Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

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.

• CAZ/AVI plus Aztreonam (Drug), also known as ceftzadime avibactam, aztreonam: Samples of the patients will be examined such as the routine blood test, blood culture et al.
• Conventional treatment (Other): Conventional treatment

Primary outcomes

• 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 outcomes

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

Other outcomes

• 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.

Sex: All

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

• Jiasheng Zhang, Doctor, Study director, Shandong First Medical University