[Neonatal sepsis by Citrobacter Freundii as a debut of cystic lymphatic malformation]. / Sepsis neonatal por Citrobacter Freundii como debut de malformación linfática quística.

Cystic lymphatic malformation (CLM) is a rare and benign entity caused by alterations in the embryological development of lymphatic structures. Its typical location is in the head and neck, although it has also been described at the abdominal level. It may not be evident in the first stages of life and its first manifestation may be a complication such as abdominal distension, hemorrhage, or sepsis, which may put the patient's life at risk. Surgical treatment is increasingly discussed, and less invasive techniques are proposed. OBJECTIVE: To describe an uncommon presentation of CLM, radiographic findings, complications, differential diagnosis, and both invasive and more conservative treatments. CLINICAL CASE: Newborn female infant consulted for fever and irritability, without specific signs on physical examination, with suspicion of sepsis. Ultrasonography showed a complex septate mass with cysts of different sizes encompassing the mesenteric vessels, supravesical location. In its most ante rior aspect, it presented a greater echogenicity that corresponded to the superinfected component. Magnetic resonance imaging identified a multitabulated cystic tumor corresponding to a complica ted mesenteric lymphangioma with signs of infection. Due to its size, which compressed the vena cava and the associated signs of complication, complete resection was decided with good subsequent evolution. CONCLUSION: The treatment of CLM in pediatric age is increasingly individualized and can vary from surgical resection to less invasive approaches that could reduce acute intraoperative or postoperative complications and mortality. In our case, the infection acted as sclerotherapy, mana ging to delimit the CLM and helping to improve the prognosis.

Severe neonatal COVID-19: Challenges in management and therapeutic approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may manifest as a life-threatening respiratory infection with systemic complications. Clinical manifestations among children are generally less severe than those seen in adults, but critical cases have increasingly been reported in infants less than 1 year of age. We report a severe case of neonatal COVID-19 requiring intensive care and mechanical ventilation, further complicated by a multidrug-resistant Enterobacter asburiae super-infection. Chest X-rays, lung ultrasound, and chest computed tomography revealed extensive interstitial pneumonia with multiple consolidations, associated with persistent increased work of breathing and feeding difficulties. SARS-CoV-2 RNA was detected in respiratory specimens and stools, but not in other biological samples, with a rapid clearance in stools. Serological tests demonstrated a specific SARS-CoV-2 antibody response mounted by the neonate and sustained over time. The therapeutic approach included the use of enoxaparin and steroids which may have contributed to the bacterial complication, underlying the challenges in managing neonatal COVID-19, where the balance between viral replication and immunomodulation maybe even more challenging than in older ages.

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis.

Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case-control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls. The relative gene expressions were quantified by TaqMan Real-Time qPCR and correlated to the clinic-laboratory data. MYD88, NFKB1, and IL6 relative expressions were significantly higher in sepsis cases than controls. Higher levels of MYD88 and IL6 were found in male neonates and contributed to the sex-based separation of the cases by the principal component analysis. ROC analysis revealed MYD88 and NFKB1 transcripts to be good biomarkers for sepsis. Furthermore, patients with high circulatory MYD88 levels were associated with poor survival, as revealed by Kaplan-Meier curves analysis. MYD88, NFKB1, and IL6 transcripts showed association with different poor-outcome manifestations. Clustering analysis split the patient cohort into three distinct groups according to their transcriptomic signature and CRP levels. In conclusion, the study TLR pathway-related transcripts have a gender-specific signature, diagnostic, and prognostic clinical utility in neonatal sepsis.

Staphylococcus epidermidis in feedings and feces of preterm neonates.

