Effect of hemoperfusion using polymyxin B-immobilized fiber on IL-6, HMGB-1, and IFN gamma in a neonatal sepsis model

To evaluate effects of polymyxin B direct hemoperfusion (PMX-DHP) on a neonatal sepsis cecal ligation and perforation (CLP) model, in 24 anesthetized and mechanically ventilated 3-d-old piglets, 16 were assigned to CLP and an arteriovenous extracorporeal circuit from 3 h until 6 h post-CLP, with a PMX-column in PMX-DHP-treated group (8 piglets) and 8 as sham. Plasma lipopolysaccharide (LPS) was measured at before CLP and at 3 and 9 h. Changes in mean systemic blood pressure (mSBP), mean pulmonary blood pressure, serum IL-6, tumor necrosis factor alpha, interferon gamma, and highly mobile group-1 box protein were measured before CLP and at 1, 3, 6, and 9 h. LPS was lower in the sham and PMX-DHP groups than in the control at 9 h. The mSBP was higher in the sham and PMX-DHP groups than in the control at both 6 h. IL-6 was lower in the sham and PMX-DHP groups than in the control at 6 h. HMGB-1 was lower in the PMX-DHP group than in the control at 6 h. IFN-gamma was only detected in the control group at 9 h. Survival times in the PMX-DHP group were longer than in the control. Thus, PMX-DHP improved septic shock in a neonatal septic model.     

Total hydroperoxide and biological antioxidant potentials in a neonatal sepsis model

Oxidant/antioxidant imbalance plays an important role in septic shock. The present study examined changes in circulating oxidative components in a neonatal sepsis model. Subjects were 14 newborn mixed-strain piglets randomly divided into two groups: a cecal ligation and perforation (CLP) model (n = 7) and sham (n = 7). Blood samples for total hydroperoxide (TH), biological antioxidant potential (BAP), tumor necrosis factor (TNF) alpha, interleukin (IL)-6, and IL-10 were collected pre-CLP and at 1, 3, and 6 h post-CLP. TH and BAP levels at 1 h post-CLP were significantly higher in the CLP group than in the sham group. In the CLP group, TH decreased gradually and reached baseline levels by 6 h post-CLP, while BAP remained elevated. Linear correlations were identified between serum TH and BAP at 1 h post-CLP, serum TH and TNF-alpha at 1 h post-CLP, and BAP and IL-6 at 6 h post-CLP. Changes in and correlations between circulating oxidative and inflammatory state components in a neonatal sepsis model were clarified. This is the first study to reveal that the presence of oxidant/antioxidant imbalance in sepsis and septic shock changes during the disease course.     

新生儿呼吸衰竭时气体交换障碍及临床评估

目的     

Effect of polymyxin B sulfate on endotoxin activity in a gram-negative septicemia model.

The antiendotoxin effect of polymyxin B was investigated in experimentally induced septicemia in rabbits. The Pasteurella multocida organisms were sensitive to the antibacterial action of penicillin but not to polymyxin B. Animals pre-treated with polymyxin showed positive blood cultures and significantly reduced plasma endotoxin levels (Limulus test) with normal white blood cell and platelet counts when analyzed 6 hr after the injection of live organisms. Polymyxin therapy given after the animals had established septicemia-endotoxemia reduced the plasma endotoxin levels and improved the survival, but had no effect on the leukopenia and thrombocytopenia. The best survival data were obtained in rabbits who were treated with both penicillin and polymyxin. The data suggest that polymyxin is effective in neutralizing the endotoxic effects from live organisms and that the timing and perhaps duration of the polymyxin treatment is of critical importance. In addition, a modified Limulus lysate method was developed which showed that quantitative plasma endotoxin determination could be made more sensitive by prior heating of the plasma to remove the natural inhibitors.     

