Mechanism of action of
fluoroquinolones:
the basics...
2 key enzymes in DNA replication:
Ternary complex
DNA - enzyme - fluoroquinolone
Ternary complex
DNA - enzyme - fluoroquinolone
Resistance to fluoroquinolones: the basics
Fluoroquinolones are the
first entirely
man-made antibiotics:
do we understand our molecule ?
The pharmacophore common to all fluoroquinolones
From chloroquine to nalidixic acid...
From nalidixic acid to
the
1st fluoroquinolone (1 of 4)
From nalidixic acid to
the
1st fluoroquinolone (1 of 4)
From nalidixic acid to
the
1st fluoroquinolone (1 of 4)
From nalidixic acid to
the
1st fluoroquinolone (1 of 4)
From norfloxacin to the other 1st generation fluoroquinolones: pefloxacin
From norfloxacin to the other 1st generation fluoroquinolones: ofloxacin
From norfloxacin to the other 1st generation fluoroquinolones: ciprofloxacin
"1st generation" fluoroquinolones
The "first generation" of fluoroquinolones
From ofloxacin to levofloxacin...
The present "first generation" of fluoroquinolones ...
How to improve the
chemotherapeutic usefulness of
the "first generation"
fluoroquinolones
The “second generation” fluoroquinolones
The “third generation” fluoroquinolones
Activity against S. pneumoniae
Resistance au
fluoroquinolones :
les mécanismes de base ...
Resistance au
fluoroquinolones :
rôle des mutations au niveau de la cible
Is there a SAR for emergence of resistance ?
Is there a SAR for emergence of resistance ?
Fluoroquinolones with a C8-methoxy
Frequent side effects of
fluoroquinolones:
is there a SAR ?
Fluoroquinolone with low or no drug interactions..
Rare side effects of fluoroquinolones:
SAR of pharmacokinetic parameters
SAR of main
pharmacokinetic parameters:
how to get a long half life
Resistance: do not forget the correct dosing...
Pharmacokinetic parameters in relation with efficacy
Optimizing dosage for fluoroquinolones
Dosage is key to success | |
Dosage should match bacterial sensitivity | |
peak, AUC/MIC are keys to success | |
use a single, appropriate dose for long-life fluoroquinolones (moxifloxacin), or | |
repeat the dose for short-lived fluoroquinolones (all others so far…) | |
for fluoroquinolones, the limit is an MIC
of 0.5 µg/ml |