Marine Butin

Les infections néonatales tardives (INT, survenant après 3 jours de vie) sont fréquentes et sont associées à une mortalité et une morbidité importantes chez les nouveau-nés prématurés. Dans ce contexte, il a été récemment décrit un clone de Staphylococcus capitis, appelé NRCS-A, impliqué spécifiquement dans ces INT dans différents services de réanimation néonatale (RN) à travers la France, et présentant un profil multirésistant atypique chez cette espèce, incluant notamment une sensibilité diminuée à la vancomycine, qui est pourtant l'antibiotique de première ligne en cas de suspicion d'INT. Dans le cadre de ce travail, nous avons démontré la distribution endémique du clone NRCS-A dans au moins 17 pays à travers le monde, spécifiquement dans les services de RN. De plus des données épidémiologiques issues des services de RN français ont identifié une prévalence élevée du clone dans certains services, illustrant sa capacité à s'implanter puis à persister dans ces services. Une caractérisation génétique du clone NRCS-A a été réalisée afin de mettre en évidence d'éventuels facteurs génétiques pouvant favoriser son implantation dans les services de RN. Cette analyse a démontré le rôle des éléments génétiques mobiles dans l'émergence du phénotype multirésistant du clone NRCS-A. En revanche aucun gène de virulence spécifique du clone n'a pu être mis en évidence. L'analyse des gènes spécifiques du clone a toutefois permis d'identifier le gène nsr codant pour la résistance à la nisine, bactériocine active sur de nombreuses bactéries à Gram positif et sécrétée par les bactéries de la flore commensale digestive. Ce gène pourrait donc conférer un avantage sélectif au clone NRCS-A pour s'implanter dans le microbiote des nouveau-nés prématurés. La persistance du clone dans les services de RN évoque la présence de réservoirs inertes ou humains au sein de ces services. Grâce à la mise au point d'une technique d'identification de S. capitis par gélose chromogénique sélective, nous avons pu démontrer la diffusion et la persistance de S. capitis dans un service de RN, sans toutefois identifier un réservoir unique responsable de cette colonisation. Nous avons également observé une inefficacité partielle des mesures de décontamination. Il n'existe en revanche pas de portage chronique chez le personnel soignant, ni de colonisation vaginale chez les femmes enceintes. Par ailleurs, nous avons pu mettre en évidence par repiquages successifs in vitro une capacité particulière du clone NRCS-A à acquérir de façon rapide et stable une résistance à la vancomycine sous pression de sélection par cet antibiotique. Cette capacité constitue un avantage sélectif majeur pour ce clone et pourrait avoir favorisé son implantation et sa persistance dans les services de RN où la pression de sélection par la vancomycine est élevée. Pour compléter ces résultats, une étude de cohorte prospective menée en RN a permis de démontrer que l'administration de vancomycine constituait un facteur de risque indépendant de survenue d'INT à S. capitis. Au-delà de la problématique spécifique des INT à S. capitis en RN, nos travaux illustrent plus largement un des enjeux majeurs de santé publique qui est l'impact écologique potentiel de l'utilisation des antibiothérapies probabilistes à large spectre sur l'émergence et la sélection de bactéries multirésistantes impliquées secondairement dans des infections nosocomiales. Ces travaux ouvrent de nouveaux axes de recherche concernant d'une part la meilleure compréhension de la physiopathologie des INT à S. capitis, et d'autre part plus largement les modalités de prévention des INT en RN et d'amélioration du diagnostic précoce des INT

Bacillus cereus is an emerging cause of fulminant nosocomial bacteremia in premature infants. Here we aimed to report the successful management of two succ

