Cell Wall Synthesis

Question 1

Penicillin G, V

Answer 1

Prototype β-lactam antibiotics (penicillinase-sensitive)

• Penicilling G → IV and IM form
• Penicillin V → oral

Question 2

Penicillin G, V mechanism

Answer 2

1. Bind penicillin-binding proteins (transpeptidases).
2. Block transpeptidase cross-linking of peptidoglycan in cell wall.
3. Activate autolytic enzymes.

Question 3

Penicillin G,V clinical use

Answer 3

1. ​Mostly used for gram-positive organisms
   
   1. S. pneumoniae
   2. S. pyogenes
   3. Actinomyces
2. Gram negative cocci
   
   1. N. meningitidis
3. Spirochetes
   
   1. T. pallidum

Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes.

Penicillinase sensitive.

Question 4

Penicillin G, V toxicity

Answer 4

• Hypersensitivity reactions
• Hemolytic anemia

Question 5

Penicillin G, V resistance

Answer 5

Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

Question 6

Aminopenicillins

Answer 6

• ​amoxicillin
• ampicllin

Penicillinase-sensitive penicillins

Question 7

Aminopenicillin mechanism

(and bioavailability)

Answer 7

• Same as penicillin → wider spectrum,
• Penicillinase sensitive.
• Also combine with clavulanic acid to protect against destruction by β-lactamase.

(amoxicillin and ampicillin)

Note that amoxicillin has greater oral bioavailability than ampicllin.

Question 8

Aminopenicillin clinical use

Answer 8

Exteneded spectrum penicillin

1. H. influenzae (gram negative)
2. H. pylori (gram negative, oxidase positive, comma shaped)
3. E. coli (gram negative rod)
4. Listeria monocytogenes (gram positive rod)
5. Proteus mirabilis (gram negative rod)
6. Salmonella (gram negative rod)
7. Shigella (gram negative rod)
8. enterococci (gram positive cocci)

Question 9

Aminopenicillin toxicity

Answer 9

• hypersensitivity reactions
• rash
• pseudomembranous colitis (ie C. dif, a gram positive rod)

Question 10

Aminopenicillin resistance

Answer 10

Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

Question 11

Penicillinase-resistant penicillins

Answer 11

1. Dicloxacillin
2. Nafcillin
3. Oxacillin

Question 12

Penicillinase resistant penicillins mechanism

Answer 12

(dicloxacillin, nafcillin, oxacillin)

Same as penicillin → narrow spectrum.

Penicillinase resistant because bulky R group blocks access of β-lactamase to β-lactam ring.

Question 13

Penicillinase resistant penicillins clinical use

Answer 13

(dicloxacillin, nafcillin, oxacillin)

S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site).

Question 14

Penicillinase resistant penicillins toxicity

Answer 14

• Hypersensitivity reactions
• interstitial nephritis

Question 15

Antipseudomonals

Answer 15

• Piperacillin
• Ticarcillin

Question 16

Antipseudomonal mechanism

Answer 16

(piperacillin, ticarcillin)

Same as penicillin. Extended spectrum.

Question 17

Antipseudomonal clinical use

Answer 17

(piperacillin, ticarcillin)

Pseudomonas spp. and other gram-negative rods.

Susceptible to penicillinase; use with β-lactamase inhibitors.

Question 18

Antipseudomonal toxicity

Answer 18

(piperacillin, ticarcillin)

Hypersensitivity reactions.

Question 19

Beta lactamase inhibitors

Answer 19

1. Clavulanic Acid
2. Sulbactam
3. Tazobactam

Often added to penicillin antibiotics to protect the antibiotic from destruction by β-lactamase (penicillinase).

Question 20

Cephalosporins (generations 1-4) mechanism

[and what don’t they cover]

Answer 20

β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.

Organisms typically not covered by cephalosporins are LAME:

• Listeria
• Atypicals (Chlamydia, Mycoplasma)
• MRSA
• Enterococci

Exception: ceftaroline covers MRSA.

Question 21

First generation cephalosporins

Answer 21

1. Cefazolin (IV)
2. cephalexin (oral)

Question 22

First generation cephalosporin clinical use

Answer 22

1st generation (cefazolin, cephalexin)—

1. gram-positive cocci
2. gram-negative rods
   
   1. Proteus mirabilis
   2. E. coli
   3. Klebsiella pneumoniae

Cefazolin used prior to surgery to prevent S. aureus wound infections.

