Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

Sponsor

Qianfoshan Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05850871

Collaborator

(none)

427

Enrollment

Location

Arms

24.8

Anticipated Duration (Months)

17.2

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Carbapenem-Resistant Enterobacteriaceae Infection	Drug: CAZ/AVI plus Aztreonam Other: Conventional treatment	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

427 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 6, 2023

Anticipated Primary Completion Date :

Jan 31, 2025

Anticipated Study Completion Date :

Jan 31, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Positive rate of Metallo-β-lactamases (MBL) producing Enterobacterales [two years]
Positive rate and subtype distribution of Metallo-β-lactamases (MBL) producing Enterobacterales

Other Outcome Measures

Curation index as assessed by MBL producing Enterobacterales compared with MBL negative Enterobacterales. [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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