25 MB of information …25 MB of information …

CONTENT OF THE CD-romCONTENT OF THE CD-rom

Learning appropriate use of antibiotics (PK/PD and guidelines):Learning appropriate use of antibiotics (PK/PD and guidelines): a CD-rom course for healthcare professionals and students a CD-rom course for healthcare professionals and students

E. Ampe, Y. Glupczynski, P.M. Tulkens, and F. Van Bambeke

Unité de Pharmacologie cellulaire et moléculaire, Université catholique de Louvain - Brussels - Belgium Laboratoire de microbiologie, Cliniques universitaires UCL, Mont-Godinne

Mailing address:P.M. TulkensUCL 73.70 av. Mounier 731200 Brussels - Belgiumtulkens@facm.ucl.ac.be

ABSTRACTObjectives: In a context of growing resistance and limited supply of new molecules, a rational use of antibiotics should be a high priority. Our objective is to train healthcare professionals and students in PK/PD and in a correct implementation of guidelines, since this could help to improve antibiotic use in both short and mid-terms.

Methods: We developed a PK/PD – guidelines course on CD-rom, targeted to both physicians and pharmacists but also usable by students. The course was prepared by a team of 2 pharmacists, 1 clinical microbiologist, and 1 pharmacologist. Sources of information were (i) textbooks, review papers and primary papers by internationally recognized experts (ii) materials presented at training workshops of the International Society for Antiinfective Pharmacology (ISAP; www.isap.org) during the last 3 years, (iii) national and, if not available, international guidelines for the management of respiratory tracrtor urinary tract infections.

Results: The course is organized as a series of Power Point presentations covering in a progressive fashion the followings topics : (1) bases in microbiology (in vitro properties of antibiotics); (2) pharmacokinetics (definition of the main parameters); (3) pharmacodynamics, with (A) the concepts, (B) the methods and pertinent models, and (C) the data, including the parameters to take into account to optimize the dosage of the main antibiotic classes; (4) resistance, including (A) the main mechanisms and (B) the use of pharmacodynamics to avoid the selection of resistance; (5) the appropriate use (including appropriate dosages) of antibiotics in (A) respiratory tract and (B) urinary tract infections.

Conclusions:This course promotes continuous education in the pharmacology and pharmacotherapy

of antibiotics, in a format easily usable for courses and seminars to both students and professionals.

OBJECTIVES

to develop an educational programme in which pharmacists and infectious disease specialists train healthcare professionals and students in PK/PD and in a correct implementation of guidelines.

to distribute to people following this course a CD-rom as a support that can be consulted at any time.

INTRODUCTION

Optimizing the use of current antibiotics based on pharmacokinetics and pharmacodynamics and rational application of guidelines can contribute to the limitation of resistance development.

In this respect, education of students and healthcare professionals appears as a priority and can be facilitated by making available to them easy-to-consult informative supports.

WHAT WE HOPE AND WHAT WE WILL DO:

the CD-rom should be a continuous information source that could be used for teaching pharmacology and pharmacotherapy of antibiotics to

students and healthcare professionals. may be easily consulted by healthcare professionals at any moment.

We will regularly update it and plan to evaluate its impact on education of students and on the quality of antibiotic prescribing of junior physicians

SECTION 2. DEFINITION SECTION 2. DEFINITION OF PK PARAMETERSOF PK PARAMETERS

SECTION 3. DEFINITION SECTION 3. DEFINITION OF PD PARAMETERSOF PD PARAMETERS

GUIDELINES RESPIRATORY TRACT INFECTIONS

Principles

Application of PK:PD concepts

SECTION 4. GUIDELINESSECTION 4. GUIDELINES

ACKNOWLEDGMENTS: We thank W. Peetermans (KUL- UZ Gasthuisberg) for useful comments and Bayer Belgium for financial support

UCL PK/PD Course 0-9September 2004

Programme, please ...1. Basic introduction to key microbiological parameters

2. Pharmacokinetics (PK) : the basics

3. Pharmacodynamics (PD)

A. the concepts

B. the methods

C. actual data on the main classes of antibiotics

4. Resistance

A. mechanisms and epidemiology

B. PK/PD to fight resistance

5. Clinical guidelines or how to implement PK/PD …

References

What you always wished to know but never dared to askbecause it seemed so basic … and did not know how to begin with all that stuff ...

UCL PK/PD Course 2-5September 2004

What is PK for ?

PK is the way to see if the drug can be made useful …

• does it reach the target in sufficient amounts ?

• for long enough ?

• does it each non-desired targets ?

Co

nc

.

Time0 25

0.0

0.4

Pharmacokinetics= conc. vs time

UCL PK/PD Course 3C-3September 2004

from pharmacokinetics to pharmacodynamics...

0 6 18 2412

Con

cent

ratio

n

MIC

AUC > MIC

AUC / CMI

t > MIC

Time ~ conc > MIC

CmaxCmax / CMI

Time (h)

UCL PK/PD course 1-9September 2004

MIC distributions : unimodal populations

50% 90%

MIC50MIC50 MIC90MIC90

MIC (µg/ml)0.06 012 0.25 0.5 211 840.03

SECTION 1. DEFINITION OF SECTION 1. DEFINITION OF MICROBIOLOGICAL MICROBIOLOGICAL

PARAMETERSPARAMETERS

UCL PK/PD course 5B-7september 2004

Pharyngitis: algorithm for treatment

clinical and epidemiologicalcharacteristics

StreptoPharyngitis

not suspected

StreptoPharyngitis suspected

(4 Centor’s criteria)

Patient at risk

Rapid Ag test

Throat swab culture

Symptomatic treatment Antibiotic treatment

+

+ -

-

- Fever > 38°- no cough- tonsil exsudate-Adénopathies sous-mandibulaires

- anticancer treatment- patients suffering from AAR- -hemolytic strepto B epidemy ina closed community

- severe general symptoms - Cardiac valve abnormality

justifying prophylaxis for Osler’sendocarditis

UCL PK/PD course 5B-17september 2004

Why such high doses ?

… and, hence, insure optimal coverage (T > CMI = 60 % ) for MIC < 4 mg/L

PK data: Fonseca et al (2003) AAC 47:997-1001

Limit of " R " (fully resistant) S. pneumoniae

Increasing the dosis to 80 mg/kg divided in 3 administrations will cause a dubbeling of the concentrations …

P878P878

GUIDELINES URINARY TRACT INFECTIONS

Principles

Applications of PK/PD concepts

UCL PK/PD Lessen 5C-47september 2004

Acute prostatis : treatment

First choice:

• Fluoroquinolones– Ciprofloxacin if suspicion of P. aeruginosa, 500 mg X 2 po

Second choice :

• Cotrimoxazol, 800/160 mg X 2 po

Alternatieves:

• Cephalosporins (cefuroxim)

• Amoxicillin + clavulanic acid

Minimal duration : 2 weeks, often 4 weeks(prevention of chronic infection)

UCL PK/PD Lessen 5C-14september 2004

We are in search of AB thatconcentrate in urine…

0-6 6-12 12-240.01

0.1

1

10

100

1000urine

serum

time interval (h)

con

cen

trat

ion

(m

g/L

)

PK data: Boy et al, Int J Antimicrob Agents . 2004 23 Suppl 1:S6-16

0-2 2-4 4-81

10

100

1000

SM-urine

SM-serum

TMP-urine

TMP-serum

time interval (h)

co

nc

en

tra

tio

n (

mg

/L)

PK data: Tartaglione et al , Antimicrob Agents Chemother. 1988  32 : 1640–1643

Ciprofloxacine, 500 mg po cotrimoxazole, 160/800 mg po