antimicrobial resistance

Question 1

main causes of resistance

Answer 1

• poor compliance
• inadequate treatment/diagnosis
• poor healthcare infrastructure
• lack of education/knowledge

Question 2

treatment TB

Answer 2

initial phase:
- isoniazid (INH)
- rifampicin (RF)
- pyrazinamide (PZA)
- duration 2 months
- PZA only active during initial phase due to host immune response lowering pH in macrophages
continuation phase:
- isoniazid (INH)
- rifampicin (RF)
- treatment continued for 4 months
- destroys remaining bacteria from initial phase
- treatment may be extended for meningitis or resistant TB

Question 3

mode of action of TB drugs

Answer 3

• bacteriostatic (inhibit growing bacteria)
• bactericidal (kill bacteria outright)
• PZA is bactericidal against TB at low pH but bacteriostatic against growing bacteria

Question 4

isoniazid (INH)

Answer 4

• isonicotinic acid hydrazide
• targets the ketoenoyl-reducatse enzyme InhA in cell wall mycolic acid biosynthesis
• prodrug activated to a building complex with InhA

Question 5

rifampicin (RIF)

Answer 5

• prevents protein synthesis binding to DNA-dependent RNA polymerase b-subunit
• broad spectrum bactericidal activity
• helps sterilize “persistors” and active mycobacteria

Question 6

pyrazinamide (PZA)

Answer 6

• bactericidal against “persisting” slow growing mycobacteria
• mode of action unclear but it is a prodrug requiring activation to the acid form pyrizinoic acid (POA)
• requires low pH macrophage environment (intracellular)

Question 7

tissue schizontocides

Answer 7

• inhibit growth of the pre-erythrocytic stages of the parasite in the liver
• sometimes called ‘casual prophylactics’

Question 8

anti-malarial drugs

Answer 8

type I :
- anti-folates inhibit dihydrofolate production
- sulfadioxine, dapsone
type II :
- anti-folates inhibits dihydrofolate reductase
- pyrimethamine, proguanil

Question 9

hypnozoitocides

Answer 9

• used to eradicate the dormant liver stage of vivax infections
• disrupts the redox process in the pentose-phosphate pathway
• primaquine

Question 10

blood schizontocides

Answer 10

• act rapidly
• act only on erythrocytic stage of infection
• some used ‘prophylactically’ but mainly for treating established malarial infection
• prevent hemozoin formation leading to cell death by binding to heme in the parasite
• chloroquine, quinine