Markers of NETosis Do Not Predict Neonatal Early Onset Sepsis: A Pilot Study (original) (raw)

Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis

Critical Care

Background: Neutrophil extracellular traps (NETs) are innate defense mechanisms that are also implicated in the pathogenesis of organ dysfunction. However, the role of NETs in pediatric sepsis is unknown. Methods: Infant (2 weeks old) and adult (6 weeks old) mice were submitted to sepsis by intraperitoneal (i.p.) injection of bacteria suspension or lipopolysaccharide (LPS). Neutrophil infiltration, bacteremia, organ injury, and concentrations of cytokine, NETs, and DNase in the plasma were measured. Production of reactive oxygen and nitrogen species and release of NETs by neutrophils were also evaluated. To investigate the functional role of NETs, mice undergoing sepsis were treated with antibiotic plus rhDNase and the survival, organ injury, and levels of inflammatory markers and NETs were determined. Blood samples from pediatric and adult sepsis patients were collected and the concentrations of NETs measured. Results: Infant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia produced significantly higher levels of NETs than the adult mice. Moreover, compared to that of the adult mice, this outcome was accompanied by increased organ injury and production of inflammatory cytokines. The increased NETs were associated with elevated expression of Padi4 and histone H3 citrullination in the neutrophils. Furthermore, treatment of infant septic mice with rhDNase or a PAD-4 inhibitor markedly attenuated sepsis. Importantly, pediatric septic patients had high levels of NETs, and the severity of pediatric sepsis was positively correlated with the level of NETs. Conclusion: This study reveals a hitherto unrecognized mechanism of pediatric sepsis susceptibility and suggests that NETs represents a potential target to improve clinical outcomes of sepsis.

Neonatal Sepsis: Current Issues

Neonatal sepsis is an entity of worldwide concern. It is peculiar in that it is not a circumscribed disease. It is a scourge both in developed and developing countries as it has been recognised as one of the greatest causes of perinatal mortality. In 2005, it was estimated that about 1.6 million neonatal deaths in developing countries were caused by neonatal infections[1]. In these countries, neonatal infections were found to cause 34 out of 1000 deaths compared to 5 out of 1000 neonatal deaths in developed countries[2]. It was found to be the sixth greatest cause of death neonates in the United States in 2011[3]. Among major causes of neonatal death are perinatal asphyxia and prematurity[1]. Despite decades of history on the subject, a definition has yet to be established for neonatal sepsis. Over the years, the definition has included the isolation of a causative microorganism (bacteria, fungi, virus) from clinical samples obtained from the baby. Loosely, it is a term used to designate a systemic condition of bacterial, viral, or fungal (yeast) origin that is associated with haemodynamic changes and other clinical manifestations and results in substantial morbidity and mortality[4]. In 2005, the International Paediatric Sepsis Consensus Conference defined sepsis as a “systemic inflammatory response syndrome (SIRS) in the presence of or as a result of suspected or proven 5infection.”[5] New born infants are predisposed to infections which lead to sepsis and the reason for this is discernible in the nature of their immune systems. The immune system of the new born is greatly devoid of several components and those which are present are largely underdeveloped[3]. This state leaves them susceptible/vulnerable to infections by a host of organisms which range from viruses, fungi, bacteria et cetera[3].

Perinatal Risk Factors and Early Onset of Neonatal Sepsis

International Journal of Pediatric Research, 2022

Background: Neonatal sepsis contributes significantly to neonatal morbidity and mortality and is an ongoing major global public health challenge particularly in developing countries. Objective: The study aims to determine the prevalence of early neonatal infections and risk factors associated with neonatal intensive care. Methods: In a cross-sectional study that included all newborns admitted to the neonatal intensive care of Tishreen University Hospital from October 2019 for one year and who fulfilled clinical and laboratory criteria for early neonatal sepsis, blood samples were drawn for laboratory analysis (CBC, CRP) with a blood culture. Results: 197 neonates (28.14%) had early neonatal sepsis. The majority of patients (80.71%) had negative blood cultures. The most common pathogen of the early neonatal infection was Staphylococcus albicans, Streptococci, and E. coli. The current study found that the most prevalent risk factor for early neonatal infection was a cesarean section, followed by maternal infections, male newborn sex, low birth weight, prematurity, maternal age greater than 30 years and less than 20 years, early rupture of membranes, need for resuscitation, and Meconium amino fluid. Conclusion: The current study confirmed an important prevalence of early neonatal sepsis in Tishreen University Hospital with its association with many risk factors; the most prevalent factors were cesarean section, the gender of the male newborn, low birth weight, and prematurity.