新生猪多器官功能障碍综合征模型建立的实验研究

目的：探讨采用盲肠结扎加穿孔(CLP)建立新生猪多器官功能障碍综合征(MODS)模型的方法及实验与临床意义。方法：选用健康长白新生猪14只,随机分成实验组(E组,n=9)和对照组(C组,n=5),实验组施行盲肠结扎加穿孔(CLP)制成MODS动物模型,对照组只行剖腹和盲肠探查术。动态观察两组血清生化指标(ALT,AST,ALB,BUN,Cr,CKMB,lac)及血小板、血气分析(PaO2,PaCO2)的变化,通过光镜观察动物各重要生命器官组织形态学变化。结果：与对照组相比,实验组动物在CLP后血ALT,AST,BUN,Cr,CKMB,lac24h即已开始升高,48～96h明显升高,48h时ALT为83.0±9.3U/L、AST为348.8±132.9U/L、BUN为10.5±2.5mmol/L、Cr为79.2±9.0μmol/L、CKMB为5152.0±1857.8U/L、lac为12.3±4.0mmol/L(P<0.01),96h后开始有所降低,但仍高于0h;ALB24h后开始降低,各时间点均低于对照组,但差异无显著性;血小板24h开始降低,96h与0h比较差异有显著性;PaO2和PaCO248h时实验组与对照组差异有非常显著性(P<0.01);实验组动物死亡率与对照组差异有显著性(P<0.05),MODS的发生率为56%。实验组动物肺、肝、心、肾、胃肠道等器官均有不同程度的病理改变。结论：CLP诱发了新生猪多个器官的功能障碍,该实验可用于新生动物MODS模型的探讨。     

Half a decade of neonatal sepsis, Riyadh, Saudi Arabia

In a retrospective study to determine the pattern of neonatal sepsis, all cases admitted to the Neonatal Intensive Care Unit (NICU) between October 1983 and July 1988 at King Khalid University Hospital, in Riyadh were studied. During the review period there were a total of 2117 admissions to the NICU. Of those 1252 (59 per cent) underwent septic screening sometimes during their stay in the NICU. The number of babies with proven bacteremia, i.e.; positive blood and or cerebrospinal fluid culture was 190 (15 per cent). Gram-positive organisms were cultured from 132 (69 per cent) and Gram-negative organisms from 47 (25 per cent) of the babies. The single most frequent organism was Staphylococcus epidermidis accounting for 36 per cent (58/190) of all proven cases. These results differ appreciably from other studies reported previously from Riyadh as well as from some other parts of the world, and stress the need to recognize Staphylococcus epidermidis as an increasingly important pathogen in the newborn nursery.     

Effect of fresh frozen plasma and gammaglobulin on humoral immunity in neonatal sepsis.

Fresh frozen plasma and intravenous immunoglobulin are used as prophylaxis against, and for the treatment of, neonatal infection. It is assumed that any beneficial effect is mediated through the humoral immune factors contained in each preparation. The effect of fresh frozen plasma and intravenous immunoglobulin on humoral immune markers (immunoglobulins and IgG subclasses, complement components and activation products, and C reactive protein) was investigated over a 24 hour period after their randomised administration to 67 infants with suspected infection. Thirty infants without suspicion of infection were studied as controls. Compared with control infants, infants with suspected infection had increased concentrations of C reactive protein, reduced concentrations of fibronectin, and increased concentrations of the complement activation marker C3d, but similar concentrations of IgG, IgG subclasses, IgA, and IgM. After intravenous immunoglobulin treatment (500 mg/kg) concentrations of total IgG and all IgG subclasses increased, as did IgA and complement component C4. Concentrations of C reactive protein decreased after intravenous immunoglobulin treatment and were significantly lower than baseline after 24 hours. In contrast, no change in IgG or IgG subclass concentrations occurred after fresh frozen plasma administration. At 24 hours after fresh frozen plasma administration, concentrations of IgA, IgM, and C4 were significantly higher than baseline and serum IgA was significantly higher than in infants tested 24 hours after intravenous immunoglobulin treatment. These results confirm the rational basis for intravenous immunoglobulin treatment but question the value of fresh frozen plasma, particularly in the light of its attendant problems as an untreated blood product.     

Elevated inflammatory mediators and pulmonary hypertension after applying an extracorporeal circuit in a neonatal sepsis model

Purpose  

We aimed to study the changes in cytokines, oxidative mediators, and pulmonary blood pressure in a neonatal sepsis model when applying an extracorporeal circuit (ECC).     

