Predicting neonatal sepsis in ventilated neonates

Objective  To show the value of serial endotracheal aspirate culture in predicting organisms causing sepsis in ventilated neonates. Methods  We studied 100 newborns in Zeynep Kamil Maternity and Children’s Training and Research Hospital Neonatal Intensive Care Unit. Endotracheal aspirate and blood cultures were taken first on the third day and then once a week till extubation. Results  Blood and endotracheal cultures showed the same organism only in 17.6% of the patients. There was no relationship among 86.4% of the patients. The rate of culture positivity increased as the birth weight decreased, gestation week got smaller and the duration of intubation prolonged. Conclusion  The antibiotherapy arranged according to the endotracheal aspirate cultures is not suitable for a possible sepsis agent. Moreover, resistant organisms may occur in hospitals if the antibiotics used unnecessarily.     

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.     

Intravenous immunoglobulin for prophylaxis of nosocomial sepsis

A total of 76 premature newborn infants with gestational age of 34 weeks or less were enrolled in a randomized controlled study to determine whether intravenously administrated immunoglobulin (IVIG) is able to prevent nosocomial sepsis. Forty infants were given 0.5 g/kg IVIG on the first day of life and 36 infants with similar gestational age and birth weight were selected as controls and did not receive IVIG. The frequency of proven sepsis, with a positive blood and/or cerebrospinal fluid culture, was significantly lower in infants who received IVIG as compared to controls (42.5vs 80.0%) (p<0.01). The mortality rate attributable to infection was not different in IVIG recipients and in controls (41vs 48%) (p>0.05). The overall mortality rates in the two groups were not different either (35.0vs 44.4%) (p>0.05). The majority of micro-organisms isolated from the blood culture of the patients were gram negative microorganisms (Klebsiella, Enterobacter). IVIG therapy was believed to be effective for prophylaxis of nosocomial infection, but such therapy was not able to reduce overall mortality rate or mortality rate due to systemic infection in prematurely born infants in our intensive care unit where the causative pathogens are usually gram negative microorganisms.     

Sensitivity and specificity of daily tracheal aspirate cultures in predicting organisms causing bacteremia in ventilated neonates

The sensitivity of daily tracheal aspirates in predicting neonatal bacteremia was ascertained from 48 of 354 ventilated neonates who became septic during a 4-year period. Fourteen babies (designated Group A) had a positive blood culture on the first day of life; 28 infants (Group B) and 6 infants (Group C) had bacteremia beyond the first day. Group C infants became septic as a result of intraabdominal pathology. Pathogens isolated from blood were correlated with those from preceding daily tracheal aspirates. The overall sensitivity of tracheal cultures in predicting results of blood cultures was 81% (Group A, 71%; Group B, 93%; Group C, 50%). The specificity of daily tracheal aspirates was ascertained from 28 of 50 ventilated infants who were nonseptic and had negative blood cultures during a 6-month period. Only 18 had consistently sterile tracheal aspirates (specificity, 64%). The mean number of days of intubation was 6.6 for the 10 false positive and 3.6 for the 18 true negative. Because of low positive predictive value (0.26) the role of daily tracheal aspirate culture is limited to providing early information regarding potential pathogens when sepsis occurs rather than to identify babies who are going to become septic.     

Serum cortisol and thyroid hormone levels in neonates with sepsis

Objective: To evaluate the thyroid hormone and cortisol levels in neonates with sepsis in relation to the final outcome. It was hypothesized that the hormonal level could act as some prognostic guideline.Methods: Forty nine neonates, aged 8–28 days, diagnosed as neonatal sepsis were selected for the study. Neonates below 8 days of age, 35 weeks of gestation and 2000 g of birth weight were excluded from the study. Twenty FT-AGA neonates beyond day 7 of life served as control for the study. The hormones were estimated by radioimmunoassay.Results: The neonates with sepsis had significantly higher mean serum cortisol and lower mean serum total T₄ at admission as compared to healthy neonates. The mean serum total T₃ level was also lower, but the difference was not statistically significant. The mean serum TSH levels were comparable in both groups. The levels normalised following recovery. Sixteen neonates succumbed to the disease process. The non-survivors had significantly lower mean total T₃ and total T₄ levels as compared to the survivors.Conclusion. The endocrinal abnormalities are of transient nature as a response to sepsis. Low total T₃ and total T₄ are the predictors of adverse outcome in neonates with sepsis.     

