Personalized Optimization of Antibiotic Therapy in Pulmonary Sepsis Critically Ill Patients Through Application of Rapid Microbiological Diagnostic Technologies and Pharmacokinetic/Pharmacodynamic Modelling
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Rapid ID/AST method, Conventional biological methods.
- Who it may be relevant to
- Registry conditions: Pulmonary Sepsis. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
Severe community-acquired and nosocomial pneumonia are associated with substantial morbidity and mortality. Early and appropriate antimicrobial therapy (AAT) is consistently the most effective intervention for reducing mortality. Cure is most likely when pharmacokinetic (PK) / pharmacodynamics (PD) targets associated with maximum antibiotic (ABX) activity are achieved. However, the process of optimizing antibiotic therapy for critically ill patients remains a complicated challenge. A key issue is pathogen identification (ID) with subsequent antibiotic susceptibility testing (AST) results which allow for selection of AAT. Standard laboratory procedures typically require 2-3 days to provide ID and AST results. Optimal ABX dosing/dosing intervals depend in large part on PK properties in individual patients, and antibacterial effects on the infecting bacteria (PD). Alterations in the primary PK parameters, namely volume of distribution (Vd) and clearance (CL), are commonly observed, and are the most influential parameters in determining ABX dosing and exposure. ABX dosing/dosing intervals that do not account for these features are likely to lead to suboptimal ABX exposure and therapeutic failures. Because of 48-72-hours delays in ID/AST, initial treatment is frequently inappropriate in coverage, unnecessarily broad in spectrum, and/or suboptimal in dosing. Methods for rapid bacterial growth, ID, AST and minimum inhibitory concentration (MIC) identification were developed and are capable of quantitative ID in 1-2 hours and major AST in 6-8 hours using clinical specimens. Rapid ID of the infecting pathogen and its individual AST could significantly impact the early selection of AAT and, combined with therapeutic drug monitoring data, could be used to calculate optimized dosing regimens that are personalized for the patient in order to achieve appropriate PK/PD targets. Hypothesis: Application of these rapid ID/AST systems, together with prospective PK/PD monitoring of antibiotic plasma concentrations, will significantly shorten time from "sample to answer" for pathogen ID/AST, enhance personalized prescribing of antibiotics, optimize the time to targeted effective and AAT, and result in decreased treatment failure.
Interventions
- Diagnostic test Rapid ID/AST method
1. BioFire® Film Array® Blood Culture Identification 2 BCID2 panel, bioMérieux/BioFire Diagnostics, CE marked (FDA cleared) 2. BioFire® FilmArray® Pneumonia Panels, CE marked (FDA cleared) 3. SPECIFIC REVEAL® Rapid Antimicrobial Susceptibility test (AST) System, bioMérieux/Specific Diagnostics, CE-IVD and -IVDR marked - Diagnostic test Conventional biological methods
Usual care
Primary outcome measures
- Rate of treatment failure [Time frame: Up to 10 days after inclusion]
Secondary outcome measures (12)
- Time to availability of pathogen [Time frame: Up to 180 days]
- Time to achieve targeted optimized therapy [Time frame: Up to 180 days]
- Time to antibiotic switches [Time frame: Up to 180 days]
- Number of started, stopped, added or adjusted (escalation or de-escalation) antibiotics [Time frame: Up to 180 days]
- Time to Aantibiotic dose adjustments to achieve PK/PD targets [Time frame: Up to 180 days]
- All-Cause mortality [Time frame: Up to 180 days]
- All-Cause mortality [Time frame: Up to 180 days]
- All Cause Mortality [Time frame: At day 90]
- All Cause Mortality [Time frame: At day 180]
- SOFA score assessment [Time frame: Up to 28 days]
- Organ-failure free days (SOFA<6) [Time frame: Up to day 28]
- Proportion of patients requiring invasive mechanical ventilation [Time frame: At day 7]
Eligibility criteria
Inclusion criteria
- Patients hospitalized in ICU
- 18 years of age or older
- With a pulmonary sepsis defined a s documented or suspected acute pulmonary infection (nosocomial and community-acquired pneumonia) and a SOFA score >2.
- Written Informed consent from the patient whenever possible or written ascent from next of kin whenever present at inclusion. When a patient would not be capable of consenting prior to randomization, his/her deferred consent will be gotten.
Exclusion criteria
- COVID-19 patients
- Severe anaphylactic beta-lactam allergy
- First measurements of prescribed antibiotic concentration (TDM) not possible within 24 hr after randomization
- Pregnancy or lactation
- Any decision of limitation of care
- Pre-existing medical condition with a life expectancy of less than 3 months
- Absence of affiliation to social security
- Patient under guardianship, curatorship and deprived of liberty
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Diagnostic
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT06956053 · APHP180673