Treatment of bacterial infections Flashcards
What is an antibiotic?
Derived from microorganisms.
Can be broad or narrow spectrum.
Semisynthetic?
Chemical modification of antibiotics.
Synthetic?
Chemically synthesised in the lab (antibacterical).
What are the 4 key mechanisms of antibiotic action?
Inhibit bacterial cell well.
Inhibit bacterial DNA synthesis.
Inhibit bacterial protein synthesis.
Act as antimetabolites.
Staphylococcal aureus?
Gram +ve.
Grow in grape like clusters on skin and responsible for wound infections.
MRSA.
Streptococcal pneumoniae.
Gram +ve.
Grow in chain like clusters.
Cause pneumonia and meningitis.
Escherichia coli
Gram -ve.
Rod like
Many urinary tract infections.
Haemophilus influenzeae
Gram -ve.
Vaccination about HiB but other forms cause respiratory tract/ear infections.
Explain gram positive bacteria.
Peptidoglycan cell wall ~ 30nm
= thick, interacts with gram stain.
Plasma membrane.
Explain gram negative bacteria.
Outer membrane (protective) with water filled 'porin' channels. Proteins joining outer membrance to peptidoglycan (~3nm) across periplasmic space. Inner plasma membrane.
Stains poorly - thick outer membrane where stain can’t get through and then very thin peptidoglycan therefore takes up little stain.
Explain the bacterial peptidoglycan cell wall.
N-acetylmuramic acid (NAMA) and N-acetylglucosamine (NAG) are linked via sugar residues.
NAMA and NAMA peptide side chains are linked by amide linkage.
Explain the formation of the peptidoglycan cell wall.
NAMA, NAG and amide linkage (building blocks) are formed inside the cell and transported across the plasma membrane attached to a lipid transporter.
Released and linked to each other by TRANSGLYCOSYLASE enzyme into a linear strand.
Linear strand are crossed linked by TRANSPEPTIDASE.
Lipid transporter returns to the cell interior.
Explain the general inhibition of the cell wall production.
B-lactam antibiotics (bacteriocidal)
- penicillins, cephalosporins, carbapenems, monobactams.
They prevent the amide bonds forming between NAMA peptide side chains by inhibiting transpeptidase and transglycosylase.
Explain the structure of B lactam.
4 ring structure - highly reactive and interacts with transglycosylase and transpeptidase…therefore NO CELL WALL FORMATION.
What is the effect of changing th side chains of B lactam?
Alter…
…oral bioavailability (stability in stomach acid/interactions with food)
…susceptibility to B-lactamase
…spectrum of activity.
What is clavulanic acid?
Inhibits many forms of B-lactamase.
What is B-lactamase?
Destroys the B-lactam rings - doesn’t interact with and inhibit enzymes - cell wall is still produced.
Benzyl penicillin?
Pencillin antibiotic.
Pen G.
Broad spectrum, gram -ve, not orally active, susceptible to B-lactamase.
Methicillin?
Penicillin antibiotic - resistant to Blactamase but by other methods. Not orally active. nephrotoxic.
Axmocillin.
Penicillin antibiotic - administered with clavulanic acid - co-amoxiclav.
Name a cephalosporin antibiotic.
Cefalexin. Good for gram +ve not -ve, susceptible to B-lactamase.
Side effects of b-lactams?
Upset the gut flora - GI disturbances
Hypersensitivity reactions; rash - anaphylatic shock.
Convulsions if given intrathecally.
Name 3 other antibacterials that interfere with the cell wall production.
Cycloserine - prevent NAMA side chain formation
Vancomycin - inhibit release of cell wall building block from lipid transporter (good for +ve).
Bacitracin - prevent recycling of lipid transporter.
Explain the inhibition of DNA synthesis.
By Fluroquinolones eg ciprofloxacin.
Inhibit the folding of DNA by DNA gyrase
Good for +ve and -ve, orally active
BUT - doesn’t cross BBB, antacids prevent absorption from gut.
