Lecture 9: Antimicrobial Chemotherapy

Question 1

what was the first penicillin

Answer 1

benzylpenicillin

Question 2

how do penicillins work

Answer 2

bind bacterial transpeptidases (involved in peptidoglycan synthesis)

Question 3

how are penicillins excreted

Answer 3

in urine, so have to make sure the patient has a functioning kidney before prescribing

Question 4

what is the functional unit of penicillins

Answer 4

beta lactam ring

Question 5

characteristics of benzylpenicillin

Answer 5

• must be injected intravenously and is degraded by stomach acid when taken orally
• has rapid renal clearance, so requires frequent dosing (6x a day)

Question 6

characteristics of phenoxymethylpenicillin

Answer 6

• chemically modified benzylpenicillin
• orally active
• rapid renal clearance, needs dosing of 6x a day

Question 7

characteristics of aminopenicillin

Answer 7

• orally active and long half life, taken 3x a day

- eg amoxicillin

Question 8

which bacteria aren’t affected by penicillins

Answer 8

pseudomona bacteria, so have developed special antipseudomonal penicillins eg piperacillin

Question 9

which bacteria are resistant to penicillin and how did it develop this

Answer 9

staphylococcus aureus, developed beta-lactamases which hydrolyse the beta-lactam ring

Question 10

which drugs are unaffected by beta-lactamases

Answer 10

methicillin and flucloxacillin

Question 11

features of beta-lactamase inhibitors

Answer 11

• have weak antibiotic activity
• are competitive inhibitors
• example is clavulinic acid
• widely used now is co-amoxiclav which is a mix of amoxicillin and clavulinic acid

Question 12

what is MRSA resistant to and how

Answer 12

• all beta-lactam antibiotics

- acquisition of mecA gene which encodes a different transpeptidase enzyme that doesn’t bind penicillins

Question 13

which bacteria is universally sensitive to penicillin

Answer 13

streptococcus pyogenes

Question 14

how do many Gram negatives develop resistance

Answer 14

• make beta lactamase

- antibiotic efflux pumps

Question 15

which bacteria are resistant to penicillins and why

Answer 15

mycoplasmas and chlamydias as they have no cell wall

Question 16

what are the main ways of developing antibiotic resistance

Answer 16

• enzymatic degradation of the drug
• target modification
• efflux of antibiotic from the bacteria
• reduced penetration through the cell wall

Question 17

what are cephalosporins

Answer 17

• a big family of beta lactams
• have two modifiable side chains
• product of cephalosporium acremonium mould
• have altered water solubility, delayed excretion, activity against transpeptidases of different bacterial species and resistant to beta lactamases

Question 18

what are the generations of cephalosporins and how are they taken

Answer 18

1: cephalexin, orally
2: cefuroxime, IV and orally
3: ceftriaxone, IV only
4: cefepime, IV only

Question 19

features of macrolides

Answer 19

• eg clarythromycin
• bind the 50S subunit of bacterial ribosome
• block protein synthesis
• some streptococcus are resistant due to target site mutations

Question 20

reasons why antibiotics may be ineffective

Answer 20

• patient infected with resistant strain
• resistance develops on treatment (rare)
• wrong diagnosis
• wrong germ
• poor patient compliance
• poor tissue penetration due to obesity

Question 21

what are the genetic bases for antibiotic resistance

Answer 21

• gene transfer through mobile genetic elements

- genetic mutations (rare)