Neoteric physiologic and immunologic methods for assessing early-onset neonatal sepsis

Septicemia is a growing problem among low birth weight infants. Early identification and treatment of sepsis in these infants would help to reduce the high mortality and morbidity seen with this disorder. Newer techniques may make earlier diagnosis a reality. In the following review article, early-onset sepsis in the premature infant is described, specifically focusing on the neonatal inflammatory response, neutropenia, and its somewhat inconsistent and delayed role as a marker for sepsis risk factors. Physiological signs, laboratory indicators, skin temperature, peripheral perfusion, and the interaction of macro-environmental factors are also discussed. Newer (neoteric) immunologic and cytokine markers of sepsis are reviewed. Finally, thermography, a noninvasive bioinstrument measuring vasoactive peripheral perfusion, which has potential for early recognition of neonatal septicemia, is described.     

新生儿早发型与晚发型败血症临床特征分析

目的分析比较新生儿早发型与晚发型败血症的感染途径、高危因素、临床特点及病原菌分布情况,指导临床早期诊断、治疗与干预。方法根据发病时间对我院2006年1月至2011年12月收治的88例新生儿败血症患儿进行分组,分为早发型组与晚发型组,并进行对照分析。结果在感染途径方面,两组患儿均以呼吸道感染多见（44．7％与46．O％）,两组比较差异无统计学意义（P=0．906）。两组间出生情况相比较,早产、出生体质量低、羊水污染、窒息均是新生儿败血症早期发病的高危因素。两组患儿临床特点相比较,早期发病者多以吃奶差（57．9％,22／38）入院,而晚期发病者易出现发热（42．0％,21／50）。血培养阳性4l例,阳性率46．6％（41／88）,两组血培养阳性标本中均以革兰阳性菌为主,分别是75．0％（15／20）、90．4％（19／21）,而金黄色葡萄球菌及凝固酶阴性葡萄球菌是主要致病菌。结论早产、出生体质量低、羊水污染、窒息均是新生儿败血症早期发病的高危因素。早发型败血症常常表现为吃奶差,而晚发型败血症患儿易出现发热。早发型及晚发型败血症的常见致病菌均为革兰阳性菌,以金黄色葡萄球菌及凝固酶阴性葡萄球菌多见。针对有高危因素的患儿,应结合其临床特点早期行病原学检查,进一步明确诊断,指导临床合理用药。     

Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock

Objective: To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II).¶Design: Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period.¶Patients and methods: A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms.¶Results: PCT values were highest in patients with septic shock (12.89 - 4.39 ng/ml; P < 0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91 - 3.87 ng/ml vs 0.53 - 2.9 ng/ml; P < 0.001, and 0.41 - 3.04 ng/ml; P < 0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26 - 1.62, 16.09 - 2.06, and 17.42 - 1.72 points, respectively), but was significantly higher in patients with septic shock (29.27 - 1.35, P < 0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock.¶Conclusions: In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.     

Procalcitonin for early diagnosis and differentiation of SIRS,sepsis, severe sepsis,and septic shock

Objective To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II). Design Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period. Patients and methods A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms. Results PCT values were highest in patients with septic shock (12.89±4.39 ng/ml;P<0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91±3.87 ng/ml vs 0.53±2.9 ng/ml;P<0.001, and 0.41±3.04 ng/ml;P<0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26±1.62, 16.09±2.06, and 17.42±1.72 points, respectively), but was significantly higher in patients with septic shock (29.27±1.35,P<0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock. Conclusions In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.     

Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis

Sepsis and severe sepsis cause significant morbidity and mortality among populations worldwide; the rapid diagnosis poses a considerable challenge to physicians in acute care settings. An ideal biomarker should allow, with high diagnostic accuracy, for an early and rapid recognition of sepsis. Procalcitonin (PCT) is a recently rediscovered biomarker that fulfills many of these requirements, especially in comparison to "older" and commonly used biomarkers, and that has demonstrated superior diagnostic accuracy for a variety of infections, including sepsis. While blood cultures are still considered the "gold standard" for the diagnosis of bacteremia and sepsis, and are perhaps one of the most important functions of the clinical microbiology laboratory, PCT provides important information in early stages of sepsis as well as during antimicrobial treatment. In fact, PCT can be useful for antimicrobial stewardship and its utilization may safely lead to significant reduction of unnecessary antimicrobial therapy. However, PCT is also less than a universal and perfect biomarker, as it can also be increased in noninfectious disease conditions. Laboratories and clinicians must appreciate the complexity of diagnostic algorithms for sepsis and understand the particular information that biomarkers, such as PCT, can offer. In that context, it is necessary to not only recognize the importance of critical clinical awareness and thorough physical patient examination, but also to understand traditional microbiological methods and the need for highly sensitive biomarker assays in order to facilitate an early diagnosis and goal-directed therapy in patients suspected of sepsis. This review is intended to provide additional information for clinicians and microbiologists to better understand the physiology and diagnostic utility of procalcitonin for sepsis and other infectious disease conditions.     

Procalcitonin as a diagnostic test for sepsis: health technology assessment in the ICU

Elevation in the serum concentration of procalcitonin (PCT) is associated with systemic infection. This association has led to the proposed use of PCT as a novel biomarker of bacterial sepsis. The advantages and limitations of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) definitions of sepsis are an important consideration that affects the impact of any diagnostic test for sepsis and these issues are discussed. Our main objective is to perform a systematic health technology assessment of PCT as a diagnostic test for sepsis. In an adult intensive care unit (ICU) population, we identify a specific and important question-can PCT accurately distinguish sepsis in patients with systemic inflammatory response syndrome (SIRS) who have a suspected infection? Likelihood ratios are calculated from published data to attempt to find the best answer. The published evidence does not support a general claim that PCT is a useful decision support tool for diagnosing sepsis in patients who have SIRS. Procalcitonin has a slightly better ability to exclude the diagnosis of sepsis. The role for using PCT testing in the ICU will continue to evolve along with our understanding and definition of sepsis.     

A metabolomic approach for diagnosis of experimental sepsis

Background

The search for reliable diagnostic biomarkers of sepsis remains necessary. Assessment of global metabolic profiling using quantitative nuclear magnetic resonance (NMR)-based metabolomics offers an attractive modern methodology for fast and comprehensive determination of multiple circulating metabolites and for defining the metabolic phenotype of sepsis.

Objective

To develop a novel NMR-based metabolomic approach for diagnostic evaluation of sepsis.

Methods

Male Sprague?CDawley rats (weight 325?C375?g) underwent cecal ligation and puncture (n?=?14, septic group) or sham procedure (n?=?14, control group) and 24?h later were euthanized. Lung tissue, bronchoalveolar lavage (BAL) fluid, and serum samples were obtained for ¹H NMR and high-resolution magic-angle spinning analysis. Unsupervised principal components analysis was performed on the processed spectra, and a predictive model for diagnosis of sepsis was constructed using partial least-squares discriminant analysis.

Results

NMR-based metabolic profiling discriminated characteristics between control and septic rats. Characteristic metabolites changed markedly in septic rats as compared with control rats: alanine, creatine, phosphoethanolamine, and myoinositol concentrations increased in lung tissue; creatine increased and myoinositol decreased in BAL fluid; and alanine, creatine, phosphoethanolamine, and acetoacetate increased whereas formate decreased in serum. A predictive model for diagnosis of sepsis using these metabolites classified cases with sensitivity and specificity of 100%.

Conclusions

NMR metabolomic analysis is a potentially useful technique for diagnosis of sepsis. The concentrations of metabolites involved in energy metabolism and in the inflammatory response change in this model of sepsis.     

Molecular microbiological methods in the diagnosis of neonatal sepsis

Neonatal sepsis is a major cause of neonatal mortality and morbidity. The current gold standard for diagnosis of sepsis, namely blood culture, suffers from low sensitivity and a reporting delay of approximately 48–72 h. Rapid detection of sepsis and institution of antimicrobial therapy may improve patient outcomes. Rapid and sensitive tests that can inform clinicians regarding the institution or optimization of antimicrobial therapy are urgently needed. The ideal diagnostic test should have adequate specificity and negative predictive value to reliably exclude sepsis and avoid unnecessary antibiotic therapy. We comprehensively searched for neonatal studies that evaluated molecular methods for diagnosis of sepsis. We identified 19 studies that were assessed with respect to assay methodology and diagnostic characteristics. In addition, we also reviewed newer molecular microbiological assays of relevance that have not been fully evaluated in neonates. Molecular methods offer distinct advantages over blood cultures, including increased sensitivity and rapid diagnosis. However, diagnostic accuracy and cost–effectiveness should be established before implementation in clinical practice.     

血清白介素—6早期诊断新生儿败血症

目的评价血清中白介素-6（IL-6）检测对于早期诊断新生儿败血症的价值。方法ELISA法检测对例血培养阳性的败血症新生地急性期血清IL－6浓度,同时检测C-反应蛋白（CRP）、WBC、中性粒细胞计数（PMN）以及杆状核中性粒细胞（I）与中性粒细胞总数（T）之比,并评价各项指标的临床诊断价值。结果IL－6单独诊断时可靠性最高,其敏感性、特异性、阳性预测值（PPV）、阴性预测值（NPV）、约登指数分别为85％、95％、炒叽、86％及0．80,IL-6结合CRP诊断的准确性明显优于经典的评价指标（CRP、WBC、PMN、I／T）。结论IL－6结合CRP可能是早期诊断新生儿败血症的有价值的参数。     

