Lecture 7 Antimicrobials

Question 1

What are the key biological processes of bacteria?

Answer 1

• Cell wall
• Cell membrane
• DNA replication
• Transcription
• Protein synthesis

Question 2

What are some sources of antimicrobials?

Answer 2

• Natural (Penicillin)
• Semi-synthetic
• synthetic

Question 3

What are some things to consider on drug choice?

Answer 3

• absorption
• Tissue distribution
• Metabolism/excretion
• Time-dependent killing
• concentration-dependent killing

Question 4

Bactericidal vs bacteriostatic .

Answer 4

Death versus inhibit growth- use cidal when immunocompromised or using prosthetics.

Question 5

MIC, MBC

Answer 5

minimum inhibitory concentration, minimum bactericidal concentration

Question 6

When would you want to to give combination therapy?

Answer 6

• Empiric therapy
• Prevent resistance
• Enhanced efficacy 
- Synergy
- Additive

Question 7

What are some susceptibility tests?

Answer 7

• Broth Dilution

- Diffusion tests (Kirby-bauer disc diffusion, ETEST)

Question 8

Which antibiotics attack cell walls?

Answer 8

• β-lactams (penicillins and cephalosporins)

- Glycopeptides (vancomycin)

Question 9

What are abx for cell membrane?

Answer 9

• Polymyxins

Question 10

What abx is used for DNA synthesis?

Answer 10

• [Fluro]quinolones (e.g. ciprofloxacin)
• Sulfonamides and trimethoprim (e.g. Bactrim)
• Metronidazole

Question 11

What abx attacks transcription?

Answer 11

• Rifampin

Question 12

Which abx attacks protein synthesis?

Answer 12

• Aminoglycosides (e.g. gentamycin)
• Macrolides (e.g. azithromycin, “Z-pack”)
• Tetracyclines
• Lincosamides (e.g. clindamycin)

Question 13

Which abx are 30s inhibitors?

Answer 13

• aminoglycosides
• tetracyclines
• glycineglycine

Question 14

What are some 50s inhibitors

Answer 14

• erythromycin
• clindamycin
• chloraphenocol
• oxazolidonone
• streptogramine

Question 15

Why care about resistant mechs?

Answer 15

helps in:

• susceptibility testing
• predict resistance without testing
• predict MIC
• Risk of infection control

Question 16

What are some mechs of resistant?

Answer 16

• efflux
• restricting enzymes
• target modification
• Restrict access to target

Question 17

How is resistance expressed?

Answer 17

• intrinsic (chromosomal)
• De Novo mutations
• acquired

Question 18

What are the biggest concern for infection control

Answer 18

• constitutive

- inducible

Question 19

What are some intrinsic resistance?

Answer 19

• Impermeability

- biofilms

Question 20

What is Target site mutation

Answer 20

A mutation of the actual site can occur, inhibiting a abx,

e.g. mutations in topoisomerase confer fluoroquinolone resistance

Question 21

What is target site protection?

Answer 21

Blocks target site from abx

e.g. methylation of 16S rRNA alters binding of erythromycin to ribosome

Question 22

How does inactivation by hydrolysis help pathogens resist?

Answer 22

e.g. β-lactamase inactivation of β- lactams by hydrolysis of drug

Question 23

What is inactivation by steric hinderance?

Answer 23

• Modify abx

e. g. aminoglycoside- modifying enzymes

Question 24

What is the problem with efflux pump resistance?

Answer 24

• Can be broad or narrow spectrum

- Up regulation of pumps can lead to multi-drug resistance (tetracylcines, macrolides etc)

Question 25

How can you end up with multi drug resistance?

Answer 25

- encode multiple genes - Encode gene that can target multiple abx - selective pressure

Question 26

What are some hints in drug names?

Answer 26

* cef... = cephalosporin * ...cillin = penicillin * ...cillin/... = beta-lactam/beta-lactamase inhibitor * ...floxacin = fluroquinolone * ...cycline = tetraclycine * ...mycin does not indicate drug class

Question 27

What are some Beta-Lactams?

Answer 27

``` (most are broad) • Penicillins • Cephalosporins • Monobactams • Carbapenems (most effective) ```

Question 28

How do Beta-lactams work?

Answer 28

Bind to penicillin binding protein, disrupts peptidoglycan and prevents crosslinks form occurring. Inhibits cell growth

Question 29

What are some adverse affects of Beta-lactams?

Answer 29

* Allergies mild to anaphylaxis * Diarrhea * Stevens-Johnson syndrome * Interstitial nephritis * Neutropenia and thrombocytopenia * Clostridium difficile infection/overgrowth • Seizures

Question 30

What is a relatively broad spectrum penicillin?

Answer 30

Ampicillin, Penicillin G/V

Question 31

What is a narrow spectrum penicillin?

Answer 31

Nafcillin

Question 32

What is a broad spectrum penicillin combo that is good for resistant strains?

Answer 32

Piperacillin/tazobactam (Zosyn)

Question 33

What are the subclasses for cephalosporins?

Answer 33

Gen 1-5 (5 is best) . Going down to 5, goes from good with g+ to good with G+ and -. 5th is best for resistance.

Question 34

What do cephalosporins do not work on what organism?

Answer 34

Cephalosporins don’t treat Enterococcus!

Question 35

What are three general mechs to resist Beta-lactams?

Answer 35

- decreased penetration (barrier) - inactivation of abx by enzyme - Alteration of target site

Question 36

What type of resistance is resistant to all beta-lactamses?

Answer 36

AmpC Beta- lactamases, Enterobacters biggest problem.