Enterobacteriaceae InfectionsMERIMINCT05516433
Effect of Imipenem and Meropenem on the Digestive Microbiota and the Emergence and Carriage of Multidrug-resistant Bacteria
An observational study of Enterobacteriaceae Infections, run by Fondation Hôpital Saint-Joseph at 2 sites in France.
Trial summary
Among enterobacteria, ESBL production is the leading cause of multidrug resistance. The first cases of ESBL-producing Enterobacteriaceae (EBLSE) infections were described in the 1980s and subsequently spread worldwide. Since the turn of the century, the prevalence of EBLSE infections, particularly among E. coli and K. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Enterobacteriaceae Infections
- How many people
- 100 participants
- Where
- 2 sitesFrance
- Study dates
- 23 Jan 2023to 31 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patient hospitalized in the intensive care unit of the Groupe Hospitalier Paris Saint-Joseph or the Avicenne Hospital, with an infection requiring probabilistic or documented treatment with a carbapenem (imipenem or meropenem)
Who may be able to join
- Patient ≥ 18 years old
- Patient hospitalized in the intensive care unit of the Groupe Hospitalier Paris Saint-Joseph or the Avicenne Hospital
- Patient with an infection requiring probabilistic or documented treatment with a carbapenem (imipenem or meropenem)
- French speaking patient
- Patient or relative able to give his or her non-objection
Who cannot join
- Patients with a carbapenem allergy
- Pregnant or breastfeeding woman
- Patient under guardianship or curatorship
- Patient deprived of liberty
- Patient under court protection
Trial locations and contacts
2 sites in 1 country.
France2 sites, 2 recruiting
- Not yet recruiting
Hôpital Avicenne
Bobigny, 93000
Jean-Ralph Zahar, MD
- Recruiting
Groupe Hospitalier Paris Saint-Joseph
Paris, 75014
Benoit PILMIS, MD
About this study
Among enterobacteria, ESBL production is the leading cause of multidrug resistance. The first cases of ESBL-producing Enterobacteriaceae (EBLSE) infections were described in the 1980s and subsequently spread worldwide.
Since the turn of the century, the prevalence of EBLSE infections, particularly among E. coli and K. pneumoniae, has increased dramatically. The emergence of multidrug-resistant enteric bacteria (MRE) is currently a real public health problem. The European network for monitoring antibiotic resistance in cooperation with Santé Publique France evaluated the rate of resistance to third generation cephalosporins (C3G) among clinical strains at 10.2% for Escherichia coli and 28.8% for Klebsiella pneumoniae. The consequences of infections with multi-resistant enteric bacteria, mainly represented by ESBL, are currently well known, both from an individual point of view (increased mortality and length of hospitalization) and from a collective point of view (increased costs of care).
Read more
The current reference treatment for ESBL-producing Enterobacteriaceae infections is based on carbapenems.
Imipenem and meropenem are the two most commonly used carbapenems in clinical practice. Despite their similar spectrum of action, these two molecules have different pharmacokinetic properties, notably concerning their half-life and their elimination routes (mainly urinary for imipenem, mixed: biliary and urinary for meropenem).
Some studies have suggested that imipenem has a low impact on the digestive microbiota. However, no studies comparing the impact of imipenem and meropenem have been conducted.
Woerther et coll. explained in their work that the digestive microbiota confers resistance to colonization by MREs. The impact of antibiotics on the microbiota probably leads to a breakdown of this barrier and a loss of this resistance to colonization. Moreover, each antibiotic therapy does not impact the digestive microbiota in the same way and it seems that antibiotics with a high activity against strict anaerobic species and/or a high biliary elimination are the most impacting. It is therefore essential, in the era of multidrug resistance, to look at the influence of antibiotics on the digestive microbiota and on the emergence and carriage of MRE.
In a context where the incidence of multi-resistant bacteria is constantly increasing, it seems relevant to conduct a study aiming at comparing the respective impact of the use of imipenem and meropenem on the emergence of MRE and on the digestive microbiota at the individual level. This study aims at comparing the microbiological impact (in terms of emergence of bacterial resistance and in terms of impact on the diversity of cultivable digestive bacteria). It will be a comparative study with matching of patients according to age, service and previous duration of hospitalization. Indeed, the usual management of patients with an infection requiring treatment with a carbapenem is different between the 2 participating centers. Thus, according to the usual management of patients in these 2 participating centers, patients at Avicenne Hospital are treated with meropenem and patients at the Paris Saint-Joseph Hospital Group with imipenem, except in the case of a need for a high daily dose (osteoarticular infection, for example) due to the neurological toxicity of imipenem at high dosage. In the case of high-dose use, meropenem will be the preferred molecule.
- Conditions
- Enterobacteriaceae Infections
- Medical subject headings
- Enterobacteriaceae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Imipenem | Prescribing rules differ from one department to another: Imipenem is the preferred drug at Saint-Joseph Hospital. | |
| Meropenem | Prescribing rules differ from one department to another: Meropenem is the preferred carbapenem at Avicenne Hospital. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ecological impact of imipenem and meropenem on the microbiota (modification of bacterial diversity)
This outcome corresponds to the rate of modification in bacterial diversity judged by the loss of at least one bacterial species in the microbiota after initiation of antibiotic therapy.
Measured: Month 1
Ecological impact of imipenem and meropenem on the microbiota (abundance)
This outcome corresponds to the rate of diminution in bacterial abundance within the microbiota, defined as a decrease of at least 2 logs in abundance.
Measured: Month 1
Secondary outcomes (2)
Evaluate the change in bacterial diversity
This outcome corresponds to the rate of loss of at least one bacterial species in the microbiota after initiation of antibiotic therapy.
Measured: Month 1
Change in bacterial abundance
This outcome corresponds to the rate of loos corresponding to at least 2 log decrease in bacterial abundance.
Measured: Month 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2022
- Study start23 Jan 2023
- Primary completion22 Jan 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Enterobacteriaceae InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondation Hôpital Saint-Joseph
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benoit PILMIS, MD, Principal investigator, Fondation Hôpital Saint-Joseph
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05516433
- Sponsor's protocol ID
- MERIMI
- Acronym
- MERIMI
- Status last verified
- Feb 2023
- First submitted
- 17 Aug 2022
- Last updated
- 27 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Schwaber MJ, Navon-Venezia S, Kaye KS, Ben-Ami R, Schwartz D, Carmeli Y. Clinical and economic impact of bacteremia with extended- spectrum-beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2006 Apr;50(4):1257-62. doi: 10.1128/AAC.50.4.1257-1262.2006.
PubMed 16569837Gudiol C, Calatayud L, Garcia-Vidal C, Lora-Tamayo J, Cisnal M, Duarte R, Arnan M, Marin M, Carratala J, Gudiol F. Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome. J Antimicrob Chemother. 2010 Feb;65(2):333-41. doi: 10.1093/jac/dkp411. Epub 2009 Dec 3.
PubMed 19959544Woerther PL, Lepeule R, Burdet C, Decousser JW, Ruppe E, Barbier F. Carbapenems and alternative beta-lactams for the treatment of infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae: What impact on intestinal colonisation resistance? Int J Antimicrob Agents. 2018 Dec;52(6):762-770. doi: 10.1016/j.ijantimicag.2018.08.026. Epub 2018 Aug 31.
PubMed 30176355Ruppe E, Burdet C, Grall N, de Lastours V, Lescure FX, Andremont A, Armand-Lefevre L. Impact of antibiotics on the intestinal microbiota needs to be re-defined to optimize antibiotic usage. Clin Microbiol Infect. 2018 Jan;24(1):3-5. doi: 10.1016/j.cmi.2017.09.017. Epub 2017 Sep 29. No abstract available.
PubMed 28970162Ruppe E, Lixandru B, Cojocaru R, Buke C, Paramythiotou E, Angebault C, Visseaux C, Djuikoue I, Erdem E, Burduniuc O, El Mniai A, Marcel C, Perrier M, Kesteman T, Clermont O, Denamur E, Armand-Lefevre L, Andremont A. Relative fecal abundance of extended-spectrum-beta-lactamase-producing Escherichia coli strains and their occurrence in urinary tract infections in women. Antimicrob Agents Chemother. 2013 Sep;57(9):4512-7. doi: 10.1128/AAC.00238-13. Epub 2013 Jul 8.
PubMed 23836184Holub M, Mizrahi A, Miot O, Pean de Ponfilly G, Huriez P, Cachera L, Genty T, Zahar J-R, Leveque N, Le Monnier A, Pilmis B. Comparative impact of imipenem and meropenem on intestinal carriage and relative fecal abundance of multidrug-resistant bacteria, with detection of residual antibiotics in rectal swabs. Microbiol Spectr. 2026 Sep 17:e0123526. doi: 10.1128/spectrum.01235-26. Online ahead of print.
PubMed 42752244
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Imipenem and Meropenem on the Digestive Microbiota and the Emergence and Carriage of Multidrug-resistant Bacteria
- ClinicalTrials.gov ID
- NCT05516433
- Acronym / sponsor ID
- MERIMI / MERIMI
- Conditions
- Enterobacteriaceae Infections
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Fondation Hôpital Saint-JosephUniversity, hospital or other
- Study start
- 23 Jan 2023 (actual)
- Primary completion
- 22 Jan 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 25 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Among enterobacteria, ESBL production is the leading cause of multidrug resistance. The first cases of ESBL-producing Enterobacteriaceae (EBLSE) infections were described in the 1980s and subsequently spread worldwide.
Since the turn of the century, the prevalence of EBLSE infections, particularly among E. coli and K. pneumoniae, has increased dramatically. The emergence of multidrug-resistant enteric bacteria (MRE) is currently a real public health problem. The European network for monitoring antibiotic resistance in cooperation with Santé Publique France evaluated the rate of resistance to third generation cephalosporins (C3G) among clinical strains at 10.2% for Escherichia coli and 28.8% for Klebsiella pneumoniae. The consequences of infections with multi-resistant enteric bacteria, mainly represented by ESBL, are currently well known, both from an individual point of view (increased mortality and length of hospitalization) and from a collective point of view (increased costs of care).
The current reference treatment for ESBL-producing Enterobacteriaceae infections is based on carbapenems.
Imipenem and meropenem are the two most commonly used carbapenems in clinical practice. Despite their similar spectrum of action, these two molecules have different pharmacokinetic properties, notably concerning their half-life and their elimination routes (mainly urinary for imipenem, mixed: biliary and urinary for meropenem).
Some studies have suggested that imipenem has a low impact on the digestive microbiota. However, no studies comparing the impact of imipenem and meropenem have been conducted.
Woerther et coll. explained in their work that the digestive microbiota confers resistance to colonization by MREs. The impact of antibiotics on the microbiota probably leads to a breakdown of this barrier and a loss of this resistance to colonization. Moreover, each antibiotic therapy does not impact the digestive microbiota in the same way and it seems that antibiotics with a high activity against strict anaerobic species and/or a high biliary elimination are the most impacting. It is therefore essential, in the era of multidrug resistance, to look at the influence of antibiotics on the digestive microbiota and on the emergence and carriage of MRE.
In a context where the incidence of multi-resistant bacteria is constantly increasing, it seems relevant to conduct a study aiming at comparing the respective impact of the use of imipenem and meropenem on the emergence of MRE and on the digestive microbiota at the individual level. This study aims at comparing the microbiological impact (in terms of emergence of bacterial resistance and in terms of impact on the diversity of cultivable digestive bacteria). It will be a comparative study with matching of patients according to age, service and previous duration of hospitalization. Indeed, the usual management of patients with an infection requiring treatment with a carbapenem is different between the 2 participating centers. Thus, according to the usual management of patients in these 2 participating centers, patients at Avicenne Hospital are treated with meropenem and patients at the Paris Saint-Joseph Hospital Group with imipenem, except in the case of a need for a high daily dose (osteoarticular infection, for example) due to the neurological toxicity of imipenem at high dosage. In the case of high-dose use, meropenem will be the preferred molecule.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imipenem | – | –Prescribing rules differ from one department to another: Imipenem is the preferred drug at Saint-Joseph Hospital. |
| Meropenem | – | –Prescribing rules differ from one department to another: Meropenem is the preferred carbapenem at Avicenne Hospital. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient hospitalized in the intensive care unit of the Groupe Hospitalier Paris Saint-Joseph or the Avicenne Hospital, with an infection requiring probabilistic or documented treatment with a carbapenem (imipenem or meropenem)
Key inclusion criteria (5 listed)
- Patient ≥ 18 years old
- Patient hospitalized in the intensive care unit of the Groupe Hospitalier Paris Saint-Joseph or the Avicenne Hospital
- Patient with an infection requiring probabilistic or documented treatment with a carbapenem (imipenem or meropenem)
- French speaking patient
- Patient or relative able to give his or her non-objection
Key exclusion criteria (5 listed)
- Patients with a carbapenem allergy
- Pregnant or breastfeeding woman
- Patient under guardianship or curatorship
- Patient deprived of liberty
- Patient under court protection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Ecological impact of imipenem and meropenem on the microbiota (modification of bacterial diversity)
Time frame: Month 1
This outcome corresponds to the rate of modification in bacterial diversity judged by the loss of at least one bacterial species in the microbiota after initiation of antibiotic therapy.
