High-dose intravenous immunoglobulin versus albumin 4% in paediatric toxic shock syndrome: a randomised controlled feasibility study.

PURPOSE: Toxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent efficacy and safety data are needed. Our objective was to determine whether a randomised clinical trial (RCT) assessing intravenous IG in TSS in children is feasible. METHODS: We performed a multicentre, feasibility, double-blind RCT assessing efficacy of high-dose intravenous IG versus albumin 4% (control group) within the first 12 hours of shock onset. Included patients were aged above 1 month and below 18 years with suspected TSS and septic shock. Feasibility was assessed by measuring inclusion rate, protocol compliance and missing data regarding death and the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score. Other secondary clinical outcomes were evaluated during hospital stay, at 60 day and 1 year. RESULTS: 28 patients, admitted in 6 paediatric intensive care units during 36 consecutive months and followed for 1 year, received the allocated treatment: 13 in intravenous IG group, 15 in control group. The median age was 10.6 years and the sex ratio was 1. Inclusion rate was above 50%, protocol deviations were below 30% and missing data regarding death and PELOD-2 Score below 10%. No difference concerning secondary clinical outcomes between groups was observed, and more adverse events were reported in the control group. CONCLUSION: It seems to be feasible to conduct an RCT assessing intravenous IG efficacy and safety in paediatric TSS but must be realised internationally, with choice of a clinically relevant endpoint and a specific design in order to be realistic. TRIAL REGISTRATION NUMBER: NCT02219165.

Neonatal hemodynamics of recipient twins after fetoscopic selective laser coagulation for twin-to-twin transfusion syndrome: An unicist classification.

To characterize the neonatal hemodynamic profiles in recipients born after twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic selective laser coagulation (FSLC). Retrospective analysis during the first month of life of recipient twins. Of the 480 newborns born during an 11-year period, 138 recipient twins with prenatal FSLC were classified into four groups: no hemodynamic impairment (NoHI, n = 102, 74%), isolated high blood pressure (HighBP, n = 18, 13%), right ventricular outflow tract obstruction (RVOTO, n = 10, 7%), and cardiac failure (CF, n = 8, 6%). The time (median (IQR)) between FSLC and birth was significantly shorter in the HighBP (36 days (23-54)) and CF (44 days (18-54)) groups than in the RVOTO (91 days (68-112)) and NoHi (82 days (62-104)) groups (p < 0.001).     Conclusion: Four distinct and well-characterized groups of recipients were identified based on their hemodynamics. High blood pressure and heart failure occurred in approximately 20% of the infants and were associated with a time between laser coagulation and birth of less than 2 months. What is Known: • Twin-to-twin transfusion syndrome (TTTS) is characterized by a hemodynamic imbalance that leads to high fetal and neonatal mortality if left untreated. One-third of recipient twins born without prenatal fetoscopic laser coagulation (FSLC) develop a life-threatening cardiac failure. What is New: • Four distinct groups of recipient twins with prenatal FSLC have been identified based on their hemodynamics. High blood pressure and cardiac failure occurred in 20% of the infants and were associated with an interval between FSLC and birth of less than 2 months.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Surviving Sepsis Campaign Research Priorities 2023.

OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. METHODS: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. RESULTS: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? CONCLUSIONS: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Whole blood no-lyse no-wash micromethod for the quantitative measurement of monocyte HLA-DR.

BACKGROUND: Monocyte (m)HLA-DR expression appears to be a potent marker of immunosuppression in critically ill patients. The persistence of low mHLA-DR expression is associated with an increased risk of nosocomial infections and mortality. To adapt this measurement to pediatric requirements and provide extensive 24/7 access, we have developed a whole blood no-lyse no-wash micromethod (MM) and compared it with the standardized method (SM). METHODS: mHLA-DR was quantified by flow cytometry using Quantibrite™ Anti-HLA-DR PE/Monocyte PerCP-Cy™5.5 with either the SM performed in a diagnostic hematology laboratory using manufacturer protocol, or a whole blood no-lyse no-wash MM using an Attune flow cytometer located in the pediatric ICU. Median fluorescence intensity was measured in both techniques and converted to antibodies per cell (AB/C) calibrated with BD Quantibrite™ PE beads. Blood and Quantibrite™ reagent volume used with the MM was reduced by 5-fold compared to SM. In addition to Quantibrite™ Anti-Human HLA-DR PE/Monocyte PerCP-Cy™5.5, MM required anti-CD45 and anti-CD19 labeling. RESULTS: We determined the expression of mHLA-DR in 34 patients, 20 adults, and 14 children admitted to ICU. Correlation between MM and SM was excellent (Pearson's correlation: y = 0.8192x + 678.7, r = 0.9270, p < 0.0001). The estimated bias was 2467 ± 1.96 × 3307 AB/C; CI 95% [-4016; +8949]. CONCLUSIONS: The no-lyse no-wash whole blood microvolume method for measuring mHLA-DR expression allows for simplified sample preparation without compromising accuracy of the data. This method may simplify immune monitoring of critically ill patient by the deployment of a point of care method.

Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants.

BACKGROUND: The safety of the monoclonal antibody nirsevimab and the effect of nirsevimab on hospitalizations for respiratory syncytial virus (RSV)-associated lower respiratory tract infection when administered in healthy infants are unclear. METHODS: In a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen. RESULTS: A total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P = 0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P = 0.006) in Germany, and 83.4% (adjusted 95% CI, 34.3 to 97.6; multiplicity-adjusted P = 0.003) in the United Kingdom. Treatment-related adverse events occurred in 86 infants (2.1%) in the nirsevimab group. CONCLUSIONS: Nirsevimab protected infants against hospitalization for RSV-associated lower respiratory tract infection and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings. (Funded by Sanofi and AstraZeneca; HARMONIE ClinicalTrials.gov number, NCT05437510).

Blood Purification with oXiris© in Critically Ill Children with Vasoplegic Shock.

INTRODUCTION: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As such, circulating cytokines and danger- and pathogen-associated molecular patterns (such as endotoxins) are recognized as central in the pathogenesis of sepsis and organ dysfunction. Removing these compounds by extracorporeal blood filtration, commonly considered blood purification, may improve the septic patients' condition. This study aimed to assess the vaso-inotropic support evolution over time in pediatric patients with vasoplegic shock treated with oXiris©. METHODS: All patients aged below 18 years admitted at the Paris Saclay University Quaternary Pediatric Intensive Care Unit with vasoplegic shock and acute kidney injury and treated with oXiris© between October 2017 and January 2020 were included. The vaso-inotropic score and the 28-day mortality were assessed. Improvement under treatment was defined as a 50% decrease in the vaso-inotropic score following 24 h of oXiris© therapy. RESULTS: Eleven pediatric patients aged 2-15 years and weighing 11-60 kg were admitted with vasoplegic shock and acute kidney injury. They received thirteen sessions of oXiris© therapy for septic shock (N = 7) and liver failure (N = 6). Eight patients did not improve their condition during the session, and five ultimately died (37.5% survival). Five patients improved, decreasing their inotropic support by >50% in 24 h. Among them, four survived (80%). CONCLUSION: Hemofiltration and extracorporeal blood purification with oXiris© can be used in pediatric patients with vasoplegic shock with rapid improvement in hemodynamics in selected patients.

Ultrasound guided percutaneous catheterization of the brachiocephalic vein by small caliber catheter: An alternative to epicutaneo-caval catheter in newborn and premature infants.

BACKGROUND: Umbilical Venous Catheter (UVC) and Epicutaneo-Caval Catheters (ECC) are reference catheters in the neonatal period. However, many factors such as the corpulence of neonates, poor venous capital, and anatomical variants can complicate ECC insertion or make it impossible. In newborns with failed ECC insertion, we developed an hybrid technique that combines the insertion of a long-lasting silicone or polyurethane small caliber catheter, usually used as a ECC in newborns, with the ease and speed of ultrasound guided puncture of the brachiocephalic vein (BCV). METHODS: Three years retrospective single center experience of ultrasound guided BCV insertion of silicon or polyurethane small caliber central catheter in a tertiary neonatal intensive care in case of insertion fail of ECC. RESULTS: Twenty-one echo guided BCV-ECC insertions were performed in 20 newborns. Median age was 16 days (range: 0-110 days), median weight was 1700 g (range: 605-4960 g) at insertion. In most cases, insertion was on the left side (17/21). No failures were noted. Only one attempt was necessary in all cases. Insertion time, when noted, was always of <45 min. The median duration of use of these catheters was 11 days (range 3-35 days). No complication was noted during insertion or catheter use, including catheter-related infections and thrombosis. CONCLUSION: Echo guided percutaneous catheterization of the brachiocephalic vein with a long lasting silicone or polyurethane small caliber catheter is a safe alternative to the ECC if insertion has failed. However, it requires a mastery of ultrasound-guided insertion technique in term and premature neonates.