Interpreting positive cultures of endotracheal aspirates: factors associated with treatment decisions in ventilated neonates

Aims: Diagnosis of ventilator‐associated pneumonia in newborns is challenging because of ease of colonisation, non‐specific chest radiograph changes and lack of a consensus definition. The aims of this study were to review treatment decisions in neonates with culture‐positive endotracheal aspirate and to assess impact on respiratory outcomes using blinded review of radiological studies. Methods: Charts from all very low birthweight neonates ventilated for >48 h and with positive culture were assessed. Chest radiographs were reviewed by a radiologist masked to the grouping of the episode (treated/not treated). Clinical, investigational and radiological features used in practice were assessed on impact on treatment decisions. Association between treatment and outcomes was assessed. Results: Seventy‐four episodes of culture‐positive endotracheal aspirate were analysed in 38 babies. Fifty‐eight episodes were treated with antibiotics. Gestational age at birth and birthweight in both groups (treated vs. non‐treated) were statistically comparable (25.5 ± 3.1 vs. 27.2 ± 2.3 weeks and 809 ± 302 vs. 870 ± 262 g). Comparative chest radiographs were available in 51 of 58 treated episodes; deterioration was noted in 42 (82.3%). Ventilatory parameters were significantly higher in the treatment group and showed a significant improvement after antibiotics. Twenty‐three babies developed chronic lung disease. Odds ratio (of having chronic lung disease when treatment is initiated) was 4.5 (95% confidence interval = 0.97–20.8, P= 0.06). Conclusions: Treated culture‐positive aspirate episodes were accompanied by higher ventilatory requirements, increased symptoms and elevated septic markers. Need for treatment was associated with greater likelihood of developing chronic lung disease.     

Nosocomial sepsis in neonates with single lumen vascular catheters

Catheter-related sepsis is commonly encountered in the neonatal intensive care unit. We retrospectively studied infants with vascular catheters at 2 NICUs. Data were obtained from the computerised admission records available at both the hospitals. Our aims were to describe the clinical and microbial profile of nosocomial sepsis in infants with vascular catheters [umbilical artery (UA), umbilical venous (UV), central venous Broviac (CV), percutaneously placed central venous (PC), peripheral artery (PA)], and to determine the association between catheter type, duration and sepsis in a subset of the population. Nosocomial sepsis (positive blood culture after the 3rd postnatal day) occurred in 217 of 2091 (10.4%) infants. Infected infants, in contrast to non-infected, had a significantly (P < 0.001) greater number of multiple catheters (2.3 vs 1.4) had lower birth weights (1.2 vs 2.1 kg), were younger (28 vs 33 weeks) and had lower 1 and 5 minute Apgar scores (4.3 and 6.7 vs 5.5 and 7.4). The most common organism was coagulase negativeStaphylococcus. In a subset population as analyses revealed, longer duration of UA use was associated with higher infection rates [13.6% with UA use for ≥ 8 days vs 1.3% for ≤ 7 days ( P < 0.0001)]. PC use had a lower rate of sepsis than CV use (5.1% vs 15.2%; P < 0.05). Use of intravascular catheters should be balanced between the need for vascular access and the risk of sepsis.     

Removal of percutaneously inserted central venous catheters in neonates is associated with the occurrence of sepsis

BACKGROUND: Clinical signs of sepsis are frequently observed after removal of a percutaneously inserted central venous catheter (PCVC) in neonates admitted at our Neonatal Intensive Care Unit (NICU). To substantiate this finding and to evaluate the effect of antibiotics administered at the time of removal of a PCVC, we conducted a retrospective study among all infants with a PCVC, admitted at our NICU during 2002 and 2005. METHODS: Clinical data, infectious complications and use of antibiotics were studied retrospectively. RESULTS: A PCVC was inserted in 345 infants. Sepsis occurred in 90/345 (26%) infants, in 50/90 (56%) during indwelling PCVC and in 40/90 (44%) after removal of the PCVC. Of the latter 40 sepsis episodes, 24 (60%) occurred within 5 days after removal of a PCVC with a clustering of 21 cases of sepsis within 72 h after the removal. The remaining 16 episodes occurred after 7 days. Administration of antibiotics during removal of the PCVC significantly reduced the incidence of sepsis: 22/213 (10.3%) cases of sepsis occurred when no antibiotics were administered versus 2/132 (1.5%) cases of sepsis when antibiotics were administered (p = 0.002). CONCLUSION: Our study suggests that peripherally inserted central venous catheters are associated with sepsis not only during the indwelling period of the catheter, but also after removal. Administration of antibiotics targeted at the time of removal of the catheter significantly reduced the incidence of sepsis. Future prospective studies are warranted to confirm this observation.     

