Enterobacter cloacae complex outbreak in a neonatal intensive care unit: multifaceted investigations and preventive measures are needed.

We report the investigation to control an Enterobacter cloacae complex outbreak in a neonatal intensive care unit from November 2020 to February 2021. Pulsed-field gel electrophoresis showed that five of eight cases were infected with a clonal strain. Breast pumps, shared among mothers in the unit, could have contributed to the spread of the clonal spread.

[Suboptimal care and severe bacterial infection in the French Caribbean area]. / Soins sub-optimaux et infections bactériennes sévères communautaires aux Antilles françaises.

OBJECTIVE: To study the frequency and types of suboptimal care in initial management of children suffering from a severe bacterial infection (SBI), in a French region where little is known about pediatric SBI epidemiology. METHOD: Retrospective single-center study over a 6-year period. Children between 3 months and 15 years of age, deceased or surviving and admitted to the pediatric intensive care unit of the university-affiliated hospital of Martinique for a community-onset SBI were included in this study. The optimality of the medical care before admission to the pediatric intensive care unit was assessed in a blinded fashion by two independent experts. RESULTS: Twenty-nine of the 30 children suffering from SBI could be analyzed. The median age was 3.7 years (IQR: 1.7-10.4); the mortality rate was 14 % (95 % CI: 1-27 %). Most frequently infections were pulmonary infections (48 %; 95 % CI: 29-67 %), followed by septic shock (44 %; 95 % CI: 25-63 %). Microbiological cultures were positive in 55 % (95 % CI, 36-74 %) (n=16) of the cases, with five pneumococcus and four Streptococcus pyogenes. Of the 29 children included in the study, 72 % (95 % CI: 55-89 %) (n=21) had received at least one episode of suboptimal care. Suboptimal care comprised delay in diagnosis (identification of serious symptoms) in 65 % (95 % CI: 47-83 %), a delay in seeking care in 41 % (95 % CI: 22-60 %), and a delay in the initiation of antibiotics or hemodynamic support in 45 % (95 % CI: 26-64 %) and 38 % (95 % CI: 20-56 %) of the cases, respectively. CONCLUSION: Suboptimal care was frequent in the initial management of SBI, particularly because of a delay in seeking care and the failure of physicians to recognize early signs of SBI. A large public information campaign, focusing on healthcare accessibility and better education of physicians in the early recognition of SBIs are means of improvement that need to be explored.

[Evaluating a child after a febrile seizure: Insights on three important issues]. / Évaluation d'un enfant après une crise fébrile : focus sur trois problèmes de pratique clinique.

Febrile seizures (FS) are the most common seizures seen in the paediatric population in the out-of-hospital and emergency department settings, and they account for the majority of seizures seen in children younger than 5 years old. An FS is a seizure accompanied by fever, without central nervous system infection, occurring in children between 6 months and 5 years old. Five criteria have been used and taught to classify any FS as simple or complex FS. These factors do not bear the same significance for clinical practice, in particular, the decision to perform a lumbar puncture for cerebrospinal fluid analysis to rule out an intracranial infection. Moreover, epidemiological studies have illustrated that some factors are predictive of febrile seizure recurrence while others are predictive of epilepsy occurrence. On this basis, a workshop was organized to provide an answer to three clinical practice questions: when should a lumbar puncture be performed in a child who has experienced a seizure during a fever episode, is the prescription of a rescue drug required with a risk of a prolonged febrile seizure recurrence, when should a neurological consultation be requested (risk of later epilepsy)? Based on a review of the literature and on a 1-day workshop, we report here the conclusion of the working group. A lumbar puncture is required in any child with meningitis symptoms or septic signs or behaviour disturbance. A lumbar puncture should be discussed based on the clinical symptoms and their progression over time when a child has experienced a focal FS or repetitive FSs without signs of meningitis or sepsis or behaviour disturbance. The lumbar puncture is not necessary in case of simple FS without signs of meningitis, including in infants between 6 and 12 months old. An early clinical evaluation (at least 4 h after the first clinical assessment) could be helpful, in particular in infants younger than 12 months of age. A rescue drug might be prescribed when there is a high risk of prolonged FS (i.e., risk higher than 20%): age at FS<12months OR a history of a previous febrile status epilepticus OR if the first FS was a focal seizure OR abnormal development/neurological exam/MRI OR a family history of nonfebrile seizure. A neurological consultation should be requested for any child who has experienced a prolonged FS before the age of 1 year, for children who have experienced prolonged and focal FS or repetitive (within 24h) focal FS, for children who have experienced multiple complex (focal or prolonged or repetitive) FS, for children with an abnormal neurological exam or abnormal development experiencing a FS. Although childhood febrile seizures in most cases are benign, witnessing such seizures is always a terrifying experience for the child's parents. Most parents feel that their child is dying or could have severe brain injury related to the episode. Therefore, the group also suggests a post-FS visit with the primary care physician.

