Antibiotics- Inhibition of DNA syntheses and integrity; Inhibitors of folate synthesis and function

Question 1

Inhibition of DNA syntheses and integrity

Inhibitors of folate synthesis and function

Answer 1

Sulfonamides, Trimethoprim, Quinolones

Question 2

Antifolate antibiotics- Mechanism sulfonamide and Trimethoprim

Answer 2

Blockade of folic acid synthesis

Question 3

Antifolate antibiotics- Mechanism sulfonamide and Trimethoprim–> Sulfamethoxazole

Answer 3

•Interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from para-aminobenzoic acid

Question 4

Antifolate antibiotics- Mechanism sulfonamide and Trimethoprim–> Trimethoprim

Answer 4

•Inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway

Question 5

Antifolate antibiotics- Mechanism fluoroquinolones

Answer 5

• Interfere with bacterial DNA synthesis by inhibiting DNA gyrase
• Inhibits the relaxation of supercoiled DNA that is catalyzed by DNA gyrase, a step required for normal transcription and duplication

Question 6

What do Sulfonamides with Trimethoprim result in?

Answer 6

synergistic inhibition of folic acid synthesis

Agent: Trimethoprim-sulfamethoxazole (Bactrim)

Question 7

What is the activity specturum of sulfonamides with Trimethoprim (agent: Trimethoprim-sulfamethoxazole)

Answer 7

1. UTI*
2. Traveler’s diarrhea
3. Respiratory infections (bronchitis)
4. Ear infections
5. Sinus infections
6. P jiroveci pneumonia (in HIV)
7. Toxoplasmosis (in HIV)
8. Nocardiosis
9. MSSA or MRSA-skin/soft tissue infections*

*= highlighted in red on slide

Question 8

Are sulfonamides with trimethoprim bacteristatic or bactericidal?

Answer 8

Combination is bactericidal- “sequential blockade”

Question 9

What are ADEs of sulfonamides with trimethoprim (agent- Trimethoprim-sulfamethoxazole)?

Answer 9

1. Rash
2. Fever
3. Bone marrow suppression
4. Hyperkalemia 
5. high incidence of adverse effects in AIDs patients
   
   • neutropenia, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Question 10

What is dosing of Trimethoprim-sulfamethoxzaole based on?

Answer 10

aka TMP-SMX or TMP-SMZ

dosing is based on the trimethoprim component

Question 11

What stage of pregnancy should TMP/SMX be avoided?

Answer 11

1st trimester or >32weeks –> can result in neural tube and cardiovascular defects

Question 12

How do quinolones work?

Answer 12

Quinolones inhibit DNA replication via binding to DNA gyrase (gram-negative organisms) and topoisomerase IV (gram-positive organisms)

Question 14

Quinolones- Agent

Answer 14

1. Ciprofloxacin
2. Levofloxacin
3. Gatifloxacin (ophthalmic only)
4. Gemfloxacin
5. Moxifloxacin
6. Ofloxacin

Question 15

Activity spectrum of Quinolones

Answer 15

1. Urogenital infections
2. GI tracts infections
3. Bacterial conjunctivitis
4. Activity versus gonococci rapidly declining

Question 17

What are ciprofloxacin and ofloxacin mainly used for?

Answer 17

Urinary tract infections

**They do not work in the lungs**

Question 18

What are Levofloxacin, gemfloxacin and moxifloxacin generally used for?

Answer 18

These are “respiratory” fluoroquinolones with enhanced activity against gram-positive cocci and atypicals (chlamydia, mycoplasma)

Question 19

What are ADEs of Quinolones

Answer 19

1. CNS effects (dizziness, headache)
2. Tendinitis due to effects on cartilage
   
   • Try to avoid in young children and pregnancy
3. Peripheral neuropathy
4. Neuromuscular-blocking activity (also seen in aminoglycosides)
5. QTc prolongation (levofloxacin, gemifloxacin, and moxifloxacin)

Question 20

What is synergism?

Answer 20

Inhibitory or killing effects of two or more antimicrobials used together are significantly greater than expected from their effects when used individually

Synergism is marked by a fourfold or greater reduction in the MIC or MBC of each drug when used in combination versus when used alone.

Question 21

Empiric treatment

Answer 21

•antimicrobial agent used before pathogen is identified for particular illness or susceptibility is known.

Question 22

What is guided treatment

Answer 22

•effective antimicrobial agent identified by susceptibility testing of infecting microorganism.

Question 23

In what neuromuscular disease should quinolones be avoided?

Answer 23

Fluoroquinolones are associated with negative implications for patients with MG because they disrupt neuromuscular transmission. Macrolides should also be avoided in these patients.