Clinical trial NCT04812847: Multidrug Resistant Gram-negative Pathogen Infections in High Risk Neonates in the Northeast of Mexico
Official title: Infecciones Por patógenos Gramnegativos Con Multirresistencia a Drogas en Neonatos de Alto Riesgo en el Noreste de México
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infant Newborn Disease
Keywords: Drug Resistance, Multiple, Bacterial.
Lead sponsor: Instituto Tecnologico y de Estudios Superiores de Monterey
Sponsor class: OTHER
First posted: 2021-03-24
Enrollment: 597
Sex: ALL
Minimum age (years): 1
Maximum age (years): 180
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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).

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.

Eligibility 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.

Primary outcomes:
measure: Burden of Gram Negative organisms infections
timeFrame: Through study completion, an average of three months
Secondary outcomes:
measure: Odds ratio for the occurrence of Gram-negative MDR infections
timeFrame: Through study completion, an average of three months
measure: Risk factors for the occurrence of Gram-negative MDR infections.
timeFrame: Through study completion, an average of three months
Other outcomes:
Locations:
city: Ciudad Guadalupe
country: Mexico
facility: Hospital Regional Materno Infantil de Alta Especialidad, Secretaría de Salud
state: Nuevo León
Study officials:
affiliation: Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud
name: Victor Javier Lara-Diaz, MD, PhD
role: STUDY_CHAIR
affiliation: Tecnológico de Monterrey, Centro de Biotecnología FEMSA
name: Cuauhtémoc Licona-Cassani, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, GIEE on Translational Omics
name: Marion Genevieve Brunck, PhD
role: PRINCIPAL_INVESTIGATOR
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