Lecture 9: Antimicrobial Chemotherapy Flashcards
what was the first penicillin
benzylpenicillin
how do penicillins work
bind bacterial transpeptidases (involved in peptidoglycan synthesis)
how are penicillins excreted
in urine, so have to make sure the patient has a functioning kidney before prescribing
what is the functional unit of penicillins
beta lactam ring
characteristics of benzylpenicillin
- must be injected intravenously and is degraded by stomach acid when taken orally
- has rapid renal clearance, so requires frequent dosing (6x a day)
characteristics of phenoxymethylpenicillin
- chemically modified benzylpenicillin
- orally active
- rapid renal clearance, needs dosing of 6x a day
characteristics of aminopenicillin
- orally active and long half life, taken 3x a day
- eg amoxicillin
which bacteria aren’t affected by penicillins
pseudomona bacteria, so have developed special antipseudomonal penicillins eg piperacillin
which bacteria are resistant to penicillin and how did it develop this
staphylococcus aureus, developed beta-lactamases which hydrolyse the beta-lactam ring
which drugs are unaffected by beta-lactamases
methicillin and flucloxacillin
features of beta-lactamase inhibitors
- have weak antibiotic activity
- are competitive inhibitors
- example is clavulinic acid
- widely used now is co-amoxiclav which is a mix of amoxicillin and clavulinic acid
what is MRSA resistant to and how
- all beta-lactam antibiotics
- acquisition of mecA gene which encodes a different transpeptidase enzyme that doesn’t bind penicillins
which bacteria is universally sensitive to penicillin
streptococcus pyogenes
how do many Gram negatives develop resistance
- make beta lactamase
- antibiotic efflux pumps
which bacteria are resistant to penicillins and why
mycoplasmas and chlamydias as they have no cell wall
what are the main ways of developing antibiotic resistance
- enzymatic degradation of the drug
- target modification
- efflux of antibiotic from the bacteria
- reduced penetration through the cell wall
what are cephalosporins
- a big family of beta lactams
- have two modifiable side chains
- product of cephalosporium acremonium mould
- have altered water solubility, delayed excretion, activity against transpeptidases of different bacterial species and resistant to beta lactamases
what are the generations of cephalosporins and how are they taken
1: cephalexin, orally
2: cefuroxime, IV and orally
3: ceftriaxone, IV only
4: cefepime, IV only
features of macrolides
- eg clarythromycin
- bind the 50S subunit of bacterial ribosome
- block protein synthesis
- some streptococcus are resistant due to target site mutations
reasons why antibiotics may be ineffective
- patient infected with resistant strain
- resistance develops on treatment (rare)
- wrong diagnosis
- wrong germ
- poor patient compliance
- poor tissue penetration due to obesity
what are the genetic bases for antibiotic resistance
- gene transfer through mobile genetic elements
- genetic mutations (rare)
