Antibiotics

Question 1

Beta-lactam antibiotics

Answer 1

Antibiotic drugs that contain the beta-lactam ring functional unit.

Includes:
Penicillin
Cephalosporins
Monobactams

Beta lactam binds to transpeptidase in the cell wall of bacteria, and prevents the further synthesis of the cell wall.

However not all bacteria use the same transpeptidase- like pseudomonas.

Question 2

Penicillin G

Answer 2

Benzylpenicillin, contains the benzene ring as its R group.

This antibiotic can only been administered intravenously.

It has rapid renal clearance so it does not stay in the blood for very long.

It is mainly effective against Gram negative bacteria and some Gram - bacteria.

Question 3

Penicillin

Answer 3

Beta-lactam antibiotic that help destroy bacteria by binding to transpeptidase.

Transpeptidase is the enzyme involved in synthesising peptidoglycan.

Penicillin inhibits the cell wall formation by inhibiting transpeptidase.

Good at targeting:
Staphs, Streps, and Neisseria

Question 4

Penicillin V

Answer 4

Phenoxymethylpenicillin

Type of penicillin that can be taken orally but is rapidly excreted.

Has to be taken 6 times a day.

Question 5

Aminopenicillin

Answer 5

Beta-lactam penicillin with a positively charged amino group as its ‘R group’.

Includes:
Amoxicillin
Ampicillin
Bacampicillin

Question 6

Amoxicillin

Answer 6

Aminopenicillin that is orally administered. More effective against gram negative bacteria that penicillin V

Has a longer half life than penicillin V, so can be taken three times a day.

Action:
Inhibits bacterial cell wall production.

Interaction:
Can increase levels of other protein bound drugs.

Adverse effects:
Allergies
Destruction of the commensal flora.

Diseases treated:
S.pyogenes infections- sore throat, skin infections
Pneumococcal- respiratory tract
Coliform- urinary tract

Question 7

Antibiotic administered to treat S.pyogenes infections

Answer 7

Amoxicillin.
Clarythromycin (if allergic to penicillin)
Vancomycin (non-penicillin)

Question 8

Treatment against pseudomonas

Answer 8

Antipseudomonal penicillin

Normal penicillins are ineffective against pseudomonas as they have a different transpeptidase enzyme to synthesise their cells walls.

Antipseudomonals include:
Piperacillin

Question 9

Bacterial antibiotic resistance mechanism

Answer 9

4 main methods of resistance:
Enzymatic degradation of drug
Target modificiation
Efflux pumps
Reduced penetration of cell wall

Certain strains of bacteria synthesise enzyme beta lactamase which hydrolyzes the beta-lactam ring in beta-lactam antibiotics.

S.aureus and E.coli can develop resistance through this mechanism

Question 10

Drugs synthesised resistant to staphylococcal beta-lactamase

Answer 10

Methicillin- not used clinically. Used in labs to determine antibiotic sensitivity of bacteria (seen in MRSA)

Flucloxacillin: used clinically, mainly for S.aureus

Question 11

Beta lactamase inhibitors

Answer 11

Drugs developed to target bacteria that are resistant to beta lactam drugs, especially penicillin.

The inhibitors bind to beta lactamase produced by the bacteria, preventing it from hydrolysing the beta lactam ring.

Includes:
Clavulanic acid

Question 12

Co-amoxiclav

Answer 12

Beta-lactamase inhibitor composed of amoxicillin bound to clavulanic acid.

This prevents amoxicillin from being degraded by beta lactamase enzymes produced by the bacteria.

Question 13

MRSA

Answer 13

Methicillin-resistant S. aureus
Strain of S. aureus resistant to all beta-lactam antibiotics.

This is tested by testing its sensitivity to methicillin, hence its name.

This strain contains a different transpeptidase to make peptidoglycan, coded by mecA gene.

Question 14

mecA gene

Answer 14

Gene possessed by MRSA and other bacteria Streps reisistant to all beta-lactam antibiotics.

The gene codes for penicillin binding protein 2A (PBP2A) used to synthesise the cell wall.

PBP2A is a transpeptidase that cannot bind to penicillin, so penicillins are infective in removing bacteria with this gene.

Question 15

Efflux pumps

Answer 15

Active transport protein pumps that are present in many Gram negative bacteria with antibiotic resistance:
E. coli

The pump allows antibiotics to be moved out of the cell, preventing it from having an effect.
The gene to make this protein is coded in mobile genetic elements, like plasmid and transposons, which allow the spread of resistance across species.

Question 16

Mycoplasma resistance to penicillin

Answer 16

Has no cell well, so penicillin are infective.

Examples:
M. pneumoniae

Question 17

Cephalosporins

Answer 17

Beta-lactam antibiotic made from cephalosporium acremonium

Contains two R groups which gives many different antibiotics and properties:

Altered water solubility
Delayed secretion
Action against transpeptidases of different species
Resistance to degradation of beta-lactamase

The higher generations affect Gram negative bacteria and are administered IV

Question 18

Macrolide

Answer 18

Non bata-lactam penicillin that targets protein synthesis in bacteria.

Macrolides binds to the 50s subunit in ribosome.

Effective against Gram positives, many Gram negatives and bacteria without cell walls.

HOWEVER, some Streps are resistant due to target site mutations

Examples:
Clarythromycin

Question 19

Clarythromycin

Answer 19

Macrolide antibiotic taken orally used for patients allergic to penicillin.

Used to treat:
S. pyogenes
Pneumococcal infections
Coliform infections
Chlamydia 

Has high affinity to proteins

Metabolism:
Hepatic, excreted via liver. Excreted in the bile.

Half life:
1-6 hours

Adverse effects:
Nausea
Diarrhoea
Arrhythmia

Interactions:
Can bind to other proteins involved in drug metabolism, like cytochrome p450

Question 20

Reasons why some patients may not get better with antibiotics

Answer 20

Poor tissue penetration: could be due to oedema or poor blood flow.

Patients may not take adhere to treatment plans

Patient could be resistant to antibiotics

Patient risk factor, like obesity.

Antibiotic could select out commensals and cause another infection

Question 21

Vancomycin

Answer 21

Glycopeptide that inhibits peptidoglycan production, hence cell wall production.

Has to be taken IV as it is very big.

Only active against Gram positive bacteria and the very resistant strains like MRSA.

Half life:
4-8 hours

Excretion:
Via the urine, not metabolised

Adverse effects:
Ototoxic
Nephrotoxic
Also interacts with other ototoxic and nephrotoxic drugs

Narrow therapeutic window

Question 22

Bacteria species that most commonly causes cellulitis

Answer 22

S. pyogenes

Question 23

Organism that commonly causes thrush

Answer 23

Candida albicans (orally)

Candidal vulvovaginitis (vagina)

Question 24

Genetic mechanisms of antibiotic resistance

Answer 24

1. Acquisition of a resistant genes like mecA, gene for beta lactamase, from mobile genetic elements
   Patient is usually infected with resistant strain, it is rare for bacteria to acquire this during infection.
2. Mutation:
   Occurs spontaneously in bacteria.
   The mutations are selected for if they cause resistance