L27- β-lactams: cephalosporins

Question 1

Cephalosporins:

• bacterio-(static/cidal)
• (2) MOA
• (3) is the main mechanism of resistance
• (4) is the different in resistance compared to penicillin

Answer 1

1- bacteriocidal

2- β-lactam ring will bind and inhibit PBP and cell wall synthesis

3- PBP modification

4- β-lactamase is not as effective for cephalosporins –> rarely combined with β-lactamase inhibitor

Question 2

describe susceptibility of Gram+/- bacteria between all cephalosporin generations

Answer 2

1st: Gram+&raquo_space;> Gram-
2nd: Gram+ > Gram-

3rd: Gram+ &laquo_space;Gram-
4th: Gram+ = Gram-
5th: Gram+ &laquo_space;Gram-

Question 3

(1) is resistant to cephalosporin generations 1-4

(2) are resistant to all cephalosporins

Answer 3

1- MRSA

2- (LAME)
listeria, legionella
acinetobacter
mycoplasma
enterococci spp.

Question 4

1st Generation cephalosporins:

• (1) agents
• resistant to (2)
• effective against (3) bacteria

Answer 4

1- cefazolin, cephalexin

2- Staph. penicillinase (a β-lactamase)

3- Gram+: P. mirabilis, E. coli, K. pneumoniae

Question 5

1st generation cephalosporins are the drugs of choice for….

Answer 5

• Cefazolin and Cephalexin rarely used for infections

* Cefazolin for surgical prophylaxis (since they are usually Gram+ infections)

Question 6

2nd generation cephalosporins:

• (1) agents
• effective against (2)

Answer 6

1- cefaclor, cefoxitin, cefotetan, cefamandole

2- Gram+ bacteria (less than 1st), Gram- bacteria (more than 1st, less than 3rd, 4th, 5th)

Question 7

describe 2nd generation cephalosporin clinical uses

Answer 7

(cefaclor, cefoxitin, cefotetan, cefamandole)
-sinusitis, otitis, LRIs

Cefoxitin, Cefotetan- prophylaxis and therapy for abdominal / pelvic cavity infections (due to inc Gram- compared just to intra-abdominal - mostly Gram+, therefore 1st gen. cephalosporin)

Question 8

3rd generation cephalosporins:

• (1) agents
• effective against (2)

Answer 8

1- ceftriaxone, cefoperazone, cefotaxime, ceftazidime, cefixime

2- Gram- cocci mostly

Question 9

indicate the 3rd generation cephalosporin with the most clinical uses, and what it is the drug of choice for

Answer 9

Ceftriaxone:
-gonorrhea (in combination w/ erythromycin)

• empirically for meningitis
• prophylaxis for meniginits

-disseminated Lyme disease = CNS or joint involvement (not non-disseminated – use tetracycline)

Question 10

Cefaperazone, Ceftazidime has strong activity against ______ bacteria (specific)

Answer 10

(3rd gen. cephalosporins)

Pseudomonas aerugiosa

Question 11

4th generation cephalosporins:

• (1) agents
• effective against (2)

Answer 11

1- Cefipime

2- broad spectrum — Gram+/- bacteria

Question 12

Cefipime is often used to treat….

Answer 12

(4th gen. cephalosporin)
-mixed infections with susceptible organisms

-eg. complicated UTIs, complicated intra-abdominal infections, febrile neutropenia

Question 13

5th generation cephalosporins:

• (1) agent
• (2) route of administration
• (3) clinical uses

Answer 13

1- Ceftaroline

2- parenteral

3- MRSA (mainly Gram- bacteria)- restricted to this use

Question 14

Ceftaroline is often used to treat….

Answer 14

(5th gen. cephalosporin)

skin and soft tissue MRSA infections: especially if Gram- pathogens are co-infecting

Question 15

Cephalosporin Pharmacokinetics:

• (1) is the common route of administration, (2) are the exceptions
• (3) gen. are able to cross BBB and reach CSF
• (4) route of elimination, (5) are the exceptions

Answer 15

1- parenteral
2- Oral: cephalexin (1st), cefaclor (2nd), cefixime (3rd)

3- 3rd gen. (ceftriaxone, cefoperazone, cefotaxime, ceftazidime, cefixime) –> therefore used in meningitis prophylaxis

4- kidney, urine
5- ceftriaxone (3rd), cefoperazone (3rd) via bile

Question 16

Cephalosporin AEs:

• (1) possibly due to predisposition with penicillins
• (2) via IM admin.
• (3) via IV admin.
• (4) developing after therapy
• (5) via ceftriaxone (3rd)

Answer 16

1- cross-allergic reaction (although if minor penicillin allergy, usually no reaction –> give cephalosporin –> only avoid if severe penicillin reaction)

2- pain at injection site
3- thrombophlebitis

4- superinfection, eg. C. diff.

5- Kernicterus (neonatal brain damage via jaundice)

Question 17

(1) cephalosporins contain methyl-thiotetrazole group. These are able to cause (2) and (3) as AEs.

Answer 17

1- cefamandole (2nd), cefotetan (2nd), cefoperazone (3rd)

2- hypoprothrombinemia (Tx w/ vitK inj.)

3- disulfiram-like reactions (avoid alcohol)