Sepsis In Preterm Infants Research Articles

Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Recurrent Late-Onset Sepsis in Extremely Low Birth Weight Infants Is Associated with Motor Deficits in Early School Age

Introduction: Sepsis is regarded as a risk factor for brain injury in preterm infants. We herein hypothesize that extremely low birth weight infants (ELBWI, birth weight <1,000 g) having survived recurrent blood culture-proven late-onset sepsis (LOS) episodes are more likely to have an adverse long-term neurologic outcome. Methods: In a large multicenter observational study of ELBWI ≤28 6/7 weeks, we evaluated the impact of recurrent LOS (blood culture-proven, after day 7 of life) on development at 5–6 years. Neurodevelopment, behavior, and motor qualities were tested by blinded investigators. Univariate and logistic regression analyses were performed. Results: The cohort consisted of 1343 ELBWI including 1,080 infants without LOS, 186 infants with one LOS, and 77 with recurrent LOS, i.e., 55 infants with two and 22 infants with three LOS episodes. After Bonferroni-Holm correction, multiple logistic regression analysis revealed recurrent sepsis to be significantly associated with adverse motor development (critical MABC-2 testing: 3.3 [1.5–7.3], p = 0.003, p_B = 0.012), whereas no significant impact of recurrent LOS was found on intelligence quotient and behavioral difficulties. Odds of having critical motor testing results for infants with recurrent LOS were 1.7 times (95% confidence interval 1.4–2.3) that of infants with one LOS. Conclusion: Recurrent sepsis in preterm infants is associated with adverse long-term motor development. However, infants with recurrent infections are also more likely to have preterm-related complications, and reasons for a worse neurodevelopmental outcome remain to be elucidated.

Prediction for late-onset sepsis in preterm infants based on data from East China.

AimTo construct a prediction model based on the data of premature infants and to apply the data in our study as external validation to the prediction model proposed by Yuejun Huang et al. to evaluate the predictive ability of both models.MethodsIn total, 397 premature infants were randomly divided into the training set (n = 278) and the testing set (n = 119). Univariate and multivariate logistic analyses were applied to identify potential predictors, and the prediction model was constructed based on the predictors. The area under the curve (AUC) value, the receiver operator characteristic (ROC) curves, and the calibration curves were used to evaluate the predictive performances of prediction models. The data in our study were used in the prediction model proposed by Yuejun Huang et al. as external validation.ResultsIn the current study, endotracheal intubation [odds ratio (OR) = 10.553, 95% confidence interval (CI): 4.959–22.458], mechanical ventilation (OR = 10.243, 95% CI: 4.811–21.806), asphyxia (OR = 2.614, 95% CI: 1.536–4.447), and antibiotics use (OR = 3.362, 95% CI: 1.454–7.775) were risk factors for late-onset sepsis in preterm infants. The higher birth weight of infants (OR = 0.312, 95% CI: 0.165–0.588) and gestational age were protective factors for late-onset sepsis in preterm infants. The training set was applied for the construction of the models, and the testing set was used to test the diagnostic efficiency of the model. The AUC values of the prediction model were 0.760 in the training set and 0.796 in the testing set.ConclusionThe prediction model showed a good predictive ability for late-onset sepsis in preterm infants.

Effects of early administration of buccal colostrum on reducing late onset sepsis among preterm in neonatal intensive care: Quasi-experimental, cohort study

