肝素结合蛋白在感染性疾病中的应用现状

感染性疾病是一类严重威胁人类健康的疾病,由感染性疾病发展所引起的严重脓毒症和脓毒症休克是重症患者死亡的重要原因,全球每年新增数百万脓毒症患者,且其病死率大于25%[1]。由于20%~30%的严重脓毒症患者初期症状缺乏特异性[2],而现有的脓毒症和脓毒症休克诊断标准不具备早期识别能力。因此,如何尽早识别脓毒症及脓毒症休克,以达到早期干预、降低多器官功能衰竭发生率、减少病死率成为脓毒症诊治领域的重难点[3]。《中国严重脓毒症/脓毒症休克治疗指南》中提到肝素结合蛋白(HBP)是早期诊断脓毒症、脓毒症休克的有效指标[4],因此HBP将可能作为新的标志物,在脓毒症及其他感染性疾病的早期诊断中发挥重要作用。笔者就HBP在临床中的应用现状作一综述,以期为临床诊断与治疗提供参考。     

降钙素原、乳酸、D-二聚体与脓毒症患者病情严重程度及预后的相关性

<正>脓毒症是一种由感染所致的全身炎症反应综合征,具有病情凶险、进展快、临床预后差的特点,如不及时治疗可进展为严重脓毒症、脓毒症休克等,表现为低血氧症、代谢性酸中毒及多器官功能障碍,是患者致死的重要病因。脓毒症可涉及多种病理生理变化,其中凝血功能异常可贯穿疾病全过程,出现D-二聚体水平异常升高^[1]。细菌学是诊断脓毒症的可靠指标,降钙素原是诊断患者细菌感染的可靠指标,能指导临床进行早期抗感染治疗,对诊断脓毒症的诊断及治疗具有重要指导意义^[2]。乳酸是细胞无氧呼吸的代谢产物,     

脓毒症患者早期抗生素治疗的研究进展

脓毒症是感染引起的危及生命的全身反应综合征，具有较高的病死率。抗感染治疗是脓毒症患者抢救的核心措施。抗生素治疗的时机目前仍存在争议：早期抗生素治疗的观点认为早期抗生素治疗可以降低脓毒症患者病死率，同时抗生素延迟使用导致脓毒症病死率增加；反对早期抗生素治疗观点认为早期抗生素治疗与脓毒症病死率不相关或仅与较长的延迟相关，而且早期使用抗生素的危害是非脓毒症患者也被经验性应用了抗生素治疗，会导致多重耐药的发生率增高，继而导致患者病死率增加。因此，脓毒症患者抗生素治疗因人而异，提高脓毒症患者早期诊断，针对性的个体化的治疗更有益。本文对脓毒症患者早期抗生素治疗与脓毒症患者预后的关系进行阐述。     

提高精准抗感染诊疗能力,改善儿童脓毒症预后北大核心CSCD

脓毒症因其发病机制复杂,病死率高,治疗难度大,一直是国际上关注的热点问题。重症感染引发的严重脓毒症/脓毒性休克是导致儿童致死、致残的主要原因之一。2020年儿童脓毒症相关器官功能障碍和脓毒性休克诊治国际指南仍十分强调早期、精准抗感染治疗是降低病死率的关键措施[1]。但在临床实际工作中,普遍存在病原学诊断耗时长、阳性率低,耐药菌感染逐年增多且确定耐药性耗时长等问题;在抗感染治疗方面,亦存在经验性治疗药物选择不准确,盲目使用广谱抗感染药物或联合用药,重症感染患儿按照药品说明书推荐方法使用常达不到理想疗效等突出问题。因此,如何提高病原学快速诊断能力,实现早期、精准抗感染治疗是解决上述问题,改善患者预后的关键措施。     

NOD样受体家族核苷酸结合寡聚化结构域样受体3炎性小体在脓毒症中的作用

正脓毒症是感染、烧/创伤、休克等急危重患者的严重并发症。根据最新定义,脓毒症是宿主对感染所导致的免疫反应失调而引起的危及生命的器官功能障碍[1]。脓毒症患者病情重,发展快,病死率高。最近的一篇Meta分析指出住院治疗患者脓毒症发病率为437/100 000例,病死率为17%;而严重脓毒症的发病率为270/100 000例,病死率为26%[2]。脓毒症是一个临床综合征,目前尚无治疗脓毒症的特     

脓毒症并发急性呼吸窘迫综合征的观察与护理

脓毒症(Sepsis)是指感染引起的全身炎症反应综合征, 是目前 ICU 中的首要死亡原因。急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)为临床常见的危重症之一,是由肺内原因和/或肺外原因引起的,以顽固性低氧血症为显著特征的临床综合征。脓毒症并发ARDS的患者预后差,病死率极高。我国多中心研究报告显示,各ICU脓毒症并发ARDS的病死率高达50%-90%[1-2]。由于脓毒症并发呼吸窘迫综合征临床治疗预后普遍较差,因此,如何在医生进行诊断、治疗的同时,通过我们的观察及护理去改善患者的临床预后,是我们护理工作的重要目标。我院ICU自2013年1月-2016年5月我科共收治脓毒症并发ARDS的患者38例,现回顾总结将临床观察及护理报道如下。     

中性粒细胞CD64结构和功能特点及其早期诊断脓毒症研究中的进展

<正>脓毒症是指由感染引起的全身炎症反应综合征(SIRS),临床上证实有细菌存在或有高度可疑感染灶。其病情凶险,进展迅速,病死率高。在美国严重脓毒症发病率平均每年增长13.0%~13.3%[1],全球每年有数百万人发病,约1/4脓毒症患者因抢救无效而死亡[2]。目前临床诊断脓毒症指标WBC,CRP对于早期诊断的敏感度和特异度均不高,而作为金标准的血培养阳性率低,等待结果时间较长。白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α[3]、降钙素原(PCT)[4]可作为脓毒症的早期诊断指标,但细胞因子达峰值时间早,循环中半衰期短[5],     

脓毒症还面临更多的挑战:定义及诊断

正脓毒症是一种复杂且富有挑战性的综合征,表现形式多样、病情变化快速。早期识别和及时干预治疗有助于降低脓毒症相关的发病率和病死率[1]。最近,章和他的同事[2]代表转化医学协会发表了一份相关指南,标题为"脓毒症的早期识别和诊断的临床实践指南"。本文着重介绍了临床上早期而又准确的诊断脓毒症的困难性。临床上,对脓毒症的诊断存在众多不同的定义且关于新的诊断的证据又不断改     

脓毒症患者机体中降钙素原、心肌脂肪酸结合蛋白的水平及其与疾病严重程度的关系研究

正脓毒症是由于机体受到感染而导致的一种全身炎性反应综合征(SIRS)。有研究者提出,脓毒症及其并发症出现高死亡率的主要原因在于未能对该病进行早期诊断[1]。血清降钙素原(PCT)对相关疾病的早期诊断具有较高的特异性以及敏感性[2],目前已广泛地应用于临床细菌感染性疾病的诊断[3]。为了有效评估脓毒症发病严重程度及患者预后状况,本研究主要探讨人心型脂肪酸结合蛋白(H-FABP)及PCT与脓毒症发病程度及患者预后状况之间的相关关系,现报道如下。     

常用生物标记物在脓毒症中的应用现状及展望

全世界每年因脓毒症而死的人数是惊人的,且其发生率呈逐年递增,但脓毒症的疗效却没有得到明显提高[1]。脓毒症的发病机制复杂,仅通过患者症状和体征来进行诊断和分层是极其困难的,但脓毒症的早期诊断和分层对于及时或特异地给予治疗是十分重要的[2]。1脓毒症的定义及所面临的困扰     

新型感染标志物在脓毒症早期诊断中的应用及研究进展

脓毒症(sepsis)是感染引起宿主反应失调,导致危及生命的器官功能障碍症候群,病情危急,死亡率高.血培养是诊断的金标准,但培养及鉴定时间较长,而临床治疗需要在脓毒症早期杀灭病原菌以控制患者病情,提高治愈率,减少用药时间,降低死亡率.因此,迫切需要能够快速、准确诊断早期脓毒症的实验室指标以指导临床抗生素治疗.血清炎性介...     

