Beta Lactam Antibiotics & Cell Wall Synthesis Inhibitors

Question 1

List the natural penicillins

Answer 1

1. Penicillin G - IV, IM

2. Penicillin V - PO

Question 2

List the anti-staphylococcal penicillins

Answer 2

1. Methicillin - *discontinue for clinical use
2. Oxacillin - PO
3. Dicloxacillin - PO
4. Nafcillin - IV, PO

Question 3

List the extended spectrum (amino-) penicillins and associated beta lactamase inhibitors

Answer 3

1. Ampicillin + sulbactam - IV

2. Amoxicillin + clavulanic acid - PO

Question 4

List the anti-pseudomonal penicillins and associated beta lactamase inhibitors

Answer 4

1. Ticarcillin + clavulanic acid - IV

2. Pipericillin + tazobactam - IV

Question 5

What are the clinical indications for use of natural penicillins (penicillin G, V)

Answer 5

Gram(+) cocci:

1. Strep pneumoniae* - pneumococcal pneumonia
2. Strep pyogenes - pharyngitis, Scarlet Fever
3. Strep viridans group - endocarditis

• = resistance significant

Question 6

Why were anti-staphylococcal penicillins created?

Answer 6

(Widespread penicillin G/V resistance due to bacterial production of beta lactamase prompted need to discover other penicillins that were less susceptible to degradation by beta lactamases (aka poor substrates for beta lactamases) and could cover strains of staph aureus, and gram(+) streptococci that produce beta lactamase

Question 7

Why do anti-staphylococcal penicillins have excellent activity against staph aureus?

Answer 7

(= methicillin, nafcillin, oxacillin, dicloxacillin)
chemical appendages make these penicillins poor substrates for beta lactamase –> excellent activity against staph aureus

Question 8

What gram (+) diseases do the extended spectrum amino-penicillins cover?

Answer 8

= ampicillin, amoxicillin
RESPIRATORY INFECTIONS - CAP, sinusitis, bronchitis, pharyngitis
- Amoxicillin is active against penicillin sensitive S.pneumonia and often used for pharyngitis in children because of “Taste”

Question 9

What gram(-) diseases do the extended spectrum amino-penicillins cover?

Answer 9

= ampicillin, amoxicillin
Bronchitis in COPD
*Respiratory infections

Question 10

Extended spectrum amino-penicillins are used against what gram(+) cocci and gram(-) organisms?

Answer 10

Gram(+) cocci:
1. Strep. pneumoniae*
2. Strep pyogenes*
3. Strep viridans group
4. Enterococci 
Gram(-): 
1. H. influenza*

*= Respiratory infections

Question 11

Anti-pseudomonal pencillins are used when?

Answer 11

= ticarcillin, piperacillin, (ureidopenicillin?)
Used when situation favors development of pseudomonas aeruginosa infections
- p. aeruginosa = opportunistic pathogen that can cause serious infections that are difficult to treat
**for EMPIRICAL therapy of serious infection, e.g. PNA, when suspected organisms are gram(-) and if pseudomonas aeruginosa is a concern

Question 12

What populations are at risk for pseudomonas aeruginosa infections?

Answer 12

Burn patients
Cystic fibrosis patients
Injection drug users
Immunosuppressed patients

Question 13

What are some examples of when you would use an anti-pseudomonal penicillin?

Answer 13

• Severe PNA in a hospitalized patient with structural lung disease (COPD)
• Neutropenic fever - sepsis
• Aspiration PNA in a hospitalized patient or stroke victim

Question 14

List the 1st generation cephalosporins

Answer 14

Cefazolin, cephalexin, cephradrine

Question 15

List the generation, route and distinctions for: cefazolin

Answer 15

1st generation
Parenteral, IV, IM
Penetrates well into BONE

Question 16

List the generation, route and distinctions for: cephalexin

Answer 16

1st generation
PO
2x daily for pharyngitis

Question 17

List the generation, route and distinctions for: cephradrine

Answer 17

1st generation
parenteral and oral
–

Question 18

What is the spectrum of activity for 1st generation cephalosporins?

Answer 18

Gram(+) cocci, streptococci and staph aureus. NOT ACTIVE AGAINST: MRSA, MRSE, enterococci

MRSE = methicillin-resistant staph epidermis

Question 19

What are the clinical uses for 1st generation cephalosporins?

Answer 19

Surgical prophylaxis if skin flora are likely pathogens; soft tissue and skin infections due to S. aureus, S. pyogenes

Question 20

List the 2nd generation cephalosporins

Answer 20

1. Cefoxitin
2. cefotetan
3. cefaclor
4. cefuroxime axetil

Question 21

List the generation, route, and distinctions for: cefoxiitn

Answer 21

2nd generation
IV, IM
Active vs anaerobes, e.g B. fragilis
(Same as cefotetan)

Question 22

List the generation, route, and distinctions for: cefotetan

Answer 22

2nd generation
IV, IM
Active vs anaerobes, e.g. B fragilis
(Same as cefoxitin)

Question 23

List the generation, route, and distinctions for: cefaclor

Answer 23

2nd generation
PO
Serum-sickness (skin and joint adverse reactions) in pediatrics

Question 24

List the generation, route, and distinctions for: cefuroxime axetil

Answer 24

2nd generation
PO
poor substrate for beta-lactamase

Question 25

What is the spectrum of activity for 2nd generation cephalosporins?

