Cephalosporins, Carbapenems, and Monobactams

Question 1

The cephalosporins are divided into generations based on:

Answer 1

• antimicrobial activity

- resistance to beta-lactamase enzymes

Question 2

Which is the only beta-lactam that does NOT exhibit cross-allergenicity?

Answer 2

aztreonam (a monobactam)

Question 3

Describe the structure of cephalosporins and how it relates to function.

Answer 3

contain a beta-lactam ring attached to a 6-membered dihydrothiazine ring; this confers greater stability against some beta-lactamase enzymes

Question 4

What are the 3 main mechanisms of resistance for the cephalosporins?

Answer 4

1) Production of beta-lactamase enzymes
2) Alteration of PBPs, leading to decreased binding affinity (MRSA, PRSP)
3) Alteration of outer membrane, leading to decreased penetration of PBPs

Question 5

What is the most common mechanism of resistance to the cephalosporins?

Answer 5

production of beta-lactamase enzymes (hydrolyze beta-lactam ring and cause inactivation)

Question 6

Which generation of cephalosporins is the most stable against beta-lactamase enzymes?

Answer 6

4th generation

Question 7

Which generation of cephalosporins has activity against anaerobes?

Answer 7

2nd generation (specifically, cephamycins)

Question 8

Which of the 3rd generation cephalosporins retain the best activity against gram (+) aerobes?

Answer 8

ceftriaxone and cefotaxime (esp. against PRSP)

Question 9

Which of the 3rd generation cephalosporins have activity against pseudomonas aeruginosa?

Answer 9

ceftazidime and cefoperazone

Question 10

Which is the only 4th generation cephalosporin currently available?

Answer 10

cefepime

Question 11

Which organisms are cephalosporins NOT active against?

Answer 11

• MRSA
• Enterococcus spp.
• Listeria monocytogenes
• Stenotrophomonas maltophilia
• C. diff
• Atypical bacteria (incl. Legionella)

Question 12

What are the major adverse effects associated with cephalosporins?

Answer 12

• hypersensitivity

- MTT side chain (leading to hypoprothrombinemia and ethanol intolerance)

Question 13

Which antibiotics are considered to be the most broad spectrum agents available?

Answer 13

carbapenems

Question 14

Which bacteria are NOT covered by carbapenems?

Answer 14

• MRSA
• PRSP
• VRE
• Coag. (-) Staph
• C. diff
• Atypical bacteria
• S. maltophilia

Question 15

The structural changes in carbapenems result in what?

Answer 15

extended spectrum of activity and beta-lactamase stability

Question 16

What are the 4 carbapenem antibiotics commercially available in the U.S.?

Answer 16

DEMI (doripenem, ertapenem, meropenem, imipenem)

Question 17

What is the primary target for carpanemens (MOA)?

Answer 17

PBP-2

Question 18

Which carbapenems are used more often for gram (+) vs. gram (-) aerobes?

Answer 18

• gram (+): imipenem and doripenem

- gram (-): meropenem and doripenem

Question 19

What is the only monobactam currently available?

Answer 19

aztreonam

Question 20

Which carbapenem is UNABLE to target Pseudomonas aeruginosa?

Answer 20

ertapenem

Question 21

Which carpabenem is the best for CSF penetration?

Answer 21

meropenem

Question 22

What is unique about elimination of imipenem?

Answer 22

It undergoes hydrolysis by a dihydropeptidase enzyme in the renal brush border to a nephrotoxic metabolike; thus, it is co-marketed with cilastatin, a DHP inhibitor, to reduce nephrotoxicity.

Question 23

What is an important carbapenem adverse effect to know?

Answer 23

CNS effects, including confusion, dizziness, hallucinations, and seizures
*risk factors for seizures=pre-existing CNS disorder, high doses, renal insufficiency

Question 24

Describe the spectrum of activity of monobactams.

Answer 24

preferentially work on gram (-) aerobes (including pseudomonas) and have little-no activity against gram (+)s or anaerobes.

Question 25

True or false: cephalosporins display effective activity against enterococcus.

Answer 25

False! The cephalosporins do NOT have activity against enterococcus.