10. Carbapenems. Monobactams. Beta-lactamase inhibitors. Pharmacotherapy of respiratory infectons.

Question 1

List the Carbapenems.

Answer 1

1. Imipenem
2. Meropenem
3. Ertapenem
4. Doripenem

“imi, mero, erta and dori”

Question 2

List the Monobactams.

Answer 2

1. Azetreonam

Question 3

What spectrum does Carbapenems cover?

Answer 3

1. Broadest spectrum of all B-lactams: Gram +/- anaerobes and aerobes, but still no intracellular
2. resistant to most beta-lactamases!
3. Effective for Staph (not MRSA), Strep (not penicillin-resistant pneumococci), Enterococci, Gram - rods (E. coli, etc.), Gram - cocci and anaerobes (B. fragilis) and Pseudomonas (exc. ertapenem)
4. Ineffective for C. difficile (a Gram + anaerobe)

Question 4

What spectrum does Azetreonam cover?

Answer 4

Narrow-spectrum only for Gram-negative aerobes (cocci + rods):

1. Gonococci,
2. Meningococci
3. E.coli
4. Pseudomonas (even aminoglycoside-resistant strains) etc.

Question 5

What is a pharmacokinetic importance of Imipenem?

Answer 5

That usually imipenem is in combo with cilastatin to inhibit degradation by renal dipeptidase.

Question 6

What is the DOA of Ertapenem?

Answer 6

Ertapenem has the longest duration of action.

Question 7

Can Meropenem penetrate the CNS?

Answer 7

Meropenems are excellent BBB penetration → good for Meningitis.

Question 8

What are the indications of Azetreonam?

Answer 8

Gram-neg infection if pt is allergic to other B-lactams.

1. Severe airway/urinary tract infections
2. Post-op infections
3. Sepsis
4. Meningitis

Question 9

What are the side effects of Azetreonam?

Answer 9

1. GI symptoms
2. Allergy (no cross-rxn with other B-lactam allergies!)

Question 10

How are the pharmacokinetics like for Azetreonam?

Answer 10

1. Given parenteral admin - IV or IM
2. Reaches high pulmonary concentration
3. Cleared renally

Question 11

What is the resistance mechanism behind Azetreonam?

Answer 11

Resistant to most beta-lactamases!

Question 12

What are the side effects of carbapenems?

Answer 12

1. Allergy: cross-allergy with penicillin exists
2. Skin rashes
3. GI effects: diarrhea, pseudomembranous colitis, nausea, vomiting
4. Seizures: more common with imipenem + in renal dysfunction

Question 13

What are the indications of carbapenems?

Answer 13

They are considered reserve abx only

1. Severe infections - meningitis, endocarditis, osteomyelitis, severe pneumonia
2. Polymicrobial infections
3. Sepsis
4. Acinetobacter first-line agent (except ertapenem). Some strains are carbapenem resistant “MACI” (multi-resistant acinetobacter) in which case highly nephro-/neurotoxic colistin is used instead.

Question 14

What is the resistance mechanism behind carbapenem therapy?

Answer 14

Resistance occurs only when microbe produces an ESBL, shows ↓ permeability (Gram negs) or have efflux pumps.

Question 15

What are the pharmacokinetic parameters like for Carbapenems?

Answer 15

1. ALL are parenteral and ALL are renally cleared
2. good tissue / fluid distribution, including CSF

Question 16

What are some contraindications of imipenem?

Answer 16

Imipenem is contraindicated in epilepsy due to ↑ seizure risk than other carbapenems.

Question 17

Which micro-organisms are ineffective to ertapenem therapy?

Answer 17

Ineffective for Pseudomonas and Acinetobacter!