Efficacy of Polymyxin B Against Infections Caused by Extensively Drug-resistant (XDR) Gram-Negative Bacteria

Study Overview
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Brief Summary
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The objective of the study is to evaluate the efficacy of Polymyxin B for treatment Gram negative bacterial infection. The hypothesis of study is Polymyxin B would be the new antibacterial agents for Thai Gram negative infected patients in case of desirable outcomes and minimal side effects.

Detailed Description
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Investigator is notified by doctors who take care of gram negative infected patients. Investigator inform patient or their relatives about all topics in project, eligible criteria, method, material and monitoring treatment. After patient or their relatives are appreciated to join this project, investigator collect data in case record form;electronics form, then implement the drug. Duration of treatment is determined by site and severity of infection, approximately 7-14 days. Sample size calculation, by prevalence formula, we estimate the mortality rate about 50 %, deviation 10 %,and 2-sided 95% Confidence interval, therefore,97 persons We estimate gather data about 100 persons. Statistical descriptive analysis for descriptive data. During the study is performing, all unexpected adverse event definitely report to Siriraj institutional Review Board immediately, in addition to subjects or their relatives.

Official Title
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Efficacy of Polymyxin B Against Infections Caused by Extensively Drug-resistant (XDR) Gram-Negative Bacteria

Conditions
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Hospital Infection

Intervention / Treatment
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* Drug: Polymyxin B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 year-old The infection caused by carbapenem-resistant (CR) Enterobacteriaceae, CR P.aeruginosa or CR A. baumannii which susceptible to colistin The duration of treatment approximately between 7-14 days Kidney function, according to Kidney Disease Improving Global Outcomes (KDIGO) classification, should less than stage 4 and no replacement therapy in all modality. The patients are anticipated to live more than 48 hrs after participation. In case of Colistin administration beforehand, it should not exceed 24 hrs. All of participants should be willing to join this project. Exclusion Criteria: Pregnancy and lactation End stage renal disease who take renal replacement therapy Any type of Neuromuscular disease Body mass index exceed 30 Infection that require treatment more than 14 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polymyxin B<br>Polymyxin B 1.5-2.5 mg/kg/day intravenous q 12 hrs duration 7-14 days | Drug: Polymyxin B<br>* administrate drug by 0.75-1.25 mg/kg/dose intravenously q 12 hrs both saline and dextrose solution can be dissolved duration 7-14 days<br>* Other names: X-Gen Phamaceuticals, USA Polymyxin B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality rate | mortality rate of gram negative bacteria infected patients receiving Polymyxin B at day 28 after enrollment | participants will be followed for the duration of hospital stay, an expected average of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse drug reactions | we assess adverse drug reactions in 2 aspects; nephrotoxicity and neurotoxicity | participants will be followed for the duration of hospital stay, an expected average of 4 weeks | 
| microbiological clearance | we perform culture and staining to assess bacterial clearance after apply the study drug every 3 days until culture is negative | participants will be followed for the duration of hospital stay, an expected average of 4 weeks | 
| Peak Plasma Concentration (Cmax) of polymyxin B | we do the blood test for drug level at before the third date dose then 1,2,4 hours after administration of the polymixin B and before the fourth dose. | participants will be followed for the duration of hospital stay, an expected average of 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polymyxin B, carbapenem resistant bacteria