Session 5 - Antibiotics

Question 1

How do antibiotics damage bacteria but not host cells?

Answer 1

By exploiting the differences that exist between the structure and physiology of the prokaryotic bacterial cells and the host eurkaryotic cells

Question 2

What are two different overall mechanisms by which antibiotics effect bacteria

Answer 2

Bacteriostatic (inhibit bacterial growth)

Bacteriacidal (kill bacteria)

Question 3

Give four sites on bacteria targeted by antibiotics

Answer 3

Peptidoglycan cell wall
Nucleic acids
Protein synthesis
Cytoplasmic membrane

Question 4

Why can bacterial cell walls be targeted, and by which three main classes of AB?

Answer 4

Peptidoglycan cell wall only present in prokaryotic cell.

Penicillins
Cephalosporins
Glycopeptides

Question 5

Why can nucleic acids be targeted, and by which three classes of AB?

Answer 5

Bacterial genome is a single, circular strand of DNA unenclosed by a nuclear envelope, in contrast to eukaryotic chromosomal arrangement within the nucleus Antifolates
Quinolones
Rifampicin

Question 6

How can protein synthesis be targeted, and name three ABs which do thus

Answer 6

Bacterial ribosome (50s+30s subunits) is different to the mammalian ribosome (60s+40s subunits)	Aminoglycosides
Tetraclyclines
Macrolides
Chloramphenicol
Fusidic acid

Question 7

How can the cell membrane of bacteria be targeted, and give 1 AB that does thus

Answer 7

Bacterial plasma membrane does not contain any sterols, unlike mammalian. Polymyxins

Question 8

Give four primary reasons for prophylaxis of bacterial infections

Answer 8

o	Peri-operative (Prevention of surgical site infections)
o	Short term
	Meningitis contacts
o	Long term
	Asplenia (encapsulated bacteria)
	Immunodeficiency

Question 9

Give two ways ABs can be used to treat significant bacterial iunfections

Answer 9

o Treatment of cultured, proven infection

o Empirical treatment of suspected infection

Question 10

What is the ideal antibiotic? (2)

Answer 10

o Clean killing of infecting bacteria
 Minimal impact on non-target commensal organisms
 No resistance in any surviving pathogens
o No adverse effects on patient

Question 11

Give 8 factors which help determine the likely infectious agent in an infection

Answer 11

o	Anatomical Site
o	Duration of illness
o	Past medical history
o	Occupational history 
o	Travel history
o	Time of year
o	Age
o	Personal background

Question 12

Give four factors which determine which antibiotics are likely to be effective

Answer 12

o	Community or healthcare onset?
o	Severity of infection
o	Baseline rate of resistance
o	Immune status of patient
	Immunocompromised patients will need IV Antibiotics immediately

Question 13

What three factors do you need to consider when choosing best antibiotic?

Answer 13

o Efficacy
o Cost
o Administration Route

Question 14

Give some common antibiotic adverse drug reactions

Answer 14

Pharmcological (toxicities, drug interactions)
Allergic reactions
Impact on normal flora (c.diff)

Question 15

What is therapeutic drug monitoring?

Answer 15

Therapeutic drug monitoring is used to ensure and adequate, non-toxic dose.

Question 16

Give two antibiotics which require therapeutic monitoring

Answer 16

Gentomicin

Vancomycin

Question 17

What class of AB is gentomicin>

Answer 17

Aminoglycoside

Question 18

What are the effects of gentomicin?

Answer 18

 Dose related ototoxicity and nephrotoxicity at high plasma levels

Question 19

What type of AB is vancomycin?

Answer 19

Glycopeptide

Question 20

Give five side effects of vancomycin

Answer 20

 Dose related ototoxicity and nephrotoxicity at high plasma levels
 Fever, rashes
 Local phlebitis at site of infection

Question 21

Give two overarching methods via which bacteria develop AB resistance

Answer 21

Chromosomal gene mutation

Horizontal Gene transfer

Question 22

What is chromosomal gene mutation and how does it pre-dispose to development of AB resistant pop of bacteria?

