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Integration of indi...
Integration of individual preclinical and clinical anti-infective PKPD data to predict clinical study outcomes
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- Aranzana-Climent, Vincent (författare)
- Uppsala universitet,Institutionen för farmaci,Univ Poitiers, Inserm U1070, PHAR2, Poitiers, France.
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- van Os, Wisse (författare)
- Uppsala universitet,Institutionen för farmaci,Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria.
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- Nutman, Amir (författare)
- Israel Minist Hlth, Natl Inst Antibiot Resistance & Infect Control, Tel Aviv, Israel.;Tel Aviv Univ, Fac Med & Hlth Sci, Tel Aviv, Israel.
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- Lellouche, Jonathan (författare)
- Israel Minist Hlth, Natl Inst Antibiot Resistance & Infect Control, Tel Aviv, Israel.;Ariel Univ, Adelson Sch Med, Ariel, Israel.
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- Dishon-Benattar, Yael (författare)
- Rambam Hlth Care Campus, Infect Dis Inst, Haifa, Israel.;Univ Haifa, Cheryl Spencer Dept Nursing, Haifa, Israel.
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- Rakovitsky, Nadya (författare)
- Tel Aviv Sourasky Med Ctr, Div Epidemiol & Prevent Med, Tel Aviv, Israel.
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- Daikos, George L. (författare)
- Laikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece.
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- Skiada, Anna (författare)
- Laikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece.
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- Pavleas, Ioannis (författare)
- Laikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece.
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- Durante-Mangoni, Emanuele (författare)
- Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Osped Colli Monaldi Hosp, Naples, Italy.
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- Theuretzbacher, Ursula (författare)
- Ctr Antiinfect Agents, Vienna, Austria.
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- Paul, Mical (författare)
- Rambam Hlth Care Campus, Infect Dis Inst, Haifa, Israel.;Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel.
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- Carmeli, Yehuda (författare)
- Israel Minist Hlth, Natl Inst Antibiot Resistance & Infect Control, Tel Aviv, Israel.;Tel Aviv Univ, Fac Med & Hlth Sci, Tel Aviv, Israel.
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- Friberg, Lena (författare)
- Uppsala universitet,Institutionen för farmaci
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(creator_code:org_t)
- John Wiley & Sons, 2024
- 2024
- Engelska.
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Ingår i: Clinical and Translational Science. - : John Wiley & Sons. - 1752-8054 .- 1752-8062. ; 17:7
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and meropenem dosing history, and (iii) disease scores and demographics. The individual information was integrated into PKPD models, and the predicted change in bacterial count at 24 h for each patient, as well as patient characteristics, was correlated with clinical outcomes using logistic regression. The in vivo fitness was the most important factor for change in bacterial count. A model-predicted growth at 24 h of ≥ 2-log10 (164/207) correlated positively with clinical failure (adjusted odds ratio, aOR = 2.01). The aOR for one unit increase of other significant predictors were 1.24 for SOFA score, 1.19 for Charlson comorbidity index, and 1.01 for age. This study exemplifies how preclinical and clinical anti-infective PKPD data can be integrated through pharmacodynamic modeling and identify patient- and pathogen-specific factors related to clinical outcomes - an approach that may improve understanding of study outcomes.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
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Aranzana-Climent ...
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van Os, Wisse
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Nutman, Amir
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Lellouche, Jonat ...
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Dishon-Benattar, ...
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Rakovitsky, Nady ...
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visa fler...
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Daikos, George L ...
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Skiada, Anna
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Pavleas, Ioannis
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Durante-Mangoni, ...
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Theuretzbacher, ...
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Paul, Mical
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Carmeli, Yehuda
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Friberg, Lena
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Infektionsmedici ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Farmaceutiska ve ...
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Clinical and Tra ...
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Uppsala universitet