High-throughput screening of bacterial pathogens in clinical specimens using 16S rDNA qPCR and fragment analysis

Molecular-based detection of bacterial pathogens directly from clinical specimens permits rapid initiation of effective antimicrobial treatment and adequate patient management. Broad-range polymerase chain reaction (PCR) amplification of the 16S rRNA gene (16S rDNA qPCR) is used in many diagnostic laboratories as a complement to cultural identification of bacterial pathogens. However, efforts for automation of 16S rDNA PCR workflows are needed in order to reduce turnaround times and to enhance reproducibility and standardization of the technique. In this retrospective method evaluation study, clinical specimens (N?=?499) from patients with suspected bacterial infections were used to evaluate 2 diagnostic semiautomated workflows for rapid bacterial pathogen detection. The workflows included automated DNA extraction (QIASymphony), 16S rDNA qPCR, fragment or melting curve analysis, and amplicon sequencing. Our results support the use of the 16S rDNA qPCR and fragment analysis workflow as it enabled rapid and accurate identification of bacterial pathogens in clinical specimens.     

微生物室与临床密切配合提高肺部感染的病原学诊断水平

病原学诊断不明是造成抗菌药物不合理使用的一个重要原因.微生物室应当与临床密切配合,评估呼吸道标本的质量.微生物枪验人员应当加强直接涂片和各种染色等基本功的训练,并开展快速检测手段,提高肺部感染的病原菌诊断水平.     

Multiplex PCR pathogen detection in two severely burned patients with suspected septicemia

The case studies reported in this article strive to illustrate the clinical value of multiplex polymerase chain reaction (PCR)-based pathogen detection in patients with burn sepsis. Adult (age ≥18 years) burn patients (≥20% TBSA) presenting with signs and symptoms of burn sepsis were enrolled into a prospective, observational trial. Patients received PCR testing in parallel to routine blood cultures. The authors report two cases in which PCR was used to rapidly detect pathogens in whole blood from burn patients with suspected septicemia. PCR identified Escherichia coli in 5.8 hours in case 1. Blood and sputum cultures required 17 hours for Gram stain results. Empiric ceftriaxone therapy was initiated. Blood cultures required an additional 18 hours to identify the same pathogen detected by PCR. Ceftriaxone was replaced with ciprofloxacin for improved coverage. Follow-up antimicrobial susceptibility results revealed intermediate ciprofloxacin resistance. Meropenam therapy was initiated. In case 2, PCR detected Pseudomonas aeruginosa in 5.45 hours while blood cultures remained negative. Respiratory cultures became positive for P. aeruginosa 2 days later. Serial PCR samples continued detecting P. aeruginosa despite negative blood cultures and appropriate antimicrobial therapy. The patient later became hypotensive and coagulopathic and expired. For both patient cases, PCR identified high-risk pathogens faster than culture methods. In the second patient case, PCR identified the presence of pathogen DNA despite negative cultures before the onset of septic shock and presumptive disseminated intravascular coagulation. These results warrant further investigation to determine the clinical significance of pathogen DNA in burn sepsis.     

Bench-to-bedside review: The promise of rapid infection diagnosis during sepsis using polymerase chain reaction-based pathogen detection

Early infection diagnosis as the cause of a patient's systemic inflammatory syndrome is an important facet of sepsis care bundles aimed at saving lives. Microbiological culture provides the main route for infection diagnosis but by its nature cannot provide time-critical results that can impact on early management. Consequently, broad-spectrum and high-potency antibiotics are essential during the immediate management of suspected sepsis in critical care but are associated with the development of drug-resistant organisms and superinfections. Established molecular laboratory techniques based on polymerase chain reaction (PCR) technology can detect pathogen DNA rapidly and have been developed for translation into a clinical diagnostic setting. In the setting of sepsis in critical care, emerging commercial systems are now available for the analysis of whole blood within hours, with the presumed aim of adoption into the current care bundles. In this review, we consider the importance of early infection diagnosis in sepsis, how this is limited by culture approaches and how the emerging PCR methods are showing promise in early clinical observational studies. The strengths and weaknesses of culture and PCR pathogen detection in whole-blood samples will be highlighted and recommendations made for urgent appropriately powered diagnostic validation studies in advance of clinical effectiveness trials before these emerging PCR pathogen detection techniques can be considered for adoption in clinical practice.     

