Neonatal Sepsis and Neutrophil Insufficiencies

Sepsis has continuously been a leading cause of neonatal morbidity and mortality despite current advances in chemotherapy and patient intensive care facilities. Neonates are at high risk for developing bacterial infections due to quantitative and qualitative insufficiencies of innate immunity, particularly granulocyte lineage development and response to infection. Although antibiotics remain the mainstay of treatment, adjuvant therapies enhancing immune function have shown promise in treating sepsis in neonates. This article reviews current strategies for the clinical management of neonatal sepsis and analyzes mechanisms underlying insufficiencies of neutrophil defense in neonates with emphasis on new directions for adjuvant therapy development.     

Inflammatory and immunological markers in preterm infants: correlation with disease

Newborn infants often suffer from bacterial and viral infections without presenting typical symptoms. Therefore, reliable methods for detecting and monitoring sepsis in the newborn would be beneficial. In older patients C-reactive protein (CRP) and neopterin have proved useful serum markers of infection and inflammation. Both of these markers are regulated by cytokines, and it has been proposed that cytokines themselves could be used to monitor immune activation and infection. This study has examined the levels of CRP, neopterin, soluble IL-2R, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in cord blood samples from both pre-mature and term neonates. Having established reference ranges for these analytes, serial measurements were made in babies requiring intensive care support. The results suggest that in preterm infants the simultaneous measurement of CRP and neopterin, and possibly soluble IL-2R, may provide an accurate early diagnosis of sepsis and may be of use in differentiating between bacterial and viral etiologies. In addition, serial measurement of these markers may help in the early diagnosis of necrotizing enterocolitis (NEC).     

Infections fongiques invasives du grand prématuré

Fungal infections were frequent in premature baby (<1500 g) and were associated with significant morbidity and mortality. In this paper we review the risk factors for invasive fungal infections and clinical settings. A better understanding of the mechanism of fungal infection in preterm infants is important in treatment and prevention. The early neonatal intensive care unit course favours colonization and proliferation of fungi since many preterm infants have central catheters and are exposed to broad spectrum antibiotics and parenteral nutrition. The majority of fungal infections in preterm neonates are due to Candida, with a small number due to other yeasts such as Malassezia. Candida is an opportunistic pathogen, which adheres to the skin, mucosal, and catheter surface. C. albicans account for 50% of cases of fungal sepsis. C. parapsilosis is the second most prevalent species in very low birth weight children; its frequency increased from 1995 to 2000. Risk factors for fungal colonization are: very low birth weight, exposure to broad spectrum antibiotics, parenteral nutrition and use of corticosteroids. Colonization of the skin, gastro-intestinal tract and respiratory tract and central vascular catheter precede infection. The majority of preterm infants with fungal infections develop thrombocytopenia, but this is a common feature shared with other sepsis. The evaluation of infants with fungal sepsis should include cerebrospinal fluid examination and culture of urine with surveillance for endocarditis, renal, liver and brain abscesses and endophthalmitis. The mortality rate can reach 30%, and is higher in very low birth weight infants.     

Connection between gut microbiome and brain development in preterm infants

Dysbiosis of the gut microbiome in preterm infants predisposes the neonate to various major morbidities including neonatal necrotizing enterocolitis and sepsis in the neonatal intensive care unit, and adverse neurological outcomes later in life. There are parallel early developmental windows for the gut microbiota and the nervous system during prenatal to postnatal of life. Therefore, preterm infants represent a unique population in which optimization of initial colonization and microbiota development can affect brain development and enhance neurological outcomes. In this review, we will first discuss the factors affecting the assembly of neonatal gut microbiota and the contribution of dysbiosis in preterm infants to neuroinflammation and neurodevelopmental disorders. We then will discuss the emerging pathways connecting the gut microbiome and brain development. Further we will discuss the significance of current models for alteration of the gut microbiome (including humanized gnotobiotic models and exposure to antibiotics) to brain development and functions. Understanding the role of early optimization of the microbiome in brain development is of paramount importance for developing microbiome-targeted therapies and protecting infants from prematurity-related neurodevelopmental diseases.     

