Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

Study Overview
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Brief Summary
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The first aim of this study is to explore the drug resistance mechanism of Enterobacteriaceae bacteria and to evaluate the treatment effect of ceftazidime-avibactam (CAZ-AVI) in combination with aztreonam (ATM) against Metallo-β-lactamases (MBL) producing Enterobacterales in vivo. The investigators then use CRISPR/Cas9 technology to remove Enterobacteriaceae bacteria resistance and virulence genes

Detailed Description
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Clinical information of subjects, including diseases, departments, medication history, days of hospitalization, and treatment outcomes will be collected; Bacterial species names will be identified and drugs sensitivity will be detected; For patients with bloodstream infection of MBL-producing Enterobacterales, ceftazidime-avibactam (CAZ-AVI) was administered at the dose of 2.5 g every 8 hours and aztreonam (ATM) at the dose of 2 g every 8 hours. The primary outcome measure was 30-day all-cause mortality, while secondary outcomes were clinical failure at day 14 and length of stay (LOS) after bloodstream infection diagnosis. Cox regression analysis, including a propensity score (PS) for receiving CAZ-AVI plus ATM, was conducted to assess the primary and secondary outcomes. The CRISPR/Cas9 gene curation technology was used to eliminate the drug resistance and virulence factors of Enterobacteriaceae in the mouse intestinal colonization model.

Official Title
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Evaluation of Ceftazidime-avibactam Plus Aztreonam in Patients Infected by MBL-producing Enterobacterales and CRISPR/Cas9-based Strategy for Curing Drug-resistant Genes

Conditions
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Carbapenem-Resistant Enterobacteriaceae Infection

Intervention / Treatment
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* Drug: CAZ/AVI plus Aztreonam
* Other: Conventional treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects clinically suspected of infection caused by Enterobacterales Subjects with bloodstream infection by MBL-producing Enterobacterales Exclusion Criteria: Infections caused by viruses, fungi, atypical pathogens, and other non-Enterobacteriaceae bacteria subjects who are unwilling to enter the research group
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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAZ/AVI plus Aztreonam<br>CAZ-AVI was administered at the dose of 2.5 g every 8 hours and ATM at the dose of 2 g every 8 hours | Drug: CAZ/AVI plus Aztreonam<br>* Samples of the patients will be examined such as the routine blood test, blood culture et al.<br>* Other names: ceftzadime avibactam, aztreonam;|
| Active Comparator: Conventional treatment<br>Other active antibiotics were administered, including colistin, tigecycline, fosfomycin, meropenem. | Other: Conventional treatment<br>* Conventional treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day all-cause mortality | The primary outcome measure was 30-day all-cause mortality | two years | 
| clinical failure at day 14 | severe comorbidities, mechanical ventilation or septic shock at day 14 | two years | 
| length of stay after diagnosis | length of stay (LOS) after blood stream infection diagnosis | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive rate of Metallo-β-lactamases (MBL) producing Enterobacterales | Positive rate and subtype distribution of Metallo-β-lactamases (MBL) producing Enterobacterales | two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRISPR/Cas9, carbapenem resistance, Enterobacteriaceae