Micro - Antimicrobials (Other Antibiotics affecting bacterial cell walls)

Question 1

What kind of drugs are cephalosporins, and what is their general mechanism? How do they compare to Penicillin in terms of susceptibility to penicillinase? Are they bacteriostatic or bactericidal?

Answer 1

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

Question 2

What are the generations of cephalosporins?

Answer 2

Cephalosporins (generations I, II, III, IV, V)

Question 3

What organisms are typically not covered by cephalosporins? What is the exception?

Answer 3

Organisms typically not covered by cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci; Exception: ceftaroline covers MRSA

Question 4

What are 2 examples of 1st generation cephalosporins?

Answer 4

1st generation (cefazolin, cephalexin)

Question 5

What coverage do 1st generation cephalosporins provide?

Answer 5

1st generation (cefazolin, cephalexin) - gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae; Think: “1st generation - PEcK”

Question 6

What type of drug is cefazolin? How is it used clinically?

Answer 6

1st generation cephalosporin; Cefazolin used prior to surgery to prevent S. aureus wound infections

Question 7

What are 3 examples of 2nd generation cephalosporins?

Answer 7

2nd generation (cefoxitin, cefaclor, cefuroxime)

Question 8

What coverage do 2nd generation cephalosporins provide?

Answer 8

Gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcensens; Think: “2nd generation - HEN PEcKS”

Question 9

What are 3 examples of 3rd generation cephalosporins?

Answer 9

3rd generation (ceftriaxone, cefotaxime, ceftazidime)

Question 10

In general what kind of coverage do 3rd generation cephalosporins provide?

Answer 10

Serious gram-negative infections resistant to other Beta-lactams

Question 11

What kind of drug is ceftriaxone? What 2 conditions does it treat?

Answer 11

3rd generation cephalosporin; Ceftriaxone - Meningitis and gonorrhea

Question 12

What kind of drug is ceftazidime? What organism does it classically cover?

Answer 12

3rd generation cephalosporin; Ceftazidime - Pseudomonas

Question 13

What is an example of a 4th generation cephalosporin?

Answer 13

Cefepime

Question 14

What advantage in coverage do 4th generation cephalosporins have?

Answer 14

Increased activity against Pseudomonas and gram-positive organisms

Question 15

What is an example of a 5th generation cephalosporin?

Answer 15

Ceftaroline

Question 16

What coverage do 5th generation cephalosporins have? Which organism do they not cover?

Answer 16

Broad gram-positive and gram-negative organism coverage, including MRSA; does not cover Pseudomonas

Question 17

What are 2 toxicities of cephalosporins?

Answer 17

(1) Hypersensitivity reactions (2) Vitamin K deficiency

Question 18

What are 2 interactions that cephalosporins have with other drugs?

Answer 18

(1) Low cross-reactivity with penicillins (2) Increase nephrotoxicity of aminoglycosides

Question 19

What kind of drug is aztreonam? Is it susceptible or resistant to Beta-lactamases?

Answer 19

A monobactam; Resistant to Beta-lactamases

Question 20

What is the specific mechanism of aztreonam?

Answer 20

Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3

Question 21

With what other antimicrobial is aztreonam synergistic? With what other antimicrobial does it have no cross-allergenicity?

Answer 21

Synergistic with aminoglycosides. No cross-allergenicity with penicillins

Question 22

What is versus is not the coverage of aztreonam?

Answer 22

Gram-negative rods only - no activity against gram-positives or anaerobes

Question 23

What are 2 patient populations for which aztreonam may be used?

Answer 23

For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides

Question 24

What toxicity is associated with Aztreonam?

Answer 24

Usually nontoxic; occasional GI upset

Question 25

What are 4 examples of Carabapenems?

Answer 25

(1) Imipenem (2) Meropenem (3) Ertapenem (4) Doripenem

Question 26

What kind of drug is Imipenem? What kind of spectrum for coverage does it have? Is it Beta-lactamase susceptible or resistant?

Answer 26

Imipenem is a broad-spectrum, Beta-lactamase resistant carbapenem

Question 27

With what other drug is Imipenem always administered, and why? What is the mechanism of this other drug?

Answer 27

Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules; Think: “With imipenem, ‘the kill is lastin’ with cilastatin’”

Question 28

What are 2 newer carbapenems? Which has limited Pseudomonas coverage?

Answer 28

Newer carbapenems include ertapenems (limited Pseudomonas coverage) and doripenem

Question 29

What is the clinical use/coverage for carbapenems?

Answer 29

Gram-positive cocci, gram-negative rods, and anaerobes

Question 30

What kind of spectrum do carbapenems have? What is their limitation in clinical use, and why?

Answer 30

Wide spectrum, but significant side effects limit use to life-threatening infections or after other drugs have failed

Question 31

What are 2 advantages of Meropenem?

Answer 31

Meropenem has a decreased risk of seizures and is stable to dehydropeptidase I

Question 32

What are 3 toxicities associated with Carbapenems?

Answer 32

(1) GI distress (2) Skin rash (3) CNS toxicity (seizures) at high plasma levels

Question 33

What is the specific mechanism of Vancomycin? Is it bacteriostatic or bactericidal?

Answer 33

Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors; Bactericidal

Question 34

What is the coverage/clinical use of vancomycin?

Answer 34

Gram positive only - serious, multi-drug resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis)

Question 35

What are 4 toxicities associated with vancomycin?

Answer 35

(1) Nephrotoxicity (2) Ototoxicity (3) Thrombophlebitis (4) Diffuse flushing - Red Man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate); Think: “Well tolerated in general - but NOT trouble free”

Question 36

Which toxicity associated with vancomycin can be prevented? What is another name for this toxicity? How can it be prevented?

Answer 36

Diffuse flushing - Red Man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate)

Question 37

What is the mechanism of resistance to vancomycin?

Answer 37

Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac. Think: “Pay back 2 D-alas (dollars) for vandalizing (vancomycin”)