Antimicrobial resistance Flashcards
What is prontosil?
First example of a sulphonamide antibiotic.
It is synthetic and bacteriostatic.
What is protonsil used for?
Use to treat UTIs (urinary tract infection), RTIs (respiratory tract infection), bacteraemia (bacteria in blood stream) and prophylaxis (antibiotics given to present disease beforehand) in HIV sufferers.
What is the function of beta lactams?
They interfere with the synthesis of the peptidoglycan component of the bacterial cell wall. They bind to penicillin-binding proteins. These proteins usually catalyse a number of steps in the synthesis of peptidoglycan.
What are 2 examples of beta lactams?
Penicillin and methicillin
What is an antimicrobial?
Chemical that selectively kills or inhibits microbes
What is the dIfference between bactericidal, bacteriostatic and antiseptic.
Bactericidal - kills bacteria
Bacteriostatic - stops bacteria growing
Antiseptic - chemical kills or inhibits microbes that is used topically (are applied directly to skin or mucous membranes)
What is the minimal inhibitory concentration?
The lowest concentration of antibiotic required to inhibit growth. As bacteria become more resistant the MIC increases.
How does antibiotic resistance occur?
- A population of bacterial cells contain a few cells with antibiotic resistance due to random mutations in DNA.
- In the absence of selection pressure the resistant strains have no advantage or have a disadvantage and therefore there is a low prevalence of resistant strains in patient population.
- However in the presence of a selection pressure, for example antibiotics, the antibiotic resistant bacteria out-compete the wild type bacteria leading to high prevalence of antibiotic resistant strains in patient population.
What are 5 consequences of antibiotic resistance?
- Effective therapy takes longer
- Additional approaches e.g. surgery required
- More expensive
- More toxic drugs required e.g. vancomycin
- Use of less effective antibiotics
GIve 5 examples of gram negative antibiotic resistant bacteria
- Pseudomonas aeruginosa - cystic fibrosis
- E-coli - neonatal meningitis, septicaemia, UTI/GI infection
- Salmonella - GI infection, typhoid fever
- Acinetobacter baumannii (MDRAB) - UTI, pneumonia
- Neisseria gonorrhoeae - gonorrhoea
Give 5 examples of gram positive antibiotic resistant bacteria
- Staphylococcus aureus (MRSA, VISA) - pneumonia, septicaemia, infective endocarditis
- Streptococcus pneumoniae - pneumonia, septicaemia
- Clostridium difficile - Antibiotic associated diarrhoea
- Enterococcus - UTI, bacteraemia, infective endocarditis
- Mycobacterium tuberculosis - tuberculosis
What are aminoglycosides?
Bactericidal antibiotics that target protein synthesis, RNA proofreading and cause damage to cell membrane.
2 examples of aminoglycosides
Gentamicin and streptomycin
What is rifampicin?
Bactericidal antibiotic that targets the RNA polymerase beta subunit and causes secretions to go orange/red.
Spontaneous resistance is frequent.
Vancomycin
A bactericidal antibiotic that targets the lipid component of cell wall biosynthesis as well as crosslinking D-alanine residues.
Has limited use due to its toxicity however is become more common due to bacteria being resistant to most other types of antibiotics.
Linezolid
A bacteriostatic antibiotic which inhibits the intiation of protein synthesis by binding to the 50S rRNA subunit.
Daptomycin
A bactericidal antibiotic that targets the bacterial cell membrane.
Give 3 examples of antibiotics that inhibit cell wall synthesis
Penicillin, Cephalosporins and vancomycin
Give 3 examples of antibiotics that inhibit protein synthesis
Streptomycin, Erythromycin and tetracyclines
Give 2 examples of antibiotics that inhibit nucleic acid replication and transcription
Quinolones, rifampin
Give 1 example of an antibiotic that injures the plasma membrane
Polymyxin B
Give 2 examples of antibiotics that inhibit the synthesis of essential metabolites
Sulfanimide, trimethoprim
What are the 4 mechanisms of antibiotic resistance?
- Altered target site
- Inactivation of antibiotic
- Altered metabolism
- Decreased drug accumulation
2 examples of bacteria that alter target sites
Staphylococcus aureus (MRSA) - encodes an alternative penicillin binding protein with a low affinity for beta lactams
- Streptococcus pneumoniae - acquires the erm gene which encodes an enzyme that methylates the antibiotic target site of erythromycin.
Give 2 examples of enzymes that can inactivate antibiotics
- beta-lactamase
2. chloramphenicol acetyl-transferase
How might altered metabolism lead to antibiotic resistance?
Increased production of an enzyme substrate that out competes the antibiotic inhibitor. For example the production of PABA confers resistance to sulfonamides.
How might decreased drug accumulation lead to antibiotic resistance?
Reduced penetration of antibiotic into bacterial cell or increased efflux of antibiotic out of cell prevents antibiotic from reaching threshold concentration required for the drug to be effective.
2 examples of macrolides and mechanism
Erythromycin and azithromycin
Targets 50S ribsomal subunit preventing amino-acyl transfer and thus truncation of polypeptides.
What are quinolones?
Synthetic broad spectrum bactericidal antibiotic that inhibits DNA replication.
3 sources of antibiotic resistant genes
- Plasmids
- Transposons - these intergrate into plasmid and chromosomal DNA and allow the transfer of genes between both.
- Naked DNA - DNA from dead bacteria can be released into the environment.
3 ways genes responsible for antibiotic resistance can be shared between bacteria
- Transformation - uptake of extracellular DNA
- Conjugation - formation of a pilus between bacteria that transfers DNA.
- Transduction - DNA transfer between bacteria facilitated by virus
What could be other reasons for antibiotic treatment failure?
- Inappropriate choice of antibiotic for organism
- Poor penetration of antibiotic into target site
- Inappropriate dose
- Inappropriate administration (oral vs IV)
Give 5 examples of hospital acquired infections
- MRSA
- VISA
- Clostridium difficile
- Vancomycin-resistant enterococci
- E-coli
Give 7 risk factors for hospital acquired infections
- High number of ill people
- Crowded wards
- Presence of pathogens
- . Broken skin
- Indwelling devices
- Antibiotics may suppress normal flora
- Transmission by staff in contact with multiple patients
What is the role of commensal flora?
Commensal organisms can out-compete pathogens in our body with respect to adhesion, metabolism and growth. Therefore pathogens cannot colonise sufficiently for infection.
5 methods of addressing antibiotic resistance
- Prescribing strategies - tighter controls, temporary withdrawals of certain classes etc..
- Reduce use of broad-spectrum antibiotics
- Quicker identification of infections caused by resistant strains
- Combination therapy
- Knowledge of local strains/ resistance patterns
What are 2 reactive approaches to antibiotic resistance?
Modification of existing medications to enhance efficacy
- Use combinations of antibiotic and inhibitor
