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      Dynamics of the digestive acquisition of bacterial carriage and integron presence by French preterm newborns according to maternal colonization: The DAIR3N multicentric study

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          Abstract

          Objectives

          The study aimed to describe the dynamics and risk factors of Gram-negative bacteria (GNB) acquisition in preterm infants.

          Methods

          This prospective multicenter French study included mothers hospitalized for preterm delivery and their newborns, followed until hospital discharge. Maternal feces and vaginal fluids at delivery, and neonatal feces from birth to discharge were tested for cultivable GNB, potential acquired resistance, and integrons. The primary outcome was the acquisition of GNB and integrons in neonatal feces, and their dynamics, evaluated by survival analysis using the actuarial method. Risk factors were analyzed using Cox models.

          Results

          Two hundred thirty-eight evaluable preterm dyads were included by five different centers over 16 months. GNB were isolated in 32.6% of vaginal samples, with 15.4% of strains producing extended-spectrum beta-lactamase (ESBL) or hyperproducing cephalosporinase (HCase), and in 96.2% of maternal feces, with 7.8% ESBL-GNB or HCase-GNB. Integrons were detected in 40.2% of feces and 10.6% of GNB strains. The mean (SD) length of stay of newborns was 39.5 (15.9) days; 4 died in the hospital. At least one infection episode occurred in 36.1% of newborns. The acquisition of GNB and integrons was progressive from birth to discharge. At discharge, half of newborns had ESBL-GNB or HCase-GNB, independently favored by a premature rupture of membranes (Hazard Ratio (HR), 3.41, 95% confidence interval (CI), 1.71; 6.81), and 25.6% had integrons (protective factor: multiple gestation, HR, 0.367, 95% CI, 0.195; 0.693).

          Conclusion

          In preterm newborns, the acquisitions of GNB, including resistant ones, and integrons are progressive from birth to discharge. A premature rupture of membranes favored the colonization by ESBL-GNB or Hcase-GNB.

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          Most cited references29

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          Access to effective antimicrobials: a worldwide challenge.

          Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.
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            Integrons.

            Integrons are genetic elements able to acquire and rearrange open reading frames (ORFs) embedded in gene cassette units and convert them to functional genes by ensuring their correct expression. They were originally identified as a mechanism used by Gram-negative bacteria to collect antibiotic resistance genes and express multiple resistance phenotypes in synergy with transposons. More recently, their role has been broadened with the discovery of chromosomal integron (CI) structures in the genomes of hundreds of bacterial species. This review focuses on the resources carried in these elements, on their unique recombination mechanisms, and on the different mechanisms controlling the cassette dynamics. We discuss the role of the toxin/antitoxin (TA) cassettes for the stabilization of the large cassette arrays carried in the larger CIs, known as superintegrons. Finally, we explore the central role played by single-stranded DNA in the integron cassette dynamics in light of the recent discovery that the integron integrase expression is controlled by the SOS response.
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              Is meconium from healthy newborns actually sterile?

              In a previous study, bacteria were able to be isolated from umbilical cord blood of healthy neonates and from murine amniotic fluid obtained by caesarean section. This suggested that term fetuses are not completely sterile and that a prenatal mother-to-child efflux of commensal bacteria may exist. Therefore, the presence of such bacteria in meconium of 21 healthy neonates was investigated. The identified isolates belonged predominantly to the genuses Enterococcus and Staphylococcus. Later, a group of pregnant mice were orally inoculated with a genetically labelled E. fecium strain previously isolated from breast milk of a healthy woman. The labelled strain could be isolated and PCR-detected from meconium of the inoculated animals obtained by caesarean section one day before the predicted date of labor. In contrast, it could not be detected in samples obtained from a non-inoculated control group.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                14 March 2023
                2023
                : 14
                : 1148319
                Affiliations
                [1] 1INSERM UMR, Limoges University, Limoges University Hospital , Limoges, France
                [2] 2Department of Pediatrics, Mother-Child Hospital, Limoges University Hospital , Limoges, France
                [3] 3Epidemiology, Biostatistics, and Research Methodology Centre (CEBIMER), Limoges University Hospital , Limoges, France
                [4] 4Department of Pediatrics, Neonatology and Maternity Unit, Pellegrin University Hospital , Bordeaux, France
                [5] 5Bacteriology Laboratory, Pellegrin University Hospital , Bordeaux, France
                [6] 6Department of Pediatrics and Neonatology, CHU Toulouse , Toulouse, France
                [7] 7Bacteriology and Hygiene Department, Federative Institute of Biology, CHU Toulouse University Hospital , Toulouse, France
                [8] 8Department of Pediatrics, Pau Hospital , Pau, France
                [9] 9Medical Biology Laboratory, Pau Hospital , Pau, France
                [10] 10Department of Pediatrics and Neonatology, « Côte Basque » Hospital , Bayonne, France
                [11] 11Microbiology Laboratory, « Côte Basque » Hospital , Bayonne, France
                Author notes

                Edited by: Alina Maria Holban, University of Bucharest, Romania

                Reviewed by: Steven L. Foley, National Center for Toxicological Research (FDA), United States; Qin Qi, Macquarie University, Australia

                *Correspondence: Fabien Garnier, Fabien.GARNIER@ 123456unilim.fr

                This article was submitted to Infectious Agents and Disease, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2023.1148319
                10043237
                1191bf73-4fd5-439d-be44-d479f8aded2f
                Copyright © 2023 Patry, Bothorel, Labrunie, Renesm, Lehours, Benard, Dubois, Ponthier, Meyer, Norbert, Villeneuve, Jouvencel, Leysenne, Chainier, Luce, Grélaud, Ploy, Bedu and Garnier.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 January 2023
                : 21 February 2023
                Page count
                Figures: 3, Tables: 4, Equations: 0, References: 31, Pages: 9, Words: 6151
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                integrons,digestive acquisition,antimicrobial resistance,preterm newborn infant,resistance markers,gram-negative bacteria

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