State the mechanism of resistance that may develop with the drugs used. (4 marks)

I think that listing out general mechanisms of resistance would be fine.

General mechanisms of resistance (applies to antibiotics generally)

• Mutation of the antibiotic target
• Mutation of the bacterial enzyme required to activate the antibiotic
• Enzymes which can breakdown the antibiotic
• Efflux pumps which can pump the drug out of the bacterium.

Specific mechanisms of resistance:

Rifampicin:

• Mutation of RNA polymerase causing reduced binding
• Resistance occurs rapidly if used as monotherapy

Isoniazid

• Underexpression of enzyme required to convert drug into active metabolite

Ethambutol

• Increased production of arabinosyltransferase
• Efflux pumps

Pyrazinamide

• Mutation of the enzyme required to convert pyrazinamide into active compound.

Refs

Medbullets

Mechanisms of pyrazinamide action and resistance