Antimicrobial Therapies Flashcards
What is an antibiotic
Antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms
What does bacteriocidal bacteria do
Kills bacteria
What does bacteriostatic bacteria do
Stops bacteria from growing
Why is antibiotic resistance bad
Requirement for additional surgeries More expensive therapy More toxic drugs Less effective second choice drug Increased time to effective therapy
What type of antibiotic is aminoglycosides
Bactericidal
What do aminoglycosides target
Protein synthesis (30s ribosomaml subunit), RNA proofreading and causes damage to cell membrane Toxicity is high - hearing loss
What type of antibiotic is rifampicin
Bactericidal
What does rifampicin target
RpoB subunit of RNA polymerase
Secretions go orange/red
Spontaneous resistance is frequent
What type of antibiotic is vancomycin
Bactericidal
What does vancomycin target
Lipid II component of cell wall biosynthesis as well as wall crosslinking via D-ala residues
Used against MRSA
What type of antibiotic is linezolid
Bacteriostatic
What does linezolid do
Inhibits the initiation of protein synthesis by binding to 50s rRNA subunit
Does not affect gram negative bacteria due to LPS in the membrane
What type of antibiotic is daptomycin
Bactericidal
What does daptomycin target
Bacterial cell membrane
Cannot target LPS in gram negative
Toxicity limits dose - only inpatient settings
What type of antibiotic is beta-lactams
Bacteriostatic
What do beta-lactams target
Interfere with synthesis of peptidoglycan compoment of the bacterial cell wall
What is selective toxicity
Target things in bacteria which aren’t present in humans
e.g. LPS layer and peptidoglycan layer
What do macrolides target
Gram positive but sometimes gram negative
Targets 50s ribosomal subunit preventing amino-acyl transfer and truncation of polypetides
What do quinolones target
DNA gyrase in gram neg
Topoisomerase 4 in gram pos
DNA damage and death of organism
What type of antibiotic is quinolones
Bactericidal
What is the breakpoint of antibiotics
Clinically-achieveable concentration of given antibiotic in host tissues
What is the minimal inhibitory concentration
Lowest concentration of drug to inhibit growth
What are the 4 mechanisms of antibiotic resistance
Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation
What is the action of altered target sites
Mutation in gene encoding target site
MRSA - alternative penicillin binding protein with low affinity to beta-lactams
Streptococcus pneumoniae - acquires genes which encodes enzyme that methylates target site
What is the action of inactivation of antibiotic
Beta-lactamase enzyme which inhibits the beta lactame ring
Enzymatic degradation of alteration of antibiotic
ESBL and NDM-1 - broad-spectrum beta-lactamase
What is the action of altered metabolism
Enzymes substrates are produced that outcompete target site
Bacteria switch to other metabolic pathways
What is the action of decreased drug accumulation
Decrease penetration of antibiotic
Increase efflux of AB out of the cell
What are some exogenous causes of antibiotic resistance
Plasmids - extra-chromosomal circular DNA
Transposons - DNA that jumps, integrate into chromosomal DNA
Naked DNA - DNA from dead bacteria
How to bacteria take up DNA
Transformation - take up DNA from environment
Transduction - Virus infect bacteria, take up DNA and then infect other bacteria
Conjugation - bacterial sex to share plasmids
Non-genetic mechanisms for treatment failure
Matrix incased communities of bacteria Intracellular location Slow growth - doesn't replicate fast Spores - antibiotic, antiseptic, heat resistant Persisters - dormant organisms
Other reasons for treatment failure
Inappropriate choice of organisms
Poor penetration of target site
Inappropriate dose
Inappropriate administration
What are some hospital acquired infections
Methicillin-resistant S. aureus Vancomycin-insensitive S aurues Clostridium difficle Vancomycin-resistant enterococci E coli P aeruginosa Acineterbacter baumannii Stenotrophomonas maltophilia
Risk factors for HAI
High number of ill people Crowded wards Presence of pathogens Broken skin Indwelling devices Transmission by staff
How do we address resistance
Tighter control Temporary withdrawal of antibiotics Restriction for serious infections Reduce use of broad-spectrum antibiotics Quicker identification of infections Combination therapy
How can beta lactams be modified to be more effective
Methicillin - prevent cleavage of beta-lactams
Augmentin - beta-lactamase inhibitor
How can we prevent the gut flora biome from being destroyed
Use of non-pathogenic competitor strains