早发型与晚发型新生儿败血症临床特点及病原学比较

摘要 目的 研究早发型和晚发型新生儿败血症临床特点、病原菌分布及菌株耐药状况。方法 对2015年1-12月收治的83例早发型与晚发型新生儿败血症病例的临床和病原学资料进行回顾性分析。结果 晚发型患儿常为足月儿,早发型常为早产或低出生体重儿;早发型患儿反应低下、硬肿、喂养困难发生率明显高于晚发型;晚发型组肺炎和化脓性脑膜炎发生率高于早发型组;早发型败血症病原以肺炎克雷伯菌、大肠埃希菌主,晚发型败血症病原以凝固酶阴性葡萄球菌为主。结论 应根据早发型和晚发型新生儿败血症在临床特点及病原分布差异指导临床诊断和治疗。     

血清CRP、PCT、sTREM-1在新生儿早发型败血症中的诊断意义

目的 探讨血清C反应蛋白(CRP)、降钙素原(PCT)、可溶性髓系细胞触发受体-1(sTREM-1)在新生儿早发型败血症诊断中的价值.方法 选取2019年5月至2020年10月江西省儿童医院收治的100例患儿作为研究对象,将诊断为早发型败血症的50例患儿纳入观察组,未诊断为早发型败血症的50例患儿纳入对照组,记录2组患...     

Maternal colonisation with group B streptococcus and effectiveness of a culture-based protocol to prevent early-onset neonatal sepsis

This study was conducted to find out the group B streptococcus colonisation of pregnant women in Kocaeli, Turkey. A culture plus individualised high-risk-based antibiotic prophylaxis was compared with high-risk-based approach alone. The screening of women was performed via vaginal and anal cultures for group B streptococcus (GBS). The maternal GBS colonisation rate was found to be 6.5%. All colonised women or preterm labours with unavailable culture results until delivery received prophylactic antibiotics. Neonatal colonisation rate and early-onset neonatal sepsis due to GBS was 1/200. The unscreened 900 women received prophylactic antibiotics due to a risk factor-based approach. The neonatal colonisation rate was 17/900 (p = 0.1), and the rate of early-onset neonatal sepsis was 3/900 (p = 0.6). A culture plus individualised high-risk-based antibiotic prophylaxis provided an insignificant change in neonatal colonisation and early-onset neonatal sepsis with GBS when compared with high-risk-based approach alone.     

The neonatal early-onset sepsis calculator to reduce empiric antibiotic use in newborns exposed to chorioamnionitis

BackgroundTerm and late preterm newborns exposed to maternal chorioamnionitis (CAM) have traditionally received early-onset sepsis (EOS) evaluations and empiric antibiotics despite their clinical appearance leading to ineffective maternal/infant bonding, NICU admissions and unnecessary antibiotic exposure.MethodsPre/post-interventional quality improvement project in a level III NICU to reduce empiric antibiotic therapy and EOS evaluations in newborns exposed to CAM using the Neonatal Early-Onset Sepsis (NEOS) Calculator.ResultsMean empiric antibiotic treatment days for newborns exposed to CAM during the pre-implementation period was 3.14 days and 1.33 days during post-implementation period, an 81% reduction. A 16.7% reduction in EOS evaluations between the pre- and post-implementation periods was noted. Antibiotic use in newborns exposed to CAM decreased from 100% during the pre-implementation data collection to 41.7%.DiscussionThe NEOS calculator may reduce unnecessary antibiotic use and diagnostic testing in newborns exposed to CAM while lowering healthcare expenditures in the assessment of EOS in newborns.ConclusionsThese findings emphasize the importance of implementing an evidence-based protocol for newborns exposed to CAM.     

前降钙素在烧伤患者并发脓毒症预测中的应用

目的 动态监测血浆前降钙素(PCT)对烧伤并发脓毒症患者预测的价值.方法 将72例烧伤患者按是否并发脓毒症分为两组;选择同期烧伤科收治的32例烧伤二期行瘢痕松解或改型的患者为对照组.患者于入院后2、4、6、8、10、16、20 d,对照组于人院后2d收集血标本.采用双抗体夹心免疫发光法(ILMA)测定血浆PCT水平,用酶联免疫吸附法(ELISA)测定血浆C-反应蛋白(CRP)水平.结果 未并发脓毒症的烧伤患者血浆PCT水平较对照组轻度升高,CRP一直维持在较高水平;脓毒症烧伤患者PCT、CRP明显高于对照组(均P＜0.05).脓毒症组血浆PCT较非脓毒症组明显升高(均P＜0.05),而CRP差异无统计学意义(均P＞0.05).分别以PCT 2.2μg/L、CRP 250 mg/L作为预测感染的临界值,结果 PCT的敏感性98％、特异性94％、阳性预测值88％,均明显高于CRP(85％、82％、68％).而且脓毒症组患者的住院时间(d)较非脓毒症组明显延长(44.2±5.0比26.8±4.0,P＜0.05).结论 血浆PCT是预测烧伤患者并发脓毒症的敏感指标,进行常规PCT检测有助于早期发现创伤后感染并发症,并能预测创伤患者的转归和预后.     

Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis

The diagnosis and prognosis of sepsis after antimicrobial therapy among systemic inflammatory response syndrome (SIRS) patients were evaluated with the biomarkers procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell counts.