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

Recruiting

• Conditions: Ventilator-associated Pneumonia; Multidrug Resistant Bacterial Infection; Pharmacogenomic Drug Interaction; Polymyxin B
• Interventions: Drug: nebulized polymyxin B

• Registration Number: NCT06076603
• Lead Sponsor: Southeast University, China

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-07-01
• Study First Submitted: 2023-09-19
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-07
• Last Update Submitted: 2023-10-07
• Study First Posted: 2023-10-11
• Last Update Posted: 2023-10-11
• Primary Completion: 2024-07-01
• Study Completion: 2024-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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;

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Intravenous combined with nebulized polymyxin B	nebulized polymyxin B	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.

Primary Outcome Measures

Name	Time	Method
Blood concentration	3 days after the end of the patient's first medication use	Blood concentration
ELF concentration	3 days after the end of the patient's first medication use	Drug concentration in ELF solution

Secondary Outcome Measures

Name	Time	Method
28-day microbiological cure rate	28 days after the end of the patient's medication	the proportion of subjects of microbiological cure to the number of subjects in each group 28 days after treatment with polymyxin B.
28-day adverse reaction rate	28 days after the end of the patient's medication	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-day clinical cure rate	28 days after the end of the patient's medication	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.

Trial Locations

Locations (1)

Zhongda Hospital Affiliated to Southeast University; 🇨🇳 Nanjing, Jiangsu, China