Cephalosporins

Question 2

Describe the structural chemistry of cephalosporins?

Answer 2

Still BETA-lactams but differ in that the ring is a 6 membered ring not 5 (like in penicillins).
* Variations among the cephalosporins are made at the R1 position (alters spectrum of activity) or at the R2 position (alters pharmacokinetics).

Question 3

How are cephalosporins classified?

Answer 3

Classified based on their spectrum of activity into generations.
* The higher the generation, the wider the spectrum of activity.
* In general, as the spectrum of activity increases, there is less activity against gram positive cocci (Staph).
* None of the cephalosporins are effective against Enterococcus species, Listeria monocytogenes or MRSA.

Question 4

How are cephalosporins classified?

Answer 4

Classified based on their spectrum of activity into generations.
* The higher the generation, the wider the spectrum of activity.
* In general, as the spectrum of activity increases, there is less activity against gram positive cocci (Staph).
* None of the cephalosporins are effective against Enterococcus species, Listeria monocytogenes or MRSA.

Question 5

What happens to the spectrum of activity of cephalosporins against gram positive cocci (Staph) as the generation increases?

Answer 5

LESS ACTIVITY

Question 6

What species of bacteria are cephalosporins NOT effective against?

Answer 6

• Enterococcus, listeria, and monocytogenes or MRSA

Question 7

What are the FIRST generation cephalosporins (3)

Answer 7

Cefadroxil - ORAL
Cephalexin - ORAL
Cefazolin - IM/IV

Question 8

What are the second generation cephalosporins (FOUR)

Answer 8

Cefuroxime - ORal/IM/IV
Cefaclor - ORAL
Cefprozil - ORAL
Cefoxitin - IV

Question 9

What are the THIRD generation cephalosporins (FOUR)

Answer 9

Cefixime - ORAL
Cefotaxime - IM/IV
Ceftazidime - IM/IV
Ceftriaxone - IM/IV

Question 10

What are the fourth generation cephalosporins (two)

Answer 10

Cefepime - IM/IV
ceftobirole - IV

Question 11

What is the 5th generation Cephalosporin

Answer 11

Ceftolozane/Tazobactam - IV

Question 12

Which Generation of cephalosporins has the greatest activity of all cephalosporins against gram-positive cocci (Staph)

Answer 12

FIRST GENERATION (Cefazolin, Cephalexin and cefadroxil)

Question 13

What is the spectrum of activity of first gen cephalosporins?

Answer 13

Gram +ve
* methicillin-sensitive Staph aureus (often used as an alternative to cloxacillin) and Streptococci.

Gram -ve PEK
* Proteus mirabilis, E. coli, Klebsiella pneumoniae. * Cefazolin also covers H. Influenza, and Neiserria Gonnorhea.

MOSTLY MOUTH ANAEROBES

Question 14

What is the structure of second generation Cephalosporins?

Answer 14

Have an iminomethoxy group at the alpha position of the acyl side chain which greatly increase structural stability against beta-lactamases (i.e. H. Flu)

Question 15

Which second generation cephalosporin does food enhance its absorption?

Answer 15

cefuroxime

Question 16

Which second generation cephalosporin does food interfere the absorption of?

Answer 16

Cefaclor

Question 17

What is the spectrum of activity of SECOND GEN cephalosporins?

Answer 17

Gram +ve
* Methicillin-sensitive Staph aureus and Streptococci.
Gram -ve ** (HPEK)**
* Increased gram negative activity over the 1st Generation Cephalosporins.
* H. Influenza, and M. Catarrhalis, but still Proteus mirabilis (cefuroxime IV covers both species of proteus), E. coli, Klebsiella pneumonia. Anaerobes
* Mostly mouth anaerobes.

Question 18

How do the cephamycins (second gen cephalosporin cefoxitin) have different spectrum of activity?

Answer 18

Spectrum of activity of the cephamycins:
o E. coli, Klebsiella pneumoniae, Proteus (some strains), increased anaerobic, coverage, including Bacteroides Fragilis.
o Unreliable activity vs. gram positive bacteria.
o Cefoxitin is a good inducers of chromasomally-mediated BL; therefore, clinical use of these agents can select for resistant bacteria.

Question 19

Describe the structure of 3rd generation cephalosporins?

Answer 19

Have a aminothiazole ring instead iminomethoxy group (as second gen cephalosporins have) which increases their penetration through the outer membrane of the gram-ve bacteria thus increasing spectrum of activity.

Question 20

Which of the third gen cephalosporins are oral?

Answer 20

CEFIXIME - long half life and can be administered once daily

Question 21

Why is the third generation cephalosporin ceftriaxone avoided in neonates?

Answer 21

It has the potential to displace bilirubin.

Question 22

Which generation of cephalosporins cross the BBB and can be used to treat meningitis?

Answer 22

THIRD GEN - Cefotaxime (probably the best)

Question 23

Describe the spectrum of activity of third gen cephalosporins?

Answer 23

Gram +ve
- decreasing MSSA coverage (still okay), but equivalent strep coverage to first gen.
- Ceftazidime is the exception to the previous two points

Gram -VE
HENPEK
H. Influenza, Enterobacteriaceae, Neisseria (ceftriaxone and cefixime has good coverage), Proteus mirabilis, E.coli, and Klebsiella pneumonia

SPACE organisms:
Pseudomonas aeruginosa - Only Ceftazidime
Acinetobacter - only ceftazidime

Anareobes - mostly mouth

Question 24

Describe the 5th gen cephalosporin structure (Ceftolozane)

Answer 24

Ceftolozane is an oxyimino-aminothiazolyl cephalosporin with a pyrazole substituent at the 3position side chain instead of the lighter pyridium present in ceftazidime. This heavier sidechain provides improved steric hindrance to prevent hydrolysis mediated through AmpC βlactamases.

Question 25

Describe the spectrum of activity of 5th gen cephalosporin (Ceftolozane)

Answer 25

Gram +ve * Some streptococcal, very little staphylococcal and no enterococcal coverage.

Gram -ve (HENPEK)
Very comprehensive coverage similar to ceftazidime with extended coverage against ESBL producing E. Coli and Klebsiella species. This is primarily in vitro data and needs to be used cautiously until more data becomes available. * Enhanced coverage over Pseudomonas aeruginosa than ceftazidime * Less coverage than ceftazidime against Acinetobacter spp. and will not cover steno.

Anaerobes * Activity against b. frag is less predictable but some sources indicate susceptibility.