Staphylococcus epidermidis has emerged as the leading agent causing neonatal late-onset sepsis in preterm neonates; although the severity of the episodes caused by this species is often underestimated, it might exert relevant short- and long-term detrimental effects on neonatal outcomes. In this context, the objective of this study was to characterize a collection of S. epidermidis strains obtained from meconium and feces of preterm infants, and to assess the potential role of the enteral feeding tubes as potential reservoirs for this microorganism. A total of 26 preterm infants were enrolled in the study. Meconium and fecal samples were collected weekly during their first month of life (n = 92). Feeding samples were collected after their pass through the enteral feeding tubes (n = 84). S. epidermidis was present in the fecal samples of all the infants in, at least, one sampling time at concentrations ranging from 6.5 to 7.8 log10 CFU/g. Initially, 344 isolates were obtained and pulsed-field gel electrophoresis (PFGE) profiling allowed the reduction of the collection to 101 strains. Among them, multilocus sequence typing (MLST) profiling showed the presence of 32 different sequence types (ST). Globally, most of the STs to hospital-adapted high-risk clones and belonged to clonal complexes (CC) associated to the hospital environment, such as CC2. The virulence gene most commonly detected among the strains was altE. High resistance rates to macrolides and aminoglycosides were detected and 64% of the strains harboured the mecA gene, which was codified in SCCmec types. Our results indicates the existence of a complex and genetically diverse S. epidermidis population in the NICU environment. A better knowledge of S. epidermidis strains may help to devise strategies to avoid their conversion from symbiont to pathobiont microorganisms in the NICUs.

Progranulin as a novel biomarker in diagnosis of early-onset neonatal sepsis.

BACKGROUND: Infections are leading causes of morbidity and mortality in neonates and may also have severe long-term consequences. As early diagnosis of neonatal sepsis improves prognosis, identification of new or complementary biomarkers is of great importance. In this study, we have evaluated the diagnostic value of progranulin (PGRN) in early-onset neonatal sepsis (EOS) and compare its effectiveness with other commonly used biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP). METHODS: A total of 121 infants with gestational age of >34 weeks admitted with suspected EOS were included in this study. Before initiating therapy, blood samples for whole blood count, CRP, PCT and PGRN were obtained from all neonates. Receiver-operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. RESULTS: Serum PGRN level of infected group was significantly higher than uninfected group (median 47.72 vs. 37.86 ng/ml, respectively; Mann-Whitney p < 0.0001). The ROC area under the curve (AUC) was 0.786 [95% confidence interval (CI) 0.706-0.867; p < 0.0001] for PGRN, 0.699 (95% CI 0.601-0.797; p = 0.0001) for age adjusted PCT, and 0.673 (95% CI 0.573-0.773; p = 0.0007) for CRP. With a cut-off value of 37.89 ng/ml, the diagnostic sensitivity and negative predictive value of PGRN were 94.34% and 91.7%, respectively. PGRN could significantly predict EOS independently of PCT (p < 0.0001), and the combined use of PGRN and PCT could significantly improve diagnostic performance for EOS (0.806; 95% CI 0.73-0.88; p < 0.0001), with a specificity of 89.06% and a positive predictive value of 81.10%. CONCLUSIONS: PGRN may be used as a promising biomarker for the diagnosis of EOS, and the combined use of PGRN and PCT could improve the diagnosis of sepsis.

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/ß-catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide.

Neuroinflammation is thought to play a pivotal role in the pathogenesis of periventricular white matter (PWM) damage (PWMD) induced by neonatal sepsis. Because the complement cascade is implicated in inflammatory response, this study was carried out to determine whether C3a is involved in PWMD, and, if so, whether it would induce axonal hypomyelination. Furthermore, we explored if C3a would act through its C3a receptor (C3aR) and thence inhibit maturation of oligodendrocyte precursor cells (OPCs) via the WNT/ß-catenin signal pathway. Sprague Dawley (SD) rats aged 1 day were intraperitoneally injected with lipopolysaccharide (LPS) (1 mg/kg). C3a was upregulated in activated microglia and astrocytes in the PWM up to 7 days after LPS injection. Concomitantly, enhanced C3aR expression was observed in NG2+ oligodendrocytes (OLs). Myelin proteins including CNPase, PLP, MBP and MAG were significantly reduced in the PWM of 28-day septic rats. The number of PLP+ and MBP+ cells was markedly decreased. By electron microscopy, myelin sheath thickness was thinner and the average g-ratios were higher. This was coupled with an increase in number of NG2+ cells and decreased number of CC1+ cells. Olig1, Olig2 and SOX10 protein expression was significantly reduced in the PWM after LPS injection. Very strikingly, C3aRa administration for the first 7 days could reverse the above-mentioned pathological alterations in the PWM of septic rats. When incubated with C3a, expression of MBP, CNPase, PLP, MAG, Olig1, Olig2, SOX10 and CC1 in primary cultured OPCs was significantly downregulated as opposed to increased NG2. Moreover, WNT/ß-catenin signaling pathway was found to be implicated in inhibition of OPCs maturation and differentiation induced by C3a in vitro. As a corollary, it is speculated that C3a in the PWM of septic rats is closely associated with the disorder of OPCs differentiation and maturation through WNT/ß-catenin signaling pathway, which would contribute ultimately to axonal hypomyelination.

