Lecture 12: Antimicrobial Therapies Flashcards
How do Beta-lactam antibiotics work?
Interfere with synthesis of peptidoglycan component of bacterial cell wall.
Bind to penicillin-binding proteins —> catalyse no. Of steps in synthesis of peptidoglycan
Name some examples of beta-lactams.
Penicillin
Methicillin
What is an antibiotic?
An anti microbial agent produced by a microorganism that kills or inhibits other microorganisms.
What is an anti microbial?
Chemical that selectively kills or inhibits microbes (bacteria, fungi, viruses)
What is the difference between bactericidal and bacteriostatic antibiotics?
Bactericidal - kills bacteria
Bacteriostatic - stops bacteria growing
What is antiseptic?
Chemical that kills or inhibits microbes that is usually used topically to prevent infection
How does use of antibiotics lead to resistant strains of bacteria?
It is a selection pressure that selects for resistant strains. The resistant strains replicate whilst non resistant strains die out, so the process continues by natural selection.
Name some major antibiotic resistant bacterial pathogens. (Gram-negative)
Pseudomonas aeruginosa - CF, burn wound infections
E. Coli - GI infect, neonatal meningitis, septicaemia, UTI
Salmonella spp. - GI infect, typhoid fever
Acinetobacter Baumannii - opportunistic, wounds, UTI, pneumonia
Neisseria gonorrhoeae - gonorrhoea
Name some major antibiotic resistant bacterial pathogens. (Gram-positive)
staphylococcus aureus (MRSA, VISA) - wound + skin, pneumonia, septicaemia
streptococcus pneumoniae - pneumonia, septicaemia
clostridium difficle
enterococcus spp (VRE) - UTI, bacteraemia, infective endocarditis
mycobacterium tuberculosis - TB
How do aminoglycoside antibiotics work?
Bactericidal, target protein synthesis (30S ribosomal subunit), RNA proofreading and cause damage to cell membrane
What is a problem with aminoglycoside antibiotics?
They are quite toxic so they have limited use
How does Rifampicin work?
Bactericidal, targets RpoB subunit of RNA polymerase, spontaneous resistance is frequent, makes secretions go orange/red - affects compliance.
Name some examples of aminoglycoside antibiotics.
Gentamicin
Streptomycin
How does Vancomycin work?
Bactericidal, targets lipid II component of cell wall biosynthesis, as well as wall cross-linking via D-ala residues
How does Linezolid work?
Bacteriostatic - inhibits initiation of protein synthesis by binding to 50S rRNA subunit.
Gram-positive spectrum of activity
How does Daptomycin work?
Bactericidal, targets cell membrane, gram-positive spectrum of activity
What is selective toxicity?
The large number of differences between mammals and bacteria result in multiple targets for antibiotic therapy, so antibiotics target many different bacterial processes and are selectively toxic.
By what 4 mechanisms does antibiotic resistance occur?
- Altered target site
- Inactivation of antibiotic
- Altered metabolism
- Decreased drug accumulation
How can an altered target site arise and cause antibiotic resistance?
via acquisition of alternative gene or gene that encodes a target-modifying enzyme e.g. MRSA encodes alternative Penicillin binding protein (PBP2a) w/ low affinity for beta lactams
How can inactivation of antibiotics lead to resistance?
Enzymatic degradation or alteration, rendering antibiotic ineffective e.g. beta-lactamase (bla) and chloramphenicol acetyl-transferase (cat)
How can altered metabolism lead to antibiotic resistance?
Increased production of enzyme substrate can out-compete antibiotic inhibitor e.g. increased production of PABA (acid) confers resistance to sulphonamides or switch to other pathways reducing requirement of antibiotic
How can decreased drug accumulation lead to resistance?
reduced penetration of antibiotic into bacterial cell (permeability) and/or increased efflux of AB out of cell - can’t reach conc. required to be effective
How do macrolides work?
They target 50S ribosome subunit preventing amino-acyl transfer and stop the polypeptide from being completed - the chain keeps growing so the shape of the protein is wrong. (gram -ve and +ve)
How do quinolones work?
Bactericidal, target DNA gyrase in gram -ve and topoisomerase IV in gram +ve.
