Carbapenem-Resistant Enterobacteriaceae Infection
Conditions
Keywords
carbapenem resistance, Enterobacteriaceae, CRISPR/Cas9
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.
Interventions
DRUGCAZ/AVI plus Aztreonam
Samples of the patients will be examined such as the routine blood test, blood culture et al.
OTHERConventional treatment
Conventional treatment
Sponsors
Qianfoshan Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Positive rate of Metallo-β-lactamases (MBL) producing Enterobacterales | two years | Positive rate and subtype distribution of Metallo-β-lactamases (MBL) producing Enterobacterales |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactMingju Hao, Doctor
Backup ContactXiutao Dong, Bachelor
Outcome results
None listed