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

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

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.

Study Overview

• Status: Completed
• Conditions: Acinetobacter Infections; Colistin; Rifampin
• Intervention / Treatment: Drug: colistin monotherapy; Drug: colistin and rifampin combination therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: colistin monotherapy; 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; . 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 .
Experimental: colistin-rifampin combination; 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; 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.; Other Names: colistin/rifampin combination therapy

What is the study measuring?

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
mortality	mortality	30 days
clinical response	clinical resolution of fever, symptoms and infectious sign	14 days

Collaborators and Investigators

• Sponsor: Gangnam Severance Hospital

Publications and helpful links

General Publications

• Park HJ, Cho JH, Kim HJ, Han SH, Jeong SH, Byun MK. Colistin monotherapy versus colistin/rifampicin combination therapy in pneumonia caused by colistin-resistant Acinetobacter baumannii: A randomised controlled trial. J Glob Antimicrob Resist. 2019 Jun;17:66-71. doi: 10.1016/j.jgar.2018.11.016. Epub 2018 Nov 23.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2016
• Primary Completion (Actual): September 24, 2017
• Study Completion (Actual): June 21, 2018

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: August 6, 2018
• First Posted (Actual): August 9, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Moraxellaceae Infections; Acinetobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Colistin
• Other Study ID Numbers: 3-2016-0125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: in discuss