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Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

Primary Purpose

Carbapenem-Resistant Enterobacteriaceae Infection

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
CAZ/AVI plus Aztreonam
Conventional treatment
Sponsored by
Qianfoshan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carbapenem-Resistant Enterobacteriaceae Infection focused on measuring carbapenem resistance, Enterobacteriaceae, CRISPR/Cas9

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

Sites / Locations

  • Mingju HaoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CAZ/AVI plus Aztreonam

Conventional treatment

Arm Description

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

Other active antibiotics were administered, including colistin, tigecycline, fosfomycin, meropenem.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Positive rate of Metallo-β-lactamases (MBL) producing Enterobacterales
Positive rate and subtype distribution of Metallo-β-lactamases (MBL) producing Enterobacterales

Full Information

First Posted
April 6, 2023
Last Updated
April 29, 2023
Sponsor
Qianfoshan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05850871
Brief Title
Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies
Official Title
Evaluation of Ceftazidime-avibactam Plus Aztreonam in Patients Infected by MBL-producing Enterobacterales and CRISPR/Cas9-based Strategy for Curing Drug-resistant Genes
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 6, 2023 (Actual)
Primary Completion Date
January 31, 2025 (Anticipated)
Study Completion Date
January 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Qianfoshan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carbapenem-Resistant Enterobacteriaceae Infection
Keywords
carbapenem resistance, Enterobacteriaceae, CRISPR/Cas9

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
427 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAZ/AVI plus Aztreonam
Arm Type
Experimental
Arm Description
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
Arm Title
Conventional treatment
Arm Type
Active Comparator
Arm Description
Other active antibiotics were administered, including colistin, tigecycline, fosfomycin, meropenem.
Intervention Type
Drug
Intervention Name(s)
CAZ/AVI plus Aztreonam
Other Intervention Name(s)
ceftzadime avibactam, aztreonam
Intervention Description
Samples of the patients will be examined such as the routine blood test, blood culture et al.
Intervention Type
Other
Intervention Name(s)
Conventional treatment
Intervention Description
Conventional treatment
Primary Outcome Measure Information:
Title
30-day all-cause mortality
Description
The primary outcome measure was 30-day all-cause mortality
Time Frame
two years
Title
clinical failure at day 14
Description
severe comorbidities, mechanical ventilation or septic shock at day 14
Time Frame
two years
Title
length of stay after diagnosis
Description
length of stay (LOS) after blood stream infection diagnosis
Time Frame
two years
Secondary Outcome Measure Information:
Title
Positive rate of Metallo-β-lactamases (MBL) producing Enterobacterales
Description
Positive rate and subtype distribution of Metallo-β-lactamases (MBL) producing Enterobacterales
Time Frame
two years
Other Pre-specified Outcome Measures:
Title
Curation index as assessed by MBL producing Enterobacterales compared with MBL negative Enterobacterales.
Description
Evaluation of the efficienty of CRISPR/Cas9 technique to cure resistance genes in a mouse model colonized by multidrug resistant enterobacteriaceae. Curation index as assessed by MBL producing Enterobacterales compared with MBL negative Enterobacterales isolated from the feces sample.
Time Frame
two years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mingju Hao, Doctor
Phone
8613012995730
Email
haomingju@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiutao Dong, Bachelor
Phone
15069061985
Email
3185573520@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jiasheng Zhang, Doctor
Organizational Affiliation
The First Affiliated Hospital of Shandong First Medical University
Official's Role
Study Director
Facility Information:
Facility Name
Mingju Hao
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250014
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mingju Hao
Phone
+8613012995730
Email
haomingju@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

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