Multidrug Resistant Gram-negative Pathogen Infections in High Risk Neonates in the Northeast of Mexico
Condition: Infant Newborn Disease
Study type: Observational

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.
    

Intervention name(s): Identification of MDR characteristics
Intervention type(s): Diagnostic Test
Intervention description(s): Identification of MDR in culture media, followed by amplification of related genes from the bacterial isolates
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.
      
Biospecimen description: 
      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.
    
Keywords: Drug Resistance, Multiple, Bacterial.