Cell Wall Inhibitors II: Cephalosporin, Carbapenems, Monobactams: 9/10/15

Question 1

From 1st generation to 5th generation, how do the cephalosporins vary in terms of susceptibility to beta lactamase and ability to kill gram negative and gram positive bacteria?

Answer 1

• decreased susceptibility to beta lactamase
• increased gram negative coverage
• decreased gram positive coverage

Question 2

What are three ways that cephalosporins/carbapenems/monobactum can confer resistance?

Answer 2

1. beta lactamase: destroy beta lactam on the abx
2. decreased cellular permeability via differential porin expression
3. varying the type of Penicillin binding protein (PBP) expressed on the cell surface

Question 3

What is the mechanism of action of Cephalosporins, monobactums, and carbapenems? Are they bactericidal or bacterial static?

Answer 3

• They inhibit the creation of peptidoglycan layer by binding the the penicillin binding protein found on the cell wall of the bacterial cell.
• Bactericidal

NOTE: this is not the same PBP that PCN binds to

Question 4

What are the SPICE bacteria and how are they related to cephalosporins?

Answer 4

• Serratia spp.
• Pseudomonas aeruginosa
• Indole positive Proteae (Proteus vulgaris, Morganella morganii, Providencia spp.)
• Citrobacter spp.
• Enterobacter cloacae

*Cephalosporins induce these bacteria to produce beta lactamase

*All gram negative

Question 5

Name the first generation cephalosporins

Answer 5

cefazolin

cephalexin

Question 6

Name the 2nd generation cephalosporins

Answer 6

cephamycins

carbacephems

cefuroxime

cefprozil

Question 7

Name the 3rd generation cephalosporins

Answer 7

ceftriaxone (tri = 3rd gen)

ceftazidime

cefpodoxime

Question 8

Name the monobactam abx

Concentration or time dependent?

Bactericidal or Bacteriostatic?

Answer 8

Aztreonam

Time dependent

Bactericidal

Question 9

Name the 4th generation cephalosporins

Answer 9

Cefapime

Question 10

Name the 5th generation cephalosporin

Answer 10

Ceftaroline

Question 11

Name the carbapenems

Concentration or time dependent?

Bactericidal or Bacteriostatic?

Answer 11

imipenem

doripenem

meropenem

ertapenem

Time dependent

Bacteridical

Question 12

*Ineffectiveness against p. aeruginosum and longer half life are chacterisitc of which carbapenem?

Answer 12

ertapenum

T1/2 = 4 hours; can be dosed once per day

Question 13

Which abx from the cephalosporin/carbapenum/monobactum group can be given when the pt has a allergy to penecillin?

Answer 13

aztreonam

• no cross allergenicity with PCN or other cephalosporins or carbepenems

Question 14

*What are the bacteria that carbapenems have NO activity against?

Answer 14

• VRE: vancomycin resistant enterococci
• PRSP
• Coag neg staph
• C. diff
• Atypical bacteria
• Strenotrophomonas
• MRSA

Resistant: Strep and staph + SACC

Question 15

Imipenem must be co-administered with _______ in order to prevent ________.

Answer 15

• cilastatin
• hyper clearance of the drug

Question 16

What are the three clinical uses of carbapenems?

Answer 16

• polymicrobial infections: BROAD spectrum activity
• beta lactamase producing bacteria infections: SPICE, MSSA, etc.
• empirical treatment of hospital/nosocomial infections

Question 17

What are targets of first generation cephalosporins?

Clinical uses?

Answer 17

gram positive

• MSSA

gram negative

• PEK: Proteus, E.coli, Klebsiella
• skin infections
• some UTIs
• surgical prophylaxis
• NO CNS penetration

Question 18

What are the targets of the second generation cephalosporins?

Clinical uses?

Answer 18

gram positive

• MSSA

gram negative*

• HENPEK: H. flu, Enterbacter, Neisseria spp. Proteus, E.coli, Klebsiella

Anaerobes*

• bacteroides: B. fragilis

*prophylaxis of abd surgery and polymicrobial infections

Question 19

What are the targets of the third generation cephalosporins?

Clinical uses?

Answer 19

gram positive

PRSP (penicillin resistant strep pneumo)

gram negative

HENPPECKSSS: H. flu, Enterbacter, Neisseria spp. Proteus, P. aeruginosa, E.coli, Citrobacter, Klebsiella, Salmonella, Shigella, Serratia

Clinical uses:

Pneumo

meningitis

Question 20

What are the targets of the fourth generation cephalosporins?

Clinical uses?

Answer 20

More potent and more stable against beta lactamase producing bacteria

Gram positive: PRSP

Gram negative: HENPPECKSSS

NO Anaerobes

*Pseudomonal infections

Question 21

What is the target of the 5th generation of cephalosporin?

Clinical uses?

Answer 21

respiratory pathogens

gram positive: S. pneumo and MRSA

Clinical uses

*Community acquired pneumonia

*skin infections

Question 22

IF one has an allergy to penicillin, can cephalosporins be used as an alternative treatment?

Answer 22

NO!

If a person has a PCN reaction, they will also have a reaction to cephalosporins AND carbapenems

If a person is allergic to one cephalosporin, they have an allergy to the others.

Question 23

What are the targets of the carbapenems?

Answer 23

Gram positive

• MSSA

Gram negative:

• enterobacteria
• P. aeruginosa (but not ertapenem)

Anaerobes

• bacteroides

Question 24

What adverse effects are associated with cephalosporins?

Answer 24

1. hypersensitivity: rash (treat) vs IgE rxn (don’t treat)
2. MTT side chain: 2nd and 3rd generations have side chain that may cause:

• disulfram rxn with ethanol consumption
• hypoprothrombinemia: due to excess Vita K

Question 25

What are the targets of Monobactam?

Answer 25

• Gram NEGATIVE aerobes: enterobacteriae
• P. aeruginosa

Question 26

What are the adverse effects of Monobactams?

Answer 26

hypersensitivity

GI: vomiting, nausea, diarrhea

Question 27

What are the adverse effects of carbapenems?

Answer 27

Hypersensitivity

GI

*CNS: seizures

Question 28

Which cephalosporins do NOT penetrate the CNS?

Answer 28

1st and 2nd generation

3rd generation = yes!