Congenital bacterial sepsis in very preterm infants.

The results of body fluid and surface cultures from 148 preterm infants less than 33 weeks gestational age obtained routinely on admission to a neonatal intensive care unit were reviewed. The aim was to determine the occurrence of congenital bacterial sepsis in this population and to examine whether surface cultures yielded information helpful in management. Gastric aspirate and umbilical, nasal and ear swabs were cultured and the results were compared to those of blood cultures. Nine infants (5.4%) had congenital bacterial sepsis diagnosed by positive blood cultures. Only the results of microscopy of gastric aspirate were available within hours of birth and before the results of blood culture. Microscopy of gastric aspirate, demonstrating pus cells, alone had a sensitivity of 0.86 in predicting congenital sepsis but a specificity of 0.49; the specificity, however, rose to 0.80 if both organisms and pus cells were observed on microscopy. Thus, only this combination was a useful pre-indicator of congenital sepsis. In infants who did not develop septicaemia, treatment was modified only if Streptococcus agalactiae was cultured from surface sites; in all such cases, the organism was grown from the ear swab. Our results demonstrate that congenital bacterial sepsis is common amongst very preterm infants admitted for neonatal intensive care but routine screening of surface cultures should be restricted to an ear swab only.     

Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset.

Neonatal sepsis is a major cause of death in newborns despite sophisticated neonatal intensive care. This retrospective study reviewed the clinical characteristics of cases of culture-proven sepsis in a neonatal intensive care unit from January 1992 to December 2001. Patients were divided into those with onset of sepsis in the first 7 days of life (early-onset group) and those with onset after the seventh day of life (late-onset group). A total of 270 cases with 325 episodes of sepsis and 353 isolated pathogens were identified and included in the study. The male-to-female ratio was 1.4. The majority of cases of sepsis occurred in low birth weight (75.9%) and premature babies (76.7%). Late onset occurred in 71.9% of cases. Patients with late onset had a lower mortality rate than those with early onset (11.3% vs 28.9%). Coagulase-negative staphylococci (20.1%) was the most common organism isolated, but infection with Pseudomonas aeruginosa was associated with the highest morality rate (55.0%). Late-onset sepsis was significantly more common in very low birth weight and premature infants. The most frequently encountered pathogens in the early-onset group were group B streptococci (GBS) and Escherichia coli, while in the late-onset group, the organisms were coagulase-negative staphylococci and Enterobacteriaceae, including E. coli, Klebsiella pneumoniae, and Acinetobacter baumannii. GBS infection resulted in the highest mortality when the onset of sepsis was within the first 24 hours of life.     

Early Prophylactic versus Late Selective Use of Surfactant for Respiratory Distress Syndrome in Very Preterm Infants: A Collaborative Study of 53 Multi-Center Trials in Korea

Pulmonary surfactant (PS) therapy was proven to be highly successful for the treatment of respiratory distress syndrome in premature infants. As a results, early prophylactic (EP) PS therapy has been introduced recently in Europe, the US and Korea. However, no multi-center study was compared EP and late selective (LS) PS therapies in Korea. We performed a retrospective multi-center study to compare the outcomes of EP and LS PS therapies in very preterm infants. We analyzed clinical morbidity and mortality for 1,291 infants in 2010 (LS group) and 1,249 infants in 2011 (EP group); the infants were born <30 weeks of gestation and had birth weight ≤1,250 g, and were chosen from 53 neonatal intensive care units in Korea. Compared to the LS group (22.5%), the overall mortality was better in the EP group (19.9%) and there was no increased need for retreatment.There were additional benefits in the EP group such as fewer associated complications. To the best of knowledge, our study is the first nationwide Korean study to compare the outcomes of EP and LS therapies, and it provides evidences that EP PS therapy is important in very preterm infants to improve for survival and reduce morbidities.

