micro lecture 4

Question 1

describe the structure of Cephalosporins or Cefalosporins

Answer 1

Cephalosporium (now Acremonium)

Nucleus + 2 main side chains (R1, R2)
“more” resistant to β-lactamases (not immune)

2 major sites are modified
s

Question 2

which sites on Cephalosporins on are usually modified for each generation

Answer 2

R1: antibacterial activity including changes water solubility and PBP affinity

R2: pharmacokinetic properties

Question 3

what is a first generation Cephalosporins and describe its modification and the aim behind it.

Answer 3

cefalexin

Good for: Activity vs. G+ cocci
R1 – protection from staphylococcal
β-lactamases but not Gram negatives
R2 – nothing of note

Question 4

what is a second generation Cephalosporins and describe its modification and the aim behind it.

Answer 4

cefuroxime

More activity vs. G- than 1st Gen
Slightly less activity against G+
R1, increased polarity, better porin entry
R2, minimal but again
quite polar

Question 5

what is a 3rd generation Cephalosporins and describe its modification and the aim behind it.

Answer 5

ceftriaxone, ceftazidime
R1 Polar: Increased porin penetration
Increased affinity for some PBPs
Increased stability vs. G- β-lactamases
ceftazidime active against Pseudomonas
R2 - ceftriaxone has a long half life

Question 6

what is a 4th generation Cephalosporins and describe its modification and the aim behind it.

Answer 6

cefepime (4th)

aminothiazolyl group on R1 and polar pyrolidine group on R2
Active against Pseudomonas

Question 7

what is a 5th generation Cephalosporins and describe its modification and the aim behind it.

Answer 7

ceftaroline (5th)

good activity against G+, including MRSA (PBP2a)

Question 8

_________has low risk of penicillin allergy

Answer 8

Carbapenems: e.g. Meropenem

Question 9

list facts about Carbapenems

Answer 9

Imipenem, meropenem, ertapenem, ...
VERY broad (G+, G-, Anaerobes)

Imipenem, meropenem also against Pseudomonas

Stable to many “normal” penicillinases (not to KPC and NDM among others)

Low risk for penicillin allergy

Question 10

what is an example of a monobactam

Answer 10

aztreonam

Question 11

list facts about monobactams

Answer 11

aztreonam

Narrow spectrum: aerobic G-
Lone β-lactam ring

Totally synthetic

Combines advantageous properties from 3G cephalosporins

Very low likelihood of reaction in penicillin-allergic patients (but R1 chain is very like ceftazidime)

Question 12

_____has a very low likelihood of reaction in penicillin-allergic patients (but R1 chain is very like ceftazidime)

Answer 12

monobactams