Penicillins

Question 1

Beta Lactams

Answer 1

• Penicillins
• Cephalosporins
• Monobactams
• Carbapenems

Question 2

Beta-Lactam Mechanism of Action (MOA)

Answer 2

Inhibit cell wall synthesis by binding and inhibiting Penicillin-binding proteins (PBPs) located in bacterial cell membranes therefore they interfere with final step of peptidoglycan synthesis

Bactericidal in time-dependent manner (EXCEPT ENTEROCOCCUS spp.)

Question 3

Beta-Lactam Mechanism of Resistance (MOR)

Answer 3

1- Penicillinase (Beta-lactamase enzyme):
Most common MOR. Enzyme hydrolyzes the Beta-lactam ring, inactivating the antibiotic.

2-PBP Alteration:
Alteration of the PBP leads to decreased binding affinity of the antibiotic for the PBP.

3- decreased penetration:
Altering the outer membrane of the porin leads to a decrease in the penetration- this is only applicable to gram negative bacteria

Question 4

Beta- Lactam Pharmacokinetics

Answer 4

Short-elimination half-life so has to be dosed constantly

Eliminated by kidney (except nafcillin, oxacillin, ceftriaxone, cefoperazone)

Cross-allergenicity- except aztreonam

Question 5

Species that produce Beta-Lactamase enzymes (i.e. penicillinase)

Answer 5

Gram +: Penicillin-resistant S. Aureus
Gram-: H. Influenzae, Moraxella, N. Gonorrhea, E. Coli, Klebsiella pneumoniae, Enterobacter spp.

Gram - anaerobes: Bacteroides Fragilis

Question 6

Gram- positive beta-lactamase

Answer 6

Destroys the antibiotics extracellularly

Question 7

Gram- negative beta-lactamase

Answer 7

Attacks in the periplasmic space.

Beta-lactams come in through the porins. The beta lactamases will attack the beta lactam once it goes through the porins

Question 8

Organisms that alter PBP

Answer 8

MRSA

Penicillin-resistant S. Pneumoniae

Question 9

Natural Penicillin Spectrum of Activity

i.e. Penicillin G, Penicillin VK

Answer 9

Gram +:
Streptococci
Viridans Streptococci (Colon Cancer)

Gram -:
Nisseria spp.

Anaerobes:
Clostridium spp.

Spirochetes:
T. Pallidum

Question 10

Penicillinase-Resistant Penicillins

i.e. Nafcillin, Oxacillin, Methicillin

Answer 10

Gram +:

MSSA

Question 11

MRSA

Answer 11

caused PBP alteration mediated by mecA gene causing resistance to all beta-lactames EXCEPT CEFTAROLINE

Question 12

Aminopenicillins

i.e. Ampicillin and Amoxicillin

Answer 12

Gram +:
Enterococcus spp. Better activity than natural penicillin
Listeria monocytogenes

Gram -:
Proteus mirabilis
E. Coli
Salmonella
Shigella
BL-H. Influenzae
*Non-lactose fermenters)

Question 13

Carboxypenicillins

i.e. Ticarcillin

Answer 13

Gram -:
Pseudomonas Aeruginosa

High sodium load so be careful for patients with CHF

Question 14

Ureidopenicillins

i.e. Piperacillin

Answer 14

Anaerobes

Gram -:
Pseudomonas Aeruginosa
Klebsiella spp.

High sodium load so careful with patients with CHF

Question 15

Beta- Lactamase inhibitors Combos

i.e. Clavulanate- Ticarcillin, Ampicillin- Sulbactam, Piperacillin-Tazobactam, amoxicillin-clavulanate

Answer 15

Enhance activity of penicillins against beta lactamase producing bacteria

Gram +:
S. Aureus (Not MRSA)

Gram -:
H. Influenzae
Moraxella

Anaerobes:
Bacteroides spp.

Question 16

Penicillin Absorption

Answer 16

Degraded by Gastric Acid

PenVK absorbed better than oral PenG
Amoxicillin absorbed better than ampicillin
Dicloxacillin absorbed better than other PRPs

Question 17

Penicillin CSF Penetration

Answer 17

Only in presence of inflammed meninges

Question 18

Penicillin Elimination

Answer 18

Most eliminated by kidney

NB: Nafcillin & Oxacillin are eliminated primarily by the liver

Question 19

Augmentin (oral)

Answer 19

human or animal bite wounds

Question 20

Penicillin Adverse Effects

Answer 20

Hypersensitivity (Allergic reactions: Anaphylaxis and death):

  - Antibodies produces against metabolic by-products of the degradation of the antibiotic or the antibiotic itself
  - Desensitization is possible

Neurological: Seizures esp. in patients receiving high IV w/ renal insufficiency

Hematologic:
- Leukopenia, neutropenia, thromobocytopenia REVERSIBLE UPON DISCONTINUATION

Intestinal nephritis: damage to renal tubules via immune mediated response (Esp. Nafcillin)