Graphical Abstract

相似文献   

Extrauterine growth restriction in preterm infants: importance of optimizing nutrition in neonatal intensive care units

Extrauterine growth restriction in preterm infants secondary to suboptimal nutrition is a major problem in neonatal intensive care units. Evidence is emerging that early growth deficits have long-term adverse effects, including short stature and poor neurodevelopmental outcomes. The parenteral route of feeding is essential to maintain nutritional integrity before successful transition to the enteral route of feeding is achieved. Nevertheless, early initiation of enteral feeding in sub-nutritional trophic quantity is vital for promoting gut motility and bile secretion, inducing lactase activity, and reducing sepsis and cholestatic jaundice. Results emerging from over sixty randomized clinical trials are available for providing a template on which feeding protocols can be based. Preterm breast milk expressed from the infant's own mother is the milk of choice. Supplementation with a human milk fortifier is necessary to optimize nutritional intake. Preterm formulas are an appropriate substitute for preterm human milk when the latter is unavailable. There are over ten systematic reviews of randomized controlled trials published by the Cochrane Library that addressed feeding strategies, but most do not address long-term outcome measures of clinical importance. There is an urgent need for large-scale, long-term randomized controlled trials to help evaluate metabolic, growth, and neurodevelopmental responses of preterm infants to earlier and more aggressive nutritional management.     

早产前应用不同疗程地塞米松对于早产孕妇母儿预后的影响

目的探讨产前应用不同疗程地塞米松对于早产孕妇母儿预后的影响。方法回顾性分析85例28-34周早产母儿临床资料。结果在≤34周早产孕妇产前应用地塞米松可以显著降低新生儿呼吸窘迫综合征（NRDS）的发生率（P〈0.05）,多疗程与单疗程治疗组之间无明显差异（P〉0.05）;地塞米松未增加新生儿缺血缺氧性脑病,新生儿感染及新生儿死亡率,对孕妇产褥感染也无明显的影响（P〉0.05）;伴胎膜早破应用多疗程地塞米松组产褥感染率明显增加,高于对照组及单疗程治疗组（P〈0.05）。结论在≤34周早产孕妇应用地塞米松可预防NRDS发生,多疗程应用未增加对NRDS保护作用,对胎膜早破者增加产褥感染机率。     

Candidal and bacterial bloodstream infections in premature neonates: a case-control study.

Nosocomial bloodstream infections (BSI) in premature neonates are an important cause of morbidity and mortality. The early and efficient diagnosis of a neonatal BSI and the differentiation between bacterial and fungal BSI remains a challenging task. We compared the clinical features and blood test results in preterm infants with proven candidal or bacterial BSI in order to identify potential risk factors for developing a candidal BSI. Preterm infants with proven candidal BSI were significantly more prematurely born (mean age of gestation 27.7 vs. 29.8 weeks), had previously received significantly more antibiotics of multiple classes (mean 4.4 vs. 1.2) for significantly longer periods (mean 19.3 vs. 3.2 days), were ventilated more intensively, had a significantly longer stay at the neonatal intensive care unit before the onset of the BSI (mean 26.5 vs. 9.4 days), and had C-reactive protein values even higher than in preterm infants with a bacterial BSI (mean 90 vs. 71 mg l(-1)). The presence of thrombocytopenia ( < 150 x 10(9) cells l(-1)) in all the preterm infants with candidal BSI was a significant difference. No differences were seen with regard to birth-weight, use of central intravascular catheters, total parenteral nutrition, white blood cell count and differentiation. In conclusion, candidal BSI can be strongly expected after the third week of admittance in the most premature neonates on a respirator and treated with multiple classes of antibiotics for a prolonged period of time. The presence of these risk factors in a 'septic' premature infant on antibiotic treatment justifies the empiric use of antifungals.     

