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.

Procalcitonin is a prognosis biomarker in very preterm neonates with late onset sepsis: a pilot study.

Neonatal sepsis contributes substantially to neonatal morbidity and mortality. Procalcitonin (PCT) is a recognized biomarker for the diagnosis of late-onset neonatal sepsis (LONS); however, little is known about the prognosis value of PCT in LONS. This study aims at assessing PCT value as a prognosis biomarker in preterm infants with LONS. Retrospective single center observational cohort study. All premature infants (less than 32 weeks of gestational age) with LONS admitted in a tertiary neonatal intensive care unit. Among the 59 preterm infants included in the analysis, 48 survived (81.4%, 48/59). Deceased patients had a significantly lower postmenstrual age (30 [29-32] vs. 28 [27-30], p = 0.025) and weight (1072 [850-1320] vs. 820 [730-1065], p = 0.016) at the time of LONS diagnosis. Although PCT values were not different between both groups at the time of LONS diagnosis, it was more elevated during the first 24 h in deceased patients (12 [1.1-20.3] vs. 1.57 [0.6-4.1], p = 0.041). Accuracy of PCT for predicting 60-day mortality in preterm neonates with LONS ranged from 0.70 to 0.82 of area under the curve on receiver operating characteristic curves. Optimal PCT cut-off values at LONS diagnosis was 8.92 µg/L, 15.75 µg/L for PCT values during the first 24 h, and 6.74 µg/L between 24 and 48 h after diagnosis. The estimated survival probability at day 60 was above 95% for patient with a PCT value at sepsis diagnosis under 8.92 µg/L and less than 45% if higher (p < 0.0001). CONCLUSION: A PCT value > 8.92 µg/L obtained at LONS diagnosis suspicion seems to be a good prognosis biomarker. WHAT IS KNOWN: •Procalcitonin (PCT) is a recognized biomarker of 28-day mortality in critically ill adults with septic shock and trauma. •Failure to have decreased in PCT in the first days of critical care is associated with increased mortality. WHAT IS NEW: •Hereby, we show that PCT has a prognosis value in premature infants with late-onset neonatal sepsis. •Procalcitonin value > 8.92 µg/L at LONS diagnosis is associated with an increase at 60-day mortality.

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.

dnaJ: a New Approach to Identify Species within the Genus Enterobacter.

The taxonomy of the genus Enterobacter can be confusing and has been considerably revised in recent years. We propose a PCR and amplicon sequencing technique based on a partial sequence of the dnaJ gene for species assignment consistent with DNA-DNA digital hybridization (dDDH) and pairwise average nucleotide identity (ANI). We performed a validation of the method by comparing the type strains of each species, sequences obtained from the GenBank database, and clinical specimens. Our results show that the polymorphism of the target sequence of dnaJ allows the identification of species. Using this gene, we assigned the species to 100 strains deposited in the GenBank database that were consistent with the species assignment by dDDH and ANI. The analysis showed that using the partial dnaJ sequence is congruent with WGS as far as correct identification of Enterobacter species is concerned. Finally, we applied our dnaJ method on a national collection of 68 strains identified as Enterobacter isolated from the blood cultures of premature babies using an algorithm based on a type-strain library and the SeqScape software. For the first time, we identified Enterobacter quasihormaechei in blood cultures from four neonatal sepsis cases. We also noticed a higher prevalence of E. bugandensis (36.3%; 32/88) and E. xiangfangensis (46.5%; 41/88). E. bugandensis is a novel species recently described specifically in instances of neonatal sepsis. In conclusion, sequencing a part of the dnaJ gene could be a quick, more economical, and highly discriminating method of identifying Enterobacter species in clinical practice and research. IMPORTANCE We propose a new approach for Enterobacter species identification based on the diversity of the gene encoding the heat shock protein DnaJ. This new tool can be easily implemented in clinical laboratories in addition to identification by MALDI-TOF.

Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study.

BACKGROUND: De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit. METHODS: Retrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression. RESULTS: Out of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5-7 and 8-10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression. CONCLUSIONS: Myeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.

Presence of 2-hydroxymyristate on endotoxins is associated with death in neonates with Enterobacter cloacae complex septic shock.

Enterobacter cloacae complex species are involved in infections among critically ill patients. After a recent E.cloacae outbreak of fulminant neonatal septic shock, we conducted a study to determine whether septic shock severity and its lethal consequence are related to structural features of the endotoxin (lipopolysaccharide [LPS]) of the strains isolated from hospitalized infants and more specifically its lipid A region. It appeared that the LPSs are very heterogeneous, carrying fifteen different molecular species of lipid A. The virulence was correlated with a structural feature identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and gas chromatography coupled with mass spectrometry: the presence of 2-hydroxymyristic acid as a secondary substituent in lipid A. This is the first published evidence linking LPS structural moiety to neonatal sepsis outcome and opens the possibility of using this fatty acid marker as a detection tool for high-risk patients, which could help reduce their mortality.

Impact of early protein and energy intakes on neurodevelopment at 2 years of corrected age in very low birth weight infants: A single-center observational study.

INTRODUCTION: Aggressive nutritional strategy, particularly enhancing early provision of energy and protein, has appeared to reduce postnatal growth failure and improve later developmental outcomes. But the amount of macronutrients required remains unclear. The aim of this study was to investigate the impact of protein and energy intakes during the first two weeks after birth on neurodevelopmental outcomes. METHODS: This retrospective cohort study of very low birth weight infants born between January 2012 and December 2015 was conducted at one tertiary neonatal intensive care unit. The primary outcome was a neurodevelopmental impairment (NDI) at 2 years corrected age defined by a cerebral palsy or a 24 month Ages and Stages Questionnaires score on any of the five domains lower than 2 standard deviation below the mean score. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders. RESULTS: Among 245 (73%) infants discharged home alive, 159 (65%) had follow-up at 2 years. Infants with NDI (55/159, 35%) were more likely male gender (67.3% versus 46.2%, P = 0.02) and experienced more patent ductus arteriosus (PDA) ligation (20% versus 5.8%, P = 0.01) than control. After adjusting for confounders, first-week protein intake (OR: 2.27 [CI: 1.07-5.14]; P < 0.05), second-week non-protein energy intake (OR: 1.03 [CI: 1.01-1.05]; P < 0.01) and PDA ligation (OR: 6.81 [1.80-28.46]; P < 0.01) had significant independent association with higher likelihood of NDI at 2 years. CONCLUSION: Providing nutrition above the optimal level may not be beneficial and may even be harmful. These results confirm the recent recommendation to decrease amino acid intakes published in the latest ESPGHAN guidelines.