Comparison of Epithelial Lining Fluid and Blood Pharmacokinetics and Pharmacodynamics of Intravenous and Intravenous Plus Nebulized Polymyxin B in Multidrug Resistant Bacteria Ventilator-associated Pneumonia Patients

Study Overview
=================
Brief Summary
-----------------
The goal of this observational study is to investigate whether intravenous polymyxin B combined with nebulisation achieves better antimicrobial efficacy and clinical outcomes than intravenous use alone in patients with multidrug-resistant gram-negative bacilli infected with ventilator-associated pneumonia. The main questions it aims to answer are: When using intravenous polymyxin B to treat patients with ventilator-associated pneumonia caused by multidrug-resistant bacteria in clinical practice, is it necessary to assist with polymyxin B nebulization therapy？ If necessary, how much dose of nebulization is better? Participants will be divided into two groups based on whether they have received nebulization treatment with polymyxin B in clinical practice. Blood and alveolar lavage fluid samples will be collected after the first dose injection and reaching the steady-state dose, and the drug concentration differences in blood and ELF will be measured in patients who have received intravenous injection of polymyxin B alone and those who have received adjuvant nebulization of polymyxin B, as well as differences in clinical outcomes and side effects. Researchers will compare the differences in blood and ELF drug concentrations, clinical outcomes, and incidence of side effects between two groups of patients, to see if is it necessary to assist with polymyxin B nebulization therapy in patients with multidrug-resistant gram-negative bacilli infected with ventilator-associated pneumonia.

Official Title
-----------------
Comparison of Epithelial Lining Fluid and Blood Pharmacokinetics and Pharmacodynamics of Intravenous and Intravenous Plus Nebulized Polymyxin B in Multidrug Resistant Bacteria Ventilator-associated Pneumonia Patients

Conditions
-----------------
Polymyxin B, Ventilator-associated Pneumonia, Multidrug Resistant Bacterial Infection, Pharmacogenomic Drug Interaction

Intervention / Treatment
-----------------
* Drug: nebulized polymyxin B


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-80 years old; ICU patients; Patients with MDR-infected VAP were diagnosed by etiological culture results; Expect to receive at least 6 doses (3 days) of polymyxin B; Obtain informed consent; Exclusion Criteria: The patient has a history of severe hypersensitivity to polymyxin B; Patients cannot tolerate alveolar lavage; Oncology patients,includes hematologic malignancies; Pregnant or lactating women; Patients with other conditions that the investigators consider unsuitable for enrollment;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intravenous combined with nebulized polymyxin B<br>The intravenous combined nebulization patient group was divided into two subgroups based on the different doses received -25mg q12h and 50mg q12h. Patients in the intravenous combination nebulized polymyxin B group received a total medication dose of 1.25 to 1.5mg/kg, of which 25-50mg was used for nebulization and the remaining portion was used for intravenous administration. The specific method of nebulization is to receive nebulized bronchodilator 30 minutes before nebulization, add 25-50mg of polymyxin B to 5ml of physiological saline for dilution, use a vibrating mesh nebulizer to connect to the patient's ventilator pipeline suction tube, do not change the original ventilator parameter settings, and continue nebulization for 30 minutes. After 30 minutes, regardless of whether there is any residue of the nebulized drug, it will be discarded according to general nursing methods. | Drug: nebulized polymyxin B<br>* The experimental group received intravenous combined nebulization of polymyxin B<br>|
| Intravenous polymyxin group B<br>This group of patients received intravenous injection of polymyxin B alone, with intravenous doses of 1.25-1.5mg/kg of polymyxin B administered every 12 hours. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood concentration | Blood concentration | 3 days after the end of the patient's first medication use | 
| ELF concentration | Drug concentration in ELF solution | 3 days after the end of the patient's first medication use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day clinical cure rate | the proportion of subjects who are thought as clinical effectiveness 28 days after treatment with polymyxin B to the number of subjects in each group. | 28 days after the end of the patient's medication | 
| 28-day microbiological cure rate | the proportion of subjects of microbiological cure to the number of subjects in each group 28 days after treatment with polymyxin B. | 28 days after the end of the patient's medication | 
| 28-day adverse reaction rate | the proportion of subjects who experienced adverse reactions within 28 days after treatment with polymyxin B to the number of subjects in each group | 28 days after the end of the patient's medication |