Dosing appropriately and antibiotic: does it matter ?

16 september 2000, Toronto, Ont.

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Table of Contents

PPT Slide

The design of an ideal antibiotic ...

Will it always be ideal ?

Main causes of antibiotic failures... Adapted from Pechère J.C., 1988, 1993, 1998

Pharmacokinetics / pharmacodynamics as a step towards therapy...

Pharmacokinetics ...

Pharmacodynamics ...

Pharmacokinetic/ Pharmacodynamics in Drug Development and Evaluation of Efficacy (1/2)

PK/PD in drug develop-ment A view from FDA

Pharmacokinetic/ Pharmacodynamics and antibiotic resistance...

Are PK/PD important in resistance ?

Single dose PK/PD parameters: a first sight

Multiple doses: the issues...

Pharmacokinetic / Pharmacodynamic parameters: a 2d sight

Pharmacokinetic/ Pharmacodynamics

PK/PD patterns of antimicrobial activity (1 of 3) (after WA. Craig, 2000)

PK/PD patterns of antimicrobial activity (2 of 3) (after WA. Craig, 2000)

PK/PD patterns of antimicrobial activity (3 of 3) (after WA. Craig, 2000)

PK/PD: role of concentration Point of Principle an example with Listeria monocytogenes

The role of the peak for FQ : animal models

Peak concentrations of the main fluoroquinolones (p.o.)

Peak concentrations as a tool to determine acceptable sensitivities to fluoroquinolones (p.o.)

PK/PD of fluoroquinolones: role of the 24h-AUC MIC ciprofloxacin in hospital-acquired pneumonia

24h-AUC / MIC as a tool to determine acceptable sensitivities to fluoroquinolones (p.o.)

Peak concentrations and 24h-AUC / MIC as predictors of efficacy of FQ ...

But isn’t anything more about the peak ?

Fluoroquinolones: mode of action and resistance mechanisms

The importance of double mutation ...

Mutant-prevention concentration (MPC) (1/3)

Bactericidal activity of FQs against M. bovis 

Mutant-prevention concentration (MPC) (2/3) ...

Role of the C8-methoxy in decreasing MPC

N-1-cyclopropyl-fluoroquinolones with a C8-methoxy

Peak concentrations as a tool to prevent emergence of resistance (MPC): using “ PK / PD acceptable ” MICs

PK/PD and antibiotic efflux pumps...

PK/PD and antibiotic efflux pumps… an example with RND...

PK/PD for prevention of resistance: clinical data

PK/PD for prevention of resistance: clinical data

PK/PD for prevention of resistance: clinical data

PPT Slide

And we may have a very bright future...

Author: Paul M. Tulkens 

Email: tulkens@facm.ucl.ac.be

Home Page: http://www.md.ucl.ac.be/facm/facm-conferences.htm