Cell Wall Inhibitors

Question 1

Are β-Lactams bactericidal or bacteriostatic?

Answer 1

Bactericidal

Question 2

What is the mechanism of action of β-Lactams?

Answer 2

Inhibit cell wall synthesis

Question 3

What is the generic structure of cephalosporins comprised of?

Answer 3

A = dihydrothiazine ring
B = β-lactam ring
R = acyl side chain adaptations

Question 4

What is the mechanism of action of cephalosporins?

Answer 4

Interfere with cell wall synthesis by binding to penicillin-binding proteins (PBPs) located in bacterial cell walls. Inhibition of PBPs leads to inhibition of the final transpeptidation step of peptidoglycan synthesis.

Question 5

What are the 3 mechanisms of resistance to cephalosporins?

Answer 5

• Production of ß-lactamase
• Alteration of PBPs
• Alteration of outer membrane permeability that interferes with PBP access by the drug

Question 6

What is the general action of 1st generation cephalosporins?

Answer 6

Best activity against gram-positive aerobes, with good activity against a few gram-negative aerobes

Question 7

What Gram (+) do 1st Gen cephalosporins hit?

Answer 7

Meth-susc S. aureus*
Pen-susc S. pneumoniae
Group streptococci
Viridans streptococci

Question 8

What Gram (-) do 1st Gen cephalosporins hit?

Answer 8

PEK
P. mirabilis
E. coli
K. pneumoniae

Question 9

What are the main examples of 1st Gen cephalosporins?

Answer 9

Cefazolin

Cephalexin

Question 10

What is the general action of 2nd generation cephalosporins?

Answer 10

In general, slightly less active against gram-positive aerobes, but more active against gram-negative aerobes

Question 11

Do 2nd generation cephalosporins have action against anaerobes?

Answer 11

The cephamycins of the second generation agents have activity against anaerobes.

Question 12

What Gram (+) do 2nd Gen cephalosporins hit?

Answer 12

Meth-susc S. aureus*
Pen-susc S. pneumoniae
Group streptococci
Viridans streptococci

Question 13

What Gram (-) do 2nd Gen cephalosporins hit?

Answer 13

HENPEK
H. influenzae
Enterobacter spp. (some)
Neisseria spp.
P. mirabilis
E. coli
K. pneumoniae

Question 14

What are examples of 2nd Gen cephalosporins?

Answer 14

Cefuroxime
Cefprozil
Cefoxitin
Cefotetan

Question 15

What are the cephamycins (2nd Gen)?

Answer 15

Cefoxitin
Cefotetan
Cefmetazole

Question 16

What are the cephamycins useful for?

Answer 16

Anaerobes. They are the only cephalosporins that have activity against anaerobes

Bacteroides fragilis

Question 17

What is the general action of 3rd generation cephalosporins?

Answer 17

In general, are less active against gram- positive aerobes, but have greater activity against gram-negative aerobes, including some β-lactamase-producing strains

Question 18

What Gram (+) do 3rd Gen cephalosporins hit?

Answer 18

Less Gram (+) action

Question 19

What Gram (-) do 3rd Gen cephalosporins hit?

Answer 19

HENPECKSSS
H. influenzae
E. coli
Neisseria spp.
P. mirabilis
E. coli
Citrobacter spp.
K. pneumoniae
Serratia marcescens
Salmonella spp. 
Shigella spp.

Question 20

What are examples of 3rd Gen cephalosporins?

Answer 20

Ceftriaxone
Ceftazidime
Cefpodoxime

Question 21

What are the 3rd Gen cephalosporins that have activity against P. aeruginosa?

Answer 21

Ceftazidime

Cefoperazone

Question 22

What is the general action of 4th generation cephalosporins?

Answer 22

Extended spectrum of activity
▪ Gram-positives: similar to ceftriaxone
▪ Gram-negatives: similar to ceftazidime, including Pseudomonas aeruginosa*; also covers β-lactamase producing Enterobacter spp.

Question 23

What is the only 4th Gen cephalosporin?

Answer 23

Cefepime

Question 24

What is the general action of 5th generation cephalosporins?

Answer 24

Extended activity vs
▪ Respiratory pathogens: H. influenzae, Strep pneumoniae, Moraxella, Staph aureus
▪ Gram + pathogens of SSSI: Strep pneumoniae, MRSA.

Question 25

What are cephalosporins generally ineffective against?

Answer 25

``` MRSA Enterococcus spp. Listeria monocytogenes Stenotrophomonas maltophilia Clostridium difficile Atypical bacteria, including Legionella ```

Question 26

What is the absorption of oral cephalosporins?

Answer 26

Oral cephalosporins are well absorbed, but achieve lower serum concentrations than parenteral

Question 27

Who does cephalosporin allergy occur most frequently in?

Answer 27

Hypersensitivity reactions to cephalosporins occur most frequently in patients with a history of penicillin allergy.

Question 28

What is the mechanism of action of carbapenems?

Answer 28

Inhibition of PBP-2 prevents cell wall synthesis and it penetrates the cell wall well.

Question 29

Are carbepenems bacteriostatic/cidal?

Answer 29

Time-dependent bactericidal

Question 30

What is the general use of carbapenems?

Answer 30

The carbapenems are currently the most broad-spectrum antibiotics, with good activity against many gram positive AND gram-negative aerobes AND anaerobes.

Question 31

What do carbapenems NOT have activity against?

Answer 31

The carbapenems do NOT have activity against methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, some enterococci, Clostridium difficile, Stenotrophomonas maltophilia, Nocardia, and atypical bacteria.

Question 32

What carbapenem does not have P. aeruginosa activity?

Answer 32

Ertapenem

Question 33

What can be administered with Imipenem to reduce renal toxicity?

Answer 33

Cilastatin

Question 34

Do carbapenems require dosage adjustment in renal failure patients?

Answer 34

All carbapenems require dosage adjustment in patients with renal dysfunction

Question 35

What is the clinical use of carbapenems?

Answer 35

Polymicrobial infections

Question 36

What is the mechanism of action of monobactams?

Answer 36

Like bicyclic β-lactam antibiotics, aztreonam is bactericidal because of its ability to bind to and inhibit PBPs and ultimately inhibit peptidoglycan synthesis, which is essential for the synthesis, assembly and maintenance of bacterial cell walls.

Question 37

What is the only monobactam?

Answer 37

Aztreonam

Question 38

What is the spectrum of aztreonam action?

Answer 38

Aztreonam preferentially binds to PBP-3 in gram-negative aerobic bacteria; therefore, aztreonam only has activity against gram-negative aerobes.

Question 39

Is aztreonam P. aeruginosa active?

Answer 39

Yes

Question 40

Do monobactams penetrate the CNS?

Answer 40

Yes

Question 41

What is the major clinical use of aztreonam?

Answer 41

Aztreonam is especially useful for the treatment of gram-negative infections in patients with a history of a severe penicillin allergy.

Question 42

Do monobactams need to be adjusted for renal failure patients?

Answer 42

Yes

Question 43

What is the clinical use of Gen 1 Ceph?

Answer 43

Skin infections | Some UTIs

Question 44

What is the clinical use of Gen 2 Ceph?

Answer 44

Cephamycins VS Gram (-) anaerobes

Question 45

What is the clinical use of Gen 3 Ceph?

Answer 45

Meningitis | Pneumonia

Question 46

What is the clinical use of Gen 4 Ceph?

Answer 46

P. aeruginosa

Question 47

What is the clinical use of Gen 5 Ceph?

Answer 47

Skin and Soft Tissue Infection