Antibiotic Resistance

Question 1

Mechanisms of resistance

Answer 1

1. reduced drug entry into organism
2. increased drug export from organism
3. expression of enzyme that destroy drug
4. changes in expression of enzymes that activate drug
5. impaired drug binding to original target
6. development of new or different pathways not inhibited by drug

Question 2

daptomycin

Answer 2

• reduced drug entry
• use: complicated skin infections, bacteremia, endocarditis
• gene mutation(mprF)–>change in membrane charge–>repel positively charged drugs

Question 3

tetracycline

Answer 3

• Increased drug export
• use: broad spectrum antibiotic for acne, bronchitis, gonorrhea, and syphilis
• express efflux pump (N. gonorrhoeae, E. coli, S. pneumoniae, P. aeruginosa

Question 4

metronidazole

Answer 4

• changes in expression of enzyme that activates pro-drug
• use: abdominal infections, vaginitis, C. difficile colitis, brain abscess
• pro-drug that needs to be reduced–>mutation in rdxA gene–>decreased activation of drug

Question 5

aminoglycosides (streptomycin)

Answer 5

• expression of enzymes by organism that destroy drug
• use: combo to treat unusual severe conditions (endocarditis, tularemia, plague, tuberculosis)
• aminoglycoside-modifying enzymes modify antibiotic and alter binding of drug to target

Question 6

Amoxicillin

Answer 6

• expression of enzymes by organism that destroy drug
• use: broad spectrum antibiotic used for variety of infections
• express B-lactamase enzyme that hydrolyze lactam ring–>drug ineffective

Question 7

trimethoprim & sulfonamides

Answer 7

• impaired drug binding to original target
• use: combo for UTI
• express drug-insensitive enzymes dihydropteroate synthase and dihydrofolate reductase

Question 8

vancomycin

Answer 8

• development of new or different pathway that are not inhibited by drug
• use: bloodstream infections, endocarditis, meningitis
• substitution on peptidoglycan stem–>agent can no longer bind target