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Optimizing Patient Care Optimizing Patient Care From Bench to Bedside From Bench to Bedside and Back Again and Back Again
Optimizing Patient CareOptimizing Patient Care
From Bench to BedsideFrom Bench to Bedsideand Back Againand Back Again
Optimizing Patient CareOptimizing Patient Care
From Beside to Bench and Back AgainFrom Beside to Bench and Back Again
From bedside to bench to bedside...From bedside to bench to bedside...
Day 1
Day 2
Day 3
And back again...And back again...
• So what’s needed to complete the picture?So what’s needed to complete the picture?
» The MIC of the pathogenThe MIC of the pathogen
» Sufficient (free) drug level measurements from the Sufficient (free) drug level measurements from the patient to estimate PD target attainmentpatient to estimate PD target attainment(are 2 levels enough? or 1 if giving by continuous (are 2 levels enough? or 1 if giving by continuous infusion)infusion)
The MICThe MIC
The LevelsThe Levels
What’s needed to complete the pictureWhat’s needed to complete the picture
• For agents where the relevant PK/PD For agents where the relevant PK/PD parameter is knownparameter is known» Agreement about the PD target valuesAgreement about the PD target values
• For agents where the relevant PK/PD For agents where the relevant PK/PD parameter is not knownparameter is not known» Please work it out!Please work it out!
• More drug assays with rapid TAT and More drug assays with rapid TAT and software development to PD target software development to PD target attainment estimates (including confidence attainment estimates (including confidence intervals?) and therefore dosing intervals?) and therefore dosing individualizationindividualization
What’s also needed...What’s also needed...
• Better understanding of the variance in MIC Better understanding of the variance in MIC measurementmeasurement» the logarithmic distribution can also have a the logarithmic distribution can also have a
significant impactsignificant impact
• Recognition of natural (placebo) response Recognition of natural (placebo) response raterate
The MIC is the MIC is the MICThe MIC is the MIC is the MIC
CLSI AST Subcommittee agenda papers June 2004 and 2005 CLSI AST Subcommittee agenda papers June 2004 and 2005
Variance in MIC estimationsVariance in MIC estimations
0
5
10
15
20
25
30
35
40
45
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
1.9
2.0
2.1
2.2
Log2 SD
Fre
qu
en
cy
E. coli 25922 - Doripenem
020406080
100120140160180200
0.004 0.008 0.016 0.031 0.063 0.125
MIC
Nu
mb
er
of
res
ult
s
Log2 GeoMean =-5.700 ± 0.486
Grepafloxacin in AECBGrepafloxacin in AECBBacteriological CureBacteriological Cure
100
90
80
70
60
5010 100 1000 10000
% p
roba
bilit
y of
bac
teri
olog
ical
cur
e
AUICForrest et al., J Antimicrob Chemother.1997.40 (Suppl A):45-57 13
Are we now ready for Prime Time Are we now ready for Prime Time at the patient level?at the patient level?
ICAACICAAC
BermudaBermuda
Out to lunchOut to lunch
MadisonMadison
Victoria, AUSVictoria, AUS
And sometimes at homeAnd sometimes at home
Thank youThank you
From your extended familyFrom your extended family