Contribution of interleukin-6 in distinguishing between mild respiratory disease and neonatal sepsis in the newborn infant

The purpose of this study was to investigate if early samples of interleukin-6 (IL-6) could distinguish early bacterial sepsis from respiratory diseases in the newborn. IL-6 and C-reactive protein (CRP) were measured at onset of symptoms in newborns evaluated for sepsis during the first week of life. Five groups of children were investigated: proven sepsis, clinical sepsis, respiratory distress syndrome (RDS), transient tachypnoea of the newborn (TTN) and controls. IL-6 was also analysed at the time when CRP was at its maximum level. The results showed that initial IL-6 distinguished proven and clinical sepsis from TTN, but not from RDS. Initial CRP was of no value for diagnosis. Our conclusion is that early IL-6 makes it possible to avoid antibiotics in children with TTN and contributes to the diagnosis of sepsis faster than CRP.     

Nebulisation of surfactants in an animal model of neonatal respiratory distress

AIMS—To evaluate pulmonary deposition and gas exchange following nebulisation of two surfactants by either a jet or an ultrasonic nebuliser.METHOD—After bronchoalveolar lavage (BAL), 19 rabbits were ventilated in four groups. Group A1 (n=5) and A2 (n=6) received Technetium-99m labelled Exosurf, and groups B1 (n=4) and B2 (n=4) received radiolabelled Survanta. Groups A1 and B1 received jet nebuliser therapy, whereas groups A2 and B2 received ultrasonic nebuliser. Pulmonary deposition, distribution, and blood gases were determined.RESULTS—Pulmonary deposition as per cent of initial dose and mg lipid) was 0.28(0.10)% or 0.59(0.21) mg in group A1, 1.05(0.23)% or 2.21(0.48) mg in group A2, 0.08(0.02)% or 0.30(0.08) mg in group B1, and 0.09(0.02)% or 0.34(0.08) mg in group B2. Deposition in group A2 was greater than in other groups (p= 0.001). Group A2 showed a small improvement in blood gases.CONCLUSIONS—Even the highest deposition—ultrasonic nebuliser witosurf—achieved limited clinical effect. The aerosol route is currently not effective for surfactant treatment.     

Rupture of membranes,gastric aspirate cytology and neonatal sepsis

Gastric aspirates were examined for polymorphs in 117 infants, born after prolonged rupture of membranes of more than 12 hours duration. Of 42 infants with gastric aspirate polymorph count of more than 5 per high power field (HPF), 19 (45. 2 per cent) infants developed pneumonia and bronchopneumonia and 11 (26.2 per cent) developed septicemia. Of 75 infants with cell count of less than 5 per HPF, two infants developed pneumonia (2.5 per cent) and one developed septicemia (1.3 per cent). A polymorph count of over 65 per cent was associated with pneumonia or bronchopneumonia in all cases and a count of 30–65 per cent was associated with 20% possibility of infection. Supported in part by the Indian Council of Medical Research.     

Increase of Enterobacter in neonatal sepsis: a twenty-two-year study

BACKGROUND: Data on the incidence of Enterobacter infections in neonates over prolonged periods of time are scant. We determined the epidemiology of Enterobacter sepsis and/or meningitis and the trends of infection in a neonatal unit. METHODS: Retrospective review of sepsis and/or meningitis in inborn neonates admitted to Son Dureta University Hospital during a 22-year period. Molecular study by ribotyping of the Enterobacter strains isolated from 1995 to 1997. RESULTS: There were 513 cases of culture-proved sepsis and/or meningitis in neonates. In late onset infections Klebsiella pneumoniae and Staphylococcus epidermidis were the most frequent isolates in the period 1977 through 1991. Enterobacter was the most common isolate in the period 1992 through 1998. During this latter period Candida infections also increased, and the resistance rate of Enterobacter to cefotaxime was higher (59.2%). Decrease in early onset infections and increase in late onsets (4.6/1,000 live births) were observed in the second period. From 1977 to 1998, 45 episodes of sepsis and/or meningitis by Enterobacter species were identified in 44 patients (8.7% of all neonatal bacteremias). Three patients with Enterobacter bacteremia died (6.6%, 0.03/1,000 live births). During 1995 through 1997 5 different clones causing sepsis were identified and 3 were predominant. In 1997 there was an outbreak of Enterobacter disease. After cleaning, cohort nursing and hygiene reinforcement, Enterobacter was not isolated in the next 2 years. No change in the antibiotic policy was made. CONCLUSIONS: We observed a resurgence of Enterobacter infections in our neonatal intensive care unit. The sudden disappearance of this microorganism after reinforcement of hygienic measures, without withdrawing cefotaxime, confirms the importance of patient-to-patient transmission of this nosocomial infection. Further studies are needed to establish the role of antibiotics in the emergence of microorganisms in neonatal intensive care units.     

