Antibacterial Agents

Question 1

Define antibiotic

Answer 1

Chemical products of microbes that inhibit/kill other organisms

Question 2

Define Antimicrobial agents

Answer 2

• Antibacterial, antiviral, antifungal
• Antibiotics
• Synthetic/semi-synthetic compounds with similar effects

Question 3

What are the different types of bacterial killing?

Answer 3

• Bacteristatic= inhibit bacterial growth (protein synthesis inhibitors)
• Bactericidal= kill bacteria (cell-wall active agents)

Question 4

What is the minimum inhibitory concentration?

Answer 4

Minimum conc of antibiotic at which visible growth is inhibited
-Some antibiotics are bacteriostatic at low conc and bactericidal at high conc

Question 5

What types of antimicrobial interactions are there?

Answer 5

• Synergism (activity of 2 antimicrobials given together is greater than the sum of their activity separately)- B-lactam/aminoglycoside combination for strep endocarditis
• Antagonism (one agent diminishes activity of another)
• Indifference (activity unaffected by addition of another agent)

Question 6

Name some cell wall synthesis inhibitors

Answer 6

• B-lactams
• Glycopeptides
• Cycloserine (antiTB agent)

Question 7

Describe the structure of a bacterial cell wall

Answer 7

• Peptidoglycan major component in gram +ve & -ve bacteria
• Polymer of glucose-derivatives NAG & NAM

Question 8

How do B-lactam antibiotics work?

Answer 8

Interfere with function of penicillin binding proteins- Transpeptidase enzymes involved in the peptidoglycan cross-linking

Question 9

Describe the general structure of B-lactams

Answer 9

• Four membered B-lactam ring structure (C-C-C-N)

- Structural analogue of D-alanyl-D-alanine

Question 10

Name the groups of B-lactam antibiotics, members of each family and their spectrum

Answer 10

• Penicillins (benzylpenicillin, amoxicillin, flucloxacillin- narrow spectrum)
• Cephalosporins (Cefuroxime, ceftasidime- broad spectrum)
• Carbapenems (meropenem, imipenem-extremely broad spectrum)
• Monobactams (aztreonam- gram -ve activity only)

Question 11

Name types of glycopeptides and how they work

Answer 11

• Vancomycin, teicoplanin
• Bind directly to terminal D-Alanyl-D-alanine on NAM pentapeptides
• Inhibit binding of transpeptidases thus peptidoglycan cross-linking
• Unable to penetrate gram -ve outer membrane porins

Question 12

How are proteins synthesised in bacteria?

Answer 12

• Translation of RNA to a protein
• Takes place in ribosome
• 50S + 30S= 70S

Question 13

Give examples of Aminoglycosides, where they bind and what they are known for?

Answer 13

• Gentamicin, amikacin
• Protein synthesis inhibitors
• Bind to 30S ribosomal subunit

Question 14

Give examples of MLS, what it stands for, where they bind and what they are known for?

Answer 14

• Macrolides, Lincosamides, Streptogramins
• Protein synthesis inhibitors
• M= erythromycin, clarithromycin
• L= clindamycin
• Bind to 50S ribosomal subunit= blockage of exit tunnel or inhibit protein elongation

Question 15

Where do tetracyclines bind to, what are they known for?

Answer 15

• Protein synthesis inhibitors
• Bind to 30S ribosomal subunit
• Inhibit RNA translocation= interfere with binding of tRNA to rRNA

Question 16

Give an example of an Oxazolidinone, where it binds and what it is known for?

Answer 16

-Protein synthesis inhibitor
-Linezolid
-Binds to 50S ribosomal subunit- may also bind to 70S subunit
-Inhibits initiation of protein synthesis
-Inhibit assembly of initiation complex
-

Question 17

What are Trimethoprim & Sulphonamides inhibitors of and how? What is their combined name?

Answer 17

• DNA synthesis
• Inhibit folate synthesis (folic acid= purine synthesis precursor)
• T=Dihydrofolate reductase
• S=Dihydropteroate synthase
• Combined= Co-Trimoxazole

Question 18

Give examples of Quinolones & fluoroquinolones, what they inhibit and how?

Answer 18

• Ciprofloxacin, Nalidixic acid
• Inhibit 1 or more of 2 related enzymes- DNA gyrase & topoisomerase IV
• Involved in remodelling of DNA during DNA replication

Question 19

What is Rifampicin and how does it do this?

Answer 19

• RNA synthesis inhibitor
• RNA polymerase inhibitor
• Prevents synthesis of mRNA

Question 20

Name some plasma membrane agents

Answer 20

• Colistin (gram -ve)
• Daptomycin (gram +ve)
• Destruction of cell membrane

Question 21

What are adverse effects of antibiotics?

Answer 21

• C.Diff
• Antibiotic resistance
• Fungal infection (candidiasis)
• Nausea/vomiting, rashes

Question 22

What are the adverse reactions of aminoglycosides?

Answer 22

• Reversible renal impairment on accumulation
• Irreversible ototoxicity
• Therapeutic drug monitoring indicated

Question 23

What are the adverse reactions of B-lactams?

Answer 23

Allergic reactions: Generalised rash or anaphylaxis

Question 24

What are the adverse reactions of Linezolid?

Answer 24

Bone marrow depression

Question 25

What are signs of intolerance or allergy to B-lactams?

Answer 25

``` I= nausea, diarrhoea, headache A= skin rash, anaphylaxis, urticaria, angio-oedema, severe skin rash, bronchospasm ```

Question 26

Describe C.Diff infection

Answer 26

- Combination of enterotoxin & spore production - Hypervirulent strain 027 causes more severe disease - Produces toxins A & B - Assumed caused by abolition of colonisation resistance

Question 27

What are the most common precipitating antibiotics of C.Diff?

Answer 27

- Co-amoxiclav - Cephalosporins - Ciprofloxacin - Clindamycin

Question 28

What are the best antibiotics to use against: - Staph Aureus - Strep Pyogenes - Gram -ve Bacilli - Anaerobes - MRSA/gram +ve - last option for gram -ves

Answer 28

- SA=Flucloxacillin - SP=Benzylpenicillin - GB=Cephalosporins- avoid in elderly - A=Metronidazole - MRSA= Vancomycin - Last= Colistin

Question 29

Which antibiotics have a good and poor availability in the CSF?

Answer 29

``` Good= B-lactams in presence of inflammation Poor= Aminoglycosides & Vancomycin ```

Question 30

Which antibiotics have a good and poor availability in urine?

Answer 30

``` Good= Trimethoprim & B-lactams Poor= MLS antibiotics ```

Question 31

What are concentration dependent pharmacodynamics?

Answer 31

Main determinant of bacterial killing is the factor by which concentration exceeds MIC, administered intermittently

Question 32

What are time dependent pharmacodynamics?

Answer 32

Main determinant of killing is the amount of time for which antibiotic concentration exceeds MIC, administered frequently to maintain high levels

Question 33

Why is combination therapy used?

Answer 33

- Reduce resistance - Provide adequately broad spectrum - Increase efficacy