Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing in ICU Patients.

Study Overview
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Brief Summary
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It is difficult to determine the pathogens in the early stage of infection in critically ill patients, and empirical use of broad-spectrum antibiotics for a long time is often necessary, leading to antibiotics drug resistance. Targeted next generation sequencing (tNGS) can provide faster results for pathogen and related antibiotic resistant diagnosis. But it lacks sufficient clinical evidence. Evidence regarding the clinical diagnostic accuracy and drug resistance is needed to comprehensively evaluate targeted next generation sequencing (tNGS) for diagnosis of patients in ICU who and will be critical to inform national policy.

Detailed Description
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Infectious diseases are one of the highest mortality and morbidity diseases in humans. Due to the difficulty in identifying the pathogen in the early stage of infection, patients with severe infections often need to empirically use broad-spectrum antimicrobials for a long time. The traditional gold standard of etiological detection - etiological culture, even in sepsis patients, only about 60% of the results are positive. Therefore, the accurate identification and rapid classification of pathogenic microorganisms is very important for the patient's precise diagnosis and timely treatment. Metagenomic next generation sequencing (mNGS), which has emerged in recent years, have been shown to provide early diagnosis and targeted medication guidance for bloodstream infections and respiratory infections, but it is expensive and not able to provide related drug resistant genes. Therefore, targeted next generation sequencing (tNGS) has been derived, which is characterized by rapid sequencing and genetic testing for drug resistance. The purpose of this study is to evaluate the efficacy of etiological diagnosis and provide patients with more accurate treatment.

Official Title
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Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing Compared With Metagenomic Next-Generation Sequencing in ICU Patients.

Conditions
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Infections, Critical Illness, Diagnosis

Intervention / Treatment
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* Diagnostic Test: targeted next-generation sequencing (tNGS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The presence of an infection or clearly excluded the presence of infection. Etiological culture and/or metagenomic next-generation sequencing detection of specimens sent for testing. Exclusion Criteria: Suspected infection. Participation in other clinical trials in the past 2 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-Infection group<br>Participants received traditional etiological culture of suspected site of infection. | Diagnostic Test: targeted next-generation sequencing (tNGS)<br>* To provide rapid etiological diagnosis of patients by means of targeted next-generation sequencing.<br>|
| Infection group<br>Participants received traditional etiological culture, metagenomic next-generation sequencing of infectious sites. | Diagnostic Test: targeted next-generation sequencing (tNGS)<br>* To provide rapid etiological diagnosis of patients by means of targeted next-generation sequencing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity | The probability of being positive in clinical composite diagnosis, the probability that etiological culture, mNGS, and tNGS tests are also positive, which is also known as the true positive rate. | 1 year | 
| Specificity | It refers to the probability that cultures, mNGS, and tNGS tests are also negative in the presence of non-infection confirmed by the gold standard. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| False-positive rate | It refers to the probability that the gold-standard confirmed absence of infection is also positive for etiological culture, mNGS, and tNGS tests. | 1 year | 
| False-negative rate | It refers to the probability of being positive in the clinical composite diagnosis, and the probability that etiological cultures, mNGS, and tNGS tests will also be negative. | 1 year | 
| Positive predictive value | Positive predictive value is the probability that subjects with a positive test truly have the disease. | 1 year | 
| Negative predictive value | Negative predictive value is the probability that subjects with a negative screening test truly don't have the disease. | 1 year | 
| Kappa values | Kappa values are used to measure the agreement between two raters. The range of possible values of kappa is from -1 to 1, though it usually falls between 0 and 1. Unity represents perfect agreement, indicating that the raters agree in their classification of every case. Kappa values of 0.41 0.60 are moderately consistent, 0.61 0.80 are basically consistent, and 0.81 1.00 is almost identical. | 1 year | 
| Drug resistant gene by targeted next-generation sequencing | It refers to the distribution of drug resistance by targeted next-generation sequencing using the Comprehensive Antibiotic Resistance Database. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Targeted Next-generation sequencing, ICU, infections, Next-generation sequencing