Preventing Respiratory Syncytial Virus in Children in France: A Narrative Review of the Importance of a Reinforced Partnership Between Parents, Healthcare Professionals, and Public Health Authorities.

The highly contagious respiratory syncytial virus (RSV) is responsible for up to approximately 50,000 hospitalisations during each RSV season in children aged under 5 years in France, with the burden greatest in infants younger than 1 year who were born at term. There is a need for a strategy to universally protect young children from RSV infection, and thereby reduce the pressure that RSV places every year on RSV-infected children, their parents, and French healthcare systems. Potential strategies currently undergoing clinical investigation include passive immunisation via maternal vaccination or administration of long-acting monoclonal antibodies at or soon after birth, followed by vaccination later in infancy or childhood. An ongoing partnership and collaboration between parents, public health authorities, and frontline primary healthcare will need to be reinforced once these new RSV prevention strategies are available, to facilitate their use and ensure that all children receive adequate protection from the start of their first RSV season.

Prospective multicentre study of host response signatures in neonatal sepsis in Sub Saharan Africa.

Few biomarkers for sepsis diagnosis are commonly used in neonatal sepsis. While the role of host response is increasingly recognized in sepsis pathogenesis and prognosis, there is a need for evaluating new biomarkers targeting host response in regions where sepsis burden is high and medico-economic resources are scarce. The objective of the study is to evaluate diagnostic and prognostic accuracy of biomarkers of neonatal sepsis in Sub Saharan Africa. This prospective multicentre study included newborn infants delivered in the Abomey-Calavi region in South Benin and their follow-up from birth to 3 months of age. Accuracy of transcriptional (CD74, CX3CR1), proteic (PCT, IL-6, IL-10, IP-10) biomarkers and clinical characteristics to diagnose and prognose neonatal sepsis were measured. At delivery, cord blood from all consecutive newborns were sampled and analysed, and infants were followed for a 12 weeks' period. Five hundred and eighty-one newborns were enrolled. One hundred and seventy-two newborns developed neonatal sepsis (29.6%) and death occurred in forty-nine infants (8.4%). Although PCT, IL-6 and IP-10 levels were independently associated with sepsis diagnosis, diagnostic accuracy of clinical variables combinations was similar to combinations with biomarkers and superior to biomarkers alone. Nonetheless, CD74, being the only biomarkers independently associated with mortality, showed elevated prognosis accuracy (AUC > 0.9) either alone or in combination with other biomarkers (eg. CD74/IP-10) or clinical criterion (eg. Apgar 1, birth weight). These results suggest that cord blood PCT had a low accuracy for diagnosing early onset neonatal sepsis in Sub Saharan African neonates, while association of clinical criterion showed to be more accurate than any biomarkers taken independently. At birth, CD74, either associated with IP-10 or clinical criterion, had the best accuracy in prognosing sepsis mortality.Trial registration Clinicaltrial.gov registration number: NCT03780712. Registered 19 December 2018. Retrospectively registered.

Neonatal Hemodynamic Characteristics of the Recipient Twin of Twin-To-Twin Transfusion Syndrome Not Treated with Fetoscopic Laser Surgery.

Background: This paper's intent is to describe the neonatal hemodynamic characteristics of recipient twins of monochorionic pregnancies complicated with twin-to-twin transfusion syndrome (TTTS), born without prenatal fetoscopic selective laser coagulation (FSLC). Methods: Retrospective analysis of hemodynamic characteristics was performed during the first five days of life of recipient twins from untreated TTTS. Results: Forty-two recipient twins were included and divided into three groups: no hemodynamic impairment (NoHI) (n = 15, 36%), isolated high blood pressure (HighBP) (n = 12, 28%), and cardiac failure group (CF) (n = 15, 36%). Patients of both CF and HighBP groups had high systolic blood pressure during the first 12 h of life and ventricular hypertrophy at early echocardiography. Cardiac failure occurred at a median age of 14 h (IQR = 6−24) and was followed by a drop in systolic and diastolic blood pressure. Acute kidney injury was more frequent (93% vs. 25%, p < 0.001) and severe (p <0.001) in the CF group than in the HighBP group. The mortality rate in the CF group was 40%. Factors associated with CF were twin anemia-polycythemia sequence (p = 0.012), very preterm birth (p = 0.040), and polycythemia (p = 0.002). Conclusion: One-third of recipient twins born without prenatal FSLC developed life-threatening cardiac failure during the first 24 h of life.

