M-ROSE Combined With mNGS in Severe Hospital-acquired Pneumonia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the value of M-ROSE（microbiological rapid on-site evaluation）in severe hospital-acquired pneumonia.

Detailed Description
-----------------
Severe hospital acquired pneumonia (SHAP) is the critical risk factor leading to the death of nosocomial infection patients. Rapid identification of pathogens, guidance of individualized treatment and rational application of antibiotics can not only improve the administration of antibiotics, but also reduce the production of multi drug resistant bacteria. Metagenomic second-generation sequencing (mNGS) is an important tool to quickly identify the pathogen in ICU. However, due to the low qualified rate of lower respiratory tract specimens in patients with SHAP, easily polluted, and the difficulty to determine whether microorganisms are infectious, colonizated or polluted, the value of mNGS was limited in the etiological diagnosis of SHAP. The bedside M-ROSE system established by our research team can determine whether the lower respiratory tract specimen is qualified, whether infection exists and the pathogen of infection within half an hour. Based on the previous work, this project plans to conduct a prospective multicenter, single blind, randomized controlled study under the guidance of M-ROSE and mNGS in the individualized anti-infection strategy of SHAP, to reduce the mortality of patients with SHAP; Combined with the third-generation sequencing, the standard analysis framework for the traceability and prevention and control of drug-resistant bacteria was established to clarify the transmission route of drug-resistant bacteria, so as to provide a new solution for the prevention and control of clinical multidrug-resistant bacteria.

Official Title
-----------------
A Multi-center Prospective Clinical Study of M-ROSE Combined With mNGS to Guide the Individualized Anti-infection Treatment, Prevention and Control of Drug-resistant Bacteria in Severe Hospital-acquired Pneumonia

Conditions
-----------------
Pneumonia

Intervention / Treatment
-----------------
* Diagnostic Test: M-ROSE analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of severe hospital-acquired pneumonia Must have undergone bronchoalveolar lavage Exclusion Criteria: BALF samples were not sent for mNGS examination Age < 18 years old The hospitalization days ≤ 3 The clinical data are incomplete Mechanical ventilation time > 60 days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M-ROSE combined with mNGS group<br>The bronchoalveolar lavage fluid (BALF) of patients undergoes M-ROSE analysis and decide whether the samples are qualified, whether they indicate bacterial infection and identify pathogens, and the qualified samples are sent for mNGS analysis. The individualized anti-infection treatment is comprehensively guided according to the results of M-ROSE, mNGS and clinical examinations. | Diagnostic Test: M-ROSE analysis<br>* The M-ROSE analysis process consists of 3 procudures. Specimen quality assessment. The BALF undergoes the process of smear, diff-quik stain, gram stain and are analyzed by experts to report the cytoloy and pathogen patterns to determine whether the sample is qualified according to the cell proportions. The qualified BALF samples are: squamous epithelial cell proportion<1%, columnar epithelial cell proportion <5% . Distinguish infection and colonization. According to the cytoloy pattern, the proportion of neutrophils > 50% often strongly suggests pulmonary bacterial infection; Neutrophil phagocytosis proportion> 5% indicates infection, and phagocytosis of bacteria is the pathogen. Besides, fungal and hyphae can be found under the microscope. Preliminary identification of infectious pathogens. Identify the infected bacteria and fungi, and the results are gram-positive cocci, gram-positive bacilli, gram-negative cocci, gram-negative bacilli, yeasts and molds.<br>|
| No Intervention: mNGS group<br>BALF samples were directly sent for mNGS analysis, and anti-infective treatment was guided according to clinical examinations. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | Alive or Dead. | During the intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood leukocyte ratio tread | The changing of blood leukocyte ratio | During the intervention. | 
| 28 day outcome | Live or dead. | 28 days after admission | 
| Blood neutriphil ratio tread | The changing of blood neutriphil ratio tread | During the intervention. | 
| Blood interleukin 6 tread | The changing of blood interleukin 6 tread | During the intervention. | 
| Blood C-reactive protein | The changing of blood C-reactive protein | During the intervention. | 
| Blood procalcitonin tread | The changing of blood procalcitonin tread | During the intervention. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
M-ROSE, mNGS, severe hospital-acquired pneumonia, treatment