Changing patterns of neonatal sepsis

Sri Lanka Journal of Child Health, 2009

Despite major advances in neonatology during the past few decades, many infants still develop lifethreatening infections during the first month of life. The increasing population of very low birth weight (VLBW) premature infants, who now survive due to improved neonatal care, represent the group at highest risk for neonatal infection.

Early-onset neonatal sepsis and risk factors in the preterm infants

Perinatal Journal

Preterm bebeklerde erken bafllang›çl› sepsis ve risk faktörleri Amaç: Çal›flman›n amac›, preterm yenido¤an bebeklerde erken bafllang›çl› sepsise yol açan risk faktörlerini ve bakteriyel mikro-organizmalar› tespit etmekti. Yöntem: Aç›k uçlu çal›flma, Ocak-Aral›k 2015 tarihleri aras›nda Podgorica, Karada¤'daki Üniversite Klinik Merkezi, Çocuk Has-tal›klar› Enstitüsü, Neonatoloji Merkezi'nde prospektif olarak yürütüldü. Bulgular: Çal›flmaya baflvuran 653 bebekten (427 miad, 226 preterm), sepsis tan›s› alm›fl 71 bebek (32 sepsisli miad yenido¤an [%7.5] ve 39 sepsisli preterm yenido¤an [%17.3]) çal›flmaya dahil edildi. Sepsisli 44 yenido¤anda kan kültürü sonucu pozitifti (20 miad, 24 preterm). Yirmi dört preterm bebekten, erken bafllang›çl› sepsis 8 olguda (dominant patojen E. coli) ve geç bafllang›çl› sepsis 16 olguda (dominant patojenler Klebsiella pneumoniae ve Staphylococcus CoN) tespit edildi. Prematüre do¤um ve düflük do¤um a¤›rl›¤›, neonatal sepsis için en yayg›n risk faktörleri olarak belirlendi. Maternal preeklampsi, erken membran rüptürü ve perinatal asfiksi de, preterm yenido¤an bebeklerde erken bafllang›çl› neonatal sepsis için önemli risk faktörleri olarak belirlendi. Sonuç: Verilerimiz, prematüre do¤um ve düflük do¤um a¤›rl›¤›-n›n, maternal preeklampsi, erken membran rüptürü ve perinatal asfiksi ile birlikte sepsis için en yayg›n risk faktörleri oldu¤unu göstermektedir.

Analysis of late-onset neonatal sepsis cases in a level three neonatal intensive care unit

Neonatal Sepsis, 2020

OBJECTIVE: Newborns in neonatal intensive care units (NICUs) are at high risk for developing nosocomial infections (NIs), which may result in morbidity and mortality. In this study, we aimed to ascertain the bacteriological profiles and their antimicrobial susceptibility patterns in NIs. METHODS: We conducted a cross-sectional study in the NICU. Late-onset sepsis (LOS) cases confirmed with blood cultures were evaluated retrospectively. Laboratory parameters, demographics, and clinical data were collected and analyzed from hospital records retrospectively. RESULTS: Of the 1210 infants in the NICU, 76 (6.3%) had LOS. A total of 86 episodes of LOS were documented; in 10 infants, two pathogens were identified. The mean gestational age (GA) of the infants with LOS was 33.2±4.8 weeks (23 to 42 weeks). Gram-positive cocci (GPC) caused most of the LOS episodes (65.8%, 50/76), with coagulase-negative Staphylococcus (CoNS) as the most common cause of LOS (50%, 38/76). Gram-negative rod species (GNRs) accounted for 32.9% (25/76) of the LOS cases, and fungi accounted for 1.3% (1/76). The mortality rates for GNR and GPC were 17.9% and 6.4%, respectively (p>0.05). The mean CRP and conjugated bilirubin levels for the GPC and GNR groups were 37.5 vs. 29.5 mg/dl and 0.7 vs 1.5 mg/dl, respectively (p>0.05). GNRs had a 20–25% ceftriaxone resistance. Two (4%) GPC species were resistant to linezolid, while all were susceptible to vancomycin. All of the GNRs were susceptible to carbapenems. CONCLUSION: These results underscore the recent emergence of CoNS in NICUs. LOS due to GNRs seems to display higher C-reactive protein and conjugated bilirubin values than those due to GPC. Clinical monitoring of NIs and bacterial resistance profiles are required in all NICUs.