Antibiotics- Inhibition of DNA syntheses and integrity; Inhibitors of folate synthesis and function Flashcards
Inhibition of DNA syntheses and integrity
Inhibitors of folate synthesis and function
Sulfonamides, Trimethoprim, Quinolones
Antifolate antibiotics- Mechanism sulfonamide and Trimethoprim
Blockade of folic acid synthesis
Antifolate antibiotics- Mechanism sulfonamide and Trimethoprim–> Sulfamethoxazole
•Interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from para-aminobenzoic acid
Antifolate antibiotics- Mechanism sulfonamide and Trimethoprim–> Trimethoprim
•Inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway
Antifolate antibiotics- Mechanism fluoroquinolones
- 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
What do Sulfonamides with Trimethoprim result in?
synergistic inhibition of folic acid synthesis
Agent: Trimethoprim-sulfamethoxazole (Bactrim)
What is the activity specturum of sulfonamides with Trimethoprim (agent: Trimethoprim-sulfamethoxazole)
- UTI*
- Traveler’s diarrhea
- Respiratory infections (bronchitis)
- Ear infections
- Sinus infections
- P jiroveci pneumonia (in HIV)
- Toxoplasmosis (in HIV)
- Nocardiosis
- MSSA or MRSA-skin/soft tissue infections*
*= highlighted in red on slide
Are sulfonamides with trimethoprim bacteristatic or bactericidal?
Combination is bactericidal- “sequential blockade”
What are ADEs of sulfonamides with trimethoprim (agent- Trimethoprim-sulfamethoxazole)?
- Rash
- Fever
- Bone marrow suppression
- Hyperkalemia
- high incidence of adverse effects in AIDs patients
- neutropenia, Stevens-Johnson syndrome and toxic epidermal necrolysis.
What is dosing of Trimethoprim-sulfamethoxzaole based on?
aka TMP-SMX or TMP-SMZ
dosing is based on the trimethoprim component
What stage of pregnancy should TMP/SMX be avoided?
1st trimester or >32weeks –> can result in neural tube and cardiovascular defects
How do quinolones work?
Quinolones inhibit DNA replication via binding to DNA gyrase (gram-negative organisms) and topoisomerase IV (gram-positive organisms)
Quinolones- Agent
- Ciprofloxacin
- Levofloxacin
- Gatifloxacin (ophthalmic only)
- Gemfloxacin
- Moxifloxacin
- Ofloxacin
Activity spectrum of Quinolones
- Urogenital infections
- GI tracts infections
- Bacterial conjunctivitis
- Activity versus gonococci rapidly declining
What are ciprofloxacin and ofloxacin mainly used for?
Urinary tract infections
**They do not work in the lungs**
What are Levofloxacin, gemfloxacin and moxifloxacin generally used for?
These are “respiratory” fluoroquinolones with enhanced activity against gram-positive cocci and atypicals (chlamydia, mycoplasma)
What are ADEs of Quinolones
- CNS effects (dizziness, headache)
- Tendinitis due to effects on cartilage
- Try to avoid in young children and pregnancy
- Peripheral neuropathy
- Neuromuscular-blocking activity (also seen in aminoglycosides)
- QTc prolongation (levofloxacin, gemifloxacin, and moxifloxacin)
What is synergism?
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.
Empiric treatment
•antimicrobial agent used before pathogen is identified for particular illness or susceptibility is known.
What is guided treatment
•effective antimicrobial agent identified by susceptibility testing of infecting microorganism.
In what neuromuscular disease should quinolones be avoided?
Fluoroquinolones are associated with negative implications for patients with MG because they disrupt neuromuscular transmission. Macrolides should also be avoided in these patients.
