Antibiotics

Question 1

Difference between bacteriostatic and bactericidal antibiotics?

Answer 1

Bacteriostatic = prevent growth and allow immune system to kill
Bactericidal = kill bacteria directly

Question 2

When should you start a broad range antibiotic? What are the side effects?

Answer 2

If the microbe is unknown and treatment needs to be started immediately. Causes disruption of natural flora and Gi distress.

Question 3

What does an antibiogram consist of?

Answer 3

Susceptibility profile including Minimum inhibitory concentrations (MIC). Identifying effective therapies to exceed MIC and MBC levels.

Question 4

What are common side effects of antibiotics?

Answer 4

Tetracycline = discoloration of teeth
Streptomycin = auditory damage
Chloramphenicol = anemia
- alters flora, diarrhea, prophylaxis, Abx Resistance

Question 5

What is the problem with treating C. Difficle?

Answer 5

The antibiotics used to treat C.Diff can also prevent the natural flora from recolonizing allowing C.Diff to continue to populate without competition.

Question 6

How can bacteria develop resistance?

Answer 6

Horizontal gene transfer and spontaneous mutations.

• modify abx or target
• reduction in abx concentration by pumps/permeability

Question 7

What are the key differences in Gram Positive vs Negative?

Answer 7

Gram Positive = Significant amount of peptidoglycan layer and no outer membrane
Gram Negative = small amount of peptidoglycan with an outer membrane and porins

Question 8

What are the three main steps in synthesis of peptidoglycan?

Answer 8

1. Synthesis of the precursors that have the terminal D-Ala + D-Ala
2. Transport across the membrane to the extracellular space
3. Polymerization and cross-linking of L-Ala+L-Ala to Lys and D-Ala

Question 9

Where do beta-lactams work and how?

Answer 9

Beta-Lactams bind Penicillin Binding Proteins (PBPs) inhibiting them from cross-linking the peptides to make peptidoglycan. Beta-Lactams mimic the natural substrate in the active site.

Question 10

What are the two types of resistance from penicillin?

Answer 10

Encoding Beta-Lactamases and extended spectrum that degrade more than one B-lactams
Mutations of PBP

Question 11

What organism has B-lactamase encoded in their genome?

Answer 11

Pseudomonas. (E. Coli is frequently resistant as well)

Question 12

What type of organisms usually have Beta-Lactamase compared to mutations in PBP?

Answer 12

Beta-Lactamase = Gram Negative

PBP Mutations = Gram Positive

Question 13

How can you overcome an organism with B-lactamase?

Answer 13

Clavulanic Acid inhibits the B-lactamase and use a B-lactam at the same time.

Question 14

What are the most common organisms that are gram positive to become resistant to B-lactams?

Answer 14

Streptococcus and Staph (MRSA)

Question 15

How can you overcome gram positive cocci that is resistant to B-lactams?

Answer 15

There is not a remedy other than using a different type of antibiotic such as Vancomycin.

Question 16

What is a common Glycopeptide and how does it work?

Answer 16

Vancomycin. Binds the D-Ala-D-Ala end of the precursor peptide to prevent synthesis of peptidoglycan.

Question 17

When is Vancomycin primarily used?

Answer 17

Gram Positive organisms when resistant to B-lactams.

Can’t fit well through outer membrane of gram negative

Question 18

What organism is typically associated with vancomycin resistance?

Answer 18

enterococci in hospital settings. Vancomycin-Resistant Enterocci. (VRE) Be aware it can transfer the resistance to Staph if in the same wound or area.

Question 19

Where does cycloserine act in peptidoglycan synthesis?

Answer 19

Structurally similar to D-Ala, prevents the D-Ala-D-Ala synthesis due to having higher affinity than endogenous substrate and preventing cross-linking.
-inhibits Alanine Racemase and Synthase

Question 20

When is cycloserine usually used?

Answer 20

Used as a second-line therapy for TB treatment.

Question 21

How does Bacitracin work and where is it used?