Early prediction of chronic lung disease by tracheal aspirate cytology in ventilated newborns

We assessed the specificity of squamous metaplasia in tracheal aspirates of 69 ventilated newborns (gestational age 25–41 weeks) between days 3 and 7 of life for prediction of chronic lung disease (CLD). CLD was diagnosed when the patient was still requiring ventilation or supplementary oxygen at the postconceptional age of 36 weeks (or postnatal age of 28 days for babies born after 32 weeks gestation) and showed X-ray changes compatible with CLD. In the total population the presence of squamous metaplasia had a sensitivity of 59% and a specificity of 74% for the early diagnosis of CLD. The combination of squamous metaplasia and very low birth weight (VLBW) had a much higher specificity (94%), but a lower sensitivity (45%). Our results show that the presence of sqaumous metaplasia in VLBW babies during the 1st week of life predicts development of CLD with a specificity of 94% and may be helpful for entering patients into early treatment protocols or trials when a high risk population needs to be identified. As sensitivity of this approach is only 45%, further studies are needed to evaluate the predictive value of the combination of cytology with other markers in tracheal aspirate specimens. Conclusion The presence of squamous metaplasia in tracheal aspirates of VLBW babies between days 3 and 7 of life is significantly associated with the development of chronic lung disease. Simple microscopic evaluation of fresh tracheal aspirates enables us to identify patients at high risk of CLD at a very early stage. Received: 5 August 1997 / Accepted in revised form: 19 May 1998     

Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis

Aim: To identify which clinical signs at presentation are most predictive of sepsis subsequently confirmed by blood culture and to investigate whether the predictive power of the clinical signs varies by gestational age. Methods: Among 401 newborn infants <28 days of age with suspected sepsis, nine signs of sepsis and C‐reactive protein (CRP) values were prospectively recorded. Logistic regression assessed the association of these signs and laboratory values with a subsequently confirmed diagnosis of sepsis by positive blood culture. The analysis was stratified by gestational age with mutual simultaneous adjustment for the signs and sex. Results: Five of the nine clinical signs (feeding intolerance, distended abdomen, blood pressure, bradycardia and apnoea), along with CRP were statistically significantly associated with a positive blood culture. After simultaneous adjustment for all of the signs, apnoea, hypotension and CRP were independently predictive of positive blood culture. When the material was stratified by gestational age, differences in the association with positive blood culture were found for bradycardia, tachypnea and irritability/seizures. Conclusion: In this selected population of infants with suspected sepsis, apnoea and hypotension are independently predictive of a confirmed diagnosis, while bradycardia is more predictive among preterm infants and tachypnea among term infants.     

Endotracheal aspirate microscopy,cultures and endotracheal tube tip cultures for early prediction of ventilator associated pneumonia in neonates

Objective

To evaluate the utility of endotracheal aspirate microscopy, culture and endotracheal tube tip culture for early diagnosis of ventilator-associated pneumonia in neonates.

Methods

Inborn ventilated neonates were followed-up for ventilator-associated pneumonia using Center for Disease Control and Prevention (CDC) criteria. Endotracheal aspirate microscopy, culture and endotracheal tube tip cultures were performed.

Results

Ventilator-associated pneumonia occurred in 28/68 (41%) neonates as per CDC criteria. Endotracheal aspirate microscopy (≥5 polymorphonuclear cells per high power field) and endotracheal aspirate culture had 78.6% and 75% sensitivity, 87.5% and 90% specificity, positive predictive value of 81.5% and 84%, and negative predictive value of 85.4% and 83.72%, respectively. Mean (SD) time of result of microscopy and endotracheal aspirate culture was 55.7 (4.3) h and 108.3 (19.7) h, respectively in comparison to diagnosis made at 143.5 (23.3) h, as per CDC criteria.

