Beta lactams, Vancomycin, DNA gyrase and DNA strand breakers

Question 1

What target does both beta lactams and Vancomycin attack?

Answer 1

cell wall synthesis which takes place in the membrane

Question 2

What’s the difference between gram positive and gram negative?

Answer 2

based on the structure of their cell wall, gram positive takes up gram stain and you can’t wash the stain out with acetone , cell wall has lots of peptidoglycan however gram negative also takes up stain but can be washed with acetone, has a thin layer of peptidoglycan, lipid bilayer and lots of proteins

Question 3

What are norcardiform bacteria?

Answer 3

gram positive bacteria that is difficult to stain because the lipids confer resistance to staining, includes mycobacteria

Question 4

What is peptidoglycan?

Answer 4

structural component, has repeating disaccharide units of 2 amino sugars (NAGA and NAMA)

Question 5

What is carboxypeptidase and its function?

Answer 5

enzyme in cell membrane that acts on cell wall synthesis, cleaves of terminal D alanine for any peptide that hasn’t made a crosslink. Can be displaced just by water so not productive

Question 6

What are some examples of beta lactam antibiotic groups and what do they have in common?

Answer 6

Penicillins, Cephalosporins & carbapenems all contain lactam ring

Question 7

Why is penicillin difficult to synthesis in lab?

Answer 7

4 membered ring is constrained at 90 degree angle but carbonyl prefers 120 degrees

Question 8

How does Beta lactam ring react with Transpeptidase or Carboxypeptidase?

Answer 8

when they interact, they take part in nucleophilic substitution at the 4 membered ring carbonyl, beta lactam ring is opened and enzyme forms a covalent bond

Question 9

What is the activity and usefulness of Penicillin determined by?

Answer 9

ability to penetrate cell wall, resistance to b lactamases, affinity to penicillin binding proteins, resistance to stomach acid, formulation, pharmacokinetics, toxicology

Question 10

Which amino acids is Penicillin G made from?

Answer 10

cysteine, valine and phenylalanine

Question 11

What are some examples of Penicillins?

Answer 11

Penicillin G, Amoxicillin, Flucloxacillin, Methicillin, Ampicillin

Question 12

Describe cephalosporins and give some examples

Answer 12

active against gram negative bacteria, beta lactam antibiotics, cefaclor & ceftriaxone. Second gen given orally, third gen injected IM

Question 13

What are carbapenems?

Answer 13

another beta lactam active against gram negative bacteria, very broad spectrum and resistant to most beta lactamases

Question 14

What is Vancomycin?

Answer 14

a non-ribosomal peptide with many unusual amino acids, it’s glycosylated and product of the soil organism Amycolatopsis orientalis

Question 15

What is the mode of action of Vancomycin and its uses?

Answer 15

interferes with cell well synthesis, used for serious gram positive infection, used orally for C difficile but normally injected

Question 16

What is an alternative for Vancomycin?

Answer 16

Teicoplanin, another glycopeptide with similar mode of action

Question 17

What is DNA gyrase and why is it important?

Answer 17

a topoisomerase, it introduces supercoiling into DNA of bacteria using ATP, it maintains the negative helical tension of bacterial chromosome and its needed for DNA to fit into cell

Question 18

What are quinolones and how do they target DNA gyrase?

Answer 18

broad spectrum antibiotics, active against gram negative bacteria ,they block the A subunit of DNA gyrase and prevent supercoiling by interfering with DNA chain breakage and rejoining

Question 19

Give an example of a first gen quinolone and its uses

Answer 19

Nalidixic acid used for uncomplicated UTIs

Question 20

Give some examples of second gen quinolones and their uses

Answer 20

ciprofloxacin used infections of urinary and respiratory tract, gonorrhea, prophylaxis of meningitis and anthrax / ofloxacin & norfloxacin

Question 21

What are some problems with ciprofloxacin?

Answer 21

reduced absorption with magnesium or aluminium antacids, severe CNS disturbances can occur with NSAIDs, damage to cartilage C/I in pregnancy

Question 22

Give some examples of third gen quinolones and its uses

Answer 22

levofloxacin indicated in pneumonia and UTIs, broad spectrum and active against streptococci

Question 23

What is the class of antibacterial DNA strand breakers called and what are some examples of drugs in that class?

Answer 23

Nitrofurans including Nitrofurantoin, used to treat gram positive and negative UTIs

Question 24

What is another class of antibacterials that act in a similar way to Nitrofurans?

Answer 24

Nitroimidazoles including metronidazole

Question 25

What are Nitroimidazoles used for?

Answer 25

to treat anaerobic bacterial and protozoal infections including bacterial vaginosis, acute oral infections and C diff, protozoal infections like amoebiasis and trichomoniasis

Question 26

What is C diff and why do patients acquire it?

Answer 26

C difficile is a type of bacteria already present in some people which can cause a bowel infection, most patients acquire pathogenic strains in hospital, if the patient is treated with a broad spectrum antibiotic it will eliminate normal microflora and promote overgrowth of c difficile

Question 27

What are some symptoms of C diff?

Answer 27

diarrhoea, abdominal pain, fever and nausea, in severe cases pseudomembranous colitis which can cause fatal peritonitis and perforation of the colon

Question 28

How would you treat C diff?

Answer 28

stop use of antibiotic, rehydration, first line drug: metronidazole and second line is oral Vancomycin

Question 29

How is C diff spread?

Answer 29

resistant spores which can persist in hospital rooms for up to 40 days, passed on from person to person, usually due to poor hygiene

Question 30

Which prescribing measure can prevent infection with C diff?

Answer 30

minimise use of broad spectrum antibiotics, use narrow spectrum, review antibiotic use to minimise microflora damage

Question 31

What is Fidaxomicin?

Answer 31

a macrolide with an 18 membered ring, very effective against C diff, retained in gut making it narrow spectrum

Question 32

Which measures are used to prevent cross infection of C diff?

Answer 32

patient suspected to have C diff put in isolation, strict hygiene precautions, daily cleaning of room, linen and equipment, handwashing with soap and water