[Management of sudden unexpected infant death syndrome (SUIDS) in reference centers in France in 2013]. / Prise en charge des morts inattendues du nourrisson par les centres de référence français : état des lieux des pratiques en 2013.

In France, nearly 500 infants still die unexpectedly every year. In 2009, the French Institute for Public Health Surveillance published a survey showing great heterogeneity in the management of sudden unexpected infant death (SUID) cases. The aim of this study was to evaluate the actual diagnostic approach to SUID in the different reference centers in France and to determine the degree to which the 2007 recommendations of the French National Authority for Health (Haute Autorité de santé [HAS]) are applied. We conducted a multicenter cross-sectional epidemiological study by email sent to the 36 SIDS reference centers with questions on examinations usually performed in SIDS cases. We also submitted six SUID test cases for death classification to the different reference physicians. Twenty-nine of 36 centers (80.5%) responded. Among the recommended tests, only blood cultures, analysis of cerebrospinal fluid, and a proposal to autopsy are done in 100% of the centers. Other investigations are not carried out systematically: skeleton radiography (65.5%), cranial CT scan (58%), eye fundus (20.7%), metabolic analysis (65.5%), and blood toxicology (62%). The main reasons for non-completion of these tests were hospital practices, lack of resources, technical difficulties, cost of tests, and difficulty in interpreting results (50% reported not knowing the postmortem biological standards). None of the institutions apply the HAS recommendations entirely. The classification of causes-of-death test cases also varied between the centers, with a maximum of 62% concordance in their responses. In 2013, in France, there is still substantial heterogeneity in the diagnostic set-up of SUIDS, a non-exhaustive implementation of the recommendations of the French National Authority for Health, and an unsatisfactory SUIDS classification tool because of considerable discordance between physicians. These results explain the current difficulties in obtaining reliable epidemiological data, because many teams do not use all the investigations recommended to find the cause of death. Therefore, the establishment of a national registry would provide accurate and up-to-date epidemiological, environmental, medical, and biological data to identify the events causing death and propose appropriate means of prevention.

[New recommendations for the management of children after minor head trauma]. / Actualisation des recommandations pour la prise en charge du traumatisme crânien léger chez l'enfant.

Minor head trauma is a common cause for pediatric emergency department visits. In 2009, the Pediatric Emergency Care Applied Research Network (PECARN) published a clinical prediction rule for identifying children at very low risk of clinically important traumatic brain injuries (ciTBI) and for reducing CT use because of malignancy induced by ionizing radiation. The prediction rule for ciTBI was derived and validated on 42,412 children in a prospective cohort study. The Société Française de Médecine d'Urgence (French Emergency Medicine Society) and the Groupe Francophone de Réanimation et Urgences Pédiatriques (French-Language Pediatric Emergency Care Group) recommend this algorithm for the management of children after minor head trauma. Based on clinical variables (history, symptoms, and physical examination findings), the algorithm assists in medical decision-making: CT scan, hospitalization for observation or discharge, according to three levels of ciTBI risk (high, intermediate, or low risk). The prediction rule sensitivity for children younger than 2 years is 100 % [86.3-100] and for those aged 2 years and older it is 96.8 % [89-99.6]. Our aim is to present these new recommendations for the management of children after minor head trauma.

Lower risk of atopic dermatitis among infants born extremely preterm compared with higher gestational age.

