Newer approaches to the diagnosis of early onset neonatal sepsis

Accurate and timely diagnosis of early onset neonatal sepsis remains challenging to the clinician and the laboratory. A test with a rapid turnaround time with 100% sensitivity, rather than high specificity, which allows accurate diagnosis and appropriate antimicrobial treatment or which allows antibiotics to be safely withheld in non-infected infants, is desirable. Many potential markers (acute phase reactants, cell surface markers, cytokines) are not routinely available to the laboratory, and most likely combinations of markers will ensure greater diagnostic accuracy. In the future, molecular biology techniques offer the prospect of rapid identification of both pathogens and antimicrobial resistance markers.     

Prevention of early onset group B streptococcal sepsis in the newborn

: There is an urgent need for strategies to prevent early onset group B streptococcal sepsis in the newborn. The most effective mechanism is the identification of maternal carriers of the organism and interruption of transmission during labour. Vaginal culture is currently the most reliable method for the identification of carriers. Antibiotic prophylaxis for known carriers in labour has been demonstrated to be effective as standard management practice in a number of Australian institutions and is the best available strategy at this stage.     

Reduction in late‐onset sepsis on relocating a neonatal intensive care nursery

Aims: The aims of this study were to compare rates of late‐onset sepsis (LOS) in very preterm or very low birthweight infants before and after relocation to a new nursery and to determine risk factors for LOS. Methods: The study was undertaken at The Royal Women's Hospital, Melbourne, which relocated to a new site in June 2008. Infants with birthweight <1500 g or <32 weeks' gestation, born between July and December 2007 (n= 149) and July and December 2008 (n= 152) were included. Each septic episode was identified from blood cultures taken from patients >48 h after birth and was categorised as definite, probable, uncertain or no sepsis. Results: Overall, 117 infants had 218 septic episodes. The proportion of infants with clinical LOS decreased from 29.5% in 2007 to 22.4% in 2008 after the relocation, although this was not statistically significant. There was a significant (P < 0.05) reduction in the severity (definite LOS = most severe) of sepsis in 2008 compared with 2007, and in rates of coagulase‐negative staphylococcal LOS. Significant risk factors for LOS were: lower birthweight (g; mean ?351, 95% confidence interval (CI) ?446, ?256); lower gestational age (weeks; mean ?2.3, 95% CI ?2.8, ?1.7) and presence of a percutaneous inserted central catheter (odds ratio (OR) 2.56, 95% CI 1.03, 6.67). Conclusions: There was a significant reduction in the severity of LOS in very preterm and/or very low birthweight infants that correlated with the relocation from the old to new nursery. Smaller and more immature infants with percutaneous central catheters were more at risk.     

Serum fibronectin in neonatal sepsis: Is it valuable in early diagnosis and outcome prediction?

The value of the serum fibronectin level in early diagnosis of neonatal sepsis and as a prognostic indicator was investigated. The serum fibronectin levels and Töllner's sepsis scores of 45 neonates who were hospitalized for the suspicion of infection and of 20 healthy neonates as controls were evaluated. Depending on the findings it was concluded that serum fibronectin level varies according to the gestational age, and that the serum fibronectin level is a useful acute phase reactant in the early diagnosis of neonatal sepsis. It can also be used as a prognostic indicator in neonatal sepsis.     

Role of routine lumbar puncture in neonatal sepsis

Objective: To evaluate the utility of lumbar puncture done routinely as part of complete workup in neonatal sepsis.
Methodology: Two hundred and nine consecutive lumbar punctures performed in 169 neonates were prospectively evaluated for the diagnosis of meningitis over a 6 month period in a tertiary care referral neonatal unit.
Results: Among babies with 'suspected clinical sepsis', five (3.3%) were diagnosed to have meningitis. None of the clinically normal babies with high risk obstetric factors alone had meningitis. The lumbar puncture was traumatic in 22.9%, and in 26.3% the fluid obtained was inadequate for complete analysis. The results were inconclusive in 37% of the cases.
Conclusion: Based on this study, routine lumbar puncture may not be required in clinically normal newborns with adverse obstetric factors. In babies with clinical sepsis, though the yield is not very high; there are no reliable clinical or laboratory markers to predict which babies will have meningitis and hence these babies would warrant a lumbar puncture.     

