儿童碳青霉烯类耐药肺炎克雷伯菌医院感染的危险因素分析：单中心配对病例-病例-对照研究

目的 调查儿童专科医院住院患儿碳青霉烯类耐药肺炎克雷伯菌（carbapenem-resistant Klebsiella pneumonia,CRKP）感染及死亡的危险因素,为该类细菌的感染防治提供参考依据。 方法 采用配对病例-病例-对照研究的方法。回顾性纳入昆明市儿童医院2019年1月至2021年10月的81例CRKP感染患儿,81例碳青霉烯类敏感肺炎克雷伯菌（carbapenem-sensitive Klebsiella pneumonia,CSKP）感染患儿,及162例对照儿童（住院期间未分离出CRKP及CSKP的患儿）,比较分析各组儿童的基础疾病、既往住院暴露及该次住院暴露情况与CRKP感染及死亡的关联性。 结果 与对照组比较,既往3个月内有住院史与CRKP、CSKP感染存在较高关联强度（分别OR=14.25、10.07,P<0.01）;CRKP感染患儿特异的危险因素包括既往3个月内有碳青霉烯药物治疗史（OR=16.54,P<0.01）及该次住院接受中心静脉置管（OR=33.03,P<0.01）。而既往3个月内有碳青霉烯药物治疗史（OR=28.33,P<0.01）及该次住院抗生素经验性用药（OR=14.50,P<0.01）是导致CRKP患儿死亡的危险因素。 结论 患儿既往3个月内有住院史、碳青霉烯类药物治疗史,以及入院后接受侵入性操作是影响CRKP感染及预后的主要原因。儿童专科医院有必要开展入院时CRKP主动筛查,规范使用抗生素,并加强医院感染监测,以控制CRKP感染的发生。 ［中国当代儿科杂志,2022,24（9）：1008-1013］     

新生儿耐碳青霉烯类肠杆菌感染的防治

碳青霉烯类耐药已经逐渐成为中国新生儿重症监护室面临的严峻问题。耐碳青霉烯类肠杆菌(carbapenem-resistant enterobacteriaceae,CRE)通过产生碳青霉烯酶,水解包括碳青霉烯类在内的绝大部分β-内酰胺类抗生素,具有高度的耐药性。碳青霉烯酶根据Amber分类可分为A、B、D三类,不同碳青霉烯酶对特定β-内酰胺类抗生素的水解活性不同。目前,CRE在中国NICU住院新生儿中检出率高、病死率高、具有高度的传播性。CRE在新生儿的治疗非常困难,可选药物极其有限、药代/药效动力学数据匮乏、最佳剂量/用药间隔不确定、缺少联合用药研究等因素均给有效抗菌药物治疗带来巨大挑战。成人和儿童中针对CRE主要的抗菌药物包括碳青霉烯类、头孢他定/阿维巴坦、磷霉素、多黏菌素类、氨曲南等,但在新生儿中的使用鲜有研究。CRE一旦定植和感染,清除和治疗极其困难,因此在新生儿病房严格执行医院感染防控措施和抗菌药物使用管理,减少CRE产生、遏制传播、降低感染率是应对CRE流行的最重要措施。     

耐碳青霉烯类肠杆菌科细菌感染的治疗对策

一直以来,碳青霉烯类被认为是治疗耐药性肠杆菌科细菌的“最后一道防线”,然而近年来出现了耐碳青霉烯类肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae,CRE),世界范围内均有报道。该类细菌常是多重耐药菌、广泛耐药菌或泛耐药菌,并呈逐年增多趋势,对全球公众健康构成威胁。CRE 的主要耐药机制是产生碳青霉烯酶,该酶可灭活碳青霉烯类及大多数其他β-内酰胺类抗菌药物,使得患者处于无药可用的境地。CRE 感染主要发生在 ICU,且预后差,目前尚无理想的治疗手段,可选择的药物非常有限。本文重点介绍 CRE 的流行病学、耐药机制及治疗对策。     