Answer 21

Binds to Bactoprenol-PP preventing the recycling of lipid carriers moving peptidoglycan.
– TOPICAL ONLY – Used for both Gram +/-

Question 22

What are the two lipopeptides in the class and how do they work?

Answer 22

Daptomycin - Gram Positive Only - binds cytoplasmic membrane, narrow spectrum.
Polymyxins - Gram Negative - binds LPS on outer membrane. Toxic, limited use.

Question 23

What are the difference between bacterial ribosomes and human?

Answer 23

Bacterial - 30S and 50S = 70S

Human - 40S and 60S

Question 24

What do the tetracyclines target and what are in the class?

Answer 24

Tetracyclins target - 30S subunit to inhibit protein synthesis. Broad spectrum/bacteriostatic
Include: Doxycyline, Tetracycline, and Minocycline

Question 25

How can an organism become resistant to Tetracyclines?

Answer 25

Efflux Pumps and Ribosome mutations.

- Much more common/wide spread due to overuse

Question 26

What can be used on hard to kill Gram Negatives such as Pseudomonas Aeruginosa?

Answer 26

Aminoglycosides. Irreversibly bind 30S causing misreading and inhibition of protein synthesis.

Question 27

How are aminoglycosides typically resisted by bacteria?

Answer 27

Modifying the antibiotic with transferases inactivating it.

Question 28

How do Macrolids work and who do they work on?

Answer 28

Gram Positive. Bacteriostatic. Binds 50S and blocks elongation. Useful when allergic to B-lactams.
Included: Erythromycin and Azithromycin

Question 29

How can bacteria become resistant to Macrolids?

Answer 29

Methylating the binding site on the 50S blocking the abx

Question 30

What kind of infections is Chloramphenicol typically used for?

Answer 30

Severe infections like Typhoid or Rocky Mountain Fever, due to causing anemia because of nonselectivity.
- inhibits pepidyl transferase

Question 31

What kind of bacteria does Clindamycin usually treat?

Answer 31

Gram Positive - Community MRSA and S. Aureus (skin)

–binds 50S preventing elongation– Bacteriostatic

Question 32

What kind of cross reactivity does Clindamycin have?

Answer 32

If the bacterium is resistant to Macrolids, then they are also resistant to Clindamycin.

Question 33

How does Linezolid work?

Answer 33

Binds a unique site of the 50S Ribosome preventing formation of the 70S complex.
Gram Positive Only

Question 34

When would someone use Linezolid?

Answer 34

Used with complicated skin and structure infections, can become resistant by a single point mutation of the ribosome. Usually Staph strains.

Question 35

What are the inhibitors of DNA synthesis?

Answer 35

1st Generation - Nalidixic Acid - narrow
2nd Generation - Fluoroquinolones - Broad
- Cipro, Levo, Moxi

Question 36

What is the mechanism of action of DNA synthesis antibiotics?

Answer 36

Binds DNA Gyrase/Topoisomerase disrupting DNA replication and repair.
Resistance: Point mutations and Drug modification

Question 37

What is Metronidazole commonly used to treat?

Answer 37

Typically Anaerobic infections due to targeting DNA with free radicals.
– C. Difficle Treatment

Question 38

What are two RNA Polymerase inhibitors?

Answer 38

Rifampin and Fidaxomicin

-binds RNA Polymerase inhibiting it’s action

Question 39

What are two inhibitors of the Tetrahydrofolate pathway?

Answer 39

Sulfonamides - similar to p-aminobenzoic acid

Trimethoprim - inhibits dihydrofolate reductase

Question 40

When two antibiotics complement one another’s action they are thought to be?

Answer 40

Synergistic

Question 41

Why do bacteriostatic and bactericidal drugs not work well together?

Answer 41

Due to the bactericidal drugs killing the bacterium when they are dividing, but bacteriostatic prevent them from dividing.

Question 42

Where are biofilms typically located and how do they effective treatment?

Answer 42

Biofilms are usually found on implanted devices or tubes and the bacteria can reside there unaffected by antibiotics. Only cure is to remove the device.