An audit of postoperative sepsis in a neonatal surgical unit

An audit of 143 consecutive neonatal surgical operations performed in one neonatal surgical unit is reported. Wound infections developed in 13 patients (9.1%) and bacteraemia in 9 (6.3%). Three groups at increased risk were identified: small-for-dates infants subjected to major surgery, infants subjected to invasive monitoring, and infants over 1 week of age with Staphylococcus aureus as a skin commensal. Infections were significantly less frequent in potentially contaminated wounds if antibiotic prophylaxis had been used (7.6% compared to 26.7%: P <0.05).     

新生儿败血症病原学及药敏结果分析

目的：了解新生儿败血症病原学的分布及对抗生素敏感和耐药情况。方法：采用K-B法对新生儿败血症血培养出的细菌进行药物敏感性试验。结果：金葡菌46例(38.0%),表皮葡萄球菌23例(19.0%),大肠埃希菌20例(16.5%),腐生葡萄球菌4例(3.3%),D群链球菌4例(3.3%),其他革兰阴性菌24例(19.8%)。金葡菌、表皮葡萄球菌等对青霉素和红霉素普通耐药,对苯唑青霉素的敏感性仅达17.4%和15.8%,对头孢唑啉及丁胺卡那霉素较敏感,对万古霉素与西力欣有高度敏感性。革兰阴性杆菌对头孢噻肟等第3代头孢菌素具有很高的敏感性;头孢唑啉、丁胺卡那霉素、庆大霉素等对革兰阴性杆菌仍有较高敏感性,而氨苄青霉素的敏感率仅为29.7%。结论：表皮葡萄球菌的感染呈上升趋势;细菌耐药性的产生有加快现象;丁胺卡那霉素、万古霉素、第3代头孢菌素等仍为敏感抗生素。     

Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year prospective study

Aim: Investigate the incidence, etiological pattern and the antimicrobial resistance of late‐onset neonatal infections over a period of 5 years. Methods: Longitudinal audit of neonatal sepsis from January 2005 to December 2009, in the main maternity hospital in Kuwait. Late‐onset neonatal infection was defined as the culture of a single potentially pathogenic organism from blood or cerebrospinal fluid from an infant older than 6 days in association with clinical or laboratory findings consistent with infection. Results: The overall incidence was 16.9 (95% confidence interval: 15.8–18.0) episodes per 1000 live births. The commonest pathogen was coagulase‐negative Staphylococcus, 339 (35.7%), while Klebsiella was the most common gram‐negative infection, 178 (18.8%). Escherichia coli, Enterococcus and Enterobacter spp were each responsible for 6% of all infections. Candida caused 104 (11.0%) infections. The general pattern of infection remained unchanged over the study period. Case fatality was 11.7% (95% confidence interval: 9.7–13.9%) and was high for Pseudomonas (18.4%) and Candida (22.1%) infections. Approximately 24 and 20% of Klebsiella infections were resistant to cefotaxime and gentamicin, respectively, while 28 and 24% of Escherichia coli infections were resistant to cefotaxime and gentamicin, respectively. Conclusion: The incidence of late‐onset infection in Kuwait is high, resembling that in resource‐poor countries. The high incidence coupled with low case fatality provides an example for settings where tertiary care is introduced without strict measures against nosocomial infections. Prevention against nosocomial infections in neonatal units has the potential to further reduce neonatal mortality in these settings.