Acinetobacter baumannii colonization in ventilated preterm infants

The role ofAcinetobacter baumannii in infections in ventilated preterm infants was evaluated in 15 colonized infants (11 male, 4 female) in a pediatric intensive care unit. These cases were randomly matched by birth weight and gestational age with ventilated non-colonized controls (8 male, 7 female). Case records were reviewed for signs and symptoms of infection. Colonized infants were ventilated significantly longer (p<0.05) than controls, and had body temperatures of >37°C for a significantly longer period of time (p<0.05). No other parameter of infection differed significantly between the groups. The duration of intensive care treatment did not differ between cases and controls, nor did the weight gain during intensive care treatment. No fatalities occurred in either group.     

Defining quality of care indicators for neonatal intensive care units independent of maternal risk factors

Observed and birthweight-specific neonatal mortality rates have been used for assessing quality of neonatal care, but these are crude and affected by risk characteristics of the population served. Even when neonatal mortality rate is corrected for four risk factors, race, sex, birthweight, and multiple births, (California Data Research Facility, Santa Barbara, CA) it is possible that the corrected neonatal mortality rate is not comparable among institutions because of population differences not corrected for, eg, prenatal care. To analyze whether our high neonatal mortality rate is primarily dependent on population risk or quality of neonatal care, we used contemporaneous data collection by senior physicians and a microcomputer database system to construct indices of quality of care that are based on diagnoses graded according to disease severity. For the 1987/1988 academic year, we found: neonatal intensive care unit nosocomial infection rate, 20%; severe intraventricular hemorrhage per 100 very low birthweight infants (1500 g), 20%; bronchopulmonary dysplasia per 100 cases of severe respiratory distress syndrome, 27%; necrotizing enterocolitis per 100 neonatal intensive care unit discharges, 5%; air leak per 100 cases of severe respiratory distress syndrome, 21%; and neonatal mortality rate per very low birthweight delivery rate, 0.4. We propose that microcomputer, hospital-based analyses will improve comparisons of neonatal intensive care unit quality of care if appropriate indices can be sufficiently well-defined and shared.     

脓毒症早期诊断和治疗进展

脓毒症是一项全球性公共卫生问题,具有发病率高、病情严重和病死率高的特点,是重症监护病房(ICU)患者病死的主要原因之一。脓毒症的早期诊断是降低病死率的关键,但是目前尚无诊断的金标准。近年来,液体复苏和抗生素的综合治疗一直是脓毒症治疗的主要方法,但是在许多方面还存在许多争议。此外,免疫治疗是脓毒症治疗的热点之一。本文就脓毒症的早期诊断和治疗进展进行总结和阐述。     

Comparison of 16S rRNA gene PCR and BACTEC 9240 for detection of neonatal bacteremia

Ten percent of infants born in the United States are admitted to neonatal intensive care units (NICU) annually. Approximately one-half of these admissions are from term infants (>34 weeks of gestation) at risk for systemic infection. Most of the term infants are not infected but rather have symptoms consistent with other medical conditions that mimic sepsis. The current standard of care for evaluating bacterial sepsis in the newborn is performing blood culturing and providing antibiotic therapy while awaiting the 48-h preliminary result of culture. Implementing a more rapid means of ruling out sepsis in term newborns could result in shorter NICU stays and less antibiotic usage. The purpose of this feasibility study was to compare the utility of PCR to that of conventional culture. To this end, a total of 548 paired blood samples collected from infants admitted to the NICU for suspected sepsis were analyzed for bacterial growth using the BACTEC 9240 instrument and for the bacterial 16S rRNA gene using a PCR assay which included a 5-h preamplification culturing step. The positivity rates by culture and PCR were 25 (4.6%) and 27 (4.9%) positive specimens out of a total of 548 specimens, respectively. The comparison revealed sensitivity, specificity, and positive and negative predictive values of 96.0, 99. 4, 88.9, and 99.8%, respectively, for PCR. In summary, this PCR-based approach, requiring as little as 9 h of turnaround time and blood volumes as small as 200 microl, correlated well with conventional blood culture results obtained for neonates suspected of having bacterial sepsis.     