Conclusion

Endotracheal aspirate microscopic examination and culture can be supportive in objective diagnosis of ventilator-associated pneumonia with an added advantage of earlier prediction.

     

Citrobacter sepsis in infants

A study of blood cultures from 320 cases of neonatal sepsis showed 136 (42.5%) to be positive for bacterial growth; of these 82 (60.29%) isolates being gram negative bacilli. Citrobacter was the commonest gram negative bacilli isolated. Other commonly isolated gram negative organisms were Pseudomonas, Klebsiella, Salmonella typhimurium, Acinetobacter and Escherichia coli. Antibiotics susceptibility pattern revealed the isolates to be resistant to commonly used antibiotics.     

Acute renal failure in neonatal sepsis

Objective To evaluate the occurrence of acute renalfailure (ARF) and the factors associated with it in cases of neonatal sepsis. Methods The case control study was conducted in the referral neonatal intensive care unit of a tertiary teaching hospital. 200 out born neonates with sepsis admitted to the nursery from January to July 2003 were evaluated for presence of ARF (cases) or not (controls). Sepsis was diagnosed on the basis of either a positive sepsis screen (immature: total (I:T) neutrophil ratio >0.2, μ-ESR> age in days + 2mm or>15 mm, CRP>6mg/dl, TLC<5000 cells/mm³; 2 or more positive) or a positive blood culture in symptomatic neonates. ARF was defined as blood urea nitrogen (BUN) >20mg/dl on two separate occasions at least 24 hours apart. Oliguria was defined as urine output <1ml/Kg/hr. Results 52 out of 200 (26%) neonates with sepsis had ARF; only 15% of ARF was oliguric. The mean gestation of neonates with ARF was similar to those without ARF (36.1±4.1 wks vs. 36.6±3.5 wk; p=0.41). A significantly higher number of babies with ARF weighed less than 2500 gm as compared to those without ARF (86.5%vs 67.6%; p=0.008). The association of meningitis, disseminated intravascular coagulation (DIC) and shock was also significantly higher in neonates with ARF (46.8%vs 26.2%, p=0.01; 65.4%vs 20.3%, p<0.001; 71.2%vs 27.0%, p<0.001 respectively). Mortality in neonates who developed ARF was significantly higher (70.2%vs 25%, p<0.001). Factors including gestational age, weight, onset of sepsis, culture positivity, associated meningitis, asphyxia, shock, prior administration of nephrotoxic drugs were subjected to univariate analysis for prediction of fatality in neonates with sepsis and ARF; only shock was found to be a significant predictor of fatality (p<0.001). ARF had recovered in 22 out of 49 neonates in whom data was available; three patients had left against medical advice. The mean duration of recovery in these 22 neonates was 5.5 days (range 1–14 days). Presence of co-existing morbidities (perinatal asphyxia/congestive heart failure (CHF)/necrotising enterocolitis (NEC) or nephrotoxic drugs did not alter the frequency of recovery of ARF in septic neonates (45.5%vs 44.4%, p=0.944; 41%vs 52%, p=0.308 respectively). Conclusion Renal failure occurred in 26% neonates with sepsis. Although ARF in neonates has been reported to be predominantly oliguric, it was observed that ARF secondary to neonatal sepsis was predominantly non oliguric. Low birth weight was an important risk factor for the development of ARF. The mortality being three times higher in neonates with ARF demands a greater awareness of this entity among practitioners and better management of this condition.     

Elevated cytokine levels in tracheobronchial aspirate fluids from ventilator treated neonates with bronchopulmonary dysplasia

