antimicrobial chemotherapy Flashcards
What was the original penicillin?
benzylpenicillin (penicillin G)
How do penicillins work?
by binding bacterial transpeptidases, inhibiting cell wall formation
What is the functional unit in penicillin?
beta lactam ring
Which penicillin is naturally occuring?
benzylpenicillin (penicillin G)
Describe benzylpenicillin (penicillin G)
- poor oral bioavailibility
- rapid renal clearance, requires frequent dosing
Which penicillins are chemically modified penicillins?
- phenoxymethulpenicillin (pen V)
- amonipenicillins (e.g amoxicillin)
What is amoxicillin used against?
- S. pyogenes infections (sore throat, skin infections)
- pneumococcal infections (respiratory tract)
- susceptible E.coli infections (UTIs)
What is amoxicillins mechanism of action?
inhibition of bacterial cell wall synthesis
What is the standard dose for amoxicillin?
250-1000mg 8 hourly
What are some adverse effects of amoxicillin?
- allergy
- damage to commensal microflora
How is amoxicillin excreted?
urine
What are the mechanisms of resistance against amoxicillin?
- primarily enzymatic degradation
- target modification (e.g MRSA strains)
- efflux in some gram negatives
What is amoxicillins half life?
an hour
What are some interactions that amoxicillin can have?
can increase levels of other protein bound drugs
How is Staphylococcus aureus resistant to penicillin?
encode penicillinases which hydrolyse the beta-lactam ring
What were the first antibiotics developed to target the penicillin resistant strains of S. aureus?
- methicillin (not used clinically, only as a lab test)
- flucloxacillin (now the main one used)
What is co-amoxiclav?
amoxicillin plus clavulinic acid
How are MRSA strains now resistant to all beta-lactam antibiotics?
- target modification (modified transpeptidase enzyme)
- encoded by mecA gene
Why are mycoplasmas and chlamydias resistant to penicillin?
as they have no cell walls
How are most gram negative bacteria resistant to penicillin?
- most make beta lactamases
- develop resistance through other mechanisms like antibiotic efflux pumps
What are the 4 main ways bacteria become resistant to antibiotics?
- enzymatic degradation of the drug
- target modification
- efflux of antibiotic from bacteria
- reduced penetration through cell wall
What are some antibiotic sites of action?
- cell wall
- protein synthesis
- DNA replication
- RNA synthesis
- antimetabolites
What is the most common pathogen causing cellulitis?
Streptococcus pyogenes
What is clarythromycin?
a macrolide
What is clarythromycin used for?
used in patients that have a penicillin allergy
- S. pyrogenes infection (sore throat, skin infections)
- pneumococcal infections (respiratory tract)
- gram -ve infections such as haemophilus influenzae (respiratory tract)
What is clarythromycin’s mechanism of actions?
inhibition of protein synthesis in the bacterial ribosome (50S subunit)
What is clarythromycin’s standard dose?
500mg 12 hourly
What is clarythromycin’s half life?
1-6 hours
How is clarythromycin excreted?
metabolites in bile
What are the adverse effects on clarythromycin?
- nausea and diarrhoea
- may alter cardiac conduction, arrythmias
Which interactions can clarythromycin have?
inhibits enzymes (cytochrome p450 enzymes) involved in he metabolism of other drugs
What are the methods of resistance against clarythromycin?
primarily mutational target modification
What is vancomycin?
a glycopeptide
What is vancomycin active against?
- gram +ve bacteria
- many resistant strains including methicillin resistant S. aureus (MRSA)
What is vancomycin’s method of action?
inhibits bacterial cell wall formation by a different target to beta lactams
What is vancomycins method of resistance?
- target modification
- cell wall thickening, reduced penetration
What is the standard dose for vancomycin?
500-1500mg 12 hourly
- narrow therapeutic window, levels needed to kill bacteria are close to levels that are toxic to patients
What is vancomycin’s half life?
4-8 hours
What is vancomycins oral bioavailability?
very low
How is vancomycin excreted?
urine
What are some adverse effects of vancomycin?
- nephrotoxic
- ototoxic
What are some of the interactions that vancomycin has?
with any other nephrotoxic or ototoxic drugs
