Penicillins

Question 1

Natural Penicillins

Answer 1

Penicillin G potassium (IV, IM) 
Penicillin Benzathine (IM depot) 
Penicillin Procaine G (IM) 
Effective against:
- gram positive bacteria 
- some gram negative coverage
- some anaerobic coverage 

no anti-pseudomonal
inactivated by penicillinase
kidney elimination
poor CNS penetration

Question 2

Penicillin MOA

Answer 2

MOA: binds to the PBP and inhibits crosslinking (trasnpeptidation rxn)
- bactericidal- only with autolysin activity

Question 3

Penicillinase Resistant Pencillins

Answer 3

Nafcillin, dicloxacillin, oxocillin
- Liver metabolism
Spectrum
- lower activity against certain gram-positive bacteria
- some gram negative and anaerobe coverage

• some are acid stable
• highly protein
  bound - implications for drug interactions and loading dose
• drugs of choice against penicillinase producing
  Staphylococcus aureus.
• more than 20% of S. aureus isolates are
  resistant (MRSA)!

Question 4

Extended Spectrum

Answer 4

Ampicillin, amoxicillin
Urinary excretion
Spectrum:
- lower gram pos. coverage
- extended gram negative coverage (E. coli,
Salmonella, Shigella, H. influenzae, Proteus).
- Anaerobic coverage when combined with penicillinase inhibitors
- no antipseudomonal activity

resistance develops frequently

• susceptible to B-lactamase
• acid resistant

Question 5

Antipseudomonal penicillins

Answer 5

Piperacillin, Ticarcillin
Piperacillin> ticarcillin
- Renal excretion

Spectrum
- spectrum: bacteria covered by the extended spectrum penicillins plus some additional enteric gram negative bacilli (Proteus, Enterobacter, Providencia and Serratia species)
major use: Pseudomonas aeruginosa and Acinetobacter)

Other:

• susceptible to b-lactamase
• Acid sensitive

Question 6

Penicillin AE

Answer 6

• Allergy
• 4 hypersensitivity rxns
• Tissue irritation (Esp with IM/IV)
• Excess Na/K+: renal and cardiac toxicity
• Soft frothy stools (extended
• Overgrowth of Staph, pseudomonals, proteus, yeast
• inflammation of the mucosal surfaces
• Jarish- Herixhiemer Rxn

Question 7

Monobactams

Answer 7

Aztreonman
- monocyclic beta lactam ring
Spectrum
- active against gram - rods (pseudomonas, and serratia)
- NO activity against gram positives and anerobes

• Safe in pts with penicillin allergy

Question 8

Carbapenems

Answer 8

Imipenem: cilastatin, meropenem, ertapenem, doripenem

Spectrum:

• Broad spectrum
• anerobes, gram +, gram- rods
• Given IV

Imipenem

• Cause seizure in pts with brain trauma, propensity for seizures etc
• inactivated by the dehydropeptidases in the renal system- cilastin inhibits this

Question 9

B- lactamase Inhibitors

Answer 9

Clauvonic Acid
Sulbactam
Tazobactam

• Inhibit many but not all B-Lactams- most successful with plasmid encoded

Fixed Combinations

• Ampicillin: Sulbactam
• Amoxicillin: clavuonic Acid
• Piperacillin, Tazobactam
• Ticeracillin Clavuonic Acid

Question 10

Mechanism of resistance to pencillin

Answer 10

1. Inactivation of B-lactam via B-lactamases
   - -> some may be inducible
2. Decreased cell wall permeability- pencillin ccannot get in
3. Alteration of the PBP- pencillin cannot bind
   - -> horizontal transfer
   - -> may be inducible
   - -> mecA gene– PBP2A- resistance to all b-lactams
4. Autolytic enzymes are not activated- creates a tolerant organism (listeria, and staph)
5. No cell wall - mycoplasma
6. No PG- chlamydia