Impact of the Choice of 3rd Generation Cephalosporins on the Emergence of Resistance in the Microbiota Intestinal.

NCT02659033 | Completed Phase 3

• 2 other identifiers: CRC13-179 / P1409042014-005485-30
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

CEREMI is an open, randomised prospective study in parallel groups in healthy volunteers. This study compare the effect of a monotherapy by ceftriaxone or cefotaxime on the emergence of resistance of enterobacteria to 3rd-generation cephalosporins within the intestinal microbiota. Each volunteer will be treated for 3 days by either ceftriaxone (1 gram per day) or cefotaxime (1 gram every 8 hours).

Conditions

Emergence of Bacterial Resistance to Antibiotics

Keywords

microbiota; resistant bacteria

Outcome Measures

Primary Outcomes (1)

• The area under the curve of the 3rd generation cephalosporins resistant enterobacteria in the intestinal microbiota between D0 and D7.

  within the first 7 days

Secondary Outcomes (9)

• The area under the curve of enterobacteriaceae resistant to C3G accounts (regardless of the resistance mechanism) from D0 to D15 in each treatment group.

  within the first 15 days

• Proportion of patients with 3rd generation cephalosporins resistant enterobacteria in the intestinal microbiota (regardless of the resistance mechanism) at D30 at D90 and at D180 in each treatment group.

  D30, D90 and D180

• Area under the curve of enterobacteriaceae resistant to C3G accounts distinguishing the resistance mechanism (B lactamase,plasmid cephalosporinase or cephalosporinase) from D0 to D15 in each treatment group.

  within the first 15 days

• Proportion of patients with 3rd generation cephalosporins resistant enterobacteria in the intestinal microbiota (distinguishing the resistance mechanism) at D30 at D90 and at D180 in each treatment group.

  D30, D90 and D180

• Area under the curve of total coliform accounts from D0 to D 7 and D0 to D15 in each treatment group.

  within the first 15 days

Study Arms (2)

ceftriaxone

ACTIVE COMPARATOR

healthy volunteer who receive ceftriaxone

Drug: ceftriaxone

cefotaxime

ACTIVE COMPARATOR

healthy volunteer who receive cefotaxime

Drug: Cefotaxime

Interventions

ceftriaxone DRUG

ceftriaxone (1 gram per day)

Also known as: cephalosporin 3rd generation

ceftriaxone

Cefotaxime DRUG

cefotaxime (1 gram every 8 hours)

Also known as: cephalosporin 3rd generation

cefotaxime

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 65 years
• Volunteer regarded as healthy after detailed examination
• Subject whose entourage (person living under the same roof) does not present any chronic disease throughout the course and did not receive antibiotics within 15 days.
• Normal intestinal passage (one stool per day)
• Negative urinalysis for toxic substances
• Normal blood test (including blood and platelets counts, prothrombin, ionograms, Liver function tests)
• Negative HIV and HCV (hepatitis C virus) test, no HBV (hepatitis B virus)chronic infection
• Normal weight (BMI comprised between 19 and 29 kg/m²)
• Freely obtained consent
• Health insurance beneficiary

You may not qualify if:

• Antibiotic therapy in the previous 6 months
• Hospitalisation in the previous 12 months;
• Active infection
• Ongoing treatment
• Any chronic disease
• Allergy to one of the study drugs
• Any contraindications to β-lactam therapy in particular to penicillins or cephalosporins
• Pregnancy or no effective contraception, suckling women
• Subject, as determined by the investigating physician, could not observing during the study, or unable to communicate because of language or mental disorders barrier;
• Subject participating simultaneously in another biomedical research
• Subject can not be contacted in case of emergency;
• Subject about legally protected under tutorship or curators;
• Subject deprived of freedom under judicial or administrative constraints
• No pre-treatment stool sample obtained
• More than one stool sample missing from D1 to D7

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Bichat

Paris, 75018, France

Location

Related Publications (1)

• Burdet C, Grall N, Linard M, Bridier-Nahmias A, Benhayoun M, Bourabha K, Magnan M, Clermont O, d'Humieres C, Tenaillon O, Denamur E, Massias L, Tubiana S, Alavoine L, Andremont A, Mentre F, Duval X; CEREMI Group. Ceftriaxone and Cefotaxime Have Similar Effects on the Intestinal Microbiota in Human Volunteers Treated by Standard-Dose Regimens. Antimicrob Agents Chemother. 2019 May 24;63(6):e02244-18. doi: 10.1128/AAC.02244-18. Print 2019 Jun.

  PMID: 30936104 DERIVED

MeSH Terms

Interventions

Ceftriaxone; Third Generation Cephalosporins; Cefotaxime

Intervention Hierarchy (Ancestors)

Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; beta Lactam Antibiotics; Anti-Bacterial Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Xavier Duval, Profesor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2016
• First Posted: January 20, 2016
• Study Start: March 1, 2016
• Primary Completion: March 1, 2016
• Study Completion: December 1, 2017
• Last Updated: May 21, 2018

Record last verified: 2018-05

Locations

FR (1)