IntroductionPreterm infants are at a particularly high risk of late onset sepsis (LOS), that can lead to death, increased morbidities, prolonged hospital stay, increased cost of care, and worse long-term outcomes among survivors. Administration of buccal colostrum in the first few days of life is safe, feasible, prophylactic measure against sepsis, Necrotizing Enterocolitis (NEC) and ventilator associated pneumonia. PurposeThe purpose of this study was to evaluate the effects of Early Administration of Buccal Colostrum on preterm infants’ outcomes, including the incidence of late onset sepsis in the Neonatal Intensive Care (NICU). MethodologyThis is a quasi-experimental, retrospective-prospective, clinical trial study, that took place in the NICU of Dubai Hospital, Dubai Health Authority (DHA), in the United Arab Emirates between January 2018–April 2020. The sample consisted of preterm-neonates who were selected and assigned into two groups; experimental and control. A purposive sample that met the inclusion criteria of babies born at 34 weeks and below, and whose parents were willing to participate in this study were included. AnalysisThe sample consisted of 175 preterm neonates. Neonates in Group 1 (n = 134) received buccal colostrum within 48 h, while neonates in Group 2 (n = 41) did not. Of the neonates in (Group 1) who received colostrum within 48 h, 5 (3.7%) had late onset sepsis and 129 (96.3%) did not. On the other hand, neonates in Group 2 who did not receive colostrum within 48 h, almost half 19 (46.3%) also developed late onset sepsis and 22 (53.7%) did not (p = .001). In terms of mortality, Group 1 neonates who received colostrum within 48 h in had a survival rate of 98.5% (132). While in Group 2, 3 (7.3%) neonatal deaths occurred, and 38 (92.7%) neonates were alive 28 days after birth. Despite the death rate in Group 2 being higher compared to Group 1, the results are not statistically significant (p = . 0.085). Fisher's exact test showed that the ratio of deaths in neonates who received colostrum within 48 h in Group 1 and also developed sepsis was 1 neonatal death: 4 alive. While 3 neonates in Group 2 who did not receive Colostrum within 48 h and developed sepsis and died. These results were statistically significant with (p = .001). Neonatal deaths were higher in neonates who did not receive colostrum within 48 h and who also developed sepsis. ConclusionThis study reported strong evidence to support the proposed clinical benefits of early administration of buccal colostrum. The results also demonstrated differences in the incidence of developing LOS and proven sepsis in preterm infants who did not received buccal colostrum, compared to the infants who received buccal colostrum soon after birth. While no differences were seen in infants’ clinical outcomes in terms of direct mortality, the results did show that early administration of buccal colostrum was associated with better outcomes in neonates who also developed sepsis.

Predictive value of combining maternal peripheral blood count indicators for early-onset sepsis in preterm infants: A retrospective cohort study.

To assess the early predictive value of maternal parameters for early-onset sepsis (EOS) in preterm infants, especially including the maternal neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV). The retrospective cohort study examined a total of 231 preterm infants (69 with EOS) from May 2017 to October 2021 of the Fourth Hospital of Hebei Medical University, randomly divided (7:3) into the training set group (n = 162) and validation set group (n = 69). Thirteen clinical variables (including MPV, NLR, and PLR) were included as the research objects. By logistic regression, the factors significantly associated with EOS were distinguished. Additionally, a nomogram was constructed based on the independent risk factors, the validation of which relied on the concordance index, calibration curves, receiver operating characteristic curves, and decision curve analyses. Multivariate logistic regression proved that NLR (OR = 1.67, 95% CI = 1.18-2.36, P = .004), PLR (OR = 1.03, 95% CI = 1.01-1.04, P = .001), and MPV (OR = 1.75, 95% CI = 1.15-2.66, P = .009) were independent risk factors for EOS. The AUC of the nomogram for the training set group was 0.872 (0.814, 0.931) and 0.889 (0.843, 0.935) in the validation set group. The P values of Hosmer-Lemeshow test for the training set and validation set groups were .903 and .752, respectively. The decision curve analyses outcome indicated good clinical practicability. The C-index for the training set and validation set groups were 0.872 and 0.889, respectively. The maternal NLR, PLR, and MPV levels had good predictive value for EOS in premature infants. The nomogram in our study could help clinicians predict the occurrence of EOS.

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics’ effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age < 30 weeks) born in 9 centers in the Netherlands and Belgium between Oct. 2014 and Jan. 2019. EEAE association with NEC and LOS development was analyzed by multivariate regression. After excluding 56 EOS cases, 1259 infants were included. A total of 1122 infants (89.1%) were exposed to empirical antibiotics for the suspicion of EOS of whom 802 (63.7%) had short (≤ 72 h) and 320 (25.4%) prolonged EEAE (> 72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19–0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35–0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85–0.97]; p = 0.003).Conclusion: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored.What is Known:• Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis.• The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated.What is New:• Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged.• A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life.

Preterm sepsis is associated with acute lung injury as measured by pulmonary severity score.

Sepsis related acute lung injury (ALI) is established in adults but has not been investigated in premature infants. Herein, we used pulmonary severity score (PSS) trajectories and C-reactive protein (CRP) to examine the relation between sepsis and ALI in premature infants. This retrospective study identified 211 sepsis and 123 rule out (RO) events in 443 infants born <31 weeks and <1500 grams. The PSS was calculated prior to, at the time of, and up to 1 week after each event. Initial and peak CRP values were collected for each event. PSS significantly increased at 0 h from baseline (-72h) and remained increased at all subsequent time points (all p < 0.002) in sepsis events. Mean PSS in sepsis episodes were also higher compared to RO events at +24 h, +48 h, +72 h, and +168 h (all p < 0.004). A positive correlation was noted between peak CRP values in sepsis events and PSS at 0 h, +24 h, +48 h, and +72 h. The temporal PSS trends and correlation with CRP levels observed in sepsis but not in RO events supports the hypothesis that neonatal sepsis is associated with ALI and contributes to the accumulating evidence that neonatal ARDS occurs. To evaluate pulmonary severity scores and c-reactive protein values over time to establish an association between preterm neonatal sepsis and acute lung injury (ALI). Though sepsis is well established as the most common indirect cause of ALI leading to acute respiratory distress syndrome (ARDS) in adults and pediatrics, this phenomenon remains undefined in neonates. This study validates the proposal by the Neonatal ARDS Project that ARDS also occurs in neonates by demonstrating acute and sustained changes in markers of pulmonary injury temporally related to a diagnosis of neonatal sepsis in preterm infants.

The Use of Probiotics in Preterm Infants

Probiotics are live microorganisms that positively affect host health by altering the composition of the host microbiota. Gastrointestinal dysbiosis refers to adverse alterations of the intestinal flora and is associated with several diseases, including necrotizing enterocolitis, late-onset sepsis in preterm infants as well as atopic disease, colic, diabetes, and diarrhea in term infants. The risk factors for gastrointestinal dysbiosis are preterm birth, cesarean section delivery, and formula feeding, in contrast to term birth infants, vaginal delivery and breast milk feeding. Probiotics have been used to restore synbiosis in infants with gastrointestinal dysbiosis. Probiotics inhibit colonization of pathogenic bacteria in the gastrointestinal tract, thereby improving the barrier function of the gastrointestinal tract, and the immune function. In preterm infants, probiotics reduce mortality as well as rates of necrotizing enterocolitis and late-onset sepsis. The combined use of probiotics such as &lt;i&gt;Lactobacillus&lt;/i&gt; and &lt;i&gt;Bifidobacterium&lt;/i&gt; and the combination of probiotics with prebiotics yield better outcomes in the prevention of necrotizing enterocolitis than those achieved with a single pro- or prebiotic strain. However, the routine use of probiotics has been hindered by the lack of pharmaceutical-quality products, and a definite effect has yet to be demonstrated in preterm infants with a birth weight &lt;1,000 g. Therefore, to reduce the risk of necrotizing enterocolitis in preterm infants, probiotics should be provided along with breast milk and other strategies aimed at preventing gastrointestinal dysbiosis.

The Correlation of Antibacterial Peptides Concentration in Umbilical Cord Blood and Early Onset Sepsis in Preterm Infants.

Umbilical cord blood from singleton preterm infants was collected during delivery, and the concentration of LL37 was measured. C-reactive protein (CRP), white blood cell count (WBC), platelets (PLT), and mean platelet volume (MPV) were determined within 3 days after birth. The differences in LL37, CRP, WBC, PLT, and MPV levels between the two groups were compared. Pearson correlation method was used to analyze the correlation between these factors. The early individual value of each detected index for early onset sepsis was analyzed by ROC curve. The level of LL37 in umbilical cord blood of sepsis group was significantly higher than those in the control group (383.85 ± 46.71 vs. 252.37 ± 83.30 ng/ml). Meanwhile, the levels of CRP, WBC, and MPV in the sepsis group were significantly higher than those in the control group (CRP:5.73 ± 4.19 vs. 2.50 ± 2.77 mg/L; WBC: 13.47 ± 12.35 vs. 6.83 ± 3.55 × 109/L; MPV: 11.20 ± 1.11 vs. 8.90 ± 0.68 fL), the level of PLT was significantly lower than those in the control group (PLT: 161.00 ± 38.51 vs. 241.50 ± 49.85 × 109/L) (P < 0.05). Pearson correlation analysis showed that the expression of LL37 was negatively correlated with PLT level (r = −0.9347, P < 0.0001), and positively correlated with MPV level (r = 0.9463, P < 0.0001). ROC curve analysis showed that the area under curve of LL37 for diagnosis of early onset sepsis was 0.875, the prediction probability was 0.7, the sensitivity was 90.0% and the specificity was 80.0%.

Mean Platelet Volume and Mean Platelet Volume/Platelet Count Ratio Are Predictors of Late-Onset Sepsis in Preterm Infants: A Case-Control Study

Objective: Our aim was to assess mean platelet volume (MPV) and mean platelet volume to platelet count ratio (MPR) in the setting of late-onset sepsis (LOS) and their association with the type of bacteria causing LOS. Study design: The MPV and MPR levels were obtained at the onset of LOS and then assessed in intra/inter group analyses in preterm infants. Results: Overall, 136 preterm infants were enrolled. The MPV and MPR levels were higher during a LOS event (P < 0.001). A MPV cutoff of >9.2 was related with a sensitivity of 63% and a specificity of 73% for predicting LOS (P < 0.001). A MPR cutoff of >0.15 was related with a sensitivity of 88% and a specificity of 63% for predicting gram negative LOS (P < 0.001). Conclusion: Elevated MPV values and MPR ratios may be helpful in assessing LOS.

Evaluation of Red Blood Cell Distribution Width-Platelet Ratio as an Early Predictor of Late-Onset Sepsis in Preterm Infants

Evaluation of Red Blood Cell Distribution Width-Platelet Ratio as an Early Predictor of Late-Onset Sepsis in Preterm Infants

Evaluation and Management of Main Bacterial Infections in Premature Infants

Infection and sepsis in preterm infants are a leading cause of morbidity and mortality. Compared with full-term infants, preterm infants are more susceptible to infection owing to their distinct immune function, prolonged hospitalization, and higher likelihood of undergoing invasive procedures. Timely recognition and intervention are the key factors for good prognosis. This requires rapid and accurate diagnosis and empirical antibiotics against the pathogen based on each neonatal intensive care unit's epidemiology. Judicious anti biotics use is important following accurate identification of the causative pathogen. Simultaneous supportive management such as breast feeding should be encouraged to improve an infant’s defense mechanism. In essence, prevention is paramount because sepsis is known to contribute to significant neuro­developmental sequelae. Thorough understanding of immune function, good diagnostic protocol, appropriate antibiotics management, and strict preventive strategies may improve short- and long-term outcomes in premature infants.

Validity of serum and urinary hepcidin as biomarkers for late-onset sepsis in premature infants.

Background:Sepsis remains one of the leading causes of neonatal morbidity and mortality, particularly among premature infants. Blood culture is the ‘gold standard’ for the diagnosis of neonatal sepsis but is associated with several pitfalls.Aim of the work:We aim to evaluate the validity of measuring serum (S.Hep) and urinary hepcidin (U.Hep) concentrations as diagnostic biomarkers for late-onset sepsis (LOS) in preterm infants.Patients and Methods:The current case-control study included 73 cases of clinically and laboratory confirmed late-onset sepsis as the ‘case group’ and 50 nonseptic premature infants of comparable age and sex as the ‘control group’. S.Hep and U.Hep concentrations were evaluated at enrollment (acute sample) and after 1 week of treatment (convalescent sample).Results:Patients had a statistically significant higher concentration of both S.Hep and U.Hep as compared with nonseptic controls (p = 0.0001). Similarly, a significant reduction of both S.Hep and U.Hep was detected after 1 week of treatment (p = 0.001). A cut-off value of ⩾ 94.8 ng/ml of S.Hep and ⩾ 264 ng/mg of U.Hep/urinary creatinine showed high sensitivity, specificity, and positive predictive value in the diagnosis of neonatal LOS.Conclusions:Both S.Hep and U.Hep can function as promising accurate and rapid surrogate tests for the diagnosis of LOS. U.Hep measurement has the advantage of being noninvasive, with no hazards of phlebotomy, and is less variable throughout the day.

Probiotics (Bacillus clausii) for Prevention of Late-onset Sepsis in Preterm Infants (&lt;34 weeks): A Randomised Controlled Trial

Introduction: Late-onset Sepsis (LOS) causes significant morbidity and mortality in preterm infants. Probiotics have been suggested to improve the integrity of mucosal barrier by modifying the enteric microflora and suppress the overgrowth and translocation of pathogens in the gut, thus preventing life- threatening infections. Although probiotics have a definite role in prevention of Necrotising Enterocolitis (NEC) in preterm neonates, their effect on prevention of LOS in preterm neonates is still uncertain. Aim: To evaluate the role of probiotics in reducing incidence of LOS in preterm neonates (&lt;34 weeks). Materials and Methods: A double blinded randomised control trial was conducted in a tertiary care Neonatal Intensive Care Unit (NICU) in Karnataka, India between 1st January 2019 to 31st December 2019. Seventy haemodynamically stable preterm neonates, &lt;34 weeks of Gestational Age (GA), were randomised into ‘Probiotic’ and ‘Placebo’ groups. The probiotic group (n=36) was prophylactically administered Bacillus clausii suspension at a dose of 2.5 mL per-oral (0.4×109 spores in 1 mL) BD with breast milk, from initiation of enteral feeds till seven days, discharge/ death/LOS, whichever was earlier. The placebo group (n=34) received breast milk with sterile water 2.5 mL per- oral BD. All the neonates were investigated and managed as per standard hospital protocol. Primary outcome of the study was to find the incidence of LOS. Student’s t-test, Mann-Whitney U test, Chi-square test and Fisher’s exact test were used for statistical analysis. Results: There was no significant difference between the probiotic vs placebo group, with respect to incidence of LOS (11.11% vs 17.64%; (p&gt;0.05)) and duration of hospital stay (10.86±3.19 vs 11.23±2.98 days; (p&gt;0.05)). However, incidence of feed intolerance in the probiotic group (11.11%) was significantly less than that the other (26%) (p&lt;0.05). Conclusion: Probiotics, prophylactically fed enterally, did not reduce the incidence of LOS but provide a promising strategy to prevent feed intolerance in premature neonates.

Challenges in the Diagnosis &amp; Management of Neonatal Sepsis

Neonatal sepsis is the main cause of neonatal mortality and a major public health problem, especially in underdeveloped countries. Although recent medical services have improved neonatal care, but still challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of non-infectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically start antibiotics to infants with risk factors with and without signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries.

Optimized Detection of Central Apneas Preceding Late-Onset Sepsis in Premature Infants.

In neonatal intensive care units, respiratory traces of premature infants developing late onset sepsis (LOS) may also show episodes of apneas. However, since clinical patient monitors often underdetect apneas, clinical experts are required to investigate patients' traces looking for these events. In this work we present a method to optimize an existing algorithm for central apnea (CA) detection and how we used it together with human annotations to investigate the occurrence of CAs preceding LOS.The algorithm was optimized by using a previously-annotated dataset consisting of 90 hours, extracted from 10 premature infants. This allowed to double precision (19.7% vs 9.3%, median values per patient) without affecting recall (90.5% vs 94.5%) compared to the original algorithm. This choice caused the missed identification of just 1 additional CA (4 vs 3) in the whole dataset. The optimized algorithm was then used to annotate a second dataset consisting of 480 hours, extracted from 10 premature infants diagnosed with LOS. Annotations were corrected by two clinical experts.A significantly higher number of CA annotations was found in the 6 hours prior to sepsis onset (p-value < 0.05). The use of the optimized algorithm followed by human annotations proved to be a suitable, time-efficient method to annotate CAs before sepsis in premature infants, enabling future use in large datasets.

Prospects for clinical applications of butyrate-producing bacteria.

As the major source of energy for colonic mucosal cells and as an important regulator of gene expression, inflammation, differentiation, and apoptosis in host cells, microbiota-derived butyrate can enhance the intestinal mucosal immune barrier, modulate systemic immune response, and prevent infections. Maintaining a certain level of butyrate production in the gut can help balance intestinal microbiota, regulate host immune response, and promote the development and maintenance of the intestinal mucosal barrier. Butyrate-producing bacteria act as probiotics and play important roles in a variety of normal biological functions. Bacteriotherapeutic supplementation by using fecal microbiota transplantation to restore butyrate-producing commensal bacteria in the gut has been very successful in the treatment of recurrent and refractory Clostridium difficile (C. difficile) infection or C. difficile-negative nosocomial diarrhea. Administration of probiotics that include butyrate-producing bacteria may have a role in the treatment of inflammatory bowel diseases and in the prevention of necrotizing enterocolitis and late-onset sepsis in premature infants. Furthermore, modulating gut microbiota with dietary approaches may improve intestinal dysbiosis commonly seen in patients with obesity-associated metabolic disorders. Supplementation with a butyrate-producing bacterial stain might be used to increase energy expenditure, improve insulin sensitivity, and to help control obesity and metabolic syndrome.

Oropharyngeal administration of colostrum for preventing necrotizing enterocolitis and late-onset sepsis in preterm infants with gestational age\u2009\u2264\u200932\u2009weeks: a pilot single-center randomized controlled trial

