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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CAZ/AVI plus Aztreonam | Experimental | 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 |
|
| Conventional treatment | Active Comparator | Other active antibiotics were administered, including colistin, tigecycline, fosfomycin, meropenem. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAZ/AVI plus Aztreonam | Drug | Samples of the patients will be examined such as the routine blood test, blood culture et al. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 30-day all-cause mortality | The primary outcome measure was 30-day all-cause mortality | two years |
| clinical failure at day 14 | severe comorbidities, mechanical ventilation or septic shock at day 14 | two years |
| length of stay after diagnosis | length of stay (LOS) after blood stream infection diagnosis | two years |
| Measure | Description | Time Frame |
|---|---|---|
| Positive rate of Metallo-β-lactamases (MBL) producing Enterobacterales | Positive rate and subtype distribution of Metallo-β-lactamases (MBL) producing Enterobacterales | two years |
| Measure | Description | Time Frame |
|---|---|---|
| Curation index as assessed by MBL producing Enterobacterales compared with MBL negative Enterobacterales. | 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mingju Hao, Doctor | Contact | 8613012995730 | haomingju@163.com | |
| Xiutao Dong, Bachelor | Contact | 15069061985 | 3185573520@qq.com |
| Name | Affiliation | Role |
|---|---|---|
| Jiasheng Zhang, Doctor | Shandong First Medical University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mingju Hao | Recruiting | Jinan | Shandong | 250014 | China |
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| ID | Term |
|---|---|
| D001398 | Aztreonam |
| ID | Term |
|---|---|
| D008997 | Monobactams |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 |
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| Conventional treatment | Other | Conventional treatment |
|
| Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |