Bacterial InfectionsNCT05285046
Phenotypic Profile and Molecular Mechanism of Resistance in Carbapenemase-producing Enterobacterales and Pseudomonas Aeruginosa Isolates From Brazilian Hospitals: Implications for the Introduction of IMIPENEM-RELEBACTAM
An observational study of Bacterial Infections and Antibiotic Resistant Infection, run by D'Or Institute for Research and Education at 1 site in Brazil.
Trial summary
The global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa (CRPA) are a significant threat to health care, especially for severely ill patients. Antibiotics currently used to treat CRE and CRPA infections are usually toxic and not very effective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacterial Infections, Antibiotic Resistant Infection
- How many people
- 250 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Apr 2022to 28 Feb 2023
- 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: We will evaluate prospectively 150 (one hundred and fifty) Enterobacterales and 100 (one hundred) Pseudomonas aeruginosa isolates from 12 hospitals in Rio de Janeiro.
Who may be able to join
- Microbiologics analysis indicating carbapenem resistance
Who cannot join
- Microbiologics analysis indicating Negative class A and D cabapenemase gene
Trial locations and contacts
1 site in 1 country.
Brazil1 site
D'Or Institute for Research and Education (IDOR)
Rio de Janeiro, 22281-100
About this study
The global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa (CRPA) are a significant threat to health care, especially for severely ill patients. Antibiotics currently used to treat CRE and CRPA infections are usually toxic and not very effective. Novel treatments include beta-lactamase inhibitors with broad-spectrum activity, among them IMI-REL. IMI-REL is a promising molecule due to the ability of REL to diminish carbapenem MICs to the susceptible range, potentially restoring the activity of this potent drug. However, few studies have systematically examined IMI-REL activity against a diverse clinical collection of CRE and CRPA strains, in particular from a region where the resistance is high, and the main mechanisms are in general unknown (Brazil- Latin America). As the use of molecular diagnostics becomes increasingly available in clinical settings, it is crucial to identify molecular markers predicting antimicrobial efficacy to guide therapeutic decision-making. In the present study, we will acess different species of CRE and CRPA from clinically relevant isolates to determine if the species, clonal lineage, and resistance gene profile, have influence to the response to IMI-REL.
Read the detailed description
Prospective evaluation of 150 (one hundred and fifty) Enterobacterales and 100 (one hundred) Pseudomonas aeruginosa isolates from 12 hospitals in the city of Rio de Janeiro. A sequential number of isolates per unit will be selected considering the inclusion criteria of resistance to carbapenem, only one isolate per patient will be evaluated. The isolate will be identified in genus and species by the VITEK® MS MALDI-TOF (bioMérieux - France) mass spectrometry methodology from bloodstream isolates and respiratory specimens.
The detection of carbapenemase production by rapid colorimetric method will be performed using the RAPIDEC® Carba NP test (bioMérieux - France). The isolates that present positive carbapenemase test by colorimetric method will be submitted to the PCR extended-spectrum beta-lactamase and carbapenemase gene characterization test for the following genes: blaSHV, blaCTX-M, KPC, NDM, VIM, IMP, SME , NMC / IMI, GES, GIM, SMP, IMP, OXA 23, OXA 24, OXA 48, OXA 51 and OXA 58.
After characterization of the carbapenemase-producing genes, isolates possessing the Class A and D carbapenemase gene, it will be evaluated the susceptibility profile of imipenem-relebactam using BMD (Broth Microdilution) to determine the minimum inhibitory concentration and its respective sensitivity and resistance criteria using recent CLSI MIC breakpoints - M100, 29th Ed (Clinical and Laboratory Standards Institute - 2020) and EUCAST Version 10.0 (European Committee on Antimicrobial Susceptibility Testing V 10.0). Isolates showing positive results for carbapenemase production, but with negative PCR results for the genes described above, will be further investigated for the likely presence of other carbapenemase producing genes or other mechanisms of resistance to carbapenem antibiotics. For the study and evaluation of the genetic diversity of the isolates, the Multilocus Sequence Typing (MLST) methodology will be used. Isolates that show simultaneous resistance to carbapenems, polymyxin B and fluoroquinolones will be subjected to next generation sequencing (NGS) for further evaluation of other genes or mechanisms associated with antibiotic resistance or virulence markers.
- Being tested
- No intervention
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
What is being measured
The primary outcome is the main question the study is designed to answer.
Susceptibility profile of imipenem-relebactam
Evaluation of the susceptibility profile of imipenem-relebactam in isolates possessing the Class A and D carbapenemase gene.
Measured: immediately after the analysis.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2022
- Study start1 Apr 2022 (estimated)
- Primary completion30 Oct 2022 (estimated)
- Study completion28 Feb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bacterial 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
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- D'Or Institute for Research and Education
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fernando Bozza, PhD, Principal investigator, D'Or Institute for Research and Education (IDOR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05285046
- Sponsor's protocol ID
- 15054519.3.0000.5249B
- Status last verified
- Mar 2022
- First submitted
- 28 Feb 2022
- Last updated
- 17 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenotypic Profile and Molecular Mechanism of Resistance in Carbapenemase-producing Enterobacterales and Pseudomonas Aeruginosa Isolates From Brazilian Hospitals: Implications for the Introduction of IMIPENEM-RELEBACTAM
- ClinicalTrials.gov ID
- NCT05285046
- Acronym / sponsor ID
- 15054519.3.0000.5249B
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- D'Or Institute for Research and EducationUniversity, hospital or other
- Study start
- 1 Apr 2022 (estimated)
- Primary completion
- 30 Oct 2022 (estimated)
- Study completion
- 28 Feb 2023 (estimated)
- First posted
- 17 Mar 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.
The global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa (CRPA) are a significant threat to health care, especially for severely ill patients. Antibiotics currently used to treat CRE and CRPA infections are usually toxic and not very effective. Novel treatments include beta-lactamase inhibitors with broad-spectrum activity, among them IMI-REL. IMI-REL is a promising molecule due to the ability of REL to diminish carbapenem MICs to the susceptible range, potentially restoring the activity of this potent drug. However, few studies have systematically examined IMI-REL activity against a diverse clinical collection of CRE and CRPA strains, in particular from a region where the resistance is high, and the main mechanisms are in general unknown (Brazil- Latin America). As the use of molecular diagnostics becomes increasingly available in clinical settings, it is crucial to identify molecular markers predicting antimicrobial efficacy to guide therapeutic decision-making. In the present study, we will acess different species of CRE and CRPA from clinically relevant isolates to determine if the species, clonal lineage, and resistance gene profile, have influence to the response to IMI-REL.
Detailed description
Prospective evaluation of 150 (one hundred and fifty) Enterobacterales and 100 (one hundred) Pseudomonas aeruginosa isolates from 12 hospitals in the city of Rio de Janeiro. A sequential number of isolates per unit will be selected considering the inclusion criteria of resistance to carbapenem, only one isolate per patient will be evaluated. The isolate will be identified in genus and species by the VITEK® MS MALDI-TOF (bioMérieux - France) mass spectrometry methodology from bloodstream isolates and respiratory specimens.
The detection of carbapenemase production by rapid colorimetric method will be performed using the RAPIDEC® Carba NP test (bioMérieux - France). The isolates that present positive carbapenemase test by colorimetric method will be submitted to the PCR extended-spectrum beta-lactamase and carbapenemase gene characterization test for the following genes: blaSHV, blaCTX-M, KPC, NDM, VIM, IMP, SME , NMC / IMI, GES, GIM, SMP, IMP, OXA 23, OXA 24, OXA 48, OXA 51 and OXA 58.
After characterization of the carbapenemase-producing genes, isolates possessing the Class A and D carbapenemase gene, it will be evaluated the susceptibility profile of imipenem-relebactam using BMD (Broth Microdilution) to determine the minimum inhibitory concentration and its respective sensitivity and resistance criteria using recent CLSI MIC breakpoints - M100, 29th Ed (Clinical and Laboratory Standards Institute - 2020) and EUCAST Version 10.0 (European Committee on Antimicrobial Susceptibility Testing V 10.0). Isolates showing positive results for carbapenemase production, but with negative PCR results for the genes described above, will be further investigated for the likely presence of other carbapenemase producing genes or other mechanisms of resistance to carbapenem antibiotics. For the study and evaluation of the genetic diversity of the isolates, the Multilocus Sequence Typing (MLST) methodology will be used. Isolates that show simultaneous resistance to carbapenems, polymyxin B and fluoroquinolones will be subjected to next generation sequencing (NGS) for further evaluation of other genes or mechanisms associated with antibiotic resistance or virulence markers.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- We will evaluate prospectively 150 (one hundred and fifty) Enterobacterales and 100 (one hundred) Pseudomonas aeruginosa isolates from 12 hospitals in Rio de Janeiro.
Key inclusion criteria (1 listed)
- Microbiologics analysis indicating carbapenem resistance
Key exclusion criteria (1 listed)
- Microbiologics analysis indicating Negative class A and D cabapenemase gene
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionNo intervention | Other | – |
Primary outcome
Susceptibility profile of imipenem-relebactam
Time frame: immediately after the analysis.
Evaluation of the susceptibility profile of imipenem-relebactam in isolates possessing the Class A and D carbapenemase gene.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2022.
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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.
Fernando Bozza, PhD principal investigator
D'Or Institute for Research and Education (IDOR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bacterial Infections and Antibiotic Resistant Infection, run by D'Or Institute for Research and Education at 1 site in Brazil.
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 1 inclusion and 1 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 17 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Susceptibility profile of imipenem-relebactam (time frame: immediately after the analysis.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Mar 2022.