机械通气新生儿深部真菌感染18例

目的探讨机械通气新生儿深部真菌感染的临床和病理特点。方法分析1985~2003年我科经尸检证实深部真菌感染的曾行机械通气的18例新生儿的临床和病理资料。结果18例新生儿中,曲霉菌感染8例,白色念珠菌感染6例,毛霉菌4例。肺部真菌感染12例,肝脏真菌感染4例,脑部、胃肠道真菌感染各2例。其中2例同时存在肺部和肝脏真菌感染。结论机械通气新生儿深部真菌感染不容忽视,曲霉菌和白色念珠菌为主要病原菌。主要受累器官为肺。早期诊断是提高存活率的有效途径。     

基因检测在新生儿脓毒症早期诊断中的价值

目的 分析16S rRNA基因检测在新生儿脓毒症早期诊断中的临床价值,探讨快速、可靠地诊断该症的试验方法.方法在16S rRNA基因保守区选择一对通用引物,收集临床常见的致病菌株37株,提取细菌DNA并进行PCR检测,采用琼脂糖凝胶电泳法观察扩增结果,同时对该引物的灵敏性及特异性进行检验.对106例临床疑诊为脓毒症的新生儿于入院24 h内,在严格无菌条件下采集血标本,提取DNA进行PCR扩增,同时行血培养、血常规检查及CRP及ESR水平检测,并与同期住院的20例非感染性疾病患儿进行比较.结果 PCR检测细菌DNA均得到预期的约371 bp大小的扩增产物,该引物仅扩增细菌DNA,与病毒及人基因组DNA无交叉反应,其扩增下限为104CFU·L-1的大肠埃希菌.106例疑诊为脓毒症的患儿,血培养阳性15例,PCR检测阳性36例,PCR的阳性检出率显著高于血培养(P<0.005),20例非感染组患儿PCR结果均为阴性.依据新生儿脓毒症诊断标准,PCR的敏感性、特异性及诊断指数分别为82.93%、96.92%和179.85,优于血培养及5项非特异指标至少2项异常的诊断方法.PCR方法6～8 h即能检测出结果,改良核酸提取技术可以将检测时间缩短至4～6 h.结论 PCR方法检测细菌16S rDNA能迅速判断临床标本中是否存在细菌,对于早期诊断新生儿脓毒症具有较高的敏感性及特异性.     

激活素A在细菌性脑膜炎新生儿脑脊液中的变化及其对预后评估的价值

目的研究新生儿细菌性脑膜炎(BM)脑脊液(CSF)中激活素A(ACT A)水平的变化及其对预后判断的意义。方法对2010年3月-2011年6月在本院新生儿病房住院的48例确诊BM患儿,进行3～18个月的随访及回顾性分析,分为有并发症和后遗症组(A组)和无并发症和后遗症组(B组)。另收集同期住院的非颅内疾病患儿作为对照组(C组)。应用ELISA法动态监测3组患儿CSF中ACT A水平。结果 A组患儿急性期CSF中ACT A水平为(544.39±149.62)ng·L-1,B组CSF中ACT A水平为(480.82±128.24)ng·L-1,二组间差异无统计学意义,但2组均高于C组[(181.06±45.20)ng·L-1](Pa<0.01)。治疗1周,A组CSF中ACT A水平为(315.84±86.35)ng·L-1、B组为(338.25±99.43)ng·L-1,2组较治疗前显著下降(Pa<0.05),但2组间差异无统计学意义(P=0.432)。治疗2周,A组CSF中ACT A水平为(188.19±43.38)ng·L-1,B组为(203.86±50.73)ng·L-1,2组差异无统计学意义(P=0.281)。治疗3周,A组CSF中ACT A水平为(107.65±17.65)ng·L-1,B组为(169.36±28.90)ng·L-1,A组明显低于B组(P=0.000)。治疗4周,A组CSF中ACT A水平为(98.54±28.54)ng·L-1,B组为(181.84±35.01)ng·L-1,A组显著低于B组(P=0.000)。结论 ACT A参与新生儿BM的发病过程,动态检测CSF中ACT A水平,对评估新生儿BM的预后,可能具有重要价值。     