Answer 22

o Chromosomal gene mutates in one bacteria in a population, conferring a resistance to antibiotic
o Antibiotic kills all other bacteria, acting as a selection pressure, giving resistant bacteria an advantage
o Population of antibiotic resistant bacteria daughter cells

Question 23

Give three types of horizontal gene transfer

Answer 23

Transformation
Transduction
Conjugation

Question 24

What is transformation?

Answer 24

o Bacteria with antibiotic resistance gene releases DNA

o Uptake of DNA by recipient cell, conferring antibiotic resistance

Question 25

What is transduction?

Answer 25

o Phage infected, antibiotic resistant Bacterial donor cell | o Phage passes the DNA conferring resistance to recipient cell

Question 26

What is conjugation?

Answer 26

o Connection is made between antibiotic resistant donor cell, and recipient cell o Plasmid containing resistance gene is replicated and passes from donor cell to recipient cell o Plasmid may even become incorporated into recipient cell DNA

Question 27

Give four methods of antibiotic resistance

Answer 27

- Antibiotic Inactivation - Alteration of Drug Binding Site - Alteration of Metabolic Pathways - Reduced Intracellular Antibiotic Concentration

Question 28

What is antibiotic inactivation?

Answer 28

o Production of enzyme that inactivate the drug |  E.g. β-lactamase which inactivates Penicillins

Question 29

What is alteration of drug binding site?

Answer 29

o Modified binding sites so drugs no longer have affinity for them  E.g. Bacterial ribosome alteration, meaning Aminoglycosides and Erythromycin cannot bind

Question 30

What is alteration of metabolic pathways?

Answer 30

o Development of altered metabolic pathways  E.g. bacteria can become resistant to Trimethoprim due to acquired changes in their Dihydrofolate Redctase enzyme, which gives it very little affinity for the drug

Question 31

What is reduced intracellular antibiotic concentration?

Answer 31

o Active Efflux Mechanisms  E.g. Active transport mechanisms used (e.g. p-glycoprotein) to pump a drug out of the bacterial cell because it accumulates to an effective level o Decreased permeability  E.g. Some bacteria become resistant to Tetracycline because they alter their cell membrane to make it impermeable to the drug

Question 32

Give three stages of the emergence of antibiotic resistnace

Answer 32

1. Local selection (e.g. in a hospital) 2. Clonal dissemination (e.g. around the country) 3. Global spread

Question 33

Give five main antibiotic resistant bacteria

Answer 33

o Methicillin Resistant Staphylococcus Aureus (MRSA) o Glycopeptide Intermediate susceptibility Staphylococcus Aureus (GISA) o Glycopeptide Resistant Enterococci (GRE) o Extended Spectrum Beta Lactamase enterobacteriaceae (ESBLs) o Extensively Drug Resistant Klebsiella Pneumoniae (XDR-KP) - MDRTB

Question 34

Give four parts of anti-microbial stewardship

Answer 34

o Right antibiotic o Right time o Right dose, frequency and duration (Pharmacokinetics – ADME) o Right route

Question 35

Give two stages of infection control

Answer 35

Prevent the spread of recognised resistant bacteria | Prevent bactrerial exposure to antiotics

Question 36

How can we prevent the spread of recognised resistant bacteria?

Answer 36

 Isolation or cohorting  Hand hygiene  Decolonisation of patients

Question 37

How can we prevent bacterial exposure to antibiotics?

Answer 37

 Minimise risk of infection |  Monitor and control antibiotic prescribing

Question 38

What are two different types of AB killing?

Answer 38

Time dependent killing o Prolonged antibiotic presence at the site of infection, but not high concentration Concentration dependent killing o High antibiotic concentration at the site of infection, but short duration

Question 39

What is MIC?

Answer 39

Minimum Inhibitory Concentration – MIC The MIC is the lowest concentration of an antibiotic that will inhibit the visible growth of a microorganism after overnight incubation. A MIC is generally regarded as the most basic laboratory measurement of the activity of a microbial agent against an organism.