Multidrug Resistant Gram-negative Pathogen Infections in High Risk Neonates in the Northeast of Mexico (InfGNMDR-Neo)

• ClinicalTrials.gov Identifier: NCT04812847
• Recruitment Status: Recruiting
• First Posted: March 24, 2021
• Last Update Posted: August 6, 2021
• Sponsor: Instituto Tecnologico y de Estudios Superiores de Monterey
• Information provided by (Responsible Party): Victor Javier Lara-Diaz, M.D., Ph.D., Instituto Tecnologico y de Estudios Superiores de Monterey

Study Description

Brief Summary:

The main objective of this project is to establish a prospective cohort to measure the Gram-negative infection burden in neonates under special care in a regional referral hospital, and to characterize all microorganisms isolates from these subjects at the phenotype and genotype level, specifically in relation to the expression of multi-drug resistance (MDR) associated genes (Molecular characterization of Gram-negative MDR isolates).

Condition or disease	Intervention/treatment
Infant Newborn Disease	Diagnostic Test: Identification of MDR characteristics

Detailed Description:

The investigators propose a mixed design approach, a cohort´s study with a nested case-control analysis. Study subjects will be the gram-negative isolates at the study hospital clinical laboratory. The cohort´s exposure factor will be the presence or absence of a multidrug resistance gram-negative bacterial isolate.

The prospective cohort will allow the estimation of Gram-negative infection burden in the study population, and the characterization of all microorganisms isolates from study subjects at the phenotype and genotype level, specifically in relation to the expression of multi-drug resistance (MDR) associated genes (Molecular characterization of Gram-negative MDR isolates); the cohort will be formed by each neonate, from the admission to special care, the isolation date and then follow-up until the resolution, being it discharge either alive, dead or by transfer to another facility. Risk ratios for each of these outcomes will be calculated.

Cases-controls analysis will allow the research team to identify main risk factors present in those individuals who further had or did not have a gram-negative MDR isolate, by calculation of associated odds ratios for concurrent perinatal factors. Another project goal, to establish correlations and measure risk factors (Odds ratios) between Gram-negative infection with MDR organisms and concurrent illness and treatments offered in the special care nursery (medical [antibiotics, non-steroid anti-inflammatory drugs, steroids, others], surgical, and clinical procedures) in neonates under special care, will also be attained through the nested cases and controls study approach.

Finally, a derivative from this project will be the establishment of the North-East Mexico Regional Repository of bacterial isolates in Neonates under special care. At the first stage, this repository will preserve specimens of bacteria, both Gram-negative and Gram-positive, along with a specially developed anonymous database of the individuals hosting those infections. In the near future, the focus of this repository may expand to fungus, parasites and perhaps viral isolates preservation.

The research team has also proposed an exploratory objective, subject to budget availability, and that is the characterization and comparison of the immuno-phenotype of those individuals affected of Gram-negative infection with MDR resistant organisms, those with infection with other organisms and those not affected by infectious complications.

All gram-negative isolates will be probed for the gene expression of 38 selected antibiotic resistance loci, and 96 selected samples will be further studied by next generation sequentiation.

Study Design

• Study Type: Observational
• Estimated Enrollment: 1000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Infecciones Por patógenos Gramnegativos Con Multirresistencia a Drogas en Neonatos de Alto Riesgo en el Noreste de México
• Actual Study Start Date: June 1, 2021
• Estimated Primary Completion Date: November 30, 2022
• Estimated Study Completion Date: December 31, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Gram negative infection, MDR present; Neonates with one or more gram-negative bacterial isolates with MDR characteristics during their clinical course in the Neonatal Intensive Care Unit of the study hospital.	Diagnostic Test: Identification of MDR characteristics; Identification of MDR in culture media, followed by amplification of related genes from the bacterial isolates
Gram negative infection, MDR absent; Neonates with one or more gram-negative bacterial isolates with no MDR characteristics during their clinical course in the Neonatal Intensive Care Unit of the study hospital.	Diagnostic Test: Identification of MDR characteristics; Identification of MDR in culture media, followed by amplification of related genes from the bacterial isolates

Outcome Measures

Primary Outcome Measures :

1. Burden of Gram Negative organisms infections [ Time Frame: Through study completion, an average of three months ]
   The isolation of a gram-negative organism, from any clinical site, in neonates under clinical care in special care nursery; Incidence = New cases during the study period, Prevalence = Total cases during the study period.