Limitations of the risk factor based approach in early neonatal sepsis evaluations

Aim: Guidelines for detection of early neonatal sepsis employ a risk factor approach combined with laboratory parameters. In an era of increasing intrapartum antibiotic prophylaxis (IAP), we re-assessed the approach as a whole and each of the risk factors individually. Method: This retrospective study included infants with risk factors for sepsis or those treated with antibiotics or who had documented early sepsis. Safety of the protocol was assessed by the number of cases of either missed or partially treated late sepsis or meningitis and the sepsis-related mortality rate. Predictive value of each clinical and laboratory factor was calculated. Results: Of the 22 215 neonates, 2096 were assessed. IAP among infants with risk factors rose from 68% in 2005 to 78% in 2008 (p = 0.001). A total of 1662 asymptomatic infants had risk factors, 635 received antibiotics and one (0.06%) had sepsis. A total of 434 symptomatic infants were treated with antibiotics and of these 234 had risk factors and 20 (4.6%) had sepsis. No cases of partially treated or missed sepsis were detected. Poor predictive value was found for all risk factors except prematurity and leukopenia. Conclusion: The risk factor based approach in asymptomatic infants cannot be justified. In-hospital observation of asymptomatic infants for 2–3 days with antibiotic treatment being reserved only for symptomatic infants may be a reasonable alternative.     

新生儿输血传播病毒性肝炎及更昔洛韦的疗效

目的探讨输血传播病毒(TTV)的致病性以及更昔洛韦对其的疗效。方法对968例新生儿脐血进行TTVDNA扩增和电泳分析,阳性者动态观察临床表现,测定血清丙氨酸氨基转移酶(ALT)和直接胆红素(DB)。TTVDNA阳性且ALT和DB升高者诊断为TTV肝炎,应用更昔洛韦10mg/(kg·d)治疗1～2周。结果新生儿TTVDNA阳性38例,占4.0%。出生3d内,所有TTVDNA阳性新生儿的ALT和DB均正常[(24.8±12.0)U/L、(17.6±6.8)μmol/L],无异常临床表现;7d后15例TTVDNA阳性新生儿ALT和DB均升高[(95.5±16.4)U/L、(58.2±10.4)μmol/L],临床主要表现为黄疸加重、反应差和进奶量减少。11例肝炎患儿予更昔洛韦治疗7d后,ALT和DB恢复正常;余4例治疗14d恢复正常。所有患儿于治疗14d后外周血TTVDNA转阴。结论新生儿存在TTV感染,部分可导致肝损害,临床表现缺乏特征性。更昔洛韦具有良好的抗TTV感染效果。     

降钙素原在新生儿败血症诊断中的价值

目的　为探讨血清降钙素原 (PCT)对新生儿败血症早期诊断及鉴别诊断的价值。方法　采用免疫色谱法对 98例不同程度感染的新生儿进行PCT测定。结果　败血症患儿PCT阳性 (≥0 5ng/ml)率 95 % (其中 75 %≥ 2ng/ml,1例阴性病例为血培养阳性的脓疱疹患儿 ,临床无炎性反应表现 ) ,局部感染阳性率 5 2 6 % ,非感染 7 6 9%。所有上呼吸道感染患儿均阴性。新生儿PCT水平在败血症及其他感染患儿间有显著差异。结论　PCT是新生儿败血症早期诊断及鉴别诊断有价值的指标     

