Penicillins

Key examples

• Benzylpenicillin
• Phenoxymethylpenicillin

 

Common indications

• Streptococcal infection, including tonsillitis, pneumonia (in combination with a macrolide if severe), endocarditis and skin and soft tissue infections (added to flucloxacillin if severe).
• Clostridial infection, for example tetanus.
• Meningococcal infection, for example meningitis, septicaemia.

 

Mechanisms of action

• 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.
• Bacteria resist the actions of penicillins by making β-lactamase, an enzyme which breaks the β-lactam ring and prevents antimicrobial activity. Other mechanisms of resistance include limiting the intracellular concentration of penicillin (reduced bacterial permeability or increased extrusion) or changes in the target enzyme to prevent penicillin binding.

 

Important adverse effects

• Penicillin allergy affects 1–10% of people. This usually presents as a skin rash 7–10 days after first exposure or 1–2 days after repeat exposure (subacute [delayed] IgG-mediated reaction). Less commonly, an immediate (minutes to hours) life-threatening IgE-mediated anaphylactic reaction occurs with some or all of hypotension, bronchial and laryngeal spasm/oedema and angioedema. Central nervous system toxicity (including convulsions and coma) can occur with high doses of penicillin or where severe renal impairment delays excretion.

 

Warnings

• Penicillin can generally be used safely in most clinical situations, although a dose reduction is required for patients with renal impairment. 
• The main contraindication to penicillin use is a history of penicillin allergy. Note that allergy to one type of penicillin implies allergy to all types as it is due to a reaction to the basic penicillin structure.

 

Important interactions

• Penicillins reduce renal excretion of methotrexate, increasing the risk of toxicity.