Abstract Bronchopulmonary dysplasia (BPD) is a chronic lung disease often occurring in ventilator-treated very low birth weight infants. The aetiology of BPD is multifactorial and pulmonary immaturity, high oxygen concentrations, peak inspiratory pressure levels and large tidal volumes during prolonged mechanical ventilation are important factors. We measured in tracheobronchial aspirate fluid (TAF) the concentrations of the pro-inflammatory cytokines tumour necrosis factor , interleukin-1 (IL-1), IL-6, IL-8, and IL-1 receptor antagonist in infants requiring artificial ventilation for BPD (n=17) or respiratory distress syndrome (RDS) (n=15) or postoperatively after surgery (n=15). The median levels of all studied cytokines in TAF were higher in infants with BPD without local or systemic corticosteroid, treatment compared to the median TAF levels of BPD neonates treated with corticosteroids (P=0.06–P<0.01). The neonates with BPD not treated with corticosteroids also showed higher levels of the five studied cytokines in TAF compared to infants on short-time ventilator treatment (P<0.01–P<0.001) and compared to neonates with RDS (P=0.07–P<0.001). The corticosteroid treated neonates with BPD had TAF cytokine levels approaching those of the control neonates.Conclusion Tumour necrosis factors , IL-1, IL6, IL8 and IL 1 ra were markedly elevated in tracheobronchial aspirate fluids from neonates with bronchopulmonary dysplasia. Corticoid treatment seemed to reduce these levels.     

Comparison of ampicillin plus gentamicin vs. penicillin plus gentamicin in empiric treatment of neonates at risk of early onset sepsis

Aim: We aimed to compare the clinical efficacy of ampicillin (AMP) vs. penicillin (PEN) both combined with gentamicin in the empirical treatment of neonates at risk of early onset neonatal sepsis (EOS). Methods: We performed an open label cluster randomized equivalence study in both Estonian neonatal intensive care units, including neonates with suspected EOS, aged less than 72 h. Primary end‐point was clinical failure rate, expressed by need for change of antibiotic regimen within 72 h and/or 7‐day all cause mortality. Bowel colonization was followed with biweekly perineal swab cultures. Results: Incidence of proven EOS was 4.9%. Among neonates receiving AMP (n = 142) or PEN (n = 141) change of antibiotic regimen within 72 h (10/142 vs. 10/141; OR 1.02; 95% CI 0.40–2.59), 7‐day mortality (11/142 vs. 14/141; OR 0.76; 95% CI 0.33–1.75) and over‐all treatment failure (20/142 vs. 20/141; OR 1.01; 95% CI 0.52–1.97) occurred at similar rates. The only differences in gut colonization were lower number of patients colonised with enterococci, S. aureus and AMP resistant Acinetobacter spp. in AMP and lower number of those with S. haemolyticus and S. hominis in PEN arm. Conclusions: AMP and PEN combined with gentamicin have similar effectiveness in the empiric treatment of suspected neonatal EOS.     

脓毒症新生儿肾上腺皮质功能的研究

目的 明确脓毒症新生儿肾上腺皮质的功能状态、肾上腺皮质功能不全的发生率、肾上腺皮质功能与脓毒症病情及预后的关系.方法 将60例≥36周的脓毒症新生儿分为脓毒症组(49例)和严莺脓毒症组(11例),经化学发光免疫技术检测血清基础皮质醇水平及小剂量ACTH激发试验后的皮质醇峰值水平.结果 ①脓毒症组血清基础皮质醇平均水平为23.24 μg/dl,峰值平均水平为42.04 μg/dl;严重脓毒症组血清基础皮质醇平均水平为51.89μg/dl,峰值平均水平为60.36μg/dl;严重脓毒症组血清基础皮质醇和血清皮质醇峰值的平均水平都高于脓毒症组.②60例中肾上腺皮质功能不全18例,其血清基础皮质醇平均水平为7.69μg/dl,峰值平均水平为31.43 μg/dl;肾上腺皮质功能正常的脓毒症新生儿血清基础皮质醇平均水平为35.27μg/dl,峰值平均水平为50.16μg/dl;肾上腺皮质功能正常组血清基础皮质醇和血清皮质醇峰值的平均水平都高于肾上腺皮质功能不全组.③脓毒症组无死亡病例,严重脓毒症组死亡6例,两组差异有统计学意义;肾上腺皮质功能小全组死亡1例,肾上腺皮质功能正常组死亡5例,两组差异无统计学意义.结论 脓毒症新生儿血清皮质醇的合成分泌增加,且病情越重,血清基础皮质醇的水平越高;脓毒症新生儿的病死率与病情的严重程度呈正相关;部分脓毒症新生儿可继发肾上腺皮质功能不全,未发现脓毒症新生儿病死率与肾上腺皮质功能不全之间存在相关性.     

