Granulocytic stem cell (CFUc) proliferation in experimental group B streptococcal sepsis

Adult rats infected with group B streptococci (GBS) develop neutrophilia and display a marked increase in granulocytic stem cells (CFUc). In contrast, infected neonatal rats develop a profound neutropenia and their CFUc do not increase. In order to better understand this phenomenon, we assessed the CFUc proliferative rate in control and infected adult and neonatal rats using the technique of [3H]-thymidine suicide. Beginning only 3 h after GBS inoculation, adult rats increased CFUc proliferative activity, as illustrated by an increase in thymidine suicide, from 38 +/- 2% cell kill in control animals to 70 +/- 2% when infected (mean + S.E., P less than 0.001). In contrast, the CFUc thymidine suicide rate did not increase in infected neonates. It was noted, however, that the baseline CFUc thymidine suicide rate in uninfected neonatal rats exceeded the rate in uninfected adult rats by 2-3-fold. The CFUc thymidine suicide rate was therefore determined in uninfected premature (74 +/- 1%), newborn (70 +/- 2%), 1-wk-old (70 +/- 1%), 6-wk-old (32 +/- 1%) and 6-month-old (37 +/- 3%) rats. These findings suggest that the proliferative rate of granulocytic stem cells is already maximal or near maximal in noninfected neonatal animals. In contrast to adults, the neonates' granulocyte production from stem cells can not significantly increase, even if bacterial infection is present.     

白细胞计数对新生儿早发型败血症的诊断界值探讨

目的 评价白细胞（WBC）计数在新生儿早发型败血症（EOS）诊断中的临床应用价值,探讨WBC诊断的上限界值。方法 回顾性选取2019年1月至2020年3月收治的新生儿EOS患儿306例,以同期580例非感染患儿作为对照组,比较两组患儿一般情况、WBC计数等。根据2003年《新生儿败血症诊疗方案》（简称2003年版诊疗方案）及《新生儿败血症诊断及治疗专家共识（2019年版）》（简称2019年版专家共识）标准分别对WBC计数的诊断价值进行评价。结果 根据两种不同诊疗方案,WBC计数的阳性率均较低（分别为51.3%和32.0%）,但特异度均较高（分别为93.3%和98.6%）。经受试者工作特征曲线分析显示,2003年版诊疗方案WBC计数曲线下面积大于2019年版专家共识（P < 0.05）。结论 WBC计数在诊断EOS中的诊断上限界值以2003年《新生儿败血症诊疗方案》中≥25×10⁹/L更为合理。     

The differential leukocyte count in the assessment and outcome of early-onset neonatal group B streptococcal disease.

The usefulness of the differential white blood cell count in distinguishing early-onset group B streptococcal disease from other causes of neonatal respiratory distress was studied in 45 infants with culture-proved infection. The initial diagnosis was hyaline membrane disease in 19 infants, wet lung syndrome 13, and other causes of respiratory distress in 13. Thirty-nine (87%) had abnormal absolute neutrophil counts, 25 with neutropenia and 14 with neutrophilia. The absolute immature neutrophil count was elevated in 19 infants (42%). Forty-one infants (91%) had an abnormal immature neutrophil to total neutrophil ratio. All infected infants were identified when both the absolute total neutrophil count and ratio were used. The differential white cell count appears to be a useful tool for screening infants presenting with respiratory distress in the first 48 hours of life and for separating early-onset group B streptococcal disease from other causes of neonatal respiratory distress.     

Purpura fulminans following late-onset group B beta-hemolytic streptococcal sepsis

A 16-day-old male infant initially was in septic shock. Following intensive resuscitation, thrombohemorrhagic lesions developed over his extremities, except for the limb with an arterial line maintained by a continuous heparin sodium infusion. Blood and CSF cultures yielded group B beta-hemolytic streptococci. Results of laboratory studies and clinical appearance supported the diagnosis of purpura fulminans (PF). Systemic heparinization was therefore started, and subsequently his condition improved. Because of the distinct difference in limb sparing, we concluded heparin has a beneficial effect on the evolution of PF.     

