Cephalosporins 1

Question 1

key features in cephalosporins

Answer 1

• 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

Question 2

• goals of cephalosporin structures

Answer 2

• increase spectrum of activity

- improve PK

Question 3

R1 modifications of cephalosporins associated with…..

Answer 3

• changes in antibacterial activity

Question 4

R2 modifications of cephalosporin’s associated with…..

Answer 4

• changes in pharmacokinetics and metabolism

Question 5

mechanism of action of cephalosporins

Answer 5

• 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

Question 6

T or F

Cephalosporin’s are bactericidal

Answer 6

• True

Question 7

6 P’s of resistance in cephalosporins

Answer 7

• 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)

Question 8

cephalosporins have no activity against…..think LAME

Answer 8

• Lysteris
• Atypicals
• MRSA
• Enterococci

Question 9

1st generation cephalosporins

Answer 9

• cephalexine

- cefazolin

Question 10

2nd generation cephalosporins

Answer 10

• cefuroxime
• cefoxitin
• cefprozil
• cefotetan
• loracarbef
• cafacor

Question 11

3rd generation cephalosporins

Answer 11

• cefpodoxime
• ceftriaxone
• cefixime
• cefotaxime
• ceftazidime
• cefdinir ceftibuten

Question 12

4th generation cephalosporins

Answer 12

• cefepime

Question 13

5th generation cephalosporins

Answer 13

• ceftaroline

Question 14

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

Answer 14

1st generation

Question 15

Cefazolin 1st gen cephalosporin treats

Answer 15

• S. pneumonia (+)
• strep pyogenes (+)
• MSSA (+)
• Proteus mirabillis (-)
• e. colo (-)
• Klebsiella pneumonia (-)

Question 16

1st gen cepehalosporins indicated for

Answer 16

• good alternative to antistaphylococcal penicillins
• skin and soft tissue infections
• surgical prophylaxis
• reoccurring endocarditits
• osteomyelitis
• cannot treat CNS infetions

Question 17

• 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

Answer 17

• 2nd gen cephalosporins

Question 18

• 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

Answer 18

• cephamycins

Question 19

cefotetan and cefoxitin can be classified as

Answer 19

cephamycins

Question 20

• these antibiotics are chemically incompatible w tetracycline, aminoglycosides and heparin by forming precipitates

Answer 20

• cephamycins (cefotetan and cefoxitin)

Question 21

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

Answer 21

• the methoxy group of C7

Question 22

3 major microrganisms that can be treated w 2nd gen cephs when compared to gen 1

Answer 22

• Neisseria
• Haemophilis influenza
• Enterobacter aerogenes

Question 23

2ng gen Cefuroxime coverage according to antibiotic map

Answer 23

• S. pneumonia (+)
• Strep pyogenes (+)
• MSSA (+)
• Proteus mirabilis (-)
• E. coli (-)
• Klebsiella pneumonia (-)
• N meningitides (-)
• H. influenza (-)

Question 24

cefoxitin/cefotetan antiobiotic map coverage

Answer 24

• S. pnuemoniae (+)
• strep pyogenes(+)
• MSSA (+)
• Proteus mirabilis (-)
• E. coli (-)
• Klebsiella pneumonia (-)
• N meningitides (-)
• H. influenza (-)
• bacteriosides fragilis****important

Question 25

- greater gram neg activity thenprevious gens - good strep activity but less staph activity of previous gens - broad spectrum - strongest association w C. diff

Answer 25

3rd gen cephs

Question 26

common structural features in 3rd gen cephs

Answer 26

- R1 is an aminothiazolyl group that increases movement through outter cell membrane, increases PBO affinity and inreases gram neg b lactamase stability

Question 27

3rd gen cephs often used to treat:

Answer 27

- Neisseria gonnoreaha/meningitis - haemophilis meningitis - proteus - UTI E.coli - streptococcus pneumonia meningitis

Question 28

3rd gen ceph that treat spirochetes such as Borrelia burgdoferi (lymes disease)

Answer 28

- Cefdinir | - Cefixitime

Question 29

- 3rd gen targeted for s. pnuemoniae (pneumococcus)

Answer 29

- Cefotaxime | - Ceftriaxone (preffered bc of one dialy dosing)

Question 30

3rd gen that targets gram pos and gram neg anaerobes but NOT c.diff

Answer 30

- ceftizoxime

Question 31

- 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

Answer 31

- Citrobacter - Morganella - Providencia - Serratia - Enterobacter

Question 32

- 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

Answer 32

- Ceftazidime | - brand name is Avycaz

Question 33

antibiotic map coverage of ceftriaxone/cefotoxime 3rd gens

Answer 33

- S. pnuemoniae (+) - strep pyogenes(+) - MSSA (+) - Proteus mirabilis (-) - E. coli (-) - Klebsiella pneumonia (-) - N meningitides (-) - H. influenza (-) - Serratia (-) - Enterobacter spp (-)

Question 34

antibiotic map coverage of Ceftazidime (keep in mind this is less broad spectrum than regular 3rd gens)

Answer 34

- S. pnuemoniae (+) - strep pyogenes(+) - Proteus mirabilis (-) - E. coli (-) - Klebsiella pneumonia (-) - N meningitides (-) - H. influenza (-) - Serratia (-) - Enterobacter spp (-) - PSUEDOMONAL*** important