Recombinant CC16 regulates inflammation, oxidative stress, apoptosis and autophagy via the inhibition of the p38MAPK signaling pathway in the brain of neonatal rats with sepsis.

Sepsis has a high in clinic neonatal mortality. Moreover, a considerable number of children's brains remain affected even after the treatment of sepsis and it often leaves sequelae. Therefore, early intervention for sepsis is of considerable significance. Recent studies have shown that Club cell protein (CC16) is closely related to the p38 mitogen-activated protein kinase (MAPK) signaling pathway, which can regulate inflammation, oxidative stress, apoptosis, and autophagy during sepsis. Thus, we analyzed the neuroprotective effect of recombinant CC16 (rCC16) in a neonatal sepsis rat model. For the first time, we found that the p38MAPK signaling pathway was activated in neonatal brain tissue of rats with sepsis, and the CC16 levels decreased significantly. Secondly, after the rCC16 interference, the occurrence of inflammation, oxidative stress and apoptosis were subsequently reversed, and autophagy was further stimulated. Finally, through further intervention using the p38MAPK signaling pathway inhibitor, SB203580, or its agonist, anisomycin, we confirmed that rCC16 reduced rat mortality and improve general conditions. Simultaneously, it had also neuroprotective effect. Its mechanism could be related to oxidative stress, inflammation, and apoptosis reduced and autophagy activated by rCC16 inhibiting the p38MAPK signaling pathway. Taken together, these findings provide insight into the pathogenesis, prevention, and treatment of sepsis via the activity of rCC16.

The role of the preterm intestinal microbiome in sepsis and necrotising enterocolitis.

Late-onset sepsis (LOS) and necrotising enterocolitis (NEC) account for the highest number of deaths in premature infants and often cause severe morbidity in survivors. NEC is an inflammatory mediated condition, but its pathophysiology remains poorly understood. There is increasing evidence that in LOS the causative organism most often translocates from the gut. No causative microorganism has been consistently associated with either LOS or NEC, but an aberrant gut microbiome development could play a pivotal role. A low bacterial diversity and a delay in anaerobic bacteria colonization may predispose preterm infants to disease development. Conversely, a predominance of Bifidobacterium species and breast milk feeding might help to prevent disease onset. With numerous studies reporting conflicting results, further research is needed to better understand the role of microorganisms and type of feeding in the health status of preterm infants.

Acute Funisitis Correlates With the Risk of Early-Onset Sepsis in Term Newborns Assessed Using the Kaiser Sepsis Calculator.

