INFECTIONS: PENICILLIN, PENICILLASE-RESISTANT

Question 1

PENICILLINS, PR: INDICATIONS

Answer 1

• Staphylococcal infection, including:
  1) Skin and soft tissue infections such as cellulitis (in combination with benzylpenicillin for more severe infection)

2) Osteomyelitis and septic arthritis
3) Other infections, including endocarditis.

Question 2

PENICILLINS, PR: MOA

Answer 2

• Penicillins inhibit the enzymes responsible for cross-linking peptidoglycans in bacterial cell walls
• This weakens cell walls, preventing them from maintaining an osmotic gradient
• Uncontrolled entry of water into bacteria causes cell swelling, lysis and death
• Penicillins contain a β-lactam ring, which is responsible for their antimicrobial activity
• Side chains attached to the β-lactam ring can be modified to make semi-synthetic penicillins
• The nature of the side chain determines the antimicrobial spectrum and other properties of the drug
• For flucloxacillin, an acyl side chain protects the β-lactam ring from β-lactamases, which are enzymes made by bacteria to deactivate penicillin
• This makes flucloxacillin effective against β-lactamase producing staphylococci.
• Meticillin-resistant Staphylococcus aureus (MRSA) resists the actions of flucloxacillin by reducing penicillin binding affinity.

Question 3

PENICILLINS, PR: ADVERSE EFFECTS

Answer 3

• Minor GI upset
• Penicillin Allergy (acute/delayed)
• Liver Toxicity - cholestasis and hepatitis
• CNS toxicity can occur in high doses of penicillin or where severe renal impairment delays excretion

Question 4

PENICILLINS, PR: WARNINGS

Answer 4

• Generally safe in most situations
• Dose reduction in renal failure
• Main CI to Flucloxacillin use is a Hx of Penicillin allergy
• Prior Flucloxacillin-related hepatotoxicity

Question 5

PENICILLINS, PR: INTERACTIONS

Answer 5

• MTX

Question 6

PENICILLINS, PR: EXAMPLES

Answer 6

• Flucloxacillin