29: Antibiotic Resistance

Question 1

what do antibiotics target in bacteria?

Answer 1

cell wall as unique to bacteria
- peptidoglycan and LPS are good PAMPs since they aren’t found in humans

typically essential features for growth

Question 2

history of antibiotic discovery

Answer 2

discovered around WWII

many discovered and people thought they didn’t need new antibiotics
- research stopped for 40 years

antibiotic usage then became widespread with agriculture

Question 3

golden age of antibiotic discovery

Answer 3

1940-1960

Question 4

research gap in antibiotic discovery

Answer 4

no new registered classes of antibiotics discovered after 1984

Question 5

issues with antibiotics - clostridium difficile

Answer 5

increase the chance of getting certain infections

clostridium difficile as an opportunistic infection causing post-antibiotic diarrhoea and intestinal pain
- antibiotics to treat bacterial infections also kill healthy bacteria, leaving a void
- c. difficile inherently resistant to most antibiotics so it grows out when all others are dead

life-threatening intestinal inflammation of the colon

Question 6

antibiotics are not very selective

Answer 6

kill many beneficial organisms as a side effect

Question 7

selection for antibiotic-resistant bacteria

Answer 7

classic/natural evolution
- killing those that are not resistant so the only ones that survive are resistant

Question 8

how did we get to antibiotic-resistant bacteria?

Answer 8

misuse of antibiotics
- if you only take part of the course, it leads to antibiotic resistance in the pathogenic bacteria you’re trying to kill

extensive use of antibiotics in agriculture

overuse of antibiotics and not following instructions

Question 9

spread of antibiotic-resistant bacteria

Answer 9

only takes one or two

just as antibiotics evolved in microbes as a weapon, so too has resistance to antibiotics evolved as a defence strategy

Question 10

spread of antibiotic resistance genes

Answer 10

horizontal gene transfer - conjugation
- typically a one-way exchange of plasmid DNA

plasmids are not chromosomes but circular pieces of DNA encoding 1-10 or even 100 genes
- very stable

exchange of DNA is replicated so that the plasmid is replicated

happens within the same species of bacteria or across different species of bacteria

Question 11

four fundamental ways bacteria become antibiotic-resistant

Answer 11

inactivation and degradation
- bacteria figures out how to kill/block antibiotic

efflux
- antibiotic crosses membrane to get into bacteria but gets shuttled back out

target modification
- proteins, cell walls, etc.
- modification of the target so the antibiotic no longer binds

decreased permeability

Question 12

eskape pathogens

Answer 12

most common nosocomial infections

high rates of antibiotic resistance

estimation from CDC of 2M illnesses and 23k deaths in the US annually

Question 13

staphylococcus aureus statistics

Answer 13

1 cause of skin infection

leading cause of military infection

major cause of nosocomial infections

Question 14

s. aureus and penicillin developments

Answer 14

before antibiotics, 80% mortality rate for bacteremia

penicillin decreased deaths, and by 1950, 25% of hospital-associated s. aureus strains were resistant to penicillin

methicillin and oxacillin developed to overcome resistance problem in 1960s, but resistant strains emerged again after a year

by 1990s, MRSA responsible for 29% of hospital-acquired infections

Question 15

MRSA deaths

Answer 15

10-25k deaths annually

Question 16

MRSA in the US

Answer 16

10-40% of the population colonised with s. aureus, but only 1% colonised with MRSA and most exhibit no symptoms

1.5 M infections from s. aureus in the US annually
- 750K infections from MRSA

200K invasive infections from s. aureus annually
- 100K invasive infections from MRSA

Question 17

antibiotic of last resort

Answer 17

vancomycin