BACKGROUND: The risk of neonatal early-onset sepsis (EOS) is traditionally assessed on maternal signs of clinical chorioamnionitis. Recently, an online EOS risk calculator was developed by Kaiser Permanente using maternal and neonatal clinical parameters. We were interested in whether an increased Kaiser sepsis risk score correlates with histologic acute chorioamnionitis or acute funisitis. DESIGN: Included in this retrospective review are 119 chorioamnionitis-exposed term neonates from January 1, 2015 and December 31, 2016. Clinical charts from mother-baby pairs were reviewed. An EOS risk score was obtained using the online Kaiser Sepsis Calculator. The presence and severity of acute chorioamnionitis and acute funisitis were recorded. A SPSS software was used for statistical analysis (IBM, New Jersey, USA). RESULTS: The Kaiser Sepsis Calculator could identify 97 of 119 (81.5%) neonates without increased risk for sepsis. Histologic acute chorioamnionitis was present in 100 of 119 cases (84%), in which 44 cases (44%) show severe acute chorioamnionitis. Acute funisitis was recognized in 87 of 119 (73.1%) cases, all of which had concurrent acute chorioamnionitis. Severe funisitis was seen in 38 of the 87 cases (43.7%). The Kaiser Sepsis risk score correlates with the presence and severity of acute funisitis (P = .037 and P = .044, respectively) but not with the presence or the severity of acute chorioamnionitis (P = .105 and P = .672, respectively). CONCLUSION: Our study provides histological evidence to support that the Kaiser Sepsis Calculator may help to effectively reduce unwarranted blood culture, antibiotics exposure, and neonatal intensive care unit admission in term neonates.

Surveillance for incidence and etiology of early-onset neonatal sepsis in Soweto, South Africa.

BACKGROUND: Globally, over 400,000 neonatal deaths in 2015 were attributed to sepsis, however, the incidence and etiologies of these infections are largely unknown in low-middle income countries. We aimed to determine incidence and etiology of community-acquired early-onset (<72 hours age) sepsis (EOS) using culture and molecular diagnostics. METHODS: This was a prospective observational study, in which we conducted a surveillance for pathogens using a combination of blood culture and a polymerase chain reaction (PCR)-based test. Blood culture was performed on all neonates with suspected EOS. Among the subset fulfilling criteria for protocol-defined EOS, blood and nasopharyngeal (NP) respiratory swabs were tested by quantitative real-time reverse-transcriptase PCR using a Taqman Array Card (TAC) with 15 bacterial and 12 viral targets. Blood and NP samples from 312 healthy newborns were also tested by TAC to estimate background positivity rates. We used variant latent-class methods to attribute etiologies and calculate pathogen-specific proportions and incidence rates. RESULTS: We enrolled 2,624 neonates with suspected EOS and from these 1,231 newborns met criteria for protocol-defined EOS (incidence- 39.3/1,000 live-births). Using the partially latent-class modelling, only 26.7% cases with protocol-defined EOS had attributable etiology, and the largest pathogen proportion were Ureaplasma spp. (5.4%; 95%CI: 3.6-8.0) and group B Streptococcus (GBS) (4.8%; 95%CI: 4.1-5.8), and no etiology was attributable for 73.3% of cases. Blood cultures were positive in 99/1,231 (8.0%) with protocol-defined EOS (incidence- 3.2/1,000 live-births). Leading pathogens on blood culture included GBS (35%) and viridans streptococci (24%). Ureaplasma spp. was the most common organism identified on TAC among cases with protocol-defined EOS. CONCLUSION: Using a combination of blood culture and a PCR-based test the common pathogens isolated in neonates with sepsis were Ureaplasma spp. and GBS. Despite documenting higher rates of protocol-defined EOS and using a combination of tests, the etiology for EOS remains elusive.

Perinatal Ureaplasma Exposure Is Associated With Increased Risk of Late Onset Sepsis and Imbalanced Inflammation in Preterm Infants and May Add to Lung Injury.