Neonatal gram-negative bacteremia

A 22 months prospective study of neonatal gram-negative bacteremia was undertaken in a 15 bed NICU to find out the incidence and antibiotic resistance patterns. Clinically suspected 1326 cases of neonatal sepsis were studied during this period. More than 25% of the cases were microbiologically positive for sepsis. Among 230 (67.2%) cases of gram-negative bacteremia, the predominant isolates werePseudomonas aeruginosa (38.3%),Klebsiella pneumoniae (30.4%),Escherichia coli (15.6%) andAcinetobacter sp. (7.8%). Fifty-nine per cent of the neonates were born in hospital while 41% were from community and referral cases. Lower respiratory tract infection, umbilical sepsis, central intravenous line infection and infection following invasive procedures were the most commonly identified sources of.septicemia. Prematurity and low birth weight were the main underlying conditions in 60% of the neonates. Total mortality was 32%. Increased mortality was mainly associated with rmrhropenia, nosocomial infection and inappropriate antibiotic therapy. Resistance was increasingly noted agains’t many antibiotics. The isolates were predominantly resistant to extended spectrum cephalosporins (25%-75%), piperacillin (68%-78%), and gentamicin (23%-69%). The commonest microorganisms causing gram-negative bacteremia werePseudomonas aeruginosa followed byKlebsiella pneumoniae. The community-acquired bacteremia was mainly due to E.coli. The proportion of preterm and low birth weight babies was significantly high, and the major contributing factor in total mortality. Sensitivity to different antibiotics conclusively proved that a combination of ampicillin + sulbacfam with amikacin or ampicillin + sulbactam with ciprofloxacin is most effective.     

高迁移率族蛋白1在新生儿败血症中的表达与机制

目的 探讨高迁移率族蛋白1（HMGB1）在新生儿败血症中的表达与机制。方法 选取62例新生儿败血症患儿为败血症组,66例局部感染新生儿为局部感染组,70例健康新生儿为健康对照组。检测三组新生儿血清中IL-6、IL-8、IL-17、IL-23、C反应蛋白（CRP）和降钙素原（PCT）的含量,外周血单个核细胞中HMGB1、Toll样受体4（TLR4）、核转录因子κB（NF-κB）mRNA及TLR4、NF-κB蛋白的表达。将健康新生儿的外周血单个核细胞分为对照组、HMGB1处理组、HMGB1+TAK-242（TLR4抑制剂）组、HMGB1+PDTC（NF-κB抑制剂）组,检测各组TLR4、NF-κB、IL-8 mRNA及TLR4、NF-κB蛋白的表达。将健康新生儿的外周血单个核细胞分为对照组、LPS处理组、LPS+甘草甜素（HMGB1抑制剂）组,检测HMGB1、TLR4、NF-κB、IL-8 mRNA及TLR4、NF-κB蛋白的表达。结果 败血症组患儿血清中IL-6、IL-8、IL-17、IL-23、CRP、PCT含量均显著高于局部感染组和健康对照组（P < 0.05）。败血症组患儿外周血单个核细胞中HMGB1、TLR4、NF-κBmRNA及TLR4、NF-κB蛋白的相对表达量均显著高于局部感染组和健康对照组（P < 0.05）。HMGB1可以显著诱导外周血单个核细胞高表达TLR4、NF-κB mRNA及其蛋白（P < 0.05）;使用TAK-242可抑制TLR4、NF-κBmRNA及其蛋白的高表达,并进而抑制IL-8 mRNA的表达（P < 0.05）;使用PDTC可抑制NF-κB mRNA及其蛋白的高表达,并进而抑制IL-8 mRNA的表达（P < 0.05）。LPS可显著诱导HMGB1 mRNA,以及TLR4、NF-κBmRNA及其蛋白的高表达,进而刺激IL-8 mRNA的表达（P < 0.05）;使用甘草甜素可抑制HMGB1 mRNA的高表达,抑制TLR4、NF-κB mRNA及其蛋白的高表达,进而降低IL-8 mRNA的高表达（P < 0.05）。结论 HMGB1可能通过激活TLR4/NF-κB信号通路诱导IL-8等炎症因子的高分泌在新生儿败血症的发病中起重要作用,HMGB1阻断剂甘草甜素可抑制TLR4/NF-κB信号通路的活化及炎症因子的分泌。