ESBL + CPE AMR

Question 1

What are the uses of Beta lactam antibiotics?

Answer 1

agriculture
humans and vet medicines
food industry to prevent animal being infected
promote growth of animal and increase body mass= increased profit

Question 2

Are beta lactams bactericidal or bacteriostatic?

Answer 2

bactericidal

Question 3

What are the early Beta lactams?

Answer 3

Penicillins

Question 4

What was chemically modified to produce different penicillins?

Answer 4

The side chains

Question 5

What is the side chain of Penicillin G?

Answer 5

-H2C-CH3

Question 6

What is the side chain of Penicillin V?

Answer 6

-O-CH2-CH3

Question 7

What is the side chain of Ampicillin?

Answer 7

-CH(NH2)-CH3

Question 8

What is the side chain of Amoxicillin?

Answer 8

-CH(NH2)-CH3 and -OH on the other side of the ring

Question 9

What is the general structure of beta lactams?

Answer 9

R2-C(O)-HN= acyl side chain
Beta lactam ring square with N and =O
Thiazolidine ring= pentagon with S
COOH= side chain

Question 10

What is the MOA of beta lactams?

Answer 10

Target bacterial cell wall synthesis
Beta lactam antibiotic inhibits transpeptidation
binds to the penicillin binding protein
B lactams mimic terminal D alanine dipeptide of NAM and NAG
PBP can’t bind to NAM or NAG ends
No cross linking
weak cell wall
bacteria lyse and die because of osmotic and environmental stress

Question 11

Describe the process of bacterial cell wall synthesis?

Answer 11

 Involves peptidoglycan layer
 Sheets of n-acetyl glucosamine and muramic acid/ NAM + NAG
 Bacteria cross link NAM and NAG= more rigid cell wall so bacteria can resist environmental stress= grow
 Penicillin binding protein= transpeptidase unit recognises ends of NAM and NAG and binds to them = oversees transpeptidation

Question 12

Describe the resistance to beta lactams by enzyme mediation?

Answer 12

beta lactamase enzymes hydrolyse beta lactam ring

beta lactam inert so can’t bind to PBP

Question 13

Which enzyme hydrolyses penicillins and causes resistance?

Answer 13

Penicillinases

Question 14

How many generations of cephalosporins exist?

Answer 14

5

Question 15

What beta lactamase carrying bacteria hydrolyses 3rd generation cephalosporins?

Answer 15

Klebsiella

Question 16

What enzyme are cephalosporins stable against?

Answer 16

Penicillinases

Question 17

What properties make cephalosporins better to resistance than penicillins?

Answer 17

Single point mutation= extended spectrum activity so it could break down more beta lactams
Plasmid mediated= spread easily from bacterium to bacterium

Question 18

What is the difference between cephalosporin and penicillin structure?

Answer 18

Cephalosporin has dihydrothiazine ring attached to beta lactam ring

Question 19

What are ESBLs?

Answer 19

extended spectrum beta lactamases

group of beta lactamases that can hydrolyse certain beta lactam antibiotics

Question 20

What beta lactams do ESBLs hydrolyse?

Answer 20

1st, 2nd, 3rd gen cephalosporins

monobactam beta lactam antibiotic= aztreonam

Question 21

What beta lactams do ESBLs not hydrolyse?

Answer 21

Carbapenems

Question 22

What bacteria produce ESBLs?

Answer 22

E.coli

Question 23

When do ESBLS become a problem?

Answer 23

healthy individual= dormant and part of bacterial community

problem= sick and immunocompromised

Question 24

What are the consequences of infection with a ESBL producing bacteria?

Answer 24

1. Increased mortality
2. Increased overall healthcare costs
3. Increased length of stay in hospital
4. Increased time to find effective therapy for ESBL bacteria

Question 25

What are the treatment options for ESBL producing bacteria?

Answer 25

1. Beta lactam antibiotic + beta lactamase inhibitor | 2. Carbapenems

Question 26

Give the MOA and an example of a Beta lactam antibiotic + beta lactamase inhibitor?

Answer 26

Inhibitor binds to enzyme so more antibiotic available less hydrolysed antibiotic more bactericidal activity in bacteria in host cell Example= co-amoxiclav= amoxicillin + clavulanic acid

Question 27

Name the Carbapenems used in ESBL bacteria?

Answer 27

Imipenem Meropenem Ertapenem

Question 28

What are the indications of Imipenem and Meropenem?

Answer 28

Septicaemia, pneumonia, abdominal infection, complicated UTI

Question 29

What are the indications of Ertapenem?

Answer 29

Community acquired pneumonia, gynaecological infections, abdominal infections

Question 30

Give the stability order of the carbapenems Imipenem and Meropenem and Ertapenem and why does stability increase?

Answer 30

imipenem meropenem ertapenem due to chemical modification

Question 31

What were the consequences of frequent use of Carbapenems to treat ESBL bacteria?

Answer 31

emergence of gram negative enteric bacteria | ability to hydrolyse carbapenem antibiotics

Question 32

Name a group of Beta lactamase enzymes which hydrolyse almost all beta lactams?

Answer 32

CPE= Carbapenemase producing Enterobacteriaceae

Question 33

What groups of bacteria come under CPE?

Answer 33

e coli klebsiella all gram negative

Question 34

Where are CPE enzymes encoded?

Answer 34

On plasmids

Question 35

Give one property of CPE enzymes that means it has limited treatment?

Answer 35

highly transmissible from bacteria to bacteria

Question 36

What are the consequences of developing Carbapenem resistant infection due to CPE enzymes?

Answer 36

1. Increased mortality- lacks of effective therapy 2. Increased length of stay in hospital 3. Increased health care costs- diagnostic costs to identify CPE positive individuals, infection control, decontamination strategies in wards and antibiotic prescribing 4. Increased time to find effective therapy

Question 37

What are the treatment options for CPE enzyme producing bacteria?

Answer 37

Hospital treatment= microbiologist advice + clinical trial data Combination of antibiotics- tigecycline Repurposing older drugs = temocillin, colistin New inhibitors= relebactam and avibactam

Question 38

What is the role of a pharmacist in CPE?

Answer 38

 Effective infection control  Antimicrobial stewardship- resistance is elevated by inappropriate antibiotics use  Screening and isolation of CPE carriers via faecal or rectal swabs 3 samples over 5 days  Development of new antibiotics  Development of new beta lactamase inhibitors  Repurposing older antibiotics