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

Infecciones Por patógenos Gramnegativos Con Multirresistencia a Drogas en Neonatos de Alto Riesgo en el Noreste de México

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).

Study Overview

• Status: Completed
• Conditions: Infant Newborn Disease
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 597

Contacts and Locations

Study Locations

• Mexico
  • Nuevo León
    • Ciudad Guadalupe, Nuevo León, Mexico, 67140
      • Hospital Regional Materno Infantil de Alta Especialidad, Secretaría de Salud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 5 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Burden of Gram Negative organisms infections	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.	Through study completion, an average of three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Odds ratio for the occurrence of Gram-negative MDR infections	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.	Through study completion, an average of three months
Risk factors for the occurrence of Gram-negative MDR infections.	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.	Through study completion, an average of three months

Collaborators and Investigators

• Sponsor: 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

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: March 10, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Drug Resistance, Multiple, Bacterial.
• Other Study ID Numbers: InfGNMDR-Neo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Initially, we plan to share raw data with qualified researchers and entities worldwide, but we have not yet decided a specific repository.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No