Ch 43 - Cephalosporins and Other Cell Wall Synthesis Inhibitors

Question 1

Where did cephalosporins originate?

Answer 1

From the Cephalosporium acremonium fungi

Question 2

How does the cephalosporins work?

Answer 2

They are analogous to penicillins in:

• binding to specific PBPs
• inhbition of cell wall synthesis by blocking the transpeptidase step of peptidoglycan synthesis
• activation of autolytic enzymes

Question 3

Are cephalosporins bactericidal or bacteriostatic?

Answer 3

bactericidal

Question 4

How are cephalosporins subdivided?

Answer 4

Into first, seconds, third, and fourth generations.

- these classification are based on general features of antimicrobial activity

Question 5

In general, how do the characteristics of cephalosporins change from first- to fourth-generation agents?

Answer 5

• a decrease in gram-positive coverage
• an increase in gram-negative coverage
• an increase in CNS penetration
• an increase in resistance to β-lactamase

Question 6

First generation cephalosporins are active against which organisms?

Answer 6

• gram-positive cocci, including pneumococci, streptococci, and staphylococci.
• some gram-negative bacilli, including Preoteus mitabilis, Escherichia coli, and Klebsiella -> PEcK.

Question 7

Which drugs are in the first-generation cephalosporins, and what is the route of administration?

Answer 7

• cefadroxil -> oral
• cephalexin -> oral
• cephradine -> oral
• cefazolin -> IV

Question 8

Name some second-generation cephalosporins and state the route of administration:

Answer 8

• cefaclor -> PO
• cefuroxime axetil -> PO
• loracarbef -> PO
• cefprozil
• cefotetan -> IV
• cefoxitin -> IV
• cefuroxime -> IV

Question 9

What infections can be treated with second-generation cephalosporins?

Answer 9

• they cover the same organisms as first-generation cephalosporins, but they also have somewhat increased activity against Gram-negative organisms including Haemophilus influenzae, Neisseria, and Enterobacter.
• cefoxitin, cefmetazole, and cefotetan canbe used to treat anaerobic and aerobic infections, such as those that affect the intra-abdominal area

Question 10

Name third-generation cephalosporins and state the route of administration:

Answer 10

• cefoperazone -> IV
• cefotaxime -> IV
• ceftazidime -> IV
• ceftizoxime -> IV
• ceftriaxone -> IV
• cefpodoxime -> PO
• cefdinir -> PO
• ceftibuten -> PO

Question 11

What infections can be treated with third-generation cephalosporins?

Answer 11

• they provide expanded Gram-negative coverage but poor gram positive coverage
• good against Enterobacter, Citrobacter, and Providencia as well as β-lactamase-producing strains of Neisseria and Haemophilus.
• Pseudomonas infection can be treated with ceftazidime and cefoperazone

Question 12

Name fourth-generation cephalosporins and state the route of administration:

Answer 12

cefepine -> IV only

Question 13

What is the spectrum of fourth-generation cephalosporins?

Answer 13

• an expanded range of Gram-positive and Gram-negative organisms over third generation
• better Pseudomonas coverage
• more stable against β-lactamase
• not active against MRSA, enterococci, B. fragilis, or L. monocytogenes

Question 14

What are the cephalosporins inactive against?

Answer 14

all cephalosporins are inactive agains enterococci, methicillin-resistant staphylococci, Listeria monocytogenes, and Clostridium difficile

Question 15

How are the cephalosporins primarily excreted?

Answer 15

• through glomerular filtration

- cefoperazone and cetriaxone are exceptions, they are excreted in bile

Question 16

Are cephalosporins metabolized extensively?

Answer 16

they are excreted largely unchanged

Question 17

How does resistance occure (cephalosporins)?

Answer 17

through the same mechanisms as penicillin

Question 18

In general, what are the adverse effects of the cephalosporins?

Answer 18

• hypersensitivity
• nephrotoxicity
• intolerance to alcohol
• positive Coomb´s test result
• hypothrombinemia

Question 19

• intolerance to alcohol

Answer 19

(a disulfiram type reaction) with cefotetan and cefoperazone

Question 20

• positive Coomb´s test result

Answer 20

but rarely associated with hemolytic anemia

Question 21

• hypothrombinemia

Answer 21

with cefoperazone due to vitamin K inhibition

Question 22

Monobactams =

Answer 22

aztreonam

Question 23

Describe the mechanism of action of the monobactams:

Answer 23

monobactams disrupt bacterial cell wall synthesis by binding to PBPs and inhibiting peptidoglycan synthesis

Question 24

Describe the pharmacokinetics of aztreonam:

Answer 24

aztreonam is administered via IV or IM routes and is excreted in urine

Question 25

What are the clinical indications of aztreonam?

Answer 25

primarily aerobic Gram-negative rods (pseudomonas, klebsiella, serratia)

Question 26

What are the adverse effects of aztreonam?

Answer 26

• skin rash
• elevated liver function enzymes
• GI distress (nausea, vomiting)

Question 27

What are carbapenems?

Answer 27

• they are synthetic β-lactam antibiotics that are structurally related to the penicillins
• they are resistant to β-lactamase

Question 28

Give two examples of carbapenems:

Answer 28

• imipenem, prototype

- meropenem

Question 29

How are the carbapenems administered?

Answer 29

IV

Question 30

What is the antibacterial spectrum of carbapenems?

Answer 30

• Imipenem: is a bactericidal agent active against virtually all Gram-positive, Gram-negative, and anaerobic organisms
  
  • Methicilin-resistant Staph, vancomycin-resistant enetrococci (VRE), and Clostridium difficile are important exceptions