2019年中国多中心住院儿童抗菌药物应用分析北大核心CSCD

目的采用世界卫生组织(WHO)AWaRe分类[可广泛使用类(Access)、谨慎使用类(Watch)、保留类(Reserve)、未推荐类(Not-recommended)]方法及经典的解剖学/治疗学/化学分类系统(ATC)分析2019年中国多中心儿童及新生儿抗菌药物应用监测网调查的中国儿童抗菌药物种类分布情况。方法本研究采用横断面调查方法,在2019年9月至12月进行一次儿童抗菌药物应用的多中心横断面调查,在调查期限内选一天作为调查日,将所有住院患儿中使用抗菌药物者的信息通过基于网络的数据收集系统进行填报(https://garpec-31.mobilemd.cn/login.aspx?relogin=true)。共覆盖10个省市的13家医院。调查科室包括感染科、呼吸科、普外科、儿科重症监护病房、新生儿重症监护病房、新生儿科。根据AWaRe及ATC抗菌药物分类目录对临床应用的抗菌药物进行归类,描述儿童及新生儿抗菌药物应用种类的AWaRe及ATC分布。结果共来自13家中心的2644张抗菌药物处方纳入研究,用于儿童的抗菌药物处方数2134张(80.71%),新生儿抗菌药物处方数为510张(19.29%)。总的抗菌药物处方中,可广泛使用类368张(13.92%),谨慎使用类1973张(74.62%),保留使用类60张(2.27%)和未推荐类243张(9.19%)。排名前五的抗菌药物种类为第三代头孢菌素类1056个(39.94%)、大环内酯类492个(18.61%)、碳青霉烯类275个(10.40%)、青霉素含酶抑制剂类246个(9.30%)和第二代头孢菌素类136个(5.14%)。各中心的抗菌药物所占比例:可广泛使用类为0~30.00%,谨慎使用类为36.67%~97.20%,保留使用类为0~17.02%,未推荐类0~33.33%。用于儿童及新生儿肺炎的1360张处方中,其中可广泛使用类152张(11.18%),谨慎使用类1051张(77.28%),保留使用类37张(2.72%),未推荐类120张(8.82%)。用于儿童肺炎的抗菌药物种类为第三代头孢菌素类522个(38.38%)、大环内酯类388个(28.53%)、青霉素含酶抑制剂141个(10.37%)、碳青霉烯类117个(8.6%)和青霉素类49个(3.60%)。结论中国儿童及新生儿所应用的抗菌药物和用于儿童及新生儿肺炎的抗菌药物中以谨慎使用类、第三代头孢菌素、大环内酯类等广谱抗菌药物及易促进耐药的抗菌药物种类为主,存在广谱抗菌药物应用过度的可能。     

先天性食管闭锁新生儿肺部感染病原菌及药敏分析

目的 探讨患先天性食管闭锁(CEA)新生儿肺部感染的病原及其药敏情况.方法 回顾性分析2004年1月至2014年9月收治的CEA患儿的临床资料.结果 55例患儿纳入最终研究,共进行104次痰培养检查,检测出细菌112株,前5位的革兰阴性杆菌包括铜绿假单胞菌36株,肺炎克雷伯菌肺炎亚种29株,鲍曼不动杆菌19株,大肠埃希菌9株,嗜麦芽窄食单胞菌6株;革兰阳性球菌仅5株,溶血葡萄球菌、草绿色链球菌各2株,金黄色葡萄球菌1株.药敏分析显示,革兰阴性杆菌对半合成青霉素类及部分的头孢类抗生素敏感性<50%,对碳青霉烯类、氨基糖苷类及喹诺酮类抗菌药物敏感性>80%.革兰阳性球菌对万古霉素、替考拉林的敏感性为100%.结论 CEA患儿合并的肺部感染主要以革兰阴性杆菌为主,对半合成青霉素类及部分的头孢类抗生素敏感性较低,对碳青霉烯类、氨基糖苷类及喹诺酮类抗菌药物仍保持较高的敏感性.CEA患儿所并发的革兰阳性球菌感染对万古霉素、替考拉林仍保持较高的敏感性.     

32例儿童链球菌中毒性休克综合征药物治疗疗效分析北大核心CSCD

目的分析儿童链球菌中毒性休克综合征(streptococcal toxic shock syndrome,STSS)不同药物治疗方案的疗效。方法回顾性收集2009年1月—2023年4月在湖南省儿童医院和郴州市第一人民医院经细菌培养证实为化脓性链球菌感染且符合STSS诊断标准患儿的临床资料,分析药物治疗疗效。根据药物治疗方案分为4组:标准组(含青霉素的方案)、A组(碳青霉烯类+糖肽类/利奈唑胺)、B组(碳青霉烯类、广谱抗生素、糖肽类/利奈唑胺单用或联用,但除外A组的方案)、C组(大环内酯类/未使用抗菌药物)。结果共纳入32例STSS患儿。药敏试验显示所有菌株对氨苄西林等β-内酰胺类抗菌药物和左氧氟沙星、万古霉素敏感,对克林霉素、红霉素及四环素耐药。标准组、A组、B组、C组4组间有效率的比较差异有统计学意义(P<0.05),其中标准组有效率最高(100%),A组、B组、C组有效率分别为40%、40%、0%。结论使用含青霉素的抗菌方案可提高儿童STSS治疗疗效。     