Answer 25

- less active than 1st generation agents vs gram(+) organisms - enhanced activity vs gram(-) = E.coli, Klebsiella, H.influenza, Moraxella catarrhalis, Proteus spp.

Question 26

What are the clinical uses for 2nd generation cephalosporins?

Answer 26

When facultative gram(-) bacteria and anaerobes are likely pathogens e.g. intra-abdominal and gynecological sepsis, surgical prophylaxis for intra-abdominal and colorectal surgery

Question 27

List the 3rd generation cephalosporins

Answer 27

1. Ceftriaxone 2. Cefotaxime 3. Cetazidime 4. Cefaperazone ALL PARENTERAL!!!!

Question 28

What is the generation and distinctions for: ceftriaxone

Answer 28

``` 3rd generation = parenteral Long t(1/2) ~8 hours, 1x daily Penetrates CSF and bone Active vs NEISSERIA GONORRHEA BILIARY CLEARANCE ```

Question 29

What is the generation and distinctions for: cefotaxime

Answer 29

3rd generation = parenteral | ENTERS CSF, USEFUL FOR MENINGITIS due to H.influenza, S.pneumonia, N.meningitidis

Question 30

What is the generation and distinctions for: cetazidime

Answer 30

3rd generation = parenteral | Active vs PSEUDOMONAS AERUGINOSA

Question 31

What is the generation and distinctions for: cefaperazone

Answer 31

Disulfiram like alcohol intolerance | Active vs pseudomonas aeruginosa

Question 32

What is the spectrum of activity for 3rd generation cephalosporins?

Answer 32

Comparable to 1st generation vs S.aureus, S. pneumonia, S. pyogenes And ENHANCED ACIVITY vs gram(-) rods, enteric organisms

Question 33

List the 4th generation cephalosporin

Answer 33

Cefepime

Question 34

List the generation, route, and distinctions for: cefepime

Answer 34

4th generation IV, IM - Activity > or = to cefotaxime vs gram(-) bacteria, H. influenza, N. gonorrhea, N. meningitidis - Excellent penetration into CSF - Activity similar to ceftazidime vs pseudomonas aeruginosa

Question 35

What is the spectrum of activity of 4th generation cephalosporins?

Answer 35

Exerts gram(+) activity comparable to 1st generation cephalosporins, combined with extended gram(-) activity of 3rd generation agents. Insensitive to many beta lactamases

Question 36

What is the name of the monobactam

Answer 36

Aztreonam

Question 37

What is the activity spectrum of the monobactam aztreonam?

Answer 37

Gram(-) RODS - e.g. Klebsiella, Pseudomonas, Serratia | NOT ACTIVE vs gram(+) spp or anaerobes

Question 38

What are the distinctions associated with the monobactam aztreonam?

Answer 38

- Binds to PBP 3 of gram(-) rods - Substitute for extended spectrum penicillin or gen 3,4 cephalosporins if these are contraindicated because of hypersensitivity - Safe alternate for aminoglycosides in elderly or in patients with renal impairment - Synergistic with ahminoglycosides - Parenteral IV, IM - NOT USED ALONE in empirical therapy because of its "narrow" spectrum of activity

Question 39

What are the names of the 3 carbapenems?

Answer 39

1. Imipenem/cilastatin 2. Meropenem 3. Ertapenem

Question 40

How is imipenem/cilastatin administered?

Answer 40

IV, IM

Question 41

List the names of the 5 drugs that are used to manage penicillin hypersensitivity or MRSA

Answer 41

1. Vancomycin 2. Erythromycin 3. Clindamycin 4. Tigecycline 5. Linezolid

Question 42

When do you use vancomycin?

Answer 42

1. Penicillin hypersensitivity 2. Narrow spectrum: gram(+) cocci including: A. MRSA - methicillin resistant staph aureus B. PRSP - penicillin resistant strep pneumo

Question 43

When do you use erythromycin?

Answer 43

1. Pencillin hypersensitivity 2. Narrow spectrum: gram(+) cocci and beta lactamase secreting staph aureus BUT NOT: - MRSA - PRSP (pencillin-resistant strep pneumo)

Question 44

What do you use with penicillin to decrease toxin synthesis in life threatening streptococcal toxic shock & necrotizing fasciitis?

Answer 44

Clindamycin

Question 45

When do you use tigecycline?

Answer 45

Broad spectrum including: - MRSA - VRE = vancomycin resistant enterococcus

Question 46

When do you use linezolid?

Answer 46

``` VRSA = vancomycin resistant staph aureus VRE = vancomycin resistant enterococcus ```

Question 47

Describe cell wall biosynthesis in gram(+) bacteria (strep, staph, enterococci)

Answer 47

Cell wall synthesis involves cross-linking a unique dipeptide D-ala-D-ala to a string of glycine (1) Subunit assembly (2) Peptidoglycan elongation (transglycosylase) (3) Peptidoglycan cross-linking (transpeptidase PBPs) PBP = penicillin binding protein

Question 48

What is the MOA of penicillins and related beta lactam antibiotics? (other penicillins, carbapenems, monolactams, cephalosporins)

Answer 48

Beta-lactams (e.g. penicillins) resemble D-ala-D-ala they inhibit cross-linking enzyme(s)/transpeptidase(s) --> inhibit transpeptidase(s) and related PBPs IRREVERSIBLY (peptidoglycan cross-linking step)

Question 49

How is nafcilin cleared? And what is its associated toxicity?

Answer 49

Clearance --> hepatic, biliary | Toxicity: hypersensitivity (like all the others) + increased p450 induction