Introduction: Fresh human milk for preterm infants is associated with a reduction of bronchopulmonary dysplasia, to improve survival without major complications, and with an increased breastfeeding duration. Nevertheless, its administration is frequently restricted due to the risk of post-natal cytomegalovirus infection. Looking at 12 years of medical records in a tertiary neonatal intensive care unit using fresh milk without restriction, we retrospectively collected cases of symptomatic postnatal cytomegalovirus infection in preterm infants born under 32 weeks receiving fresh milk. We present the prevalence and outcome of postnatal milk-acquired cytomegalovirus infection. Main issue: Among 2554 preterm newborns < 32 weeks hospitalized during the study period (2009–2020), 1396 (54%) had received fresh milk, and eight newborns developed a symptomatic postnatal cytomegalovirus infection, representing an incidence of 5/1000 patients. Clinical presentation was severe in three out of the eight cases. Management: Two patients received valganciclovir, and one patient died of the infection. After 2 years of follow-up, two patients had neurodevelopmental delay, including one who had abnormalities on brain magnetic resonance imaging before the cytomegalovirus infection. Liver function was normal. Breastfeeding was continued for all surviving patients with a mean duration of 4.5 months. Conclusion: Fresh milk administration without restriction was associated with a limited number of symptomatic postnatal cytomegalovirus infections. Neonatologists must be aware of this risk to better diagnose and manage the infection. Multicenter studies are required to investigate which preterm infants are most at risk of severe postnatal cytomegalovirus, and to determine the optimal approach to prevention and treatment.

The multidrug resistant NRCS-A clone of Staphylococcus capitis (SC) has spread globally in neonatal intensive care units (NICUs) where it causes neonatal sepsis and colonisation of infants, fomites and staff. Whole genome sequencing (WGS) of international isolates has suggested a putative origin of the clone in Norway, which is closely related to Iceland geopolitically. No data have been available about the NRCS-A clone in Iceland where a case of neonatal sepsis in 2014 suggested its presence for the first time. This study examines the epidemiology of the clone in the single Icelandic NICU over a 12-year period and its relationship to international isolates. The study involved retrospective examination of the occurrence and clinical significance of SC-NRCS-A isolated from blood cultures of infants during 2009 – 2020, and prospective screening for SC among infants, staff and the environment. WGS was done on selected isolates to verify the presence of the SC-NRCS-A clone, examine phylogenetic relationship within the Icelandic isolates, and compare them with an international collection of SC-NRCS-A. SC-NRCS-A was found in blood cultures from 28 infants, of which nine with sepsis, and was a frequent coloniser of infants and diverse fomites. In staff SC-NRCS-A was detected in nares, throat and scalp. WGS of 93 isolates from blood and prospective screening specimens and comparison with international isolates revealed that the Icelandic SC-NRCS-A was distributed into two clusters, one related to Norwegian and the other to Irish SC-NRCS-A isolates. Both clusters contained isolates representing all sample sources. The study demonstrated interpatient transmission, widespread dissemination and persistence of the SC-NRCS-A clone in the Icelandic NICU. The close phylogenetic relationship of Icelandic isolates with those from Norway and Ireland suggests potential import to Iceland by NICU staff or infants receiving medical care in these neighbouring countries at some point before 2009 for the Irish clone and before 2014 for the Norwegian clone.

Background: Staphylococcus haemolyticus (SH) is an opportunistic pathogen associated with nosocomial infections, particularly bacteraemia in neonates. Epidemiological trends and genetic diversity of these infections worldwide are largely unknown. Aim: To investigate an increase in SH vascular catheter-related bacteraemia in neonates and describe the molecular epidemiology in France between 2019 and 2023. Methods: We analysed clinical and microbiological surveillance data from the French national surveillance network for central catheter-related (venous and umbilical) infections between 2019 and 2023. We also performed genomic and phylogenetic analyses of 496 strains isolated both inside (n = 383 from neonates, staff and environmental samples) and outside (n = 113 from adults) the neonatal intensive care unit (NICU) settings. Results: The proportion of SH among the 474 reported cases of nosocomial bacteraemia increased from about 20% to 30% over 5 years, mainly affecting very low birth weight preterm neonates (≤ 1,500 g). The ST29 sequence type (ST) not prevalent in previous studies was predominant, accounting for 74% of NICU strains. ST29 was characterised by phenotypic multidrug resistance to at least six classes of antibiotics (oxacillin, quinolones, gentamicin, cotrimoxazole, clindamycin and rifampicin), which distinguished it with good sensitivity and specificity from other prevalent multidrug-resistant STs identified (ST1 and ST25). ST29 strains more frequently harboured the drfG, vga-LC and mupA genes and a triple point mutation (D471E, I527M and S532N) in the rpoB gene. Conclusions: The present study highlights the success of a highly resistant ST29 lineage in French NICUs mainly affecting very low birth weight premature neonates.

