Colistin-rifampin Combination and Colistin Monotherapy in Extensively Drug-resistant Acinetobacter Baumannii

Study Overview
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Brief Summary
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The investigators aimed to confirm the utility of the synergy test results (E-tesT) in vitro to predict the efficacy and safety of colistin-rifampin combination and colistin monotherapy in extensively drug-resistant acinetobacter baumannii.

Detailed Description
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We will searched pneumonia patients with CoRAB in Gangnam Severance Hospital. Subjects will be enrolled and randomized in a blinded fashion using a computerized random number generator (permuted-block randomization) for treatment with colistin and rifampin combination and colistin only at a ratio of 1:1. We will perform the E-test MIC:MIC ratio method to predict in vitro synergy of colistin and rifampin combination therapy.

Official Title
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Comparison of Efficacy and Safety of Colistin-rifampin Combination and Colistin Monotherapy in Extensively Drug-resistant Acinetobacter Baumannii: Utility of the Synergy Test Results (E-test) in Vitro

Conditions
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Colistin, Rifampin, Acinetobacter Infections

Intervention / Treatment
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* Drug: colistin and rifampin combination therapy
* Drug: colistin monotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pneumonia, blood septicemia, urinary tract infection, or other infection or even colonization with evidence of extensively drug-resistant Acinetobacter baumannii infection Exclusion Criteria: Hypersensitivity reaction to colistin or rifampin use of colistin or rifampin in 15 days prior to screening evidence of extensively drug-resistant Acinetobacter baumannii infection in 15 days prior to screening CLcr < 15 mL/min, ALT or AST > 3xULN, total bilirubin > 2xULN, Hb < 7 gm/dL, ANC < 500/mm3, Platelet < 50,000/mm3

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: colistin monotherapy<br>The subjects will be treated with colistin monotherapy. Colistin (100 mg, colistin sodium methanesulfonate, SCD Pharm., Seoul, Korea) will be intravenously administered with 100 mL of normal saline with 8 hours interval. Treatment should be maintained daily administration for at least 7 days and up to 28 days. Duration of antibiotics treatment will be determined through discussion by pulmonology and infection specialist. | Drug: colistin monotherapy<br>* . Colistin (100 mg, colistin sodium methanesulfonate, SCD Pharm., Seoul, Korea) will be intravenously administered with 100 mL of normal saline with 8 hours interval. Treatment should be maintained daily administration for at least 7 days and up to 28 days. Duration of antibiotics treatment wil be determined through discussion by pulmonology and infection specialist .<br>|
| Experimental: colistin-rifampin combination<br>The subjects will be treated with colistin and rifampin combination therapy. Colistin (100 mg, colistin sodium methanesulfonate, SCD Pharm., Seoul, Korea) will be intravenously administered with 100 mL of normal saline with 8 hours interval. Rifampin (600 mg, rifampin, Yuhan, Seoul, Korea) will be orally administered daily. Treatment should be maintained daily administration for at least 7 days and up to 28 days. Duration of antibiotics treatment will be determined through discussion by pulmonology and infection specialist. | Drug: colistin and rifampin combination therapy<br>* Colistin (100 mg, colistin sodium methanesulfonate, SCD Pharm., Seoul, Korea) will be intravenously administered with 100 mL of normal saline with 8 hours interval. Rifampin (600 mg, rifampin, Yuhan, Seoul, Korea) will be orally administered daily. Treatment should be maintained daily administration for at least 7 days and up to 28 days. Duration of antibiotics treatment will be determined through discussion by pulmonology and infection specialist.<br>* Other names: colistin/rifampin combination therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| microbiologic response | negative conversion of culture study (eradication) | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical response | clinical resolution of fever, symptoms and infectious sign | 14 days | 
| mortality | mortality | 30 days |