Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

Not Applicable

Recruiting

• Conditions: Carbapenem-Resistant Enterobacteriaceae Infection
• Interventions: Other: Conventional treatment; Drug: CAZ/AVI plus Aztreonam

• Registration Number: NCT05850871
• Lead Sponsor: Qianfoshan Hospital

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.

Study Timeline

• Study Start: 2023-01-06
• Status Verified: 2023-04
• Study First Submitted: 2023-04-06
• Study First Submitted QC: 2023-04-29
• Last Update Submitted: 2023-04-29
• Study First Posted: 2023-05-09
• Last Update Posted: 2023-05-09
• Primary Completion: 2025-01-31
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 427

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Conventional treatment	Conventional treatment	Other active antibiotics were administered, including colistin, tigecycline, fosfomycin, meropenem.
CAZ/AVI plus Aztreonam	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Positive rate of Metallo-β-lactamases (MBL) producing Enterobacterales	two years	Positive rate and subtype distribution of Metallo-β-lactamases (MBL) producing Enterobacterales

Trial Locations

Locations (1)

Mingju Hao; 🇨🇳 Jinan, Shandong, China