Cephamycins, Carbapenems, Streptogramins, Oxazolidinones& Glycopeptides

Question 1

What is a characteristic of Cephamycins that makes them more stable against B-lactamases?

Answer 1

they have a 7a-methoxyl group
-similar to 2nd generation cephalosporins

Question 2

What is a reaction with Cefotetan?

Answer 2

hypoprothrombinemia, disulfuram-like reaction w/alcohol

Question 3

What molecular characteristics are present in carbapenems?

Answer 3

-sulfur present in the thiazolidine ring (5-membered ring)of penicillins is replaced by a methylene group
-increases reactivity by making the molecule smaller & increases ring strain

Question 4

How are carbapenems hydrolyzed and how is it overcome?

Answer 4

hydrolyzed via dehydropeptidase-1 and is overcome by co-administering cilastatin with the carbapenem

Question 5

What is structurally unique about monobactams versus penicillins?

Answer 5

the carboxylic acid (-COOH) is replaced with a sulfamic acid

Question 6

What antibiotic is considered a monobactam and what is its spectrum?

Answer 6

Aztreonam
-gram - organisms; mainly used for penicillin resistant organisms

Question 7

What allergenicity concerns are there with monobactams?

Answer 7

only reactive with ceftazidime
-not reactive with penicillins/cephalosporins

Question 8

What is mechanism of action of Vancomycin?

Answer 8

vancomycin binds in a “cup-like” way to the side chain D-alanyl-D-alanyl terminus inhibiting the transpeptidase reaction

Question 9

What are the resistance mechanisms of Vancomycin?

Answer 9

VRE
D-Ala-D-Ala mutates to D-Ala-D-Lactate and causes vancomycin to have less affinity binding to it
-inhibits transglycosylation as well

Question 10

What adverse effect can happen with Vancomycin?

Answer 10

“red man” syndrome -red skin rash and potential anaphylaxis
-ototoxicity and nephrotoxicty

Question 11

What are members of the lipoglycopeptide family?

Answer 11

Oritavancin
Telavancin
Dalbavancin (2nd gen)
-differ in T 1/2’s

Question 12

What is synercid?

Answer 12

mixture (30 Quinupristin/ 70 Dalfopristin) which are analogs of pristinamycin

Question 13

What is the mechanism of action of Dalfopristin?

Answer 13

interferes with peptidyl transferase to form a peptide bond between the A-Site and P-Site (in the 50s subunit in the ribosome)

Question 14

What is the mechanism of action of Quinupristin?

Answer 14

binds in the ribosomal tunnel and causes blockage (like constipation)

Question 15

What is the therapeutic use of Synercid?

Answer 15

vancomycin-resistant enterococcus faecium (NOT faecalis); MRSA

Question 16

What is the resistance mechanism to synercid?

Answer 16

quinupristin resistance due to adenine methylation of A2058 in the 23S rRNA or efflux pumps or enzymatic inactivation (metabolism)

Question 17

What is the mechanism of action of Oxazolidinones?

Answer 17

interacts with 50S ribosomal subunit preventing its association with fMet-tRNA and a complex of the 30S ribosomal subunit to prevent the 70S initiation complex to form
-interacts with 23S rRNA

Question 18

What mechanism of resistance is present with Linezolid?

Answer 18

G to U substitution in the peptidyl transferase center of 23S rRNA at position 2576 reducing affinity of linezolid to the 50S subunit