Question 23

Second generation cephalosporins

Answer 23

1. cefoxitin (IV)
2. cefaclor
3. cefuroxime

Question 24

Second generation cephalosporin clinical use

Answer 24

2nd generation (cefoxitin, cefaclor, cefuroxime)—

1. gram-positive cocci
2. Haemophilus influenzae
3. Enterobacter aerogenes
4. Neisseria spp.
5. Proteus mirabilis
6. E. coli
7. Klebsiella pneumoniae
8. Serratia marcescens

Question 25

Third generation cephalosporins

Answer 25

1. ceftriaxone 2. cefotaxime 3. ceftazidime

Question 26

Third generation cephalosporin clinical use

Answer 26

3rd generation (ceftriaxone, cefotaxime, ceftazidime)—serious gram-negative infections resistant to other β-lactams. Ceftriaxone—meningitis, gonorrhea, disseminated Lyme disease (borrelia). Ceftazidime—Pseudomonas

Question 27

Fourth generation cephalosporins

Answer 27

cefepime

Question 28

Fourth generation cephalosporin clinical use

Answer 28

4th generation (cefepime)— gram-negative organisms with ↑ activity against Pseudomonas and gram-positive organisms.

Question 29

Fifth generation cephalosporins

Answer 29

Ceftaroline

Question 30

Fifth generation cephalosporin clinical use

Answer 30

5th generation (ceftaroline)— broad gram-positive and gram-negative organism coverage, including MRSA. Does not cover Pseudomonas.

Question 31

Cephalosporin toxicity

Answer 31

1. hypersensitivity reactions 2. autoimmune hemolytic anemia 3. disulfiram-like reaction 4. vitamin K deficiency 5. Exhibit cross-reactivity with penicillins, ↑ nephrotoxicity of aminoglycosides.

Question 32

Cephalosporin resistance

Answer 32

Structural change in penicillin-binding proteins (transpeptidases).

Question 33

Carbapenems

Answer 33

1. imipenem 2. meropenem 3. ertapenem (limited Pseudomonas coverage) 4. doripenem

Question 34

Carbapenem mechanism

Answer 34

Imipenem is a broad-spectrum, β-lactamase–resistant carbapenem. Always administered with *cilastatin* (inhibitor of renal dehydropeptidase I) to ↓ inactivation of drug in renal tubules.

Question 35

Carbapenem clnical use

Answer 35

(imipenem, meropenem, ertapenem, doripenem) * ​Gram-positive cocci * Gram-negative rods * Anaerobes Wide spectrum, but significant side effects limit use to life-threatening infections or after other drugs have failed. Meropenem has a ↓ risk of seizures and is stable to dehydropeptidase I.

Question 36

Carbapenem toxicity

Answer 36

* GI distress * skin rash * CNS toxicity (seizures) at high plasma levels

Question 37

Monobactams

Answer 37

Aztreonam

Question 38

Monobactam mechanism

Answer 38

Prevents peptidoglycan cross-linking by binding to penicillin- binding protein 3. * Less susceptible to β-lactamases. * Synergistic with aminoglycosides. * No cross-allergenicity with penicillins.

Question 39

Monobactam clinical use

Answer 39

Gram-negative rods only—no activity against gram-positives or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.

Question 40

Monobactam toxicity

Answer 40

Usually nontoxic; occasional GI upset.

Question 41

Glycopeptides

Answer 41

* Bacitracin * Vancomycin

Question 42

Vancomycin mechanism

Answer 42

Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal. Not susceptible to β-lactamases.

Question 43

Vancomycin clinical use

Answer 43

Gram-positive bugs only—serious, multidrug-resistant organisms, including * MRSA * S. epidermidis * sensitive Enteroccocus species * Clostridium difficile (oral dose for pseudomembranous colitis)

Question 44

Vancomycin toxicity

Answer 44

Well tolerated in general—but NOT trouble free. 1. Nephrotoxicity 2. Ototoxicity 3. Thrombophlebitis 4. diffuse flushing—red man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate)

Question 45

Vancomycin resistance

Answer 45

Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac.