Sepsis In Preterm Infants Research Articles

Subclinical necrotizing enterocolitis-induced systemic immune suppression in neonatal preterm pigs.

Preterm infants are at high risks of sepsis and necrotizing enterocolitis (NEC). Some develop sepsis shortly after suspected or confirmed NEC, implying that NEC may predispose to sepsis but the underlying mechanisms are unknown. Using NEC-sensitive preterm pigs as models, we investigated the immune status in animals following development of subclinical NEC-like lesions with variable severities. Caesarean-delivered preterm pigs were reared until day 5 or day 9. Blood was analyzed for T-cell subsets, neutrophil phagocytosis, transcriptomics, and immune responses to in vitro LPS challenge. Gut tissues were used for histology and cytokine analyses. Pigs with/without macroscopic NEC lesions were scored as healthy, mild, or severe NEC. Overall NEC incidence was similar on day 5 and day 9 (61%-62%) but with lower severity on day 9, implying gradual mucosal repair following the early phase of NEC. Pigs with NEC showed decreased goblet cell density and increased MPO+ and CD3+ cell infiltration in the distal small intestine or colon. Mild or severe NEC lesions had limited effects on circulating parameters on day 5. On day 9, pigs with NEC lesions (especially severe lesions) showed systemic immune suppression, as indicated by elevated Treg frequency, impaired neutrophil phagocytosis, low expression of genes related to innate immunity and Th1 polarization, and diminished LPS-induced immune responses. In conclusion, we shows evidence for NEC-induced systemic immune suppression, even with mild and subclinical NEC lesions. The results help to explain that preterm infants suffering from NEC may show high sensitivity to later secondary infections and sepsis.NEW & NOTEWORTHY Necrotizing enterocolitis (NEC) and sepsis are common diseases in preterm infants. Many develop sepsis following an episode of suspected NEC, suggesting NEC as a predisposing factor for sepsis but mechanisms are unclear. Using preterm pigs as a model, now we show that subclinical NEC lesions, independent of clinical confounding factors, induces systemic immune suppression. The results may help to explain the increased risks of infection and sepsis in preterm infants with previous NEC diagnosis.

Preventing Fungal Sepsis in Preterm Infants: The Impact of Changing to Prophylactic Nystatin in a Tertiary Neonatal Unit

Fungal organisms pose a life-threatening risk to vulnerable premature infants. In this review, all cases of fungal sepsis in a large tertiary neonatal unit over the last 10 years (2008-2018) in premature neonates (<30 weeks gestation) were reviewed. This time frame spanned a change in prophylaxis policy from fluconazole to nystatin in 2012. The most common fungal organism causing sepsis was Candida albicans in 80% of cases and Candida parapsilosis in 13%. All fungal organisms cultured were fully sensitive; no resistant cases were seen in the last 10 years. Encouragingly, rates of infection were static (between 0 and 3 cases/year) over the last 10 years, despite the unit’s policy for antifungal prophylaxis changing from fluconazole to nystatin in 2012.

Early Detection of Late Onset Sepsis in Premature Infants Using Visibility Graph Analysis of Heart Rate Variability.

This study was designed to test the diagnostic value of visibility graph features derived from the heart rate time series to predict late onset sepsis (LOS) in preterm infants using machine learning. The heart rate variability (HRV) data was acquired from 49 premature newborns hospitalized in neonatal intensive care units (NICU). The LOS group consisted of patients who received more than five days of antibiotics, at least 72 hours after birth. The control group consisted of infants who did not receive antibiotics. HRV features in the days prior to the start of antibiotics (LOS group) or in a randomly selected period (control group) were compared against a baseline value calculated during a calibration period. After automatic feature selection, four machine learning algorithms were trained. All the tests were done using two variants of the feature set: one only included traditional HRV features, and the other additionally included visibility graph features. Performance was studied using area under the receiver operating characteristics curve (AUROC). The best performance for detecting LOS was obtained with logistic regression, using the feature set including visibility graph features, with AUROC of 87.7% during the six hours preceding the start of antibiotics, and with predictive potential (AUROC above 70%) as early as 42h before start of antibiotics. These results demonstrate the usefulness of introducing visibility graph indexes in HRV analysis for sepsis prediction in newborns. The method proposed the possibility of non-invasive, real-time monitoring of risk of LOS in a NICU setting.

Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates.

Genome-wide expression profiles have been previously employed as clinical research diagnostic tools for newborn sepsis. We aimed to determine if transcriptomic profiles could discriminate between Gram-positive and Gram-negative bacterial sepsis in preterm infants. Prospective, observational, double-cohort study was conducted in very low birth weight infants with clinical signs and culture-positive sepsis. Blood samples were collected when clinical signs became apparent. Total RNA was processed for transcriptomic analysis. Results were validated by both reverse-transcription polymerase chain reaction and a mathematical model. We included 25 septic preterm infants, 17 with Gram-positive and 8 with Gram-negative bacteria. The principal component analysis identified these two clusters of patients. We performed a predictive model based on 21 genes that showed an area under the receiver-operating characteristic curve of 1. Eight genes were overexpressed in Gram-positive septic infants: CD37, CSK, MAN2B2, MGAT1, MOB3A, MYO9B, SH2D3C, and TEP1. The most significantly overexpressed pathways were related to metabolic and immunomodulating responses that translated into an equilibrium between pro- and anti-inflammatory responses. The transcriptomic profile allowed identification of whether the causative agent was Gram-positive or Gram-negative bacteria. The overexpression of genes such as CD37 and CSK, which control cytokine production and cell survival, could explain the better clinical outcome in sepsis caused by Gram-positive bacteria. Transcriptomic profiles not only enable an early diagnosis of sepsis in very low birth weight infants but also discriminate between Gram-positive and Gram-negative bacteria as causative agents. The overexpression of some genes related to cytokine production and cell survival could explain the better clinical outcome in sepsis caused by Gram-positive bacteria, and could lead us to a future, targeted therapy.

Exposure to intrauterine inflammation and late-onset sepsis in very preterm infants.

Late-onset sepsis is an important cause of mortality and morbidity in preterm infants. As these infants rely mostly on their innate immune system to fight off infection, enhancing this immune system by appropriate stimuli may prevent late-onset sepsis. However, it remains unclear which stimuli can enhance the neonatal immune system. This study aims to investigate the influence of intrauterine inflammation on late-onset sepsis. This is a retrospective cohort study in a Neonatal Intensive Care Unit in the Netherlands. Between 2005 and 2016, 1014 infants with ≤32 weeks gestational age and/or with a birth weight ≤1500 g were included. Intrauterine inflammation was subdivided into histological chorioamnionitis, fetal inflammatory response, and funisitis. Logistic and Cox regression analyses were performed to investigate the influence of intrauterine inflammation on late-onset sepsis. Thirty-six percent of the included infants developed late-onset sepsis; 24% of placentas showed intrauterine inflammation. Late-onset sepsis incidence did not differ between infants with or without exposure to intrauterine inflammation after adjustment for gestational age (histological chorioamnionitis aHR 0.928 [CI: 0.727-1.185], p = 0.551; fetal inflammatory response aHR 1.011 [CI: 0.793-1.288], p = 0.930); funisitis aHR 0.965 [CI: 0.738-1.263], p = 0.797). Late-onset sepsis in very preterm infants seems not to be associated with intrauterine inflammation. Intrauterine inflammation is not protective of developing late-onset sepsis in premature infants. A large cohort study on the effect of intrauterine inflammation on neonatal outcome. This study adds to existing knowledge on finding appropriate stimuli to enhance the immune system of premature infants to improve neonatal outcome.

ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ЛАБОРАТОРНЫХ МАРКЕРОВ НЕОНАТАЛЬНОГО СЕПСИСА У НЕДОНОШЕННЫХ ДЕТЕЙ

Neonatal sepsis (NS) is the leading cause of mortality in premature newborns. It is a difficult diagnostic task for clinicians. This article provides a review of the literature on laboratory markers of NS. The latest methods for the diagnosis of sepsis in premature infants in various studies are considered in the article. The results of studying the diagnostic value of a general blood test, cytokines, C-reactive protein, procalcitonin, prespepsin, microRNA polymorphism, bacterial blood culture, their advantages and disadvantages, as well as diagnostic significance – sensitivity, specificity, prognostic value of positive and negative results are presented.

Prediction of Late-Onset Sepsis in Preterm Infants Using Monitoring Signals and Machine Learning.

Prediction of late-onset sepsis (onset beyond day 3 of life) in preterm infants, based on multiple patient monitoring signals 24 hours before onset. Continuous high-resolution electrocardiogram and respiration (chest impedance) data from the monitoring signals were extracted and used to create time-interval features representing heart rate variability, respiration, and body motion. For each infant with a blood culture-proven late-onset sepsis, a Cultures, Resuscitation, and Antibiotics Started Here moment was defined. The Cultures, Resuscitation, and Antibiotics Started Here moment served as an anchor point for the prediction analysis. In the group with controls (C), an "equivalent crash moment" was calculated as anchor point, based on comparable gestational and postnatal age. Three common machine learning approaches (logistic regressor, naive Bayes, and nearest mean classifier) were used to binary classify samples of late-onset sepsis from C. For training and evaluation of the three classifiers, a leave-k-subjects-out cross-validation was used. Level III neonatal ICU. The patient population consisted of 32 premature infants with sepsis and 32 age-matched control patients. No interventions were performed. For the interval features representing heart rate variability, respiration, and body motion, differences between late-onset sepsis and C were visible up to 5 hours preceding the Cultures, Resuscitation, and Antibiotics Started Here moment. Using a combination of all features, classification of late-onset sepsis and C showed a mean accuracy of 0.79 ± 0.12 and mean precision rate of 0.82 ± 0.18 3 hours before the onset of sepsis. Information from routine patient monitoring can be used to predict sepsis. Specifically, this study shows that a combination of electrocardiogram-based, respiration-based, and motion-based features enables the prediction of late-onset sepsis hours before the clinical crash moment.

Can venous cord blood neutrophil to lymphocyte ratio and platelet to lymphocyte ratio predict early-onset sepsis in preterm infants?

Background: To explore the predictive value of venous cord blood neutrophil-to-lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) for Early-onset sepsis (EOS) in preterm infants. Methods: A prospective cohort of neonates with gestational ages <32 weeks in a single hospital from January 2017 to January 2020 were enrolled. Multivariable logistic regression was used to determine independent risk factors for EOS. ROC curves were created to estimate the predictive capacity. Results: A total of 427 neonates were included in the study. 176 neonates were exposed to chorioamnionitis including 89 EOS and 87 without EOS, and the venous cord blood white blood cell (WBC), (neutrophil) N, (platelet) P, NLR and PLR in the EOS infants were significantly increased. 251 infants were unexposed to chorioamnionitis including 63 EOS and 188 without EOS, and N and NLR were significantly increased in EOS infants. After adjustment for covariates, multivariable logistic regression analysis demonstrated high NLR was independently associated with the subsequent risk of EOS in the infants both exposed and unexposed to chorioamnionitis. The most accurate discriminatory NLR for EOS threshold in infants exposed to chorioamnionitis was 2.68 (AUC = 0.949, sensitivity = 0.839, specificity = 0.933). The most accurate discriminatory NLR for EOS threshold in infants unexposed to chorioamnionitis was 2.01 (AUC = 0.852, sensitivity = 0.830, specificity = 0.762). The cutoff value of the PLR for predicting EOS in the preterm infants exposed to chorioamnionitis was 55.051, the sensitivity was 82%, the specificity was 36.7%, and the AUC was 0.579. Conclusions: Venous cord blood NLR seems to be an early, sensitive and convenient marker for preterm infants with EOS, especially in those exposed to chorioamnionitis. Meanwhile, venous cord blood PLR is not an accurate predictor of EOS in preterm infants.

The Use of Daptomycin in the Treatment of Persistent Coagulase-Negative Staphylococcal Sepsis in Premature Infants: A Case Series.