Secondary Outcome Measures :

1. Odds ratio for the occurrence of Gram-negative MDR infections [ Time Frame: Through study completion, an average of three months ]
   To identify and measure the Odds-ratio for the occurrence of Gram-negative infection with MDR resistant organisms and all concurrent perinatal factors. This will be done through a nested case and controls study approach.
2. Risk factors for the occurrence of Gram-negative MDR infections. [ Time Frame: Through study completion, an average of three months ]
   To establish correlations and measure risk factors (Relative risks) between Gram-negative infection with MDR organisms and concurrent illness and treatments offered in the special care nursery (medical [antibiotics, non-steroid anti-inflammatory drugs, steroids, others], surgical, and clinical procedures) in neonates under special care. This will be attained with a cohorts study approach.

Biospecimen Retention:   Samples With DNA

Isolated microorganism, recovered from culture plates, cryo-preserved at -80°C media until analysis, and thawed and seeded onto EMB (Eosin-Methylene Blue) agar plates, will be used for qrtPCR (quantitative real-time Polimerase Chain reaction)amplification of fragments of genes of interest.

Eligibility Criteria

• Ages Eligible for Study: up to 180 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Neonates, both at term and preterm, of any gestational age, under special care in the Neonatology Division of a tertiary care regional perinatal center in the Northeast of Mexico.

Criteria

Inclusion Criteria:

1. Neonates of either sex, and any gestational age, admitted to the special care nursery of Hospital Regional Materno Infantil (Includes also out-born and transferred babies),
2. Treating physician´s order to draw any biological sample and send it for culture at the hospital´s clinical laboratory.
3. A culture with an isolate of Gram-negative bacteria.

Exclusion Criteria:

1. Any culture negative for bacterial growth
2. Any culture with Gram-positive bacteria, or fungus growth.

Contacts and Locations

Contacts

Contact: Victor Javier Lara-Diaz, MD, PhD; +52 81 83665170; lara-diaz.vj@tec.mx

Contact: Mario Rene Alcorta-García, MD, PhD; +52 81 11995682; mario.alcorta@tec.mx

Locations

Mexico

Hospital Regional Materno Infantil de Alta Especialidad, Secretaría de Salud; Recruiting

Ciudad Guadalupe, Nuevo León, Mexico, 67140

Contact: Mario René Alcorta-García, MD, PhD +52 81 11995682 mario.alcorta@tec.mx

Contact: Victor Arízaga-Ballesteros, MD, MBio +52 81 14662028 arizagamd@yahoo.com

Sub-Investigator: Claudia Nohemí Lopez-Villaseñor, MD

Sub-Investigator: Aleyda Monreal-Malacara, MD

Sub-Investigator: Sixto F. Gutiérrez-Ramírez, MD

Sub-Investigator: Eleazar Puente-Vera, M Sc

Sub-Investigator: Angela Liliana Ruiz-Barreto, MD

Sponsors and Collaborators

Instituto Tecnologico y de Estudios Superiores de Monterey

Investigators

• Study Chair: Victor Javier Lara-Diaz, MD, PhD; Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud
• Principal Investigator: Cuauhtémoc Licona-Cassani, PhD; Tecnológico de Monterrey, Centro de Biotecnología FEMSA
• Principal Investigator: Marion Genevieve Brunck, PhD; Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, GIEE on Translational Omics

More Information

• Responsible Party: Victor Javier Lara-Diaz, M.D., Ph.D., Professor-Researcher, Instituto Tecnologico y de Estudios Superiores de Monterey
• ClinicalTrials.gov Identifier: NCT04812847
• Other Study ID Numbers: InfGNMDR-Neo
• First Posted: March 24, 2021
• Last Update Posted: August 6, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Initially, we plan to share raw data with qualified researchers and entities worldwide, but we have not yet decided a specific repository.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Victor Javier Lara-Diaz, M.D., Ph.D., Instituto Tecnologico y de Estudios Superiores de Monterey:

Drug Resistance, Multiple, Bacterial.