ESBL + CPE AMR Flashcards

1
Q

What are the uses of Beta lactam antibiotics?

A

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

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2
Q

Are beta lactams bactericidal or bacteriostatic?

A

bactericidal

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3
Q

What are the early Beta lactams?

A

Penicillins

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4
Q

What was chemically modified to produce different penicillins?

A

The side chains

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5
Q

What is the side chain of Penicillin G?

A

-H2C-CH3

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6
Q

What is the side chain of Penicillin V?

A

-O-CH2-CH3

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7
Q

What is the side chain of Ampicillin?

A

-CH(NH2)-CH3

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8
Q

What is the side chain of Amoxicillin?

A

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

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9
Q

What is the general structure of beta lactams?

A

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

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10
Q

What is the MOA of beta lactams?

A

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

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11
Q

Describe the process of bacterial cell wall synthesis?

A

 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

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12
Q

Describe the resistance to beta lactams by enzyme mediation?

A

beta lactamase enzymes hydrolyse beta lactam ring

beta lactam inert so can’t bind to PBP

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13
Q

Which enzyme hydrolyses penicillins and causes resistance?

A

Penicillinases

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14
Q

How many generations of cephalosporins exist?

A

5

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15
Q

What beta lactamase carrying bacteria hydrolyses 3rd generation cephalosporins?

A

Klebsiella

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16
Q

What enzyme are cephalosporins stable against?

A

Penicillinases

17
Q

What properties make cephalosporins better to resistance than penicillins?

A

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

18
Q

What is the difference between cephalosporin and penicillin structure?

A

Cephalosporin has dihydrothiazine ring attached to beta lactam ring

19
Q

What are ESBLs?

A

extended spectrum beta lactamases

group of beta lactamases that can hydrolyse certain beta lactam antibiotics

20
Q

What beta lactams do ESBLs hydrolyse?

A

1st, 2nd, 3rd gen cephalosporins

monobactam beta lactam antibiotic= aztreonam

21
Q

What beta lactams do ESBLs not hydrolyse?

A

Carbapenems

22
Q

What bacteria produce ESBLs?

A

E.coli

23
Q

When do ESBLS become a problem?

A

healthy individual= dormant and part of bacterial community

problem= sick and immunocompromised

24
Q

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

A
  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
25
Q

What are the treatment options for ESBL producing bacteria?

A
  1. Beta lactam antibiotic + beta lactamase inhibitor

2. Carbapenems

26
Q

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

A

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

27
Q

Name the Carbapenems used in ESBL bacteria?

A

Imipenem
Meropenem
Ertapenem

28
Q

What are the indications of Imipenem and Meropenem?

A

Septicaemia, pneumonia, abdominal infection, complicated UTI

29
Q

What are the indications of Ertapenem?

A

Community acquired pneumonia, gynaecological infections, abdominal infections

30
Q

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

A

imipenem
meropenem
ertapenem
due to chemical modification

31
Q

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

A

emergence of gram negative enteric bacteria

ability to hydrolyse carbapenem antibiotics

32
Q

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

A

CPE= Carbapenemase producing Enterobacteriaceae

33
Q

What groups of bacteria come under CPE?

A

e coli
klebsiella
all gram negative

34
Q

Where are CPE enzymes encoded?

A

On plasmids

35
Q

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

A

highly transmissible from bacteria to bacteria

36
Q

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

A
  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
37
Q

What are the treatment options for CPE enzyme producing bacteria?

A

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

38
Q

What is the role of a pharmacist in CPE?

A

 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