Daptomycin is a lipopeptide antibiotic with rapid bactericidal activity against Gram-positive bacteria. Reports regarding the use of daptomycin in infants are still limited. Thus, the objective of this report is to describe the safety and efficacy of daptomycin in premature infants with persistent coagulase-negative staphylococci (CoNS) infection. This was a retrospective chart review of 10 premature infants with persistent CoNS infection who received daptomycin therapy between January 2018 and September 2019. Four patients had endocarditis and 1 had bacterial meningitis and infectious endocarditis. The other 5 patients had persistent CoNS bacteraemia only. Daptomycin treatment was successful for 5 patients. The others died owing to multiple factors such as prematurity, sepsis, and chronic lung disease. Adverse drug reactions, including elevation of creatine phosphokinase and/or hepatotoxicity, were noted in 4 patients. Large and randomized studies are necessary to ensure daptomycin's safety and efficacy for the treatment of infants with persistent sepsis caused by Gram-positive bacteria.

Platelets and Immature Neutrophils in Preterm Infants with Feeding Intolerance.

Feeding intolerance (FI) is a common presentation of necrotizing enterocolitis (NEC) and sepsis. NEC and sepsis are associated with hematological changes, but these changes alone are not reliable biomarkers for early diagnosis. This study examined whether the combination of hematological indices and FI can be used as an early diagnostic tool for NEC or sepsis. This retrospective cohort study included infants born at <1,500 g or <30 weeks who had symptoms of FI. The exclusion criteria were congenital or chromosomal disorders, thrombocytopenia or platelet transfusion before the onset of FI, and history of bowel resection. We compared the hematological indices from infants with pathologic FI (due to NEC or sepsis) to infants with benign FI. During the study period, 211 infants developed FI; 185 met the inclusion criteria. Infants with pathologic FI (n = 90, 37 cases with NEC and 53 with sepsis) had lower birth gestational age and weight compared with 95 infants with benign FI (n = 95). Pathologic FI was associated with lower platelet count (median 152 × 103/μL vs. 285 × 103/μL, p < 0.001) and higher immature-to-total neutrophil (I/T) ratio (median 0.23 vs. 0.04, p < 0.001) at the onset of FI. Pathologic FI was also associated with a decrease in baseline platelets compared with an increase in benign FI. For diagnosis of pathologic FI, a decrease ≥10% in platelets from baseline had a sensitivity and specificity of 0.64 and 0.73, respectively, I/T ratio ≥0.1 had a sensitivity and specificity of 0.71 and 0.78, respectively, and the combination of both parameters had a sensitivity and specificity of 0.50 and 0.97, respectively. FI caused by NEC or sepsis was associated with a decrease in platelets from baseline, and a lower platelet level and higher I/T ratio at the onset of FI. These findings can help clinicians in the management of preterm infants with FI. · FI is a common presentation of NEC and sepsis in preterm infants.. · FI due to NEC or sepsis is associated with changes in platelets and I/T ratio.. · These changes could be useful as early markers for diagnosis..

Niche specialization and spread of Staphylococcus capitis involved in neonatal sepsis.

The multidrug-resistant Staphylococcus capitis NRCS-A clone is responsible for sepsis in preterm infants in neonatal intensive care units (NICUs) worldwide. Here, to retrace the spread of this clone and to identify drivers of its specific success, we investigated a representative collection of 250 S. capitis isolates from adults and newborns. Bayesian analyses confirmed the spread of the NRCS-A clone and enabled us to date its emergence in the late 1960s and its expansion during the 1980s, coinciding with the establishment of NICUs and the increasing use of vancomycin in these units, respectively. This dynamic was accompanied by the acquisition of mutations in antimicrobial resistance- and bacteriocin-encoding genes. Furthermore, combined statistical tools and a genome-wide association study convergently point to vancomycin resistance as a major driver of NRCS-A success. We also identified another S. capitis subclade (alpha clade) that emerged independently, showing parallel evolution towards NICU specialization and non-susceptibility to vancomycin, indicating convergent evolution in NICU-associated pathogens. These findings illustrate how the broad use of antibiotics can repeatedly lead initially commensal drug-susceptible bacteria to evolve into multidrug-resistant clones that are able to successfully spread worldwide and become pathogenic for highly vulnerable patients.

Staphylococcus epidermidis Sensitizes Perinatal Hypoxic-Ischemic Brain Injury in Male but Not Female Mice.

Background: Staphylococcus epidermidis is the most common nosocomial infection and the predominant pathogen in late-onset sepsis in preterm infants. Infection and inflammation are linked to neurological and developmental sequelae and bacterial infections increase the vulnerability of the brain to hypoxia-ischemia (HI). We thus tested the hypothesis that S. epidermidis exacerbates HI neuropathology in neonatal mice.Methods: Male and female C57Bl/6 mice were injected intraperitoneally with sterile saline or 3.5 × 107 colony-forming units of S. epidermidis on postnatal day (PND) 4 and then subjected to HI on PND5 (24 h after injection) or PND9 (5 d after injection) by left carotid artery ligation and exposure to 10% O2. White and gray matter injury was assessed on PND14-16. In an additional group of animals, the plasma, brain, and liver were collected on PND5 or PND9 after infection to evaluate cytokine and chemokine profiles, C5a levels and C5 signaling.Results: HI induced 24 h after injection of S. epidermidis resulted in greater gray and white matter injury compared to saline injected controls in males, but not in females. Specifically, males demonstrated increased gray matter injury in the cortex and striatum, and white matter loss in the subcortical region, hippocampal fimbria and striatum. In contrast, there was no potentiation of brain injury when HI occurred 5 d after infection in either sex. In the plasma, S. epidermidis-injected mice demonstrated increased levels of pro- and anti-inflammatory cytokines and chemokines and a reduction of C5a at 24 h, but not 5 d after infection. Brain CCL2 levels were increased in both sexes 24 h after infection, but increased only in males at 5 d post infection.Conclusion: Ongoing S. epidermidis infection combined with neonatal HI increases the vulnerability of the developing brain in male but not in female mice. These sex-dependent effects were to a large extent independent of expression of systemic cytokines or brain CCL2 expression. Overall, we provide new insights into how systemic S. epidermidis infection affects the developing brain and show that the time interval between infection and HI is a critical sensitizing factor in males.

An Overview of Diagnosis Neonatal Sepsis with Antimicrobial Management

Neonatal sepsis is one of the most prevalent major health problems, affecting an estimate of around thirty million newbornseach year throughout the world. The onset of sepsis within the first fourty-eight hours after birth is associated with prenatal and perinatal predisposing factors. The on set of sepsis between fourty-eight and seventy-two hours of life usually indicatesnosocomially acquired infections. Klebsiella Pneumonia is the leading pathogenic organism causing neonatal sepsis in Asian countries, and the most important etiological factor for neonatal sepsisis found to be low birth weight. Sepsis score is a useful method for early and rapid diagnosis of neonatal sepsis. Antibiotics are given to most neonates suspected to be infected. Ampicillin and gentamicin are the first line treatment. The occurrence of neonatal sepsis can be brought down by practising clean and safe delivery, early &amp; exclusive breast feeding, strict postnatal cleanliness which should be followed by adequate hand washing and aseptic methods. Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem. Despite major advances in neonatal medical care, the frequent presence of non-infectious conditions resembling sepsis pose a challenge to the diagnosis of neonatal sepsis, especially seen in preterm infants. Another factor complicating the diagnostic procedure is the absence of optimal diagnostic tests. Neonatal sepsis is among the leading high-risk diseases that infect newborns, especially preterm infants, warranting an aggressive line of treatment. Clinical practitioners are compelled to use broad spectrum antibiotics to neonates with high risk factors and/or signs of suspected infection. But the use of empirical antibiotic coverage and also their prolonged use contribute to the rising incidence of resistance amongst microbial strains. Apart from the high occurrence rate and mortality rate of sepsis in preterm infants, its long-term consequences also include adverse effects on growth and development. In our review, we touch upon the most common doubts and challenges faced during the diagnosis and management of neonatal sepsis. [1].

Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis: A Prospective, Multi-center Cohort Study.

Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiologic role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC. In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter-related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry. In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter-related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11). Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology.

The effects of proton pump inhibitors on the microbiome in young children.

The use of proton pump inhibitor (PPI) treatments are increasing among paediatric patients worldwide. We aimed to review the effects of PPIs on the microbiome and its associated effect on the gastrointestinal, respiratory and metabolic systems. The role of probiotics is discussed. We searched for relevant articles published in English language in PubMed and Google Scholar. Articles were extracted using subject heading and key words of interest to the topic. There is evidence that PPIs modify the microbiome of the mouth, gut and lungs. The specific adverse effects associated with PPIs were necrotising enterocolitis, late onset sepsis in premature infants, Clostridium difficile infection, asthma, obesity and small intestine bacterial overgrowth in young children. Studies on the use of probiotics to counteract adverse effects of PPIs were limited. PPIs create dysbiosis of the microbiome in the mouth, gut and lungs in the paediatric population. Probiotics could restore dysbiosis but it has very poorly been studied if probiotics can counteract or prevent PPI induced adverse effects.

Neonatal and Neurodevelopmental Outcomes Following Linezolid for Coagulase-negative Staphylococcal Infection: Real World Evidence.

Coagulase-negative staphylococci (CoNS) frequently causes late-onset sepsis in preterm infants. Vancomycin is the first-line therapy, but the emergence of reduced vancomycin-susceptibility strains has resulted in linezolid use, of which long-term safety in preterm infants is unknown. Evaluate the association between linezolid exposure and neurodevelopmental impairment (NDI) or death at 18-21 months of corrected age, in preterm infants with CoNS sepsis. Multicentric retrospective cohort study comparing long-term outcomes of preterm infants exposed to linezolid versus other antistaphylococcal antimicrobials. We included infants ≤28 weeks' gestational age (GA), with CoNS sepsis, admitted between January 2011 and June 2015 in 3 level-3 Canadian NICUs. Primary outcome was a composite of death or significant NDI (sNDI) at 18-21 months of corrected age. Secondary outcomes included NDI and individual components of the primary outcome. We assessed the relationship between linezolid exposure and outcomes using a multivariable logistic regression. Of 274 infants included, 67 (24.4%) were exposed to linezolid. Median GA was 26 weeks and clinical characteristics were similar between groups. There was no difference in composite outcome of death or sNDI among the infants of both groups, but significantly more death by 18-21 months in the linezolid group (29.9% vs. 17.6%; P = 0.01). Linezolid exposure was not associated with composite outcome of death or sNDI at 18-21 months. The association between linezolid and death may be due to indication bias. Further studies are warranted.

Development and validation of a nomogram for predicting late-onset sepsis in preterm infants on the basis of thyroid function and other risk factors: Mixed retrospective and prospective cohort study

Preterm birth and infection are common causes of neonatal death. In this study, we aimed to develop a nomogram for assessing the individual prior probability of late-onset sepsis on the basis of risk factors in preterm infants. This study is a mixed retrospective and prospective cohort study conducted in three centers. Data from January 2014 to December 2017 was used for the development cohort, and data from January 2018 to December 2018 was used for the validation cohort. In the development cohort, we identified the predicting variables of late-onset sepsis in preterm infants, from which a nomogram was obtained. Then we built nomograms, for with and without thyroid function, to predict late-onset sepsis. The nomogram was validated in the validation cohort concerning discrimination and calibration. A total of 1256 and 452 preterm infants were included in the development and validation cohort, respectively. We found thyroid hypofunction in preterm infants could increase the incidence of late-onset infection. The prediction model incorporated thyroid function, birth weight, use of endotracheal intubation, and duration of umbilical venous catheters was validated and developed as a nomogram for predicting late-onset sepsis in preterm infants. Nomogram in this study may contribute to clinical assessment and treatment decisions.

AB018. Focus on neonatal invasive infections caused by Escherichia coli

: Escherichia coli (E. coli) is a versatile bacterial species that exists as a commensal organism in the lower gastrointestinal tract of humans as well as a pathogen that causes a variety of diseases. Some pathogenic E. coli strains cause diarrheal illness (intraintestinal pathogenic E. coli), whereas others cause extraintestinal infections [extraintestinal pathogenic E. coli (ExPEC)]. Since the implementation of an intrapartum antibiotic prophylaxis program against group B Streptococcus in 1996, its global incidence with respect to newborn sepsis has decreased significantly. However, the overall incidence of E. coli has remained stable over the past few decades, and there has been a significant increase in this species in late-onset sepsis in preterm infants. E. coli is the leading cause of neonatal bacterial sepsis and meningitis. Neonatal meningitis occurs in roughly 0.2 to 1 per 1,000 live births; it is closely associated with sepsis. Even countries with highly developed health care systems encounter high rates of mortality rates (10–30%) due to the disease. Moreover, long-term neurological sequelae are common among more than half of the survivors. The worldwide burden of these extraintestinal infections is staggering. Moreover, E. coli pathogens, particularly those causing extraintestinal infections, have developed resistance to every class of antibiotics introduced to treat human infections. Several surveillance studies during the 2000s across Europe and North and South America have shown that approximately 20–45% of E. coli isolates are resistant to first-line antibiotics including cephalosporins and fluoroquinolones. The production of extended-spectrum β-lactamases (ESBLs) is the main cause of such antibiotic resistance in E. coli. We have already had surveillance results in clinical isolates in neonates. Overall non-susceptible rates to amoxicillin were 72%, tetracycline was 66%, ceftriaxone were 50%, trimethoprim-sulfamethoxazole were 48%, cefepime were 42%, and ciprofloxacin were 36%, respectively. During the 1980s and 1990s, SHV or TEM types were the major types of ESBLs identified among clinical isolates. However, since the mid2000s, CTX-M β-lactamases have become the most common and widespread type. ST131 is considered the most common ESBL-producing E. coli type that causes urinary tract infections and bloodstream infections worldwide. Since 2012, ST1193 has emerged as a new virulent clone of fluoroquinolone-resistant E. coli in several countries. Developing alternative strategies to prevent/eliminate these E. coli infections requires fully understanding the constant epidemiological surveillance of antibiotic-resistance trends of these bacteria, as well as the transmission risks. The transmission of E. coli strains from the mother to the newborn frequently occurs during passage of the neonate through the vaginal canal. Thus, programmes to screen for vaginal and rectal colonization of pregnant women by E. coli, particularly those neonates with sepsis and meningitis, may be effective for infection prevention. Few studies highlighted similarities between newborns and their mothers. It important to know well about E. coli and decrease the morbidity and mortality rates from invasive infection with E. coli among neonates.

Trajectories of the heart rate characteristics index, a physiomarker of sepsis in premature infants, predict Neonatal ICU mortality.

ObjectiveTrajectories of physiomarkers over time can be useful to define phenotypes of disease progression and as predictors of clinical outcomes. The aim of this study was to identify phenotypes of the time course of late-onset sepsis in premature infants in Neonatal Intensive Care Units.MethodsWe examined the trajectories of a validated continuous physiomarker, abnormal heart rate characteristics, using functional data analysis and clustering techniques.ParticipantsWe analyzed continuous heart rate characteristics data from 2989 very low birth weight infants (<1500 grams) from nine NICUs from 2004–2010.ResultDespite the relative homogeneity of the patients, we found extreme variability in the physiomarker trajectories. We identified phenotypes that were indicative of seven and 30 day mortality beyond that predicted by individual heart rate characteristics values or baseline demographic information.ConclusionTime courses of a heart rate characteristics physiomarker reveal snapshots of illness patterns, some of which were more deadly than others.

Can neutrophil-lymphocyte ratio be a predictor of late-onset sepsis in preterm infants?

Aim: Late-onset sepsis (LOS) persists to be a crucial reason of morbidity and mortality in preterm infants. Studying the effect of neutrophil-lymphocyte ratio (NLR) value in predicting the LOS episode and relation with the type of the growing microorganism were the aim of this study.Material and Methods: Preterm infants were classified as two groups in accordance with having culture proven LOS during the stay in neonatal intensive care unit. Premature infants with culture proven LOS was defined as study group and infants with no-LOS as control group. Study group is consisting of two subgroups in terms of the growing microorganism type. NLR values were compared within and between the groups.Results: Overall, final analysis were applied to 116 infants. NLR values were raised in the study group during LOS episode (p0.001). NLR value of the Gram-positive sepsis group (Subgroup 1) was significantly higher in comparison to Gram-negative sepsis group (Subgroup 2) (median: 2.4 and 1.8, respectively, p = 0.02). ROC analysis showed that area under the curve (AUC) of NLR was 0.723 (p0.001) and cut-off point optimized for sensitivity of 68% and a specificity of 82% was stated as NLR ≥1.57 for conforming LOS.Conclusions: These findings demonstrated that in preterm infants, NLR values rise for the duration of a LOS episode. We believe that NLR value may be a helpful for the prediction of LOS in preterm infants.