新生儿末梢血白细胞及其分类的参考区间和影响因素

目的从健康足月新生儿人群中建立末梢血白细胞及其分类的参考区间。方法自2017年11月—2018年4月招募湖北地区2家医院孕母产检正常的592例健康足月新生儿为研究对象,在生后1～4d内采集微量足跟血,2h内完成白细胞及其分类检测。结果初步建立了新生儿末梢血白细胞及其分类的参考区间,以中位数(范围)表示:WBC 20.24(9.97～40.64)×10~9/L;NEU#12.85(4.51～28.76)×10~9/L;LYM#4.63(2.22～8.50)×10~9/L;各指标受性别、分娩方式、生后日龄(1～4d)及胎龄(37～41周)影响情况如下:白细胞各参数在性别间无显著差异(P>0.05);剖宫产出生的新生儿的WBC、NEU#、EOS#均明显低于顺产组(P<0.05);生后日龄对白细胞参数存在组内差异(P<0.001);WBC、NEU#、LYM#、MON#胎龄组内存在显著差异(P<0.05)。结论初步建立了新生儿末梢血白细胞及五分类的参考区间,认为在不同性别间无显著差异,但应基于不同分娩方式、日龄以及胎龄解读检测结果。     

Newborn sepsis following antepartum group B streptococcal maternal infection in rats

Group B streptococcus is an important pathogen in man and infection due to this bacteria is responsible for significant mortality and morbidity in neonates. An animal model of neonatal infection caused by group B streptococcus that results from vertical transmission is described. Nine pregnant Sprague-Dawley rats received intraperitoneal inoculation of 10(9)-10(10) colony forming units of group B streptococcus on day 20 or 21 of gestation. Four of nine rats died following inoculation. A total of 51 pups was born to the surviving five mothers. Pups were sacrificed at 4- to 8-h intervals and cultures of blood, brain, liver, and spleen were obtained. Nineteen of 51 pups (37%) had group B streptococcus isolated from blood or tissues within the first 48 h of life. Results suggest that antepartum systemic infection in rats can result in vertical transmission of disease. This animal model can be used to further study the mechanisms of transmission of group B streptococcus and the pathogenesis and treatment of neonatal sepsis caused by this pathogen.     

Significance of placental findings in early-onset group B streptococcal neonatal sepsis

Assessment of placental pathology and its relationship to historical data, initial laboratory parameters, and outcome was undertaken in 22 cases of early-onset group B streptococcal sepsis of the neonate. Fourteen (64%) of the placentas demonstrated chorioamnionitis, six (27%) funisitis, and in nine (41%) gram stain demonstrated organisms within the membranes. Focal villous edema was observed in five (23%) cases and diffuse villous edema in four (18%). No placenta demonstrated chorangiosis. Placental inflammation was significantly (p less than 0.05) associated with prematurity, prolonged rupture of membranes, and onset of symptoms at less than 3 hours of age. No placental change was significantly associated with outcome or with neutropenia, which was the only parameter assessed that appeared to have prognostic value.     

Early-onset group B streptococcal sepsis in a preterm infant with Kostmann syndrome

A preterm infant died of group B streptococcal sepsis 7 h after birth. The infant's complete blood count showed total agranulocytosis. Histopathology of the major organs showed significant bacterial invasion without infiltration of polymorphonuclear leucocytes. Examination of the bone marrow revealed normal cellularity of the granulocyte precursors with arrested maturation. These findings are consistent with Kostmann syndrome. CONCLUSION: It is suggested that in patients with deteriorating early-onset infection, underlying congenital abnormalities in host defence, such as Kostmann syndrome, should be considered.     

新生儿B族链球菌败血症33例临床分析

目的：探讨新生儿B族链球菌(group B streptococcus,GBS)败血症的临床特点。方法收集2011年3月至2014年10月泉州市儿童医院NICU收治的GBS败血症患儿的资料,回顾性分析GB S败血症患儿的围产因素、临床表现、实验室检查、治疗与转归。结果 GB S 败血症33例,占住院患儿的2.0‰(33/16448)。其中早发型败血症21例,均为足月儿,呼吸窘迫13例、气促11例、青紫10例。晚发型败血症12例,足月儿8例,早产儿4例,以高热为首发症状入院10例,6例合并化脓性脑膜炎。33例血GB S阳性标本均对万古霉素敏感,青霉素联合美罗培南治疗有效,其中18例治愈出院,临床好转后自动出院9例,死亡2例,放弃治疗死亡4例,总病死率18.2%。结论新生儿GB S败血症临床症状明显,早发型病例以呼吸系统症状为主,晚发型病例以高热为首发症状。母孕后期应常规筛查,重视新生儿早期临床表现,尽早行病原学检测,合理足疗程使用敏感抗生素治疗。     

Fatal late onset group B streptococcal meningitis following maternal postpartum sepsis

Although maternal screening and the administration of prophylactic intrapartum antibiotics have decreased the incidence of early onset group B streptococcal (GBS) disease in neonates, there is still significant morbidity and mortality as a result of neonatal GBS disease.Maternal GBS infections are not uncommon, but with appropriate therapy there is almost a uniformly good outcome. Little is written about the appropriate management of well infants born to mothers with postpartum GBS sepsis.The question of whether well infants born to mothers with GBS puerperal sepsis should be treated empirically with antibiotics and the lack of literature concerning this issue became apparent when an untreated term infant died of late onset GBS meningitis following maternal puerperal GBS sepsis. We describe this event in the following case presentation.With the current paucity of literature regarding the management of well infants born to mothers with postpartum GBS sepsis, it seems prudent to treat such infants empirically with antibiotics (following a full septic work-up) until this matter has been investigated further.     

