Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

Qianfoshan Hospital

Status: Enrolling

Conditions: Carbapenem-Resistant Enterobacteriaceae Infection

Treatments: Drug: CAZ/AVI plus Aztreonam; Other: Conventional treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT05850871

JNQH-CT-231001

Details and patient eligibility

About

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

Full 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.

Enrollment: 427 estimated patients

Sex: All

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: Single Blind

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427 participants in 2 patient groups

CAZ/AVI plus Aztreonam

Experimental group

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

Treatment:

Drug: CAZ/AVI plus Aztreonam

Conventional treatment

Active Comparator group

Description:

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

Treatment:

Other: Conventional treatment