Background: Controversy remains concerning the impact of Ureaplasma on preterm neonatal morbidity. Methods: Prospective single-center study in very low birth weight infants <30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for Ureaplasma parvum and U. urealyticum using culture technique and polymerase chain reaction. Neonatal outcomes were followed until death or discharge. Multi-analyte immunoassay provided cord blood levels of inflammatory markers. Using multivariate regression analyses, perinatal Ureaplasma exposure was evaluated as risk factor for the development of bronchopulmonary dysplasia (BPD), other neonatal morbidities until discharge and systemic inflammation at admission. Results: 40/103 (39%) infants were positive for Ureaplasma in one or both specimens, with U. parvum being the predominant species. While exposure to Ureaplasma alone was not associated with BPD, we found an increased risk of BPD in Ureaplasma-positive infants ventilated ≥5 days (OR 1.64; 95% CI 0.12-22.98; p = 0.009). Presence of Ureaplasma was associated with a 7-fold risk of late onset sepsis (LOS) (95% CI 1.80-27.39; p = 0.014). Moreover, Ureaplasma-positive infants had higher I/T ratios (b 0.39; 95% CI 0.08-0.71; p = 0.014), increased levels of interleukin (IL)-17 (b 0.16; 95% CI 0.02-0.30; p = 0.025) and matrix metalloproteinase 8 (b 0.77; 95% CI 0.10-1.44; p = 0.020), decreased levels of IL-10 (b -0.77; 95% CI -1.58 to -0.01; p = 0.043) and increased ratios of Tumor necrosis factor-α, IL-8, and IL-17 to anti-inflammatory IL-10 (p = 0.003, p = 0.012, p < 0.001). Conclusions: Positive Ureaplasma screening was not associated with BPD. However, exposure contributed to BPD in infants ventilated ≥5 days and conferred an increased risk of LOS and imbalanced inflammatory cytokine responses.

Premature labor and neonatal sepsis caused by Actinomyces neuii.

Actinomycosis is a rare infection in patients younger than 10years of age. It mainly affects the cervicofacial region, but many other sites of infection have been recognized. About 70% of infections are due to either Actinomyces israelii or Actinomyces gerencseriae. Actinomyces neuii was first described in 1985 in two patients with post cataract endophthalmitis, A. neuii represents 17% of clinical Actinomyces isolates. Several reports indicated a well-known association between Actinomyces infections and Intrauterine devices (IUD). We are reporting a case of neonatal sepsis due to A. neuii as a first case reported from Saudi Arabia. It was thought to be the cause of the premature labor and neonatal sepsis. The prevalence of Actinomyces infection is likely underestimated and additional premature labors and abortions could have been caused by Actinomyces infections that were never detected. More studies are needed to confirm the association of maternal Actinomyces infections with preterm labor.

Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants.

BACKGROUND: Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. METHODS: In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. RESULTS: We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. CONCLUSIONS: Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

microRNA-300/NAMPT regulates inflammatory responses through activation of AMPK/mTOR signaling pathway in neonatal sepsis.

AIM: Rapid and accurate diagnosis of neonatal sepsis (NS) is highly warranted because of high associated morbidity and mortality. The study aims to evaluate the effects of miR-300 on inflammatory responses in a septic neonate mouse model. METHODS: A septic mouse model was established by intraperitoneal (i.p.) cecal slurry (CS) injection in order to validate the effect of miR-300 on the inflammatory response in endothelial cells. Bioinformatics tools and luciferase activity were employed to detect the target of miR-300. Serum inflammatory factors were determined by ELISA assay. RT-qPCR and western blot analysis were used to determine the gene expressions. Flow cytometry was employed to evaluate cell apoptosis. RESULTS: Gain- and loss-of-function studies revealed that miR-300 overexpression augmented autophagy, inhibited cell apoptosis, enhanced cell cycle entry in endothelial cells, and decreased inflammatory response through the regulation of pro- and anti-apoptotic factors in endothelial cells. The effect of miR-300on endothelial cells was upregulated after nicotinamide phosphoribosyltransferase (NAMPT) silencing and AMPK/mTOR signaling pathway activation, indicating that miR-300 influences sepsis via suppressing NAMPT and triggering the AMPK/mTOR signaling pathway. CONCLUSIONS: Our study provides evidence indicating that overexpressedmiR-300 enhances autophagy by targeting NAMPT through activation of the AMPK/mTOR signaling pathway in septic mouse models, indicating it may serve as a potential therapeutic target for sepsis.

Pilot study demonstrates that placental histology can provide an additional tool for diagnosing early-onset neonatal sepsis.