Objectives: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects premature babies and contributes to their morbidity. French BPD guidelines suggest the use of intravenous methylprednisolone pulses (IVMP) for those who require respiratory support (RS) following 36 weeks postmenstrual age (PMA). However, there is scant data on the efficacy and tolerance for this indication. Our objectives were to assess the efficacy and tolerance of IVMP in patients with severe BPD requiring RS. Study and Design: This retrospective observational study included preterm infants (<32 weeks gestational age) treated by IVMP between January 2016 and March 2021, in a single tertiary care hospital. The primary endpoint was signified by changes in the Pulmonary Severity Score (PSS). Our secondary endpoints were changes in RS and the tolerance of IVMP. Results: Data of 14 children with BPD under RS were reviewed. Their median [IQR] gestational age at birth was (26[26–29.5] weeks). After IVMP administration, the PSS did not improve significantly from baseline day 0 (D0) (0.85[0.55–1.15]) to D7 (0.74 [0.48–1.00]) or Month 1 (1.02 [0.57–1.48]). Three children (21%) experienced a decrease in RS in the following month of IVMP. There was no negative short‐term impact on growth. Five infants presented infectious complications. The development quotient was measured in 5 children at 2 years of age. Conclusion: In our study, IVMP did not improve PSS and it was associated with a high number of infections. Other studies are needed to better define the place of IVMP in these infants.

SUMMARY: Staphylococcus capitis is divided into two subspecies, S. capitis subsp. ureolyticus (renamed urealyticus in 1992; ATCC 49326) and S. capitis subsp. capitis (ATCC 27840), and fits with the archetype of clinically relevant coagulase-negative staphylococci (CoNS). S. capitis is a commensal bacterium of the skin in humans, which must be considered an opportunistic pathogen of interest particularly as soon as it is identified in a clinically relevant specimen from an immunocompromised patient. Several studies have highlighted the potential determinants underlying S. capitis pathogenicity, resistance profiles, and virulence factors. In addition, mobile genetic element acquisitions and mutations contribute to S. capitis genome adaptation to its environment. Over the past decades, antibiotic resistance has been identified for S. capitis in almost all the families of the currently available antibiotics and is related to the emergence of multidrug-resistant clones of high clinical significance. The present review summarizes the current knowledge concerning the taxonomic position of S. capitis among staphylococci, the involvement of this species in human colonization and diseases, the virulence factors supporting its pathogenicity, and the phenotypic and genomic antimicrobial resistance profiles of this species.

Low 25-Hydroxyvitamin D (25(OH)D) in preterm infants is a risk factor for bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate a beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and histological alterations in the lung evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120 nmol/L are also a risk factor for BPD or death. This retrospective single-center cohort study included only infants born at p = 0.53). The logistic regression identified weight (OR 0.997, 95% CI [0.995–0.998]) and term (OR 0.737, 95% CI [0.551–0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95% CI [0.503–2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

Low 25 OH vitamin D (25(OH)D) in preterm infants is a risk factor of bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and lung histological alterations evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120nmol/L is also a risk factor for BPD or death. This retrospective single-center cohort study included all infants born <31 weeks gestational age without major malformation with at least a determination of 25(OH)D <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120nmol/L (50.5% vs 43.9%, p=0.53). The logistic regression identified weight (OR 0.997, 95%CI [0.995-0.998]) and term (OR 0.737, 95%CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95%CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.