Cephalosporins 1 Flashcards
key features in cephalosporins
- beta lactam ring attatched to 6 member ring
- aminoadipic side chains
- dihydothiazine ring
- acetooxy group off of R 2 (this is leaving group)
- double bond between C2 and C3 in 6 membered ring
- goals of cephalosporin structures
- increase spectrum of activity
- improve PK
R1 modifications of cephalosporins associated with…..
- changes in antibacterial activity
R2 modifications of cephalosporin’s associated with…..
- changes in pharmacokinetics and metabolism
mechanism of action of cephalosporins
- inhibit last step of bacterial cell wall synthesis aka transpeptidation
- block cross linking reaction of peptidoglycans in bacterial cell wall
- not effective against MRSA or MRE
T or F
Cephalosporin’s are bactericidal
- True
6 P’s of resistance in cephalosporins
- PBPs (alterations in targeted receptor structure)
- Penetrations (limited drug passage into human cells preventing access to intracellular organisms)
- Porins (resistance caused by decreased permeability of porin channel mostly gram neg)
- pathway/process (variation of folic acid
- penicillinase (bacterial enzymes causing destructionof rug molecule)
cephalosporins have no activity against…..think LAME
- Lysteris
- Atypicals
- MRSA
- Enterococci
1st generation cephalosporins
- cephalexine
- cefazolin
2nd generation cephalosporins
- cefuroxime
- cefoxitin
- cefprozil
- cefotetan
- loracarbef
- cafacor
3rd generation cephalosporins
- cefpodoxime
- ceftriaxone
- cefixime
- cefotaxime
- ceftazidime
- cefdinir ceftibuten
4th generation cephalosporins
- cefepime
5th generation cephalosporins
- ceftaroline
what generation of cephalosporins is this?
- potential sub for pen G
- R1 side chain confers restance to many b-lactamase enzymes
- not useful for anaerobes such as clostridia or gram neg bacteroides or haemophilus influenza
- cannot treat meningitis
- good against gram pos
- not active against enterococcus
- some gram neg, but not all bc ring gets cleaved
- not useful in intracellular infetions bc cannot penetrate human cells such as chlamydia, mycoplasma, legionella, brucella, rickettsia, mycobacteria or francisella
- active against gram neg proteus mirablis, E,coli, and Klesiella pnuemonia
1st generation
Cefazolin 1st gen cephalosporin treats
- S. pneumonia (+)
- strep pyogenes (+)
- MSSA (+)
- Proteus mirabillis (-)
- e. colo (-)
- Klebsiella pneumonia (-)
1st gen cepehalosporins indicated for
- good alternative to antistaphylococcal penicillins
- skin and soft tissue infections
- surgical prophylaxis
- reoccurring endocarditits
- osteomyelitis
- cannot treat CNS infetions
- have better gram neg activity than gen 1 and slightly less gram pos activity
- more stable to gram neg beta lactamase
- some (cefprozil/locarbef) treat influenza and niessieria gonorrhoeae
- most numerous generation but least utilized in US
- 2nd gen cephalosporins
- members of this subgroup of 2nd gen cephs have methoxy group on beta lactam ring
- relatively limited activity to gram pos so not as good as true 2nd gen
- parenteral use only
- advantage is some anaerobic or faculatative gram neg infections
- cephamycins
cefotetan and cefoxitin can be classified as
cephamycins
- these antibiotics are chemically incompatible w tetracycline, aminoglycosides and heparin by forming precipitates
- cephamycins (cefotetan and cefoxitin)
what makes the cephamycins different and thus more stable against b lactamases of gram neg anaerobes but also diminishes affinity for PBP’s of staph and strem
- this modificationis what changes spectrum when compared to regular 2nd gen cephs
- increases activity against gonorrhea
- the methoxy group of C7
3 major microrganisms that can be treated w 2nd gen cephs when compared to gen 1
- Neisseria
- Haemophilis influenza
- Enterobacter aerogenes
2ng gen Cefuroxime coverage according to antibiotic map
- S. pneumonia (+)
- Strep pyogenes (+)
- MSSA (+)
- Proteus mirabilis (-)
- E. coli (-)
- Klebsiella pneumonia (-)
- N meningitides (-)
- H. influenza (-)
cefoxitin/cefotetan antiobiotic map coverage
- S. pnuemoniae (+)
- strep pyogenes(+)
- MSSA (+)
- Proteus mirabilis (-)
- E. coli (-)
- Klebsiella pneumonia (-)
- N meningitides (-)
- H. influenza (-)
- bacteriosides fragilis****important
- greater gram neg activity thenprevious gens
- good strep activity but less staph activity of previous gens
- broad spectrum
- strongest association w C. diff
3rd gen cephs
common structural features in 3rd gen cephs
- R1 is an aminothiazolyl group that increases movement through outter cell membrane, increases PBO affinity and inreases gram neg b lactamase stability
3rd gen cephs often used to treat:
- Neisseria gonnoreaha/meningitis
- haemophilis meningitis
- proteus
- UTI E.coli
- streptococcus pneumonia meningitis
3rd gen ceph that treat spirochetes such as Borrelia burgdoferi (lymes disease)
- Cefdinir
- Cefixitime
- 3rd gen targeted for s. pnuemoniae (pneumococcus)
- Cefotaxime
- Ceftriaxone (preffered bc of one dialy dosing)
3rd gen that targets gram pos and gram neg anaerobes but NOT c.diff
- ceftizoxime
- some bacteria have rapily inducible b-lactamases and thus should be avoided by 3rd gen cephs or if do use them in combo, what are these bacteria?
hint pnemonoic: Cephs May Prove Sub Efficacious
- Citrobacter
- Morganella
- Providencia
- Serratia
- Enterobacter
- special 3rd gen engineered to be active against Pseudomonas by altering aminothiazolyl group with carboxypropyl group
- however decreases staph PBPs so lacks clinical efficacy of grampus
- not active on anaerobes or atypicals
- Ceftazidime
- brand name is Avycaz
antibiotic map coverage of ceftriaxone/cefotoxime 3rd gens
- S. pnuemoniae (+)
- strep pyogenes(+)
- MSSA (+)
- Proteus mirabilis (-)
- E. coli (-)
- Klebsiella pneumonia (-)
- N meningitides (-)
- H. influenza (-)
- Serratia (-)
- Enterobacter spp (-)
antibiotic map coverage of Ceftazidime (keep in mind this is less broad spectrum than regular 3rd gens)
- S. pnuemoniae (+)
- strep pyogenes(+)
- Proteus mirabilis (-)
- E. coli (-)
- Klebsiella pneumonia (-)
- N meningitides (-)
- H. influenza (-)
- Serratia (-)
- Enterobacter spp (-)
- PSUEDOMONAL*** important
