Evidence map›Paper›PMID 38952168›Full record

Trial reportClinical and translational science2024

Integration of individual preclinical and clinical anti-infective PKPD data to predict clinical study outcomes.

Vincent Aranzana-Climent, Wisse van Os, Amir Nutman, Jonathan Lellouche, Yael Dishon-Benattar, Nadya Rakovitsky, George L Daikos, Anna Skiada, Ioannis Pavleas, Emanuele Durante-Mangoni and 4 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Vincent Aranzana-ClimentDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-1258-8054
Wisse van OsDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.ORCID 0000-0003-1709-4173
Amir NutmanNational Institute for Antibiotic Resistance and Infection Control, Israel Ministry of Health, Tel Aviv, Israel.ORCID 0000-0002-1599-2618
Jonathan LelloucheNational Institute for Antibiotic Resistance and Infection Control, Israel Ministry of Health, Tel Aviv, Israel.ORCID 0000-0002-0564-4409
Yael Dishon-BenattarInfectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel.ORCID 0000-0002-9646-5376
Nadya RakovitskyDivision of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel.ORCID 0000-0001-6051-1177
George L DaikosFirst Department of Medicine, Laikon General Hospital, Athens, Greece.ORCID 0000-0001-5365-4874
Anna SkiadaFirst Department of Medicine, Laikon General Hospital, Athens, Greece.ORCID 0000-0003-4431-3511
Ioannis PavleasFirst Department of Medicine, Laikon General Hospital, Athens, Greece.
Emanuele Durante-MangoniDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.ORCID 0000-0002-5381-3537
Ursula TheuretzbacherCenter for Anti-Infective Agents, Vienna, Austria.ORCID 0000-0003-2116-7128
Mical PaulInfectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel.ORCID 0000-0003-2317-1112
Yehuda CarmeliNational Institute for Antibiotic Resistance and Infection Control, Israel Ministry of Health, Tel Aviv, Israel.
Lena E FribergDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-2979-679X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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-log

Indexed as

Acinetobacter baumanniiAnti-Bacterial AgentsMeropenemMicrobial Sensitivity TestsAcinetobacter InfectionsAdultAgedAnimalsColistinDrug Therapy, CombinationFemaleHumansMaleMiceMiddle AgedModels, BiologicalAnti-Bacterial AgentsColistinMeropenem

Identifiers

PMID38952168
PMCPMC11217551

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.