The ideal antibiotic ...
Will it always be ideal ?
Main causes of antibiotic failures...
PK / PD ...
PPT Slide
Pharmacokinetic/ Pharmacodynamics in Drug Development and Evaluation of Efficacy
PK/PD in drug develop-ment A view from FDA
Pharmacokinetic/ Pharmacodynamics and antibiotic resistance...
PK/PD and drug devlop-ment A view from EMEA
Are PK / PD important in resistance ?
Just a few of them…
Pharmacokinetic/ Pharmacodynamics in Drug Development and Evaluation
Pharmacokinetic/ Pharmacodynamics: What are the goals ?
PK/PD and effectiveness: patterns of antimicrobial activity (after WA. Craig, 2000)
?-lactams : at least 50 % of the time above the MIC...
PK / PD in action: what can you do with a model ?-lactam *
PK / PD in action...
Improving ?-lactam efficacy by reducing the interval
PK /PD in action ...
?-lactams PK / PD and resistance
AUC / MIC - dependent antibiotics and resistance
Aminoglycosides : obtain a peak !
PK / PD in action ...
PK PD in action ...
PK/PD of fluoroquinolones
24h AUC / MIC ratio
24h AUC / MIC and FQ effectiveness: in vitro dynamic models
Peak / MIC ratio
Peak / MIC and FQ effectiveness (animal models)
Peak / MIC of FQ: clinical data
24h-AUC / MIC as a tool to determine acceptable sensitivities to standard doses of FQ
Peak concentrations as a tool to determine acceptable sensitivities to standard doses of FQ
Combining it all …(Peak and 24h-AUC / MIC) as predictors of efficacy standard doses of FQ ...
Patients may be treatable because AUC (but not Cmax) increases with decreased drug clearance
Is a 24h AUC / MIC ratio of 125 necessary ?
PK / PD bkpt for AUC / MIC
To increase both AUC and peak … increase the unit dose ...
Breakpoints ??
Why would too high breakpoints favour the emergence of resistance to FQs ?
Resistance to fluoroquinolones: the basics
PK/PD and point mutations ...
PK/PD and point mutation in DNA gyrase...
Cmax and MPC of FQ’s
Significance of MPC ?
PK/PD and antibiotic efflux pumps...
Efflux pumps...
Efflux pumps and first mutation may cooperate ...
Efflux pumps may bring intrabacterial concentrations of FQ < MPC ...
PK/PD and resistance ?
A long way indeed ...
But closer than you tought ...
Email: tulkens@facm.ucl.ac.be
Home Page: http://www.md.ucl.ac.be/facm/facm-conferences.htm
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