BACKGROUND: It is not yet known whether the risk of developing atopic dermatitis (AD) is influenced by preterm birth. Moreover, AD risk has not been assessed in a large sample of extremely preterm infants (< 29 weeks' gestation). OBJECTIVES: To determine whether the risk of AD is influenced by preterm birth. METHODS: We investigated the relationship between gestational age (GA) and AD using data from two independent population-based cohorts, including a total of 2329 preterm infants, of whom 479 were born extremely preterm. RESULTS: There was a lower percentage of children with AD in the extremely preterm group compared with those born at a greater GA (Epipage cohort, 2-year outcome: 13·3% for 24-28 weeks, 17·6% for 29-32 weeks, 21·8% for 33-34 weeks, P = 0·02; LIFT cohort, 5-year outcome: 11% for 24-28 weeks, 21·5% for 29-32 weeks, 19·6% for 33-34 weeks, P = 0·11). After adjusting for confounding variables, a lower GA (< 29 weeks) was significantly associated with decreased risk of AD in the Epipage cohort [adjusted odds ratio (aOR) 0·57, 95% confidence interval (CI) 0·37-0·87; P = 0·009] and the LIFT cohort (aOR 0·41, 95% CI 0·18-0·90; P = 0·03). CONCLUSIONS: Very low GA (< 29 weeks) was associated with a lower risk of AD compared with higher GA (29-34 weeks) and full-term birth.

Antenatal phosphodiesterase 4 inhibition restores postnatal growth and pulmonary development in a model of chorioamnionitis in rabbits.

Chorioamnionitis is implicated in the pathophysiology of bronchopulmonary disease, and the associated inflammatory response is responsible for adverse effects on alveolar development. The aim of this work was to analyze the effects of a phosphodiesterase 4 (PDE4)-selective inhibitor, rolipram (a modulator of the inflammatory response), in an experimental model of chorioamnionitis on pulmonary development and on the processes of infection and inflammation. Rabbit mothers were assigned to four groups: 1) saline serum inoculation (controls); 2) Escherichia coli intrauterine inoculation (C+); 3) rolipram infusion (R+); and 4) E. coli inoculation + rolipram infusion (C+R+). High rates of morbility and mortality were noticed in mothers and pups (5 of 13 pregnant rabbits in groups with rolipram). Alveolar development, inflammation, and infection were analyzed in pups at day 0 and day 5. At day 0, in the context of chorioamnionitis, rolipram significantly decreased birth weight (p < 0.01) relative to that of controls (p < 0.05). At day 5, weight normalized in group C+R+ but not in group C+ relative to controls (p < 0.001); moreover, alveolar airspace volume was preserved in group C+R+ but not in group C+ (p < 0.05). Interstitial volume decreased in group C+ versus controls (p < 0.05) but was preserved in group C+R+. Specific alveolar area was not significantly modified by rolipram. No significant difference was found concerning bronchoalveolar lavage cellularity, and all blood cultures remained sterile. In this model of impaired alveologenesis, rolipram significantly preserved specific alveolar density. However, PDE4 inhibition induced antenatal fetal demise and growth retardation.

[Premature rupture of membranes before 32 weeks of gestation: prenatal prognosis factors]. / Rupture prématurée des membranes avant 32 semaines d'aménorrhée: facteurs pronostiques prénatals.

OBJECTIVE: Premature preterm rupture of membranes (PPROM) accounts for a significant part of overall perinatal mortality and morbidity. This study aims to define potential prognostic factors for neonatal outcome. PATIENTS AND METHODS: One hundred and thirty-one pregnancies complicated with PPROM at between 26 and 32 weeks were retrospectively reviewed over a three-year period. The influence of chorioamnionitis on perinatal morbidity and mortality was assessed using a composite outcome. RESULTS: On admission, gestational age (GA) at diagnosis, fetal heart rate anomalies and increasing severity of clinical features of chorioamnionitis were significantly related with an adverse outcome. Significant factors associated with a favourable outcome were an administration of steroids for lung maturation, prophylactic antibiotics and tocolytic therapies. Stratifying according to GA at PPROM, the survival rates were 43 and 52% at before 22 weeks and between 22 and 26 weeks respectively. The prognosis dramatically improved after 26 weeks with an 84.6% rate of survival without impairment. Although this rate reached 97.5% after 30 weeks, there was no statistical evidence supporting any benefit to prolong pregnancies beyond this point. The complete expression of chorioamnionitis independently increased the mortality rate by 41% (OR=1.41; 95% CI [0.99-2.01]. Overall, the most relevant factor was GA at delivery, levelling the prognostic value of GA at diagnosis. DISCUSSION AND CONCLUSION: If no consensus rules PPROM at the moment, the most efficient prognosis factor before 34 weeks is mostly determined by GA at delivery.