BackgroundOropharyngeal administration of colostrum (OAC) may provide immunoprotective and anti-inflammatory effects that potentially reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis and improve short-term outcomes. Our objective was to evaluate the role of OAC in the early prevention of NEC and late-onset sepsis in preterm infants with gestational age (GA) ≤ 32 weeks.MethodsA pilot, single-center, 1:1 parallel randomized controlled trial was conducted in a 40-bed tertiary neonatal intensive care unit (NICU) in China from 1 January 2019 to 30 September 2020. Preterm infants were randomly divided into two groups with GA ≤ 32 weeks. The OAC group included preterm infants who received 0.4 ml of maternal colostrum via the oropharyngeal route every 3 h for 10 days beginning within the first 48 h after birth, and the control group included preterm infants who received normal saline instead. Data from the two groups were collected and compared.ResultsA total of 127 infants in the OAC group and 125 infants in the control group were enrolled. The incidence of NEC (Bell stage 2 or 3) and late-onset sepsis were lower in the OAC group [2.36% vs. 10.40%, relative risk (RR) 0.23 (95% confidence interval (CI) 0.07, 0.78), adjusted RR 0.23 (95% CI 0.06, 0.84); 4.72% vs. 13.60%, RR 0.35 (95% CI 0.14, 0.85), adjusted RR 0.36 (95% CI 0.14, 0.95)]. In addition, the incidence of proven sepsis and intraventricular hemorrhage (IVH) (stage 3 or 4) were lower in the OAC group [2.36% vs. 8.80%, RR 0.27 (95% CI 0.08, 0.94); 1.57% vs. 7.20%, RR 0.22 (95% CI 0.05, 0.99)], and the time to achieve full enteral feeding was shorter (23.13 ± 9.45 days vs. 28.50 ± 14.80 days). No adverse reactions were observed in either group.ConclusionsOropharyngeal administration of colostrum is a safe and simple NICU procedure that may yield a potential effect in decreasing the incidences of NEC, late-onset sepsis, and severe IVH and shorten the time to achieve full enteral feeding in preterm infants with GA ≤ 32 weeks.Trial registrationChinese Clinical Trial Registry, ChiCTR1900023697, Registered 8 June 2019, retrospectively registered.

Plasma secretory phospholipase A2 as an early marker for late-onset sepsis in preterm infants-a pilot study.

Preterm infants are particularly susceptible to bacterial late-onset sepsis (LOS). Diagnosis by blood culture and inflammatory markers have sub-optimal sensitivity and specificity and prolonged reporting times. There is an urgent need for more rapid, accurate adjunctive diagnostics in LOS to improve management and minimise antibiotic exposure. We measured the diagnostic performance of secretory phospholipase A2 type IIA (sPLA2-IIA) in very preterm infants (<30weeks gestational age) with suspected LOS. Plasma sPLA2-IIA levels were elevated in infants with LOS (n=28) compared to those without LOS (n=21; median 30,970 vs. 2534pg/ml, p<0.0001). The mean area under the curve was 0.884 (95% CI: 0.771, 0.977) with a sensitivity of 0.907 (95% CI: 0.667, 1.00) and specificity of 0.804 (95% CI: 0.600, 1.00). The positive and negative predictive values were 0.833 (95% CI: 0.664, 0.927) and 0.842 (95% CI: 0.624, 0.945), respectively. This pilot study suggests that sPLA2-IIA may have clinical utility for the early diagnosis of LOS in very preterm infants, potentially informing clinical management and antibiotic stewardship.

Progression from sepsis to septic shock and time to treatments in preterm infants with late-onset sepsis.

Late-onset sepsis (LOS) in preterm infants can progress rapidly from minimal clinical signs and symptoms to septic shock which is associated with high mortality. The aim of this study was to describe the progression from sepsis to septic shock and evaluate our management performance with emphasis on time to treatments. This was a retrospective observational study including preterm infants ≤32 weeks gestation with LOS and septic shock defined as the requirement of fluids and vasopressors. Physiological changes and time to first diagnostics and treatments were determined from the point of first appearance of clinical signs and symptoms of sepsis (TONSET ). During the 10-year observational period, 279 infants developed LOS and 25 (8.9%) progressed to septic shock. The median (interquartile range) time from TONSET to blood culture, administering antibiotics, fluid bolus and vasopressors was 8.4 (4.8-12.2), 9.2 (5.6-12.4), 14.6 (9.5-34.5) and 22.0 (14.6-44.7) h, respectively. Hypotension and raised lactate were prominent physiological changes in the progression to septic shock. Fluid bolus and vasopressors were administered when blood pressure was 20 and 41% below to what was normal before the infant became unwell. Vasopressors significantly increased blood pressure and heart rate. Mortality rate was 40% with no difference in time to treatments between survivors and non-survivors. Clinical recognition of the onset of sepsis in preterm infants remains difficult and contributes to delay of treatment. Once recognised, early administration of antibiotics, fluid bolus and vasopressors should be prioritised.