Why are bacterial cell wall components important - Answer They are required for
division
They are also essential to maintain cell shape and structural integrity
What are bacterial cell walls made of - Answer 3D meshwork of peptide cross-linked
sugar polymers
They are unique to bacteria so are major targets for antibiotics
How thick is a gram positive bacteria - Answer 50-100 molecules thick
How thick is a gram negative bacteria - Answer 1 or 2 molecules thick
Process of peptidoglycan biosynthesis - Answer First is the synthesis of murein
monomers which occurs in the cytoplasm
Next the monomers are linked to transport lipids which assemble them into linear
polymers. They then export into the inner membrane
Then they are incorporated into peptidoglycan polymer. Transpeptidase crosslinks the
glycan strands in order to maintain structural integrity
How do beta lactam antibiotics kill - Answer They can kill susceptible bacteria by
inhibiting peptidoglycan transpeptidase so there is no cross linking
Or they can use penicillin and cephalosporins which also target other penicillin binding
proteins
What factors influence beta lactam activity - Answer Resistance
Enzymatic destruction
Biofilm formation
Density and age of infection
Enzymatic destruction as a factor that influences beta lactam activity - Answer Gram+ve
bacteria produce and secrete large amounts of beta lactamases
Gram -ve produce smaller amounts in periplasmic space (strategic position)
Hydrolyse penicillins, cephalosporins
,Biofilm formation as a factor that influences beta lactam activity - Answer Bacteria that
grow on surfaces such as catheters, prosthetic joints and heart valves etc produce
more polysaccharide which makes it grow slower and so it is less sensitive
Density and age of infection as a factor that influences beta lactam activity - Answer
Number of resistant microorganism
Antibiotics most active in logarithmic growth phase
Properties of class penicillin - Answer Frequently administered with beta lactamase
inhibitor
Extended microbial activity for gram -ve
Bactericidal
Examples include amoxicillin and flucloxacillin
PK for penicillins - Answer Oral use
Therapeutic concentration in joint?
Pleural (lung)
Pericardial (around the heart) fluid
Bile
Rapid renal elimination = high concentration of drug in the urine
Short half life = 30-60mins
Unwanted effects of penicillin - Answer Normally well tolerated, high TI
Clinical use of penicillin - Answer Upper respiratory tract infections (URTI)
Urinary tract infections (UTI)
Salmonella infections
Properties of class cephalosporins - Answer Similar mechanisms of action to penicillin
More resistant to beta lactamase
Increase activity for gram -ve, increase BBB penetration and longer half life
, Examples of cephalosporins - Answer 1st gen - cefalexin
2nd gen - cefaclor
3rd gen - ceftriaxone
4th gen - cefepime
5th gen - ceftaroline
PK of cephalosporins - Answer Oral absorption except ceftriaxone which has to be
taken by IV or IM
Renal excretion, dose adjust in renal insufficiency except ceftriaxone does not need
much
High concentration in synovial joints and pericardial fluid
Ceftriaxone sufficient CNS penetration for meningitis Tx
Unwanted effects of cephalosporin - Answer Hypersensitivity similar to penicillins
Anaphylaxis, bronchospasm, urticarial
Maculopapular rash
Possible hepatotoxicity
Antibiotic associated colitis
Clinical use of cephalosporins - Answer 1st gen for skin and soft tissue infections
2nd gen for pneumonia and resistant/pregnancy UTI's
3rd gen for gonorrhoea, meningitis and CAP
4th gen for hospital acquired (nosocomial) infections
Properties of class carbapenems - Answer Similar mechanism of penicillins
Very resistant to beta lactamases
Broader spectrum than other beta lactams
Examples include imipenem, meropenem, ertapenem
PK of carbapenems - Answer Have poor oral BA
Renal excretion
Short half life except ertapenem, once daily dosing
Imipenem: rapid hydrolysis, partial inactivation (kidney) given with cilastatin
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