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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rapid ID/AST method | Experimental |
| |
| Conventional microbiological methods | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rapid ID/AST method | Diagnostic Test |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rate of treatment failure | It includes treatment failure that occurred early (≤72 hours) or late (>72 hours), or at both times. | Up to 10 days after inclusion |
| Measure | Description | Time Frame |
|---|---|---|
| Time to availability of pathogen | ID/AST, MICs and conventional results | Up to 180 days |
| Time to achieve targeted optimized therapy | It includes both pathogen-appropriate drug selection and appropriate dosing with plasma ABX concentration achieving PK/PD targets. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pierre Moine, MD PhD | Contact | 1 47 10 77 82 | +33 | pierre.moine@aphp.fr |
| Jérôme Lambert, MD PhD | Contact | 1 42 49 97 42 | +33 | jerome.lambert@u-paris.fr |
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|
| Conventional biological methods | Diagnostic Test | Usual care |
|
| Up to 180 days |
| Time to antibiotic switches | Up to 180 days |
| Number of started, stopped, added or adjusted (escalation or de-escalation) antibiotics | Up to 180 days |
| Time to Aantibiotic dose adjustments to achieve PK/PD targets | Up to 180 days |
| All-Cause mortality | At ICU | Up to 180 days |
| All-Cause mortality | At hospital discharge | Up to 180 days |
| All Cause Mortality | At day 90 |
| All Cause Mortality | At day 180 |
| SOFA score assessment | Evolution of organ failures by daily SOFA score assessment | Up to 28 days |
| Organ-failure free days (SOFA<6) | Up to day 28 |
| Proportion of patients requiring invasive mechanical ventilation | Duration of invasive mechanical ventilation | At day 7 |
| Proportion of patients requiring invasive mechanical ventilation | Duration of invasive mechanical ventilation | At day 14 |
| Proportion of patients requiring invasive mechanical ventilation | Duration of invasive mechanical ventilation | At day 28 |
| Proportion of patients requiring invasive mechanical ventilation | Duration of invasive mechanical ventilation | At day 90 |
| Ventilator free days | At day 28 |
| Vasopressor free days | At day 28 |
| Vasopressor free days | At day 90 |
| ICU length of stay | up to day 180 |
| Hospital length of stay | up to day 180 |
| Number of serious adverse events | As per MEDDRA classification | up to day 180 |