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.     

Impact of antimicrobial resistance on the treatment and outcome of patients with sepsis

Antimicrobial therapy is one of the main stones of sepsis therapy. A recent study of septic shock patients showed that each hour of delay in antimicrobial administration during the ensuing 6 h after the onset of hypotension was associated with a decrease in survival rates. However, many questions regarding the impact of infection caused by antimicrobial-resistant pathogens on the mortality of patients with sepsis still need to be clarified. There is a lack of fair studies in the literature. Most studies have had inadequate sample size, inadequate adjustment for predictors of adverse outcomes, and inadequate definition of appropriate antibiotic therapy. Despite the fact that appropriate therapy is essential to treat sepsis, it seems that severity of underlying diseases and comorbidities are more important than resistance, although the studies were not well designed to examine the real impact of resistance on outcome. Finally, new technologies such as microarray that can identify different microorganisms, genes of resistance, and virulence in a few hours might have a great impact on the treatment of sepsis due to antimicrobial-resistant pathogens in the future.     

Routine use of a real-time polymerase chain reaction method for detection of bloodstream infections in neutropaenic patients

We examined the performance of a real-time polymerase chain reaction (PCR) test (SeptiFast) for early detection of bloodstream infection in febrile neutropaenic patients. Blood samples from 201 patients were screened for pathogens by blood culture and by PCR on the first day of fever. PCR results were available earlier (median 3 days for bacteria, 5 days fungal pathogens; P ≤ 0.01). The sensitivity (0.74) and specificity (0.96) of the PCR test were acceptable for Gram negatives when culture was considered the gold standard, but sensitivity of the test was poorer for Gram-positive organisms (0.39). The PCR assay also led to 22.9% of invalid results. SeptiFast speeds the microbiological diagnosis of bloodstream infection in neutropaenic patients. However, the frequent failure of instrumental control procedures, the relatively poor sensitivity of the test, and the lack of phenotypic data on antimicrobial susceptibility associated with its high costs suggest that this assay cannot replace the blood cultures.     

Emerging methodologies for pathogen identification in positive blood culture testing

Bloodstream infections (BSIs) represent a major cause of death in developed countries and are associated with long-term loss of functions. Blood culture remains the gold standard for BSI diagnosis, as it is easy to perform and displays a good analytical sensitivity. However, its major drawback remains the long turnaround time, which can result in inappropriate therapy, fall of survival rate, emergence of antibiotic resistance and increase of medical costs. Over the last 10 years, molecular tools have been the alternative to blood cultures, allowing early identification of pathogens involved in sepsis, as well detection of critical antibiotic resistance genes. Besides, the advent of MALDI-TOF revolutionized practice in routine microbiology significantly reduced the time to result. Reviewed here are recent improvements in early BSI diagnosis and these authors’ view for the future is presented, including innovative high-throughput technologies.     

Comparative molecular and microbiological diagnosis of 19 infective endocarditis cases in which causative microbes were identified by PCR-based DNA sequencing from the excised heart valves

Infective endocarditis (IE) is traditionally diagnosed by microbiological analysis of blood cultures, following which therapeutic antibiotics are chosen based on antimicrobial sensitivity tests. However, such conventional techniques do not always lead to an accurate etiological diagnosis. Recently, PCR analysis of the 16S rRNA gene has been employed to identify organisms isolated from excised heart valves. In this study, we analyzed 19 valve samples from patients with confirmed IE, as identified by Duke's criteria. Using broad-range PCR amplification, followed by direct gene sequencing, pathological agents were identified in all samples. Although blood cultures yielded negative results in 4 cases, PCR analysis of valve samples showed positive identification of causative organisms. In 3 cases, there was a difference between blood culture and PCR in identification of pathological agents, which are likely to be misidentified by the conventional method based on the phenotypic database. Postoperative antibiotics were chosen considering the severity of lesions and the results of PCR, Gram staining, and valve cultures. All patients were cured without relapse. The broad-range PCR method was therefore beneficial for the management of IE because it enabled us to identify pathogens directly from the site of infection, even organisms that were difficult to culture or likely to be misidentified by the conventional culture method. Identification of the agents provided precise knowledge of the microbiological spectrum involved in the cases of IE.