Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT05285046 |
| Other study ID # |
15054519.3.0000.5249B |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2022 |
| Est. completion date |
February 28, 2023 |
Study information
| Verified date |
March 2022 |
| Source |
D'Or Institute for Research and Education |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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. 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.
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.
