Antimicrobials

Question 1

Which 6 classes of Abx target the cell wall & CSM?

Answer 1

• penicillins & polymyxins
• cephalosporins & carbapenems
• monobactams
• glycopeptides

Question 2

Which Abx classes target nuclei acid synthesis?

Answer 2

• folate antagonists

Targets:
DNA gyrase (quinolones)
RNA polymerase (rifmycins)

Question 3

Which Abx classes target protein synthesis?

Answer 3

50S
- macrolides
- lincomycins
- oxozolidonides
- chroamphenicol

30S
- tetracyclines
- aminoglycosides

Question 4

Bacteriostatic

Answer 4

Abx inhibit growth & replication of bacteria (i.e.- folate)

Question 5

Bactericidal

Answer 5

Abx kill bacteria (may be bacteriostatic in small doses)

Question 6

MoA: inhibition of cell wall synthesis

Answer 6

ß-lactam
- penicillins
- cephalosporins & carbapenems
- monobactams
Glycopeptides
Polymyxins

Question 7

Name 5 classes of penicillin

Answer 7

• natural
• penicillinase-resistant
• amino(penicillins)
• carboxy(penicillins)
• acyl ureido(penicillins)

Question 8

MIC

Answer 8

Minimum Inhibitory Concentration
(in vitro)
- growth inhibition

Question 9

MBC

Answer 9

Minimum Bactericidal Concentration
(in vitro)
- kill bacteria

Question 10

What does a PCR do?

Answer 10

Detects resistance mutations

Question 11

ADME: 4 principles of pharmacokinetics

Answer 11

A - Absorption (administration, bioavailability)
D - Distribution (VoD)
M - Metabolism (liver)
E - Excretion (half-life)

Question 12

What are the routes of Abx administration?

Answer 12

• topical
• aerosol
• oral
• IV
• IM

Question 13

Which Abx have good bioavailability?

Answer 13

Amox, linezolid, clindamycin, levofloxacin, ciprofloxacin, rifampicin, metronidazole

Question 14

What is the Volume of Distribution? (VoD)

Answer 14

Conc drug in blood relative to dose given:
- small = PLASMA bound
- large = FAT soluble

Question 15

What is the liver enzyme that metabolises abx?

Answer 15

CYP3A4

Question 16

What is t1/2?

Answer 16

Half-life of drug:
Time for conc drug in blood to reduce by 50% from Cmax

(Renal, gut, biliary excretion)

Question 17

What does the Cmax/MIC ratio mean?

Answer 17

Conc-dept killing: PK high conc above MIC

Question 18

What does the AUC/MIC ratio mean?

Answer 18

Time-dept killing: PK time above MIC

Question 19

What does the AUC24 ratio mean?

Answer 19

Exposure-dept killing

Question 20

What is the Post-abx effect? (PAE)

Answer 20

Time where bact growth still inhibited despite [drug]<MIC
- greater after conc-dept killing

Question 21

Antimicrobial resistance (AMR) mechanisms

Answer 21

• enzyme production
• change to target/metabolic pathways
• efflux pumps

Question 22

Name the three big AMR pathogens

Answer 22

• MRSA
• VRE
• ESBL

Question 23

What bacterial enzymes cause AMR?

Answer 23

• ß-lactamase
• carbapenamase enz

USE: decoy substrates

Question 24

Which pathways/target sites are altered to produce AMR?

Answer 24

• PBP mutations (ß-lactams)
• methylation of rRNA (macrolides & lincosomides)
• DNA gyrase mutation (quinolones)
• porin channel mutation (carbapenems)

USE: thymidine (folate antagonist)

Question 25

Which abx are affected by efflux pumps in AMR?

Answer 25

Tetracyclines

Question 26

What are the 5 main mechanisms of AMR?

Answer 26

- natural resistance - SNPs (point mutations) - transformation (uptake DNA) - transduction (bacteriophage) - conjugation (exchange genetic material)

Question 27

What are the two main forms of conjugation in bacteria?

Answer 27

- plasmids - transposons (chromosomal)

Question 28

In the rare occasion that an abx allergy is truly immune-mediated, what are the signs of a Type 1 reaction?

Answer 28

Immediate (IgE) - urticaria - angioedema - anaphylaxis MEDICAL EMERGENCY!!

Question 29

Type 2 allergic reaction to abx

Answer 29

Cytotoxic - drug-induced haemolysis

Question 30

Type 3 allergic abx reaction

Answer 30

Immune complexes (serum sickness, days) - fever - rash - arthralgia

Question 31

Type 4 allergic abx reaction

Answer 31

Delayed hypersensitivity (weeks) - DRESS - SJS - TEN ?Life threatening

Question 32

What is the most common abx allergy?

Answer 32

Penicillin allergy (oft delayed, Type 1 decrease over time, cross-reactive with cephalosporins)

Question 33

Which abx are contraindicated in pregnancy & BF?

Answer 33

- carbapenems - macrolides - quinolones (skeletal) - folate antagonists (NTDs) - tetracyclines (skeletal) - aminoglycosides (CNVIII)

Question 34

What is antimicrobial stewardship?

Answer 34

Control of abx nation-wide to reduce risk of AMR WHO: GLASS surveillance, GARDP research, IACG PHE 2018: 5-year plan

Question 35

What are OPAT services?

Answer 35

Outpt Parenteral Abx Tx service - allows discharge of pts with IV abx to avoid bed blocking

Question 36

What is MDR-TB?

Answer 36

Multi drug-resistant TB (rifampicin & isoniazid) - 80% survival, surgical resection

Question 37

What is XDR-TB?

Answer 37

Extensively drug-resistant TB - 30-50% survival + resection

Question 38

What is the significance of *Plasmodium falciparum* ?

Answer 38

Bacterial on Cambodia/Thailand border resistant to almost all anti-malarials

Question 39

What is the prevalence of resistance to ARVs in HIV?

Answer 39

1-20% (40% if re-starting)

Question 40

What is the prominent AMR in influenza A?

Answer 40

All resistant to M2 inhibitors: - amantadine - rimantadine

Question 41

What factors accelerate AMR?

Answer 41

- drug prescribing - drug access - drug quality - veterinary use - global travel - environment (genetic variability, socioeconomic factors)