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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Colonization, Asymptomatic

Intervention / Treatment
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* Drug: Neomycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neomycin, CRE, carbapenem-resistant Enterobacterales