlebitis from drug/cannula
Saves medical and nursing time
Increased convenience, comfort and mobility for patients
Earlier discharge from hospital
Significant cost reduction
Reduced risk of administration errors
Prevention and management of C. difficile infection
Antibiotics should be prescribed only when there is clinical evidence of bacterial infection
Evidence of infection should be clearly documented in the clinical record and on the prescription chart
Anti-bacterials must be reviewed daily and review/stop date adjusted
Stop anti-bacterials if cultures are negative
Switch to a narrower spectrum agent when possible
Use short course treatment if possible