AIM: We explored whether placental histology could help to diagnose early-onset neonatal sepsis (EONS), guide clinical decision-making 48 hours after birth and reduce antibiotic use. METHODS: This study comprised 109 infants born at less than 32 weeks of gestation, who were admitted to the neonatal intensive care unit of Isala, Zwolle, The Netherlands, between January 2013 and December 2013. EONS was defined as clinical symptoms plus raised serial C-reactive protein (CRP) >10 mg/L and a positive (proven EONS) or a negative (suspected EONS) blood culture. Placentas were studied for a histological inflammatory response and scored according to Redline's criteria. RESULTS: A histological inflammatory response was seen in 15/88 (17%) placentas and this occurred significantly more often in infants with a high suspicion of EONS (p < 0.05). No histological inflammatory response was seen if maternal risk factors for EONS were absent, despite a raised CRP level. Based on placental histology, the duration of antibiotic therapy was reduced from more than five days to 48 hours in 20/27 infants (74%). CONCLUSION: Histological examination of the placenta helped to diagnose EONS and guide clinical decision-making 48 hours after birth and led to a clinically relevant reduction in antibiotic use.

Application of Monte Carlo cross-validation to identify pathway cross-talk in neonatal sepsis.

To explore genetic pathway cross-talk in neonates with sepsis, an integrated approach was used in this paper. To explore the potential relationships between differently expressed genes between normal uninfected neonates and neonates with sepsis and pathways, genetic profiling and biologic signaling pathway were first integrated. For different pathways, the score was obtained based upon the genetic expression by quantitatively analyzing the pathway cross-talk. The paired pathways with high cross-talk were identified by random forest classification. The purpose of the work was to find the best pairs of pathways able to discriminate sepsis samples versus normal samples. The results found 10 pairs of pathways, which were probably able to discriminate neonates with sepsis versus normal uninfected neonates. Among them, the best two paired pathways were identified according to analysis of extensive literature. Impact statement To find the best pairs of pathways able to discriminate sepsis samples versus normal samples, an RF classifier, the DS obtained by DEGs of paired pathways significantly associated, and Monte Carlo cross-validation were applied in this paper. Ten pairs of pathways were probably able to discriminate neonates with sepsis versus normal uninfected neonates. Among them, the best two paired pathways ((7) IL-6 Signaling and Phospholipase C Signaling (PLC); (8) Glucocorticoid Receptor (GR) Signaling and Dendritic Cell Maturation) were identified according to analysis of extensive literature.

Beyond sepsis: Staphylococcus epidermidis is an underestimated but significant contributor to neonatal morbidity.

Staphylococcus epidermidis accounts for the majority of cases of neonatal sepsis. Moreover, it has been demonstrated to be associated with neonatal morbidities, such as bronchopulmonary dysplasia (BPD), white matter injury (WMI), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP), which affect short-term and long-term neonatal outcome. Imbalanced inflammation has been considered to be a major underlying mechanism of each entity. Conventionally regarded as a harmless commensal on human skin, S. epidermidis has received less attention than its more virulent relative Staphylococcus aureus. Particularities of neonatal innate immunity and nosocomial environmental factors, however, may contribute to the emergence of S. epidermidis as a significant nosocomial pathogen. Neonatal host response to S. epidermidis sepsis has not been fully elucidated. Evidence is emerging regarding the implication of S. epidermidis sepsis in the pathogenesis of neonatal inflammatory diseases. This review focuses on the interplay among S. epidermidis, neonatal innate immunity and inflammation-driven organ injury.

Early-onset Neonatal Pneumococcal Sepsis: A Fatal Case Report and Brief Literature Review.

Sepsis caused by Streptococcus pneumoniae is rare in neonates although associated with high morbidity and mortality. We report a fatal case of invasive pneumococcal disease in a term neonate whose mother was healthy and did not receive any pneumococcal vaccine. Investigation of the infection source yielded negative results. Acquisition of infection through the birth canal was considered unlikely.

Urine metabolomics in neonates with late-onset sepsis in a case-control study.

Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

Neonatal brucellosis: A case report.

Although brucellosis is not uncommon in Saudi Arabia, neonatal brucellosis has been infrequently reported. In this case of neonatal brucellosis, Brucella abortus was isolated by blood culture from both the mother and the neonate. Serology was positive only in the mother.