Patterns of cerebral inflammatory response in a rabbit model of intrauterine infection-mediated brain lesion.

Although the fetal inflammatory response syndrome seems crucial to the association between intrauterine infection and white matter disease in human preterm infants, the underlying mechanisms remain unclear. Using our previously described rabbit model of cerebral cell death in the white matter and hippocampus induced by intrauterine Escherichia coli infection, we investigated inflammatory and astroglial responses in placenta and brain tissues, in correlation with cell death distribution. Brains and placentas were studied 12, 24, or 48 h following intrauterine inoculation of E. coli or saline (groups G12, G24, and G48). Diffuse monocyte-macrophage infiltrates positive for inducible nitric oxide synthase (i-NOS) were significantly more marked in G24 and G48 placentas than in controls. In the G48 fetuses with both diffuse cell death and focal periventricular white matter cysts mimicking cystic periventricular leukomalacia, a strong rabbit macrophage and inducible nitric oxide synthase immunostaining was observed at the border of these cystic lesions. In contrast, in the fetuses with only diffuse and significant cell death, no inflammatory or astroglial responses were detected in the white matter or hippocampus. Cell death was accompanied by i-NOS immunostaining in the hippocampus but not the white matter. Hippocampal cells positive for i-NOS usually displayed a neuronal phenotype. In this model, focal white matter cysts are accompanied by a robust inflammatory response, and diffuse cell death, which may mimic the white matter and hippocampal damage seen in very and extremely pre-term infants, occur in the absence of a detectable brain inflammatory response.

Effect of maternal antibiotic treatment on fetal periventricular white matter cell death in a rabbit intrauterine infection model.

AIM: To evaluate the effects of maternal antibiotic treatment on fetal brain cell death in a rabbit intrauterine infection model. METHODS: After Escherichia coli uterine-horn inoculation in 22 pregnant rabbits, followed at various times by ceftriaxone and caesarean section, cell death in white matter (histology and fragmented DNA staining) from fetuses killed at extraction was compared across groups using the Mantel-Haenszel test and Fisher's exact test for small numbers. RESULTS: White matter cell death was consistently present at 48 h, with ceftriaxone initiation at 24 h (group 1), detectable at 84 but not 60 h, with ceftriaxone initiation at 12 h, and significantly reduced at 84 h with ceftriaxone initiation at 6 h (60% vs 100% in group 1, p < 0.001, Fisher's exact test). CONCLUSION: Early maternal antibiotic therapy delays white matter cell death in rabbit fetuses exposed to intrauterine infection. This may provide a window for preventing white matter damage.

Intrauterine infection induces programmed cell death in rabbit periventricular white matter.

An association between chorioamnionitis and periventricular leukomalacia has been reported in human preterm infants. However, whether this link is causal has not been convincingly established, and the underlying molecular mechanisms remain unclear. The objective of this study was to establish a reproducible model of cerebral white matter disease in preterm rabbits after intrauterine infection. Escherichia coli was inoculated into both uterine horns of laparotomized pregnant rabbits when gestation was 80% complete. The fetuses were delivered by cesarean section and killed 12, 24, or 48 h after the inoculation. Programmed cell death in the white matter was evaluated by hematoxylin-eosin-saffron staining and in situ fragmented DNA labeling (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). In a first group of 14 pregnant rabbits not treated with antibiotics, all fetuses delivered 48 h after inoculation were stillborn, whereas fetuses extracted 12 or 24 h after inoculation were alive. No significant cell death was detected in the live fetuses compared with the control noninfected rabbits. In a second group of five pregnant rabbits treated with ceftriaxone initiated 24 h after the inoculation and continued until cesarean section was performed 48 h after inoculation, 13 fetuses were alive, but all showed evidence of extensive programmed cell death in the white matter by hematoxylin-eosin-saffron staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. White matter damage became histologically detectable only 48 h after inoculation. Three of the 13 brains displayed periventricular white matter cysts mimicking human cystic periventricular leukomalacia. The high reproducibility of white matter damage in our model should permit further studies aimed at unraveling the molecular mechanisms of periventricular leukomalacia.