Antimicrobial resistance

Question 1

General MoA of B lactams

Answer 1

they mimic D alanine, interaction with penicillin binding proteins (PBP) blocks cross linking and compromises cell wall rigidity. Cell weakened and more prone to external stress. Will eventually lead to lysis in an actively growing cells as a result of no crosslinking

Question 2

ESBLs are resistant to which antibiotics?

Answer 2

Cephalosporins and Penicillins and able to degrade Aztreonam

Question 3

ESBLs are inhibited by what?

Answer 3

clavulanic acid

Question 4

What are ESBLs produced by?

Answer 4

E. coli and Klebsiella species

Question 5

Which B lactam subclass is not hydrolysed by ESBLs?

Answer 5

carbapenams so used to treat severe HC associated infections

Question 6

What is an infection with ESBL producing bacteria associated with?

Answer 6

increased time to effective therapy, increased length of stay, increased mortality & overall healthcare costs

Question 7

What are the treatment options for ESBL infections?

Answer 7

beta lactam + b lactamase inhibitor (co-amoxiclav) or Carbapenems

Question 8

What are CPEs?

Answer 8

a group of bacteria capable of hydrolyzing almost all beta lactams, they are encoded on plasmids and highly transmissible

Question 9

CPE infection is very difficult to treat and causes similar problems to ESBLs, what can be done about this?

Answer 9

effective infection control, development of new antibiotics, development of new lactamase inhibitors, repurposing old antibiotics

Question 10

What is the difference between bacteriostatic and bactericidal?

Answer 10

bacteriostatic (e.g. protein synthesis inhibitors such as tetracycline which bind reversibly to ribosome and inhibit growth) & bactericidal (cell killing such as b lactams)

Question 11

What are the 4 main target classes of antimicrobials?

Answer 11

cell wall synthesis, protein synthesis, nucleic acid synthesis, metabolic pathways

Question 12

What are some reasons for resistance to antibiotics?

Answer 12

natural resistance such as lack of target structure or impermeable to antibiotic / sensitive bacteria develop resistance (acquired) via enzymatic inactivation of antibiotic, modification of target, efflux mechanisms

Question 13

What is antibiotic resistance and why does it develop?

Answer 13

it’s the acquired ability of a microorganism to become desensitised to the effects of a chemotherapeutic agent. Can develop because of a selection pressure of the antibiotic, transfer of resistance genes or rapid cell division

Question 14

Give some biochemical mechanisms of antibiotic resistance

Answer 14

overproduction/ alteration of target, alternative pathway, decreased influx/increased reflux, drug modification & drug destruction

Question 15

How do microorganisms acquire ability to resist antibiotics?

Answer 15

horizontal gene transfer, transfer of genetic material between cells, even of different species, independent of cell replication via transformation, transduction, and conjugation

Question 16

Resistance plasmids have transfer operon, what does that allow it to do?

Answer 16

enables it to spread from one organism to another, encodes for conjugation

Question 17

What do biofilms do?

Answer 17

make organism less susceptible to antimicrobials

Question 18

How can we respond to AMR?

Answer 18

antimicrobial stewardship (start smart then focus), combination therapy & developing new drugs

Question 19

What does it mean if a patient is colonised with MRSA?

Answer 19

They carry it but it is causing no problems or symptoms - they are however at risk of developing an infection with MRSA

Question 20

What are the signs and symptoms of an MRSA infection?

Answer 20

High temp,
Fever
High white cell count
Inflammation at the infection site

Question 21

What are the 1st and 2nd line treatments for a serious MRSA infection?

Answer 21

IV Vancomycin &Teicoplanin, second line agents include linezolid, daptomycin and tigecycline

Question 22

What are coliforms?

Answer 22

Gram negative bacilli resident in the gut e.g. e.coli

Question 23

How is C.diff treated?

Answer 23

Oral Metronidazole

Oral Vancomycin

Question 24

How can MRSA infections be reduced in hospitals?

Answer 24

Screen at risk patients/ Isolate patients/ Decontamination therapy to the risk of infection/spread of others/ Handwashing/ Aseptic non-touching techniques/ Antibiotic prophylaxis against MRSA for surgery in colonised patients

Question 25

Which antibiotics is MRSA resistant to?

Answer 25

All B lactams including Penicillins, cephalosporins and carbapenems. Many strains also resistant to others eg macrolides, quinolones & clindamycin

Question 26

Which parts of the body can be colonized with S.aureus?

Answer 26

skin, nose, armpits, axilla (armpits) and perineum (groin)

Question 27

High level resistance to methicillin is caused by what?

Answer 27

the mecA gene, which encodes an alternative penicillin binding protein, PBP 2a

Question 28

Why do GRE infections occur?

Answer 28

glycopeptide antibiotics are used to treat MRSA infections, some patients with frequent antibiotic exposure can become colonized in bowel with GRE, infections are often IV line associated and have limited treatment options

Question 29

Describe the VRE mechanism and vancomycin susceptible enterococci mechanism

Answer 29

VSE make cell wall precursors that have high affinity for vancomycin, they bind to vancomycin and inhibit cell wall synthesis however with VRE the presence of vancomycin makes cell wall precursors that have low affinity for vancomycin so do not bind and cell wall synthesis is not inhibited

Question 30

What does antibiotic stewardship entail?

Answer 30

ensuring antibiotics are used rationally and not misused, health promotion, prescriber education, development/promotion of empiric guideline choice, restriction of reserve antibiotics, review/advise on management of infection for individual patients

Question 31

How can antibiotics be misused?

Answer 31

prescribed unnecessarily, administration delayed in critically ill patients, broad spectrum used too generously, narrow spectrum used incorrectly, dose is lower or higher than appropriate for patient, wrong duration, treatment not streamlined according to culture data results

Question 32

What important steps should be taken when someone is suspected of having C.diff?

Answer 32

– assess severity (including WCC, abdominal pain and temp, stop antibiotic precipitating condition, avoid anti-diarrhoeal agents, stop gastric acid suppressive agents, stop laxatives, assess fluid balance and ensure hydration, assess nutritional status, initiate treatment

Question 33

What steps can be taken to prevent C.diff infection?

Answer 33

careful use of antibiotics (minimise exposure to high risk agents like fluoroquinolones, cephalosporins, clindamycin / avoid prolonged courses / avoid exposure to multiple antibiotics), infection control, rigorous hand washing to prevent spread and re-infection