infection - antibiotics

Question 1

how can antibiotics be classified?

Answer 1

bactericidal (kills bacteria) / bacteriostatic (prevents growth)
spectrum: broad or narrow
target site (mech of action)
chemical structure (antibacterial class - which type of bacteria it targets)

Question 2

what are the ideal features of antimicrobial agents?

Answer 2

1. selectively toxic
2. few adverse effects
3. reaches site of infection
4. oral / IV formulation
5. long 1/2 life (infrequent dosing)
6. no interference with other drugs

Question 3

what are the classes of antibacterials and their mechanism of action?

Answer 3

1. cell wall synthesis: ß-lactams (penicillin), glycopeptides
2. cell membrane function: polymixins (colistin)
3. protein synthesis: (MAT) macrolides, aminoglycosides, tetracyclines
4. nucleic acid synthesis: quinolones (trimethoprim - UTI e.coli, rifampicin (TB)

Question 4

what is vancomycin’s mechanism of action?

Answer 4

sits on cross linking chains to prevent ‘penicillin binding protein’ to join onto cross link to join them together - binds to separate chains (interfere with cell wall)

prevents separate chains of cell wall from binding together

Question 5

what is penicillin’s MoA?

Answer 5

cell wall synthesis

interferes with the protein that reinforces the rigidity of cell wall (cross link) - inhibiting the growth of the cell

Question 6

what is the MoA of fluroquinolones?

Answer 6

nucleic acid synthesis
bind to 2 nuclear enzymes, inhibiting DNA replication
(DNA gyrase, topoisomerase IV)

Question 7

what are the mechanisms of resistance?

Answer 7

1. drug inactivating enzymes e.g. ß-lactamases, aminoglycoside enzymes
2. altered target: target enzyme has lowered affinity for antibacterial e.g. resistance to meticillin (MRSA)
3. altered uptake: decrease permeability (e.g. ß-lactams) - drug can’t get into cell OR
   increase efflux e.g. tetracyclines (drug being pumped out before it can take effect)

Question 8

what are the genetic basis of Abx resistance?

Answer 8

1. chromosomal gene mutation (random) - survives & can multiply to spread to other patients
2. horizontal gene transfer: plasmid passed via cell replication (just in cytoplasm, whole cell), OR
   plasmid INTERGRATED into bacterial DNA, os when cell divides, so does new bacterial DNA

Question 9

what are the different types of horizontal gene transfer?

Answer 9

1. conjugation (bridge between 2 cells, sexual process of bacteria)
2. transduction (bacteriophage infect cell)
3. transformation (free DNA genetic material passed directly through cell wall into organism)

Question 10

what are the different types of bacterial genetic information?

Answer 10

1. embedded within chromosome
2. plasmid - circular genetic info
3. transposon (fragments of nucleic acid in cytoplasm)

Question 11

how can you measure antibiotic activity?

Answer 11

1. disc sensitivity testing
2. minimum inhibitory concentration (lowest concentration with an inhibition on antibiotic growth) - lots of test tubes with different concentration of antibiotic, with controls

Question 12

what are the different classes of ß-lactams?

Answer 12

affect cell wall synthesis:

1. penicillins
2. cephalosporins
3. carbapenems
4. monobactams

Question 13

what are examples of penicillins?

Answer 13

mainly against streptococci (gram positive - thick cell wall):
benzylpenicillin
amoxicillin (mild CAP)
flucloxacillin (against staphylococci & streptococci)
co-amoxiclav (amoxicillin & clavulronic acid): HAP, severe CAP
tazocin (serious bac infection): piperacillin (treats pseudomonas aeruginosa - UTI) + tazobactam

Question 14

what is an example of cephalosporin?

Answer 14

ceftriaxone - treats H. influenza (CAP), good activity in CSF (meningitis - Neisseria meningitides)
normally treats gram neg (thin cell wall)

Question 15

what is an example of carbapenems? why choose carbapenems?

Answer 15

ß-lactam - cell wall synthesis:
meropenum (treats Neisseria meningitides)
very broad spectrum
mostly gram neg
safe in penicillin allergy

Question 16

what is an example of glycopeptides? (another class of cell wall synthesis inhibitors with ß-lactams)

Answer 16

vancomycin:
active against gram positive (thin cell wall)
used in MRSA, rare resistance, don’t use penicillin - high resistance
oral use - C. diff
therapeutic drug monitoring required - narrow therapeutic window - easily become toxic

Question 17

what are examples of tetracyclines?

Answer 17

inhibits protein synthesis (MAT):
tetracycline & doxycycline (mild CAP or severe CAP with co-amoxiclav)
used in atypical pneumonia e.g. legionella, mycoplasma - without cell wall
also in chlamydia
don’t give to children <12 yrs

Question 18

what is an example of aminoglycosides?

Answer 18

gentamicin (protein synthesis inhibitor)
against gram negs sepsis
good activity in blood / urine
nephrotoxic - kidneys
therapeutic drug monitoring required
sepsis, pyelonephritis (intrinsic AKI) - infection of kidney tissue

Question 19

what are examples of macrolides?

Answer 19

protein synthesis inhibitor
erythromycin & clarithromycin
used to treat atypical pneumonia
alternative to penicillin for mild gram pos infections

Question 20

what is an example of quinolones?

Answer 20

affect nucleic acid synthesis
ciprofloxacin, (also fluroquinolone - inhibit 2 DNA synthesis enzymes - DNA gyrase)
against gram neg & atypical pathogens
increasing resistance & risk of C. diff
used for gut bacterial infections: Typhoid Fever, E. coli, traveler’s diarrhoea etc.

Question 21

when would you use trimethoprim & sulphonamides?

Answer 21

inhibitors of folic acid synthesis (nucleic acid)
trimethoprim alone - UTI

combined (trimethoprim & sulphonamides): co-trimoxazole - treat PCP (pneumocystitis pneumonia in patients with depressed immunity e.g. HIV)
can be used against MRSA

Question 22

what is an example of an antifungal and what is it used to treat?

Answer 22

fluconazole used to treat candida albicans (mouth / vagina)

Question 23

what are examples of an antiviral drug and what is it used to treat?

Answer 23

aciclovir - Herpes, chicken pox, shingles

tamiflu - treat influenza A & B

Question 24

what is metronidazole used to treat?

Answer 24

antibacterial & antiprotozoal agent:
active against anaerobic bacteria & protozoa

protozoa: giardia (diarrhoea), trichomonas (vaginitis)