Adult pulmonary infections caused by carbapenem-resistant Gram-negative pathogens, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).
Conditions
Interventions
Exposure group:Exposure cohort
sample size: 85
intervention: regimen including ceftazidime-avibactam (CAZ-AVI), administered by intravenous infusion according to the package insert for at least 72 hours, with concomitant polymyxin B, tigecycline,
Non-exposure group:Non-exposure cohort
intervention: conventional treatment regimen without CAZ-AVI, using carbapenems with or without polymyxin B, tigecycline, or aztreonam according to hepatic/renal function
Sponsors
Chengdu University of Traditional Chinese Medicine Affiliated Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1) Diagnosis of pulmonary infection caused by carbapenem-resistant Gram-negative bacteria: new or progressive infiltrates, consolidation, or ground-glass opacities on chest X-ray or CT, plus at least two of the following three clinical signs: (a) fever with body temperature >38°C; (b) purulent airway secretions; (c) peripheral white blood cell count >10×10^9/L or <4×10^9/L. 2) Pathologically confirmed hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). Pathogen and antimicrobial susceptibility must be identified before the trial. Eligible lower respiratory tract secretions, protected specimen brush (PSB), bronchoalveolar lavage fluid (BALF), lung tissue, or sterile body fluid culture must be positive and consistent with clinical manifestations. Carbapenem-resistant Gram-negative pathogens (CRE and/or CRPA) must be cultured as dominant pathogens (semi-quantitative =+++ or quantitative culture =10^4 CFU/ml), and susceptibility results must meet the current CLSI/EUCAST resistance breakpoints for imipenem or meropenem. 3) Age 18 to 85 years, either sex. 4) Acute Physiology and Chronic Health Evaluation II (APACHE-II) score =25. 5) Able to understand and comply with study procedures and methods, voluntarily participate, and provide written informed consent before enrollment by the participant or family member.
Exclusion criteria
Exclusion criteria: 1) Expected survival less than 72 hours. 2) History of allergy to beta-lactam antibacterial agents, including cephalosporins and cephalosporin/beta-lactamase inhibitor combinations, or to ceftazidime-avibactam for injection or its excipients; history of allergy to carbapenems, polymyxin B, tigecycline, or aztreonam; or allergic constitution. 3) Carbapenem-resistant Acinetobacter baumannii (CRAB) is present at baseline as the main pathogen, or CRAB is judged to require targeted treatment in mixed infection. 4) More than 24 hours of effective treatment targeting CRE/CRPA (such as polymyxin or tigecycline) within 72 hours before enrollment with good clinical response; need for strong CYP3A4 inducers (such as rifampicin) during the study unless judged by the investigator as necessary and medication details are recorded. 5) Other pulmonary diseases judged by the investigator to affect efficacy evaluation, such as active pulmonary tuberculosis, cystic fibrosis, pulmonary granulomatous disease, lung transplantation, primary lung cancer or other malignant tumors metastatic to the lung, or known endobronchial obstruction. 6) Abnormal liver function: ALT or AST =5 times the upper limit of normal and total or direct bilirubin =2 times the upper limit of normal, or Child-Pugh class C. 7) Any known disease seriously affecting the immune system, such as history of HIV infection, advanced hematologic malignancy, or splenectomy. 8) Any other factor judged by the investigator to make the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical efficacy; | — |
Secondary
| Measure | Time frame |
|---|---|
| Microbiology Clearance Rate;ICU stay duration;The improvement of inflammatory markers;Ventilator duration, ventilator dependency level.; | — |
Countries
China
Contacts
Public ContactLong Kunlan
Chengdu University of Traditional Chinese Medicine Affiliated Hospital
Outcome results
None listed