Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

April 29, 2023 updated by: Mingju Hao, Qianfoshan Hospital

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

427

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shandong
      • Jinan, Shandong, China, 250014
        • Recruiting
        • Mingju Hao
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CAZ/AVI plus Aztreonam
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
Samples of the patients will be examined such as the routine blood test, blood culture et al.
Other Names:
  • ceftzadime avibactam, aztreonam
Active Comparator: Conventional treatment
Other active antibiotics were administered, including colistin, tigecycline, fosfomycin, meropenem.
Other: Conventional treatment
Conventional treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
30-day all-cause mortality
Time Frame: two years
The primary outcome measure was 30-day all-cause mortality
two years
clinical failure at day 14
Time Frame: two years
severe comorbidities, mechanical ventilation or septic shock at day 14
two years
length of stay after diagnosis
Time Frame: two years
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
Time Frame: two years
Positive rate and subtype distribution of Metallo-β-lactamases (MBL) producing Enterobacterales
two years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Curation index as assessed by MBL producing Enterobacterales compared with MBL negative Enterobacterales.
Time Frame: two years
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.
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Qianfoshan Hospital

Investigators

  • Study Director: Jiasheng Zhang, Doctor, The First Affiliated Hospital of Shandong First Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 6, 2023

Primary Completion (Anticipated)

January 31, 2025

Study Completion (Anticipated)

January 31, 2025

Study Registration Dates

First Submitted

April 6, 2023

First Submitted That Met QC Criteria

April 29, 2023

First Posted (Actual)

May 9, 2023

Study Record Updates

Last Update Posted (Actual)

May 9, 2023

Last Update Submitted That Met QC Criteria

April 29, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JNQH-CT-231001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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