Ecological impact of imipenem and meropenem on the microbiota (abundance)
Time frame: Month 1
This outcome corresponds to the rate of diminution in bacterial abundance within the microbiota, defined as a decrease of at least 2 logs in abundance.
2 secondary outcomes
Evaluate the change in bacterial diversity
Time frame: Month 1
Change in bacterial abundance
Time frame: Month 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
- Background: PubMed 16569837Schwaber MJ, Navon-Venezia S, Kaye KS, Ben-Ami R, Schwartz D, Carmeli Y. Clinical and economic impact of bacteremia with extended- spectrum-beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2006 Apr;50(4):1257-62. doi: 10.1128/AAC.50.4.1257-1262.2006.
- Background: PubMed 19959544Gudiol C, Calatayud L, Garcia-Vidal C, Lora-Tamayo J, Cisnal M, Duarte R, Arnan M, Marin M, Carratala J, Gudiol F. Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome. J Antimicrob Chemother. 2010 Feb;65(2):333-41. doi: 10.1093/jac/dkp411. Epub 2009 Dec 3.
- Background: PubMed 30176355Woerther PL, Lepeule R, Burdet C, Decousser JW, Ruppe E, Barbier F. Carbapenems and alternative beta-lactams for the treatment of infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae: What impact on intestinal colonisation resistance? Int J Antimicrob Agents. 2018 Dec;52(6):762-770. doi: 10.1016/j.ijantimicag.2018.08.026. Epub 2018 Aug 31.
- Background: PubMed 28970162Ruppe E, Burdet C, Grall N, de Lastours V, Lescure FX, Andremont A, Armand-Lefevre L. Impact of antibiotics on the intestinal microbiota needs to be re-defined to optimize antibiotic usage. Clin Microbiol Infect. 2018 Jan;24(1):3-5. doi: 10.1016/j.cmi.2017.09.017. Epub 2017 Sep 29. No abstract available.
- Background: PubMed 23836184Ruppe E, Lixandru B, Cojocaru R, Buke C, Paramythiotou E, Angebault C, Visseaux C, Djuikoue I, Erdem E, Burduniuc O, El Mniai A, Marcel C, Perrier M, Kesteman T, Clermont O, Denamur E, Armand-Lefevre L, Andremont A. Relative fecal abundance of extended-spectrum-beta-lactamase-producing Escherichia coli strains and their occurrence in urinary tract infections in women. Antimicrob Agents Chemother. 2013 Sep;57(9):4512-7. doi: 10.1128/AAC.00238-13. Epub 2013 Jul 8.
- Derived from this study: PubMed 42752244Holub M, Mizrahi A, Miot O, Pean de Ponfilly G, Huriez P, Cachera L, Genty T, Zahar J-R, Leveque N, Le Monnier A, Pilmis B. Comparative impact of imipenem and meropenem on intestinal carriage and relative fecal abundance of multidrug-resistant bacteria, with detection of residual antibiotics in rectal swabs. Microbiol Spectr. 2026 Sep 17:e0123526. doi: 10.1128/spectrum.01235-26. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benoit PILMIS, MD principal investigator
Fondation Hôpital Saint-Joseph
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Enterobacteriaceae Infections, run by Fondation Hôpital Saint-Joseph at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Benoit PILMIS, MD (144127820 ext. +33, bpilmis@ghpsj.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ecological impact of imipenem and meropenem on the microbiota (modification of bacterial diversity) (time frame: Month 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05516433, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2023.