Lecture 8: Antimicrobial Chemotherapy Flashcards
How do penicillin’s work?
Penicillin’s act by binding bacterial transpeptidases (enzymes involved in peptidoglycans synthesis in both gram positive and gram negative bacteria) to inhibit cell wall formation.
Why can penicillin not be given to individuals with kidney problems?
Penicillin’s and beta-lactams are excreted intact in urine so cannot be given to individuals with kidney problems.
What is Benzylpenicillin (penicillin G)?
A naturally occurring penicillin that has poor oral bioavailability. Rapid renal clearance so requires frequent dosing.
What is Phenoxymethylpenicillin (Pen V)?
A chemically modified penicillin that is orally active but still has rapid renal clearance.
What is amoxicillin?
A chemically modified penicillin that has good oral bioavailability, a longer half-life than penicillin V, and better activity against some Gram negative bacteria.
Where is amoxicillin used?
Used in the treatment of S. pyogenes infections (sore throat, skin infections), pneumococcal infections (respiratory tract) and susceptible E. coli infections (urinary tract infection).
What is the mechanism of amoxicillin resistance?
Primarily enzymatic degradation and efflux in some gram negative bacteria’s.
What are the adverse effects of amoxicillin?
Allergy and damage to commensal microflora.
What are the 4 main ways bacteria become resistant to antibiotics?
- Enzymatic degradation
- Target modification
- Antibiotic efflux
- Reduced penetration through the cell wall
Why are different penicillin’s needed for different bacteria?
Different bacterial species have different transpeptidases (PBPs), which have the same function but different beta-lactam binding, and so different penicillin’s are required to treat them
How do enzymatic degradation mediate antibiotic resistance?
Enzymes hydrolyse the beta-lactam ring of penicillin “penicillinases” and this confers their resistance. Bacteria have gained a gene-encoded enzyme that breaks down beta-lactamase ring of penicillin.
What type of penicillin is able to treat bacteria that have a gene-encoded enzyme that breaks down beta-lactam ring?
Flucloxacillin
What is an example of a beta-lactamase inhibitor drug?
Co-amoxiclav
What causes antibiotic resistance?
Antibiotic resistance is an inevitable consequence of use. Antibiotic misuse leads to more resistance.
What is the most common pathogen causing cellulitis?
Streptococcus pyogenes (or S.aureus)
How does the drug clarithromycin work?
Clarithromycin is a macrolide which binds to 50S subunit of bacterial ribosome to block protein synthesis.
What are the adverse effects of clarithromycin?
Nausea and diarrhoea, and may alter cardiac conduction and cause arrhythmias.
What are the mechanisms of resistance to clarithromycin?
Primarily mutational target modification.
Why don’t antibiotics always work?
Metabolism, poor dispersal of antibiotics, multiple bacterial infections, and poor compliance with antibiotics. Antibiotics can also select out commensals which may then cause other infections.
How does vancomycin work?
Vancomycin is a glycopeptide drug that inhibits bacterial cell wall (peptidoglycans) formation by a different target to beta lactams.
What bacteria is vancomycin used against?
Used against Gram positive bacterial infections and is also active against many resistant strains including MRSA.
What are the adverse effects of vancomycin?
Nephrotoxic and ototoxic
What are the mechanisms of resistance against vancomycin?
Target modification and cell wall thickening of bacteria resulting in reduced penetration of drugs.
How are bacteria genetic modified to be resistant?
- Mobile genetic elements
2. Spontaneous mutations
