Antimicrobials & Resistance

Question 1

• what are the 4 classes of antimicrobials?
• what groups can antibiotics classified into?
• give 3 ways of measuring antibiotic activity and describe each

Answer 1

• antibacterials eg penicillin, antifungal agents, antiviral agents eg aciclovir, antiprotozoal agents
• bactericidal (kills bacteria) or bacteriostatic (stops bacteria reproducing), broad of narrow spectrum, mechanism of action ie target site, chemical structure
• 1) disc sensitivity testing: antibiotic disc on Petri dish, see zone of clearance, takes 24 hrs minimum
  2) minimum inhibitory concentration (MIC):broth containing antibiotics in increasing concentrations, takes 24 hrs min.
  3) MIC- epsilometer test (E test):takes 24 hrs min.

Question 2

• name the 3 types of antimicrobial resistance and describe each.
• name the 3 mechanisms of resistance.
• how does chromosomal gene mutation cause resistance?
• briefly describe horizontal gene transfer in bacteria

Answer 2

1) intrinsic= either no target or access for the drug, usually permanent eg gram negative bacteria have an extra outer membrane so are resistant to any antimicrobials that target the peptidoglycan layer
2) acquired= acquires new genetic material or mutates, usually permanent
3) adaptive= the organism responds to stress which then induces the bacteria to switch on genes that then cause resistance
- enzymatic modification or destruction of antibiotics, enzymatic alteration of antibiotic targets, over expression of efflux pumps so less accumulation of antibiotic inside cells
- one bacteria carrying the resistance reproduces and many bacteria w resistance are born
- donor attaches its pillus to neighbour, DNA polymerase helps w replication, then transferred into new donor.

Question 3

• outline the mechanism of beta lactam antibiotics

- what are its 3 main subgroups? Describe each of these 3 subgroups in more detail.

Answer 3

• interfere w the synthesis of the bacterial cell wall peptidoglycan by inhibiting the enzyme responsible, generally bactericidal
• 3 main groups are= penicillins, cephalosporins, carbapenems
  1) penicillins=eg amoxicillin (broad spectrum), individual sensitivity testing often required, used in bacterial meningitis, bone and joint infection, pneumonia, UTIs
  2) Cephalosporins= eg ceftriaxone,individual sensitivity test may be needed, used for septicaemia, pneumonia, meningitis, UTIs esp in pregnancy
  3) Carbapenems=has C in molecular structure, eg meropenem, very broad spectrum, safe in penicillin allergy,

Question 4

• outline the mechanism of glycopeptide antibiotics, give examples and what types of gram bacteria is it used on?
• name the 5 antibacterials affecting bacterial protein synthesis.

Answer 4

• inhibit cell wall synthesis, but at a different stage in the pathway to beta-lactams (blocks addition of NAG-NAM-PEP into peptidoglycan), eg vancomycin, generally used in gram positive species only, used orally for treating C. Diffcile as it’s not absorbed by GI
• tetracyclines, aminoglycosides, macrolides, oxazolidinomes, lincosamides.

Question 5

-give the mechanism, examples, uses and side effects of the following antibacterials:
Tetracyclines
Aminoglycosides
Macrolides
Oxazolidinones
Lincosamides

Answer 5

1) act by inhibiting protein synthesis by binding to bacterial ribosomes, preventing binding of tRNA to it, bacteriostatic, eg doxycycline, used for acne, chlamydia, resp tract infection, Lyme disease, shouldn’t be given to kids under 12 and pregnant women as it causes teeth staining.
2) inhibit protein synthesis at various points:bind to bacterial ribosome subunits, leads to misreading of mRNA so wrong aa’s are inserted and protein is not working, bactericidal, eg gentamicin, work well against gram negative, potentially toxic so strict dosage
3) inhibit bacterial protein synthesis by affecting ribosome translocation, bactericidal/bacteriostatic eg erythromycin, very similar uses as penicillin
4) very broad action, good for gram positive infections, used for pneumonia, septicaemia
5) act in the same way as macrolides, work against gram positive cocci, including MRSA,

Question 6

• describe the mechanism of quinolones

- give 2 examples of antibacterial agents that interfere w folate synthesis or action and describe each.

Answer 6

• inhibit topoisomerase II, the enzyme that a neg supercoil in DNA thus allows replication. Eg ciprofloxacin, very good cover of gram negative organisms, used for complicated UTIs, gonorrhoea, can cause tendinitis rupture, CNS effects, aortic dissection
• 1. sulfonamides: metabolised into active product sulfanilamide (a structural analogue of PABA which is an essential precursor in synthesis of folic acid and needed in synthesis of DNA &RNA in bacteria), acts as a competitive inhibitor w PABA and decreases production of folic acid, bacteriostatic, not commonly used in practice eg sulfamethoxazole
• 2. trimethoprim: is a folate antagonist, bacteriostatic and bacteriocidal, used in UTIs.

Question 7

• describe metronidazole, what symptoms does it cause?

- name the 2 most common antifungal groups & describe each

Answer 7

• metronidazole acts as a protozoal agent, but also good against anaerobic bacteria, exact mechanism not established (thought to stop nucleus acid synthesis), has disulfiram like actions so must avoid alcohol when on this drug (causes hangover like symptoms)
• 1=azoles:inhibits a fungal enzyme, leading to inhibition of replication, eg fluconazole, useful in treating candida infections
• 2=polyenes: has 2 important examples; amphotericin (systemic infections), nystatin (topical), site of action is the fungal cell membrane, doughnut shaped and lodge in cell wall causing leaking.

Question 8

-there are many different groups of antivirals, name the 2 most common & describe each.

Answer 8

1- aciclovir=inhibits DNA polymerase, used in herpes simplex virus, chickenpox and shingles
2-oseltamivir=neuraminidase inhibitor, used in influenza A & B

Question 9

• what are some consequences of antimicrobial resistance?
• why can antimicrobial resistance NOT be stopped?
• give the 3 definitions of antimicrobial resistance.

Answer 9

• treatment failure, prophylaxis failure (bigger infection risk after surgery), economic costs)
• any exposure of bacteria to antimicrobials will allow resistance as they evolve and replicate, resistance is irreversible
• 1. Multi drug resistant (MDR)= non susceptibility to at least 1 agent in 3 or more microbial groups
     
     2. Extensively resistant drug (XDR)= non susceptibility to at least 1 agent in all but 2 or fewer antimicrobial groups
     3. Pan drug resistance (PDR)= non susceptibility to all agents in all antimicrobial groups (no choices left!!)