ESBL + CPE AMR Flashcards
What are the uses of Beta lactam antibiotics?
agriculture
humans and vet medicines
food industry to prevent animal being infected
promote growth of animal and increase body mass= increased profit
Are beta lactams bactericidal or bacteriostatic?
bactericidal
What are the early Beta lactams?
Penicillins
What was chemically modified to produce different penicillins?
The side chains
What is the side chain of Penicillin G?
-H2C-CH3
What is the side chain of Penicillin V?
-O-CH2-CH3
What is the side chain of Ampicillin?
-CH(NH2)-CH3
What is the side chain of Amoxicillin?
-CH(NH2)-CH3 and -OH on the other side of the ring
What is the general structure of beta lactams?
R2-C(O)-HN= acyl side chain
Beta lactam ring square with N and =O
Thiazolidine ring= pentagon with S
COOH= side chain
What is the MOA of beta lactams?
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
Describe the process of bacterial cell wall synthesis?
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
Describe the resistance to beta lactams by enzyme mediation?
beta lactamase enzymes hydrolyse beta lactam ring
beta lactam inert so can’t bind to PBP
Which enzyme hydrolyses penicillins and causes resistance?
Penicillinases
How many generations of cephalosporins exist?
5
What beta lactamase carrying bacteria hydrolyses 3rd generation cephalosporins?
Klebsiella
What enzyme are cephalosporins stable against?
Penicillinases
What properties make cephalosporins better to resistance than penicillins?
Single point mutation= extended spectrum activity so it could break down more beta lactams
Plasmid mediated= spread easily from bacterium to bacterium
What is the difference between cephalosporin and penicillin structure?
Cephalosporin has dihydrothiazine ring attached to beta lactam ring
What are ESBLs?
extended spectrum beta lactamases
group of beta lactamases that can hydrolyse certain beta lactam antibiotics
What beta lactams do ESBLs hydrolyse?
1st, 2nd, 3rd gen cephalosporins
monobactam beta lactam antibiotic= aztreonam
What beta lactams do ESBLs not hydrolyse?
Carbapenems
What bacteria produce ESBLs?
E.coli
When do ESBLS become a problem?
healthy individual= dormant and part of bacterial community
problem= sick and immunocompromised
What are the consequences of infection with a ESBL producing bacteria?
- Increased mortality
- Increased overall healthcare costs
- Increased length of stay in hospital
- Increased time to find effective therapy for ESBL bacteria
What are the treatment options for ESBL producing bacteria?
- Beta lactam antibiotic + beta lactamase inhibitor
2. Carbapenems
Give the MOA and an example of a Beta lactam antibiotic + beta lactamase inhibitor?
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
Name the Carbapenems used in ESBL bacteria?
Imipenem
Meropenem
Ertapenem
What are the indications of Imipenem and Meropenem?
Septicaemia, pneumonia, abdominal infection, complicated UTI
What are the indications of Ertapenem?
Community acquired pneumonia, gynaecological infections, abdominal infections
Give the stability order of the carbapenems Imipenem and Meropenem and Ertapenem and why does stability increase?
imipenem
meropenem
ertapenem
due to chemical modification
What were the consequences of frequent use of Carbapenems to treat ESBL bacteria?
emergence of gram negative enteric bacteria
ability to hydrolyse carbapenem antibiotics
Name a group of Beta lactamase enzymes which hydrolyse almost all beta lactams?
CPE= Carbapenemase producing Enterobacteriaceae
What groups of bacteria come under CPE?
e coli
klebsiella
all gram negative
Where are CPE enzymes encoded?
On plasmids
Give one property of CPE enzymes that means it has limited treatment?
highly transmissible from bacteria to bacteria
What are the consequences of developing Carbapenem resistant infection due to CPE enzymes?
- Increased mortality- lacks of effective therapy
- Increased length of stay in hospital
- Increased health care costs- diagnostic costs to identify CPE positive individuals, infection control, decontamination strategies in wards and antibiotic prescribing
- Increased time to find effective therapy
What are the treatment options for CPE enzyme producing bacteria?
Hospital treatment= microbiologist advice + clinical trial data
Combination of antibiotics- tigecycline
Repurposing older drugs = temocillin, colistin
New inhibitors= relebactam and avibactam
What is the role of a pharmacist in CPE?
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