儿童脓毒症血培养结果与血清降钙素原关系分析

目的探讨降钙素原(PCT)在判断细菌感染及其种类中的作用。方法回顾性分析2010年1月至2014年6月确诊为脓毒症的253例患儿的血培养结果与其PCT水平的相关性。结果 253例脓毒症患儿中,血培养阳性124例,阳性率49.01%;其中G+细菌感染71例(28.06%),G-细菌感染53例(20.95%)。253例患儿PCT中位水平为1.6(0.4~4.5)ng/ml,其中低(0.05~0.5 ng/ml)、中(~2 ng/ml)、高(~10 ng/ml)、极高组(~300 ng/ml)分别为86例、55例、75例、37例。不同PCT水平组间细菌培养阳性率的差异有统计学意义(χ2=69.14,P0.01),PCT低水平组细菌培养阳性率最低,其他三组阳性率均高于60%。不同PCT水平组间G+和G-菌检出率的差异有统计学意义(P均0.01),其中,PCT高水平组G+菌检出率最高,而PCT极高水平组G-菌检出率最高。结论 PCT对于判断儿童脓毒症是否为细菌感染有一定指导作用,其水平异常升高可考虑革兰阴性细菌感染。     

Brain temperature in newborn piglets under selective head cooling with minimal systemic hypothermia

BACKGROUND: Although selective brain hypothermia is expected to be a promising neuroprotective treatment, the thermal distribution under hypothermia is not fully investigated. We applied selective head cooling to seven newborn piglets under general anesthesia in order to investigate the mechanism of cooling. METHODS: Seven healthy, large white piglets aged within 5 days after birth were studied. Temperatures were monitored at the superficial brain (0.5 cm), deep brain (2.0 cm), scalp skin, nasopharynx, tympanum, esophagus, and rectum. A radiant heater and a warmer blanket were used to maintain the normal rectal temperature (38.5-39 degrees C). For the first piglet, the coolant temperature was widely changed from 15 degree C to - 20 degree C in order to define the practical range. Subsequently, the coolant temperature was set at 10 degree C, 0 degree C, and - 10 degree C for the remaining six piglets. The target deep brain temperature was set at 35 degree C, as the same reduction of brain temperature might provide moderate brain hypothermia in the human neonate. RESULTS: With 0 degree C coolant temperature, the deep brain temperature was cooled to 35 degree C; however, the scalp skin attached to the cooling cap became broadly blotchy and injured in all animals. When we induced minimal systemic hypothermia by 1C for a cohort of three piglets, the deep brain temperature decreased in parallel with the rectal temperature, which enabled us to achieve the target temperature with 10 degrees C coolant without injuring the scalp skin. The scalp skin and nasopharyngeal temperatures were good predictors of both superficial and deep-brain temperatures throughout the experiment. CONCLUSIONS: Our results suggest that moderate brain hypothermia may be applied to newborn infants without inducing moderate systemic hypothermia.     

早产儿细菌感染的诊治进展

早产儿细菌感染具有高发病率和高病死率,临床症状缺乏特异性,细菌培养阳性虽是诊断细菌感染的金标准,但阳性率低,诊断需结合病史、高危因素、实验室诊断手段及感染筛查评分进行综合评估,通过提高洗手依从性、早期肠道喂养、静脉丙种球蛋白应用及预防性抗微生物措施降低感染的发生,早期诊断、选择有效抗生素应用是改善预后的关键.     

Late‐onset bloodstream infections in preterm infants: A 2‐year survey

Background: We determined the prevalence and risk factors for late‐onset bloodstream infections (LO‐BSI), the distribution of pathogens and the outcomes of affected preterm infants. Methods: The records of all preterm infants (<37 weeks gestation) born between 2004 and 2005 and hospitalized in the neonatal intensive care unit for >3 days were retrieved for this retrospective matched case–control study. Results: A total of 108 out of 1459 preterm infants (7.4%) had 142 episodes of LO‐BSI. The highest LO‐BSI rate (44%) was among 198 very‐low‐birthweight infants (<1500 g). The most common causative organisms were Coagulase‐negative staphylococci and Klebsiella (60% and 13%, respectively). The mean hospital stay was 64 days for LO‐BSI preterm infants versus 48 days for non‐LO‐BSI preterm infants. Congenital malformations and peripheral catheters were independent risk factors for LO‐BSI. Crude mortality rates were 6.9% (LO‐BSI) and 3.0% (non‐LO‐BSI), with an LO‐BSI‐attributable mortality of 3.9%. Conclusion: LO‐BSI frequently affect very‐low‐birthweight infants. Strategies to prevent LO‐BSI should target peripheral catheters.