7

Question 1

What are some targets of antibiotic activity

Answer 1

Cell wall synthesis
Nucleic acid synthesis
LPS and/or TLR4 blockers
Cell membrane disrupters
RNA polymerase
Protein synthesis

Question 2

What are the guiding principals

Answer 2

Diagnosis: Pathogen
Decision-making: Treatment vs surgery
Choice of antibiotic: Specificity
Treatment regimen: Optimized for complete clearance
Follow-up: If fail, determine cause

Question 3

What are pharmacokinetics and pharmacodynamics

Answer 3

PK: Time course fluctuations of drug concentration

PD: Relationship between drug concentration and effect

Question 4

What is MIC

Answer 4

Minimal inhibitory concentration
Lowest concentration of an antibiotic that inhibits growth of the organism

Question 5

Describe the ideal antibiotic

Answer 5

Potent and selective
Low chance of resistance
Good PK
Oral
Good distribution
No interactions
Easy synthesis and stable

Question 6

What are the major mechanisms of antibiotic resistance

Answer 6

Target protection, target site modification, Decreased influx, down regulation, inactivation of antibiotic, target bypass, active efflux

Question 7

Resistance vs tolerance vs persistence

Answer 7

Resistance: characterized by higher MIC

Tolerance: slower killing

Persistence: biphasic killing

Question 8

Goal of Parson paper

Answer 8

investigate the role of persister cells in recurrent bacterial blood stream infections

Question 9

how did they identify the SNPs arising during relapsed GNB-BSI? what did they find?

Answer 9

Whole-genome sequencing
Found that the distribution of SNPs varied by species and number of SNPs varied as well

Question 10

After looking at SNPs what did they do? What did they find

Answer 10

Looked to see whetehr antibiotic selection contributed to relapse. Found that relapse unlikely due to antibiotic choice or duration

Question 11

How did they look to see if Relapsed GNB-BSI was associated with in-patient development for persister cells? what did they find

Answer 11

Used a time-kill curve screen
4/11 showed increased persisted formation

Question 12

What is a time-kill curve screen

Answer 12

Cultures are grown and antibiotics are added at fixed intervals at the MIC

Question 13

What is the PTS system

Answer 13

Main system mediating the transport and phosphorylation of carbohydrates including glucose in E.coli

Question 14

What does mutations to pts1 do

Answer 14

increases survival to antibiotic treatment
demonstrates high persisted phenotypes