Histological chorioamnionitis and neonatal leukemoid reaction in low-birth-weight infants

We investigated whether histological chorioamnionitis (HCA) is a risk factor predisposing to leukemoid reaction (LR) and whether LR is associated with the preterm parturition syndrome and the systemic fetal inflammation response syndrome. A prospective histological study on placentas was performed in preterm infants (相似文献   

Effect of telemedicine on health outcomes in 87 infants requiring neonatal intensive care.

OBJECTIVE: This is an evaluation of a telemedicine system for the rapid interpretation of neonatal echocardiograms from a regional, level III neonatal intensive care unit (NICU). The use of telemedicine to support the cardiology needs of NICUs is increasing. However, there is very little published objective information regarding health outcomes or costs resulting from such telemedicine systems. The primary hypothesis tested was that the utilization of a telemedicine system for the interpretation of neonatal echocardiograms reduces the intensive care length of stay of low birthweight (LBW) infants. STUDY DESIGN: All infants who were admitted to neonatal intensive care at New Hanover Regional Medical Center during the first six months of the system were studied by the use of echocardiograms. They were compared with infants who were born in the same period of the previous year. The outcome measures were the intensive care length of stay, rate of transfer to academic medical centers, and mortality rate. RESULTS: A statistically non-significant reduction of 5.4 days in the intensive care length of stay (LOS) of low birthweight infants was observed (p = 0.37). The cost per echocardiogram transmitted was calculated at $33 compared to previous method of sending videotapes via overnight courier. CONCLUSIONS: While the sample size was inadequate to demonstrate improvements in health outcomes, the magnitude of the change and the low costs of the system suggest that this intervention is practical for obtaining rapid diagnostic and treatment support. Larger studies are warranted to confirm these findings and determine whether faster diagnosis and earlier initiation of treatment improve health outcomes of newborn infants.     

The effects on offspring of premature parturition

The time of parturition defines the length of the intrauterine period of fetal life, a requisite to achieve adequate adaptation to the external environment. Immaturity, a condition whose severity is inversely related to the length of pregnancy, is the main determinant of the increased morbidity and mortality associated with preterm birth. Despite great advances in medical technology and expertise, mainly after the introduction of the neonatal intensive care units, only one- to two-thirds of infants from the subsets with lower birthweight/gestational age reach survival at discharge. Distinct major neurological and sensorial sequelae, including cerebral palsy, retinopathy of prematurity, and hearing loss, as well as reduced neuropsychological abilities, leading to deficient academic achievement and deterioration of several aspects of health status, are still highly prevalent among the most immature children. Interestingly, decreasing mortality rates, which are not followed by detectable increases of disability, are being observed in recent years. Future advances may be expected from clinical and basic research on uterine contractility and cervical softening. Also, changes in reproductive technology procedures, a main factor in the incidence of multiple pregnancies, and a more refined approach to obstetric care, compose some of the clinical interventions which may reduce the problem.     

Septicaemia and the prevention of multiorgan failure--the intensive care perspective

Septicaemia frequently presents without "classic" signs of infection--tachypnoea, hypotension and confusion are the commonest features. The mortality rate is 40 to 80% and in intensive care units, septicaemia accounts for 70% of all deaths. Despite the use of antimicrobial drugs to which the offending organism is sensitive, patients are still dying. Effects on distant organ systems are due to "Mediators". "Microvascular Failure" resulting in tissue hypoxia is the unifying hypothesis of multiple organ failure in septicaemia. Mortality is correlated with the number of organ system failures. Supportive management is aimed at prevention of organ failure--manipulation of the circulation being the central key. Intravascular volume expansion, vasoactive drugs, mechanical ventilation and invasive monitoring are the means. Antimicrobial therapy must be guided by 'best guess' approach with multiple agents until isolation of the offending organism can recommend specific therapy. Aggressive surgical drainage or excision, is particularly applicable in abdominal sepsis. Several adjunctive therapies aimed at mediators of sepsis, are as yet experimental.