Neonatal group B streptococcal sepsis: effects of late treatment with dazmegrel

Neonatal group B streptococcal (GBS) sepsis produces pulmonary arterial hypertension and hypoxemia that are preventable by pretreatment with the selective thromboxane A2 synthase inhibitor, dazmegrel. In the present experiment we administered dazmegrel (8 mg/kg) 2 h after the initiation of a 2 1/2 h infusion of 5 X 10(8) GBS/kg/h in ten 2- to 3-wk-old piglets. The multiple inert gas elimination technique was used to measure intrapulmonary shunt and alveolar ventilation to pulmonary perfusion mismatching. Thromboxane B2, the stable metabolite of thromboxane A2, and 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin, were assayed in arterial blood. Pulmonary arterial pressure increased immediately after initiation of the GBS infusion, rising from 12 +/- 2 to 34 +/- 4 torr (p less than 0.02); pulmonary vascular resistance increased by 400% (p less than 0.01). Arterial hypoxemia developed (p less than 0.02) in association with an increase in the low ventilation-perfusion ratio index but without a significant increase in intrapulmonary shunt. Thromboxane B2 levels increased 10-fold. Infusion of the carrier substance for dazmegrel after 2 h of GBS infusion produced no change in any variables. In contrast, infusion of the drug resulted in the return to pre-GBS infusion baseline values for both pulmonary arterial pressure and pulmonary vascular resistance. However, no improvement in arterial pO2 or in the low ventilation-perfusion ratio index occurred. Both pulmonary vascular resistance and pulmonary arterial pressure remained normal for 0.5 h after dazmegrel administration despite continued GBS infusion. Thromboxane B2 levels were decreased 30 min after dazmegrel (p less than 0.02), but remained greater than pre-GBS levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure of the urinary group B streptococcal antigen test as a screen for neonatal sepsis.

The accuracy of the urinary group B streptococcal antigen latex agglutination (LA) test for screening infants at risk of group B streptococcal (GBS) sepsis in the first 24 hours of life was prospectively studied in 236 infants for six months. Infection with GBS was defined by a positive blood culture while colonisation was defined by GBS cultured from any other site. The combination of infection and colonisation was used as the gold standard for the LA test. Although the LA test had a sensitivity of 90%, the specificity was only 70%, the positive predictive value 12% and the false positive rate 30%. The overall accuracy was only 71%. The LA test was unable to predict GBS sepsis in infants at risk of the disease. The false positive rate was unacceptably high and could not be potentially accounted for in 11 infants. However, a negative test was useful in excluding GBS disease.     

Effects of pentoxifylline on the cardiovascular manifestations of group B streptococcal sepsis in the piglet.

Pentoxifylline (PTXF) is a methylxanthine that modifies leukocyte function and inhibits cytokine release. To evaluate its effects on the cardiovascular manifestations of sepsis secondary to group B streptococci, 14 anesthetized, mechanically ventilated piglets were studied over a 240-min period. Animals were randomly assigned to a treatment group that received a PTXF bolus (20 mg/kg) followed by a continuous infusion of 5 mg/kg/h before and during group B streptococci (1 x 10(8) colony forming units/kg/min) administration and a control group that received saline as a placebo. Comparison of the hemodynamic measurements and arterial blood gases during the first 90 min of PTXF treatment with those of the control group resulted in the following 90 min values: systemic arterial blood pressure was significantly higher in the PTXF group (89 +/- 10 versus 56 +/- 30 mm Hg; p less than 0.005) as was cardiac output (0.18 +/- 0.04 versus 0.10 +/- 0.07 L/kg/min; p less than 0.005). Pulmonary vascular resistance remained lower in the PTXF-treated animals (135 +/- 117 versus 248 +/- 119 mm Hg/L/min/kg; p less than 0.001), and these animals were less acidotic as measured by pH (7.07 +/- 0.2 versus 7.31 +/- 0.1; p less than 0.05) and base deficit (-15 +/- 9 versus -5 +/- 2 mmol/L; p less than 0.05). Median survival time was significantly longer in the PTXF group (210 versus 90 min; p less than 0.002). These data demonstrate that PTXF can ameliorate some of the deleterious hemodynamic manifestations of group B streptococci sepsis and result in improved survival in a young animal model.