CIITA promoter polymorphism impairs monocytes HLA-DR expression in patients with septic shock.

Low monocyte (m)HLA-DR expression is associated with mortality in sepsis. G-286A∗rs3087456 polymorphism in promoter III of HLA class II transactivator (CIITA), the master regulator of HLA, has been associated with autoimmune diseases but its role in sepsis has never been demonstrated. In 203 patients in septic shock, GG genotype was associated with 28-day mortality and mHLA-DR remained low whereas it increased in patients with AA or AG genotype. In ex vivo cells, mHLA-DR failed to augment in GG in comparison with AG or AA genotype on exposure to IFN-γ. Promoter III transcript levels were similar in control monocytes regardless of genotype and exposure to IFN-γ. Promoter III activity was decreased in GG genotype in monocyte cell line but restored after stimulation with IFN-γ. Hereby, we demonstrated that G-286A∗rs3087456 significantly impact mHLA-DR expression in patients with septic shock in part through CIITA promoter III activity, that can be rescued using IFN-γ.

Multi-organ failure caused by lasagnas: A case report of Bacillus cereus food poisoning.

We report a Bacillus cereus, cereulide producing strain, food poisoning of two sisters. After eating a few bites of pasta cooked 3 days earlier, a 13-year-old girl developed mild symptoms. However, her 11-year-old sister suffered, 40 h after ingestion of the entire platter, a multi-organ failure including acute liver failure, rhabdomyolysis, disseminated intravascular coagulation, and acute kidney injury (AKI). She received supportive care in pediatric intensive care using mechanical ventilation, hemofiltration, and high-doses vasopressors. She was specifically treated for toxin-mediated disease using blood purification and further digestive decontamination. This report highlights the potential severity of B. cereus food poisoning but also a successful dual treatment including toxin removal and antimicrobial treatment to prevent toxin production.

Anakinra in pediatric acute fulminant myocarditis.

BACKGROUND: Acute fulminant myocarditis in children is associated with elevated mortality and morbidity with few advances in its medical management. Here we report a preliminary experience of children treated with IL-1 receptor antagonist associated with rapid myocardial function recovery. METHODS: A retrospective case series of children admitted in the Pediatric Intensive Care Unit of the Bicêtre Hospital (AP-HP Paris Saclay University) between April 2020 and January 2022 with acute myocarditis. Children were treated with subcutaneous anakinra (an IL-1 receptor antagonist). Patients characteristics, and outcome are reported. RESULTS: Of 10 children admitted with acute fulminant myocarditis, eight were treated with sub-cutaneous anakinra. Seven children had SARS-CoV-2 post-infective myocarditis associated with multisystem inflammatory syndrome in children (MIS-C) and one child Parvovirus B19 myocarditis. In all patients a rapid (< 24 h) improvement in myocardial function was observed with concomitant decrease in myocardial enzymes. All patients survived with full myocardial recovery. CONCLUSIONS: In this pilot study, use of IL-1 receptor antagonist in the initial treatment of acute fulminant myocarditis in children seems to be associated with rapid stabilization and recovery.

Contaminated Incubators: Source of a Multispecies Enterobacter Outbreak of Neonatal Sepsis.

The genus Enterobacter includes species responsible for nosocomial outbreaks in fragile patients, especially in neonatal intensive care units (NICUs). Determining the primary source of infection is critical to outbreak management and patient outcomes. In this investigation, we report the management and control measures implemented during an Enterobacter outbreak of bloodstream infections in premature babies. The study was conducted in a French NICU over a 3-year period (2016 to 2018) and included 20 premature infants with bacteremia. The clinical and microbiological characteristics were identified, and whole-genome sequencing (WGS) was performed on bacteremia isolates. Initially, several outbreak containment strategies were carried out with no success. Next, outbreak investigation pinpointed the neonatal incubators as the primary reservoir and source of contamination in this outbreak. A new sampling methodology during "on" or "in use" conditions enabled its identification, which led to their replacement, thus resulting in the containment of the outbreak. WGS analysis showed a multiclonal outbreak. Some clones were identified in different isolation sources, including patients and neonatal incubators. In addition, microbiological results showed a multispecies outbreak with a high prevalence of Enterobacter bugandensis and Enterobacter xiangfangensis. We conclude that the NICU health care environment represents an important reservoir for Enterobacter transmission and infection. Finally, extracting samples from the neonatal incubator during active use conditions improves the recovery of bacteria from contaminated equipment. This method should be used more frequently to achieve better monitoring of the NICU for HAIs prevention. IMPORTANCE Neonatal incubators in the NICU can be an important reservoir of pathogens responsible for life-threatening outbreaks in neonatal patients. Traditional disinfection with antiseptics is not sufficient to eradicate the microorganisms that can persist for long periods in the different reservoirs. Identification and elimination of the reservoirs are crucial for outbreak prevention and control. In our investigation, using a new strategy of microbiological screening of neonatal incubators, we demonstrated that these were the primary source of contamination. After their replacement, the outbreak was controlled. This new methodology was effective in containing this outbreak and could be a viable alternative for infection prevention and control in outbreak situations involving incubators as a reservoir.