儿童侵袭性铜绿假单胞菌感染抗菌药物治疗现状及菌株药敏分析

目的分析侵袭性铜绿假单胞菌感染(IPAI)抗菌药物治疗现状及分离菌株药敏试验结果。方法回顾分析2014年1月至2019年3月住院的61例IPAI患儿的临床资料及61株侵袭性铜绿假单胞菌(IPA)菌株的药敏试验结果,比较48例经验性抗铜绿假单胞菌治疗与13例非抗铜绿假单胞菌治疗患儿以及27例经验性碳青霉烯类治疗与19例非碳青霉烯类治疗患儿的临床特征。结果 61例IPAI患儿中,男37例、女24例,中位年龄2.1(0.6～9.1)岁。院内死亡12例(19.67%),脓毒症休克15例(24.59%)。经验性非抗铜绿假单胞菌治疗患儿感染后住院时长较抗铜绿假单胞菌治疗患儿延长,差异有统计学意义(P=0.042),而重症病房入住率、院内死亡、脓毒症休克发生率的差异无统计学意义(P0.05)。经验性碳青霉烯与非碳青霉烯治疗患儿的重症病房入住率、院内死亡、脓毒症休克发生率、感染后住院时长的差异均无统计学意义(P0.05)。61株IPA菌株对哌拉西林/他唑巴坦、头孢他啶、头孢吡肟的敏感率为85%～90%,对亚胺培南、美罗培南的敏感率为90%～95%。结论重庆地区IPA菌株对常用抗铜绿假单胞菌抗菌药物有较高敏感性,青霉素类或头孢菌素类或其β-内酰胺酶抑制剂复合制剂可作为经验性治疗IPAI患儿的首选抗菌药物。     

鲍曼不动杆菌耐药性及防治策略

随着抗生素的广泛应用,多重耐药的鲍曼不动杆菌(MDR-AB)感染发生率迅速上升,对碳青霉烯类抗生素耐药的不动杆菌菌株超过48%,甚至出现对常用抗菌药物全耐药现象.细菌耐药主要是由于产生抗菌药物的灭活酶、外膜蛋白缺失和膜通透性下降以及靶位或外排泵功能改变.对MDR-AB的治疗可选择药物很少,根据药物敏感试验,可选择含舒巴坦制剂、多黏菌素、替加环素、碳氢酶烯类等药物,重症病例建议联合用药.最好的解决耐药性现状的办法是防止耐药菌的传播.良好的手卫生、标准的预防措施、适当的隔离措施、耐药性监测、抗生素管理等是有效的预防方法 .     

多重耐药鲍曼不动杆菌的耐药机制及治疗进展

近年来随着广谱抗生素的大量使用,多重耐药细菌、甚至是泛耐药及全耐药细菌不断产生.鲍曼不动杆菌是一种常见的条件致病菌,目前多重耐药鲍曼不动杆菌(multidrug-resistant acinetobacter baumannii,MDRAB)的院内感染已成为最为棘手的问题之一.MDRAB的耐药机制主要在于产生抗菌药物灭活酶、靶位或细胞功能改变、外膜屏障及药物主动外排泵作用.治疗MDRAB感染的药物包括舒巴坦制剂、碳青霉烯类、多黏菌素类、四环素类及其他药物.但是由于缺乏大规模的临床研究,目前对于MDRAB的治疗尚无统一的规范,儿科的临床经验更少.     

多重耐药菌的发展趋势

多重耐药菌感染呈现增长趋势,已成为全球性棘手问题,抗菌药物选择方案很少.传统糖肽类药物抗菌活性已呈现下降趋势.虽然新的抗菌药物包括利奈唑胺、达托霉素和替加环素对某些革兰阳性菌感染有较强的抗菌活性,但对于多重耐药革兰阴性菌,包括耐碳青霉烯类铜绿假单胞菌、鲍曼不动杆菌和肠杆菌的治疗,有效药物仅限于多黏菌素和替加环素.多重耐药菌的分布呈动态变化,近年来,多数医疗机构特别是重症监护病房监测的菌株中,以革兰阴性细菌为主,部分地区多重耐药/泛耐药铜绿假单胞菌、鲍曼不动杆菌等呈现迅速增多趋势.应重视和执行多重耐药菌感染的监测、预防、隔离和抗菌药物选择等综合防控策略,以减少多重耐药菌的扩散.     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

Bibliometric data: a disaster for many non-American biomedical journals

Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

alpha -SMOOTH MUSCLE ACTIN DISTRIBUTION IN THE PULMONARY VASCULATURE COMPARING HYPOPLASTIC AND NORMAL FETAL LUNGS

We investigated the intra-acinar pulmonary vascular muscularization in the developing human fetal lung between the 17th and 24th gestational weeks, that is, during the canalicular phase of lung development. Fifteen hypoplastic and 25 normal developed lungs were included in this study using monoclonal alpha -smooth muscle (sm) actin antibodies for smooth muscle detection. Computer-aided image analysis was performed for morphometrical measurements and statistical evaluation. Alphasm-actin-immunoreactive intra-acinar vessels down to a luminal diameter of less than 10 mu m were detected in hypoplastic as well as in normally developed lungs. Crucial differences presented as follows: significantly higher density of intra-acinar vessels, especially due to alpha -sm-actin-negative vessels less than 30 mu m in luminal diameter, in the control group; significantly higher alpha -sm-actin immunoreactivity per section unit as well as per vessel in the hypoplastic lung group. As suggested by others, alpha-sm-actin-positive cells of the intra-acinar vessel wall in the developing human lung were demonstrated to be smooth muscle cells, their immediate precursors, and pericytes. We conclude that the increased alpha -sm-actin immunoreactivity represents muscularization of the vessel wall in functional terms and may be regarded as one structural cause among others for the establishment of persistent fetal circulation in hypoplastic lungs.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.