Thursday, November 15, 2007

Chap 43: B-lactam abx + other cell wall inhibitors

- active structure: B-lactam ring
- group of families: penicillins, cephalosporin, monobactam, carbapanem - hence cross reaction can occur
- all b-lactams are renally excreted --> reduce in renal impairment

- penicillins - g+ve, g-ve cocci, g-ve rods resistant (e. coli)
- antistahy penicillins - nafcillin
- extended spectrum

Mechanism of action
- histology - layers of bacterial cell wall (1st two constitute cell wall)
  • outer membrane (only in g-ve, lipid layer)
  • peptidoglycan (very thick in g+ve)
  • periplasmic space - where b-lactamase work
  • cytoplasmic membrane - where b-lactams bine
  • - binds to protein PBP (penicillin binding protein) in cytoplasmic membrane in bac cell wall - inhibit cell wall synthesis

- timentin --> can cause bone marrow dysfunction --> neutropaenia/thrombocytopenia (think about used in febrile neutropaenia)
- antipseudomonal penicillins --> home IV on piperacillin not timentin due to stability of solution in the baxter pump

- more stable than penicillin
- not active against enterococci and Listeria
- 4 major groups of increasing g-ve cover
- 1st generation: cephalothin, cephalexin, cefazolin, cephradine, cephapirin
- 2nd: cefamandole, cefoxitin
- 3rd: ceftriaxone, cefotaxime

ID stuff
Ceftazidime vs cefepeme
- antipseudomonal
- similar to timentin but lacks g+ve cover as compared to cefepeme
- hence cefepeme is the abx of choice in neutropaenic pt - to cover g+ve
- but for pseudomonas alone - should use ceftaz but reserve as last agent

- aztreonam
- g+ve, pseudomonas, serratia cover

- clavulanic acid, sulbactam, tazobactams
- resemble B-lactam, but weak antibacterial action
- active against Staphy, H influenzae, N gonorrhoea, salmonella, shigella, E. coli, Klebsiella

- structurally similar to B-lactam abx
- covers everything but NOT

  • Enterococcus faecium
  • MRSA
  • C. difficile (use flagyl)
  • Burkholderia cepacia
  • Stenotrophomonas maltophilia (use bactrim)

- glycopeptide
- produced by Streptococcus orientalis
- inhibit cell wall synthesis
- has VRE and vancomycin resistant S. aureus (VRE significance - transmit VR into SA)
- syngergistic with genta and streptomycin against E faecium and E faecalis
- given IV, only orally for C. dificcile enduced enterocolitis (but due to emergency of VRE - metronidazole is used instead)
- SE: phlebitis, 'red man'/'red neck' syndrome - antihistamine release (give phenergan/slow down infusion)

- if someone on vancomycin - no use doing MRSA swab - it will come back -ve --> still needs isolation

- similar to vanco, but given IM and IV
- allows once daily dosing due to long T1/2 --> hence easier for home IV

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