Decolonization of Carbapenem-resistant Enterobacterales (CRE) in Patients With Faecal Carriage of CRE With Neomycin

Rates of antimicrobial resistance are increasing worldwide. There is increasing evidence that physiological gut microbiota is a large reservoir of antibiotic-resistance genes. Healthy gut microbiota is known to prevent the colonization of the gastrointestinal tract by pathogens, the so-called mechanism of colonization resistance, but this protective mechanism can be altered by therapies that impair gut microbiota, including antibiotics with consequent colonization of gut pathogens, including carbapenem-resistant Enterobacterales (CRE). CRE carriers represent an epidemiological threat to other hospitalized patients and to the whole community, but are also at risk of developing clinical consequences of this colonization, including bloodstream infections from these pathogens. Neomycin has shown high efficacy in the eradication of CRE invitro. Neomycin has also been approved to treat hepatic coma by eradicating bacterial in gastrointestinal tract. Therefore, this evidence suggests that this procedure could be useful in eradicating CRE.

However, current evidence is mostly limited.

The aim of this study is to investigate the efficacy of Neomycin, compared with no intervention in eradicating gut colonization from CRE.

Study Overview

• Status: Recruiting
• Conditions: Colonization, Asymptomatic
• Intervention / Treatment: Drug: Neomycin

Detailed Description

The investigators will randomize patients colonized by CRE (diagnosed by rectal swab) to Neomycin by stratified randomization according to type of CRE species (E.coli or non-E.coli). Then, patients will be followed up, rectal swabs will be repeated, and stool samples for culture and will be collected, up to 14 days after Neomycin.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Adhiratha Boonyasiri, MD; Phone Number: +66850632181; Email: adhiratha.bon@mahidol.ac.th

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Faculty of Medicine Siriraj Hospital, Mahidol University
    • Contact: Adhiratha Boonyasiri, MD; Phone Number: +6624192688; Email: adhiratha.bon@mahidol.ac.th
    • Principal Investigator: Adhiratha Boonyasiri, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 93 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient aged >18 years
• Hospitalized in medical wards
• Presence of CRE in stool/rectal swab without symptom from active surveillance of CRE
• Sign informed consent to participate the study

Exclusion Criteria:

• CRE infected patients
• Receiving anti-CRE antibiotics
• Known allergy to neomycin or other aminoglycosides
• Receiving Cidofovir, Colistin methate sodium, foscarnet , furosemide, digoxin
• eGFR (estimated Glomerular Filtration Rate) < 30 ml/min/1.73 m2
• Had gastro-intestinal tract diseases
• Pregnancy or breast-feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Neomycin; Patients enrolled in this arm will receive Neomycin.	Drug: Neomycin; Neomycin (350 mg/tablet) 1.4 g three times a day (4.2 g per day) for 5 days; Other Names: Neomycin Sulfate
No Intervention: Non neomycin; Patients enrolled in this arm will not receive any interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with microbiological eradication at 2 weeks after neomycin administration	Microbiological eradication is defined as the disappearance of CRE in hospitalized patients' faces at 2 weeks after neomycin administration	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ์Neomycin toxicity (safety)	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	2 weeks
Incidence of ์carbapenemases in isolated CRE	Number of carbapenemases in isolated CRE	2 weeks
Number of CRE isolates susceptible to neomycin at 2 weeks after neomycin administration	Number of CRE isolates are susceptible to neomycin at 2 weeks after neomycin administration according to the Clinical and Laboratory Standards Institute (CLSI) guideline.	2 weeks
Number of CRE isolates susceptible to amikacin at 2 weeks after neomycin administration	Number of CRE isolates are susceptible to amikacin after at 2 weeks after neomycin administration according to the Clinical and Laboratory Standards Institute (CLSI) guideline.	2 weeks
Number of CRE isolates susceptible to gentamicin at 2 weeks after neomycin administration	Number of CRE isolates are susceptible to gentamicin at 2 weeks after neomycin administration according to the Clinical and Laboratory Standards Institute (CLSI) guideline.	2 weeks

Collaborators and Investigators

• Sponsor: Mahidol University

Publications and helpful links

General Publications

• Hu Y, Liu L, Zhang X, Feng Y, Zong Z. In Vitro Activity of Neomycin, Streptomycin, Paromomycin and Apramycin against Carbapenem-Resistant Enterobacteriaceae Clinical Strains. Front Microbiol. 2017 Nov 17;8:2275. doi: 10.3389/fmicb.2017.02275. eCollection 2017.
• Park SY, Lee JS, Oh J, Lee SH, Jung J. Effectiveness of selective digestive decolonization therapy using oral gentamicin for eradication of carbapenem-resistant Enterobacteriaceae carriage. Infect Control Hosp Epidemiol. 2022 Nov;43(11):1580-1585. doi: 10.1017/ice.2021.492. Epub 2022 Feb 9.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 24, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: CRE; Neomycin; carbapenem-resistant Enterobacterales
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Asymptomatic Diseases; Asymptomatic Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Neomycin
• Other Study ID Numbers: SI-CEU-02-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No