Epidemiology of Neonatal Acute Respiratory Distress Syndrome: Prospective, Multicenter, International Cohort Study.

OBJECTIVES: Age-specific definitions for acute respiratory distress syndrome (ARDS) are available, including a specific definition for neonates (the "Montreux definition"). The epidemiology of neonatal ARDS is unknown. The objective of this study was to describe the epidemiology, clinical course, treatment, and outcomes of neonatal ARDS. DESIGN: Prospective, international, observational, cohort study. SETTING: Fifteen academic neonatal ICUs. PATIENTS: Consecutive sample of neonates of any gestational age admitted to participating sites who met the neonatal ARDS Montreux definition criteria. MEASUREMENTS AND MAIN RESULTS: Neonatal ARDS was classified as direct or indirect, infectious or noninfectious, and perinatal (≤ 72 hr after birth) or late in onset. Primary outcomes were: 1) survival at 30 days from diagnosis, 2) inhospital survival, and 3) extracorporeal membrane oxygenation (ECMO)-free survival at 30 days from diagnosis. Secondary outcomes included respiratory complications and common neonatal extrapulmonary morbidities. A total of 239 neonates met criteria for the diagnosis of neonatal ARDS. The median prevalence was 1.5% of neonatal ICU admissions with male/female ratio of 1.5. Respiratory treatments were similar across gestational ages. Direct neonatal ARDS (51.5% of neonates) was more common in term neonates and the perinatal period. Indirect neonatal ARDS was often triggered by an infection and was more common in preterm neonates. Thirty-day, inhospital, and 30-day ECMO-free survival were 83.3%, 76.2%, and 79.5%, respectively. Direct neonatal ARDS was associated with better survival outcomes than indirect neonatal ARDS. Direct and noninfectious neonatal ARDS were associated with the poorest respiratory outcomes at 36 and 40 weeks' postmenstrual age. Gestational age was not associated with any primary outcome on multivariate analyses. CONCLUSIONS: Prevalence and survival of neonatal ARDS are similar to those of pediatric ARDS. The neonatal ARDS subtypes used in the current definition may be associated with distinct clinical outcomes and a different distribution for term and preterm neonates.

The Current and Future State of Pediatric Sepsis Definitions: An International Survey.

BACKGROUND AND OBJECTIVES: Definitions for pediatric sepsis were established in 2005 without data-driven criteria. It is unknown whether the more recent adult Sepsis-3 definitions meet the needs of providers caring for children. We aimed to explore the use and applicability of criteria to diagnose sepsis and septic shock in children across the world. METHODS: This is an international electronic survey of clinicians distributed across international and national societies representing pediatric intensive care, emergency medicine, pediatrics, and pediatric infectious diseases. Respondents stated their preferences on a 5-point Likert scale. RESULTS: There were 2835 survey responses analyzed, of which 48% originated from upper-middle income countries, followed by high income countries (38%) and low or lower-middle income countries (14%). Abnormal vital signs, laboratory evidence of inflammation, and microbiologic diagnoses were the criteria most used for the diagnosis of "sepsis." The 2005 consensus definitions were perceived to be the most useful for sepsis recognition, while Sepsis-3 definitions were stated as more useful for benchmarking, disease classification, enrollment into trials, and prognostication. The World Health Organization definitions were perceived as least useful across all domains. Seventy one percent of respondents agreed that the term sepsis should be restricted to children with infection-associated organ dysfunction. CONCLUSIONS: Clinicians around the world apply a myriad of signs, symptoms, laboratory studies, and treatment factors when diagnosing sepsis. The concept of sepsis as infection with associated organ dysfunction is broadly supported. Currently available sepsis definitions fall short of the perceived needs. Future diagnostic algorithms should be pragmatic and sensitive to the clinical settings.