Emergence of Resistance in Intestinal Microflora During Carbapenem Treatments

NCT ID: NCT01703299

Last Updated: 2015-05-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 35 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-03-31

Brief Summary

The use of carbapenems, very broad spectrum antibiotics of last resort, is becoming more common due to the increased prevalence in the hospital and community of extended spectrum β-lactamase (ESBL) producing gram-negative bacilli (GNB), including CTX-M type, which are resistant to all other β-lactam antibiotics. Meanwhile, it creates a selective pressure towards emergence of strains which are also resistant to carbapenems, placing patients in a catastrophic situation of therapeutic dead-end. A better understanding of the mechanisms of emergence of BGN resistant to carbapenems is necessary to optimize their use and undertake preventive measures to preserve their effectiveness. The aim of the study is to evaluate and describe the emergence of carbapenem-induced resistant GNB in patient intestinal microflora.

Detailed Description

The use of carbapenems, very broad spectrum antibiotics of last resort, is becoming more common due to the increased prevalence in the hospital and community of extended spectrum β-lactamase (ESBL) producing gram-negative bacilli (GNB), including CTX-M type, which are resistant to all other β-lactam antibiotics. Meanwhile, it creates a selective pressure towards emergence of strains which are also resistant to carbapenems, placing patients in a catastrophic situation of therapeutic dead-end. A better understanding of the mechanisms of emergence of BGN resistant to carbapenems is necessary to optimize their use and undertake preventive measures to preserve their effectiveness.

Hypotheses: Carbapenems induce in treated patients the emergence of resistant GNB in intestinal flora and have an impact on colonization resistance of the gut microbiota.

Primary objective: To determine the frequency of emergence of carbapenems resistant GNB in the intestinal flora at the end of a treatment by imipenem or ertapenem.

Secondary objective(s):

• Assess the presence of carbapenem resistant GNB in the intestinal flora before treatment.
• Evaluate the presence and / or persistence of carbapenem resistant GNB in the intestinal flora on day 3 of treatment, and 15 days and 1 month after the end of treatment.
• Determine the molecular mechanisms of resistance of strains of interest.
• Describe the gastrointestinal tract colonization by non-commensal microorganisms before and after treatment (impact on colonization resistance).
• Describe the characteristics of patients with emergence of resistance compared to patients who do not.
• Proper conservation of stool of 10 patients for metagenomic and/or metatranscriptomic analysis of changes in the intestinal flora.

Primary endpoint: Presence of carbapenem resistant GNB in the stool at the end of treatment in patients who did not before, after culture on selective media.

Secondary endpoints:

• Presence of carbapenem resistant GNB in stools before treatment, at day 3 and 15 days and 1 month after stopping treatment, after culture on selective media.
• PCR and sequencing of resistance genes from strains of interest.
• Colonization of the digestive tract by non-commensal microorganisms before and after treatment.
• Characteristics of patients with or without emergence of resistance.

Conditions

Carbapenem-induced Resistance

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

imipenem-treated patients

imipenem-treated patients

No interventions assigned to this group

ertapenem-treated patients

ertapenem-treated patients

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• age> or = 18 years old
• hospitalized
• initiating a treatment by imipenem or ertapenem-
• faeces harvested before the beginning of treatment
• written informed consent from the patient or from a relative if the patient is incapable of expressing his/her consent
• reachable by phone after hospitalization (only for patients able to express their consent).

Exclusion Criteria

• hospitalized in intensive care unit
• concomitant antibiotic treatment (except aminosid or vancomycin for less than 4 days).

• introduction of other antibiotics during carbapenem treatment (except vancomycin or aminosid)
• vancomycin treatment for more than 4 days during carbapenem treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antoine Andremont, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Beaujon

Clichy, , France

Hôpital Louis Mourier

Colombes, , France

Hôpital Bichat-Claude Bernard

Paris, , France

Hôpital Saint-Louis

Paris, , France

Hôpital Paul Brousse

Villejuif, , France

Countries

France

References

Grall N, Lazarevic V, Gaia N, Couffignal C, Laouenan C, Ilic-Habensus E, Wieder I, Plesiat P, Angebault C, Bougnoux ME, Armand-Lefevre L, Andremont A, Duval X, Schrenzel J. Unexpected persistence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in the faecal microbiota of hospitalised patients treated with imipenem. Int J Antimicrob Agents. 2017 Jul;50(1):81-87. doi: 10.1016/j.ijantimicag.2017.02.018. Epub 2017 May 10.

Reference Type: DERIVED

PMID: 28499958 (View on PubMed)

Other Identifiers

CRC11016

Identifier Type: -

Identifier Source: org_study_id