儿童酵母样真菌的培养分离及其耐药性分析

目的探讨引起医院感染酵母样真菌的类型及其耐药性,指导临床合理用药。方法对1777份住院患儿的各种标本分离出的196株酵母样真菌,采用科玛嘉念珠显色培养基培养菌,用API-20CAUX酵母样真菌鉴定试条进行鉴定,用念珠菌药敏试条ATB-FUNGUS进行药敏试验。结果酵母样真菌196株中白色假丝酵母菌150株（76.5%）,近平滑假丝酵母菌12株（6.13%）,新型隐球菌、光滑假丝酵母菌各11株（5.62%）,热带假丝酵母菌7株（3.58%）,克柔假丝酵母菌3株（1.53%）,葡萄牙假丝酵母菌2株（1.02%）。以呼吸内科、血液科所占比例较高。150株白色假丝酵母菌对5-氟胞嘧啶（5-FC）、二性霉素B（AMB）、氟康唑（FCA）、伊曲康唑（ITR）的敏感率分别为100%、100%、99.3%、88.6%。结论引起患儿真菌感染的念珠菌仍以白色假丝酵母菌为主,临床用药应依据药敏结果合理选用。     

极低出生体质量儿真菌性败血症17例分析

目的 探讨极低出生体质量儿(VLBWI)真菌性败血症的临床特征,为其早期诊断及治疗提供参考依据.方法 对新生儿重症监护室(NICU)确诊为真菌性败血症的17例VLBWI的临床资料进行回顾性分析.结果 2008年1月至2011年5月共收治VLBWI(含超低出生体质量儿)287例,确诊真菌性败血症17例,发生率为5.92%.17例真菌性败血症患儿在真菌感染前均接受过广谱抗生素和静脉营养治疗,14例曾机械通气,13例曾留置经外周的中心静脉导管(PICC).起病最早为生后7 d,最晚为生后51 d.真菌性败血症的临床表现无特异性,检测血浆(1,3)-β-D葡聚糖(BG)均明显升高(46 ～ 8 285 pg/ml).血培养白色假丝酵母菌9例,克柔假丝酵母菌4例,近平滑假丝酵母菌2例,无名假丝酵母菌2例.药敏试验显示所有菌株对氟康唑和两性霉素B均敏感.17例起初均予氟康唑治疗,其中8例因疗效欠佳改用两性霉素B脂质体治疗.治愈13例,自动出院3例,1例死亡.结论 VLBWI真菌性败血症的发生率仍较高,病原菌主要为白色假丝酵母菌和克柔假丝酵母菌,医源性因素如广谱抗生素的使用、中心静脉置管、机械通气等不容忽视.患儿临床表现无特异性,血浆BG检测可作为真菌性败血症的诊断、疗效及预后判断的重要指标.氟康唑及两性霉素B脂质体治疗真菌性败血症效果较好.     

无基础疾病儿童侵袭性真菌病的临床研究

目的 探讨无基础疾病儿童侵袭性真菌病 （IFD） 的临床特点。方法 回顾性分析49例无基础疾病侵袭性真菌病患儿的临床资料。结果 无基础疾病侵袭性真菌病儿童的病原检出率为76% （37/49）,其中新型隐球菌 （17例,46%）、白色假丝酵母菌 （10例,27%）、曲霉菌及近平滑假丝酵母菌 （各3例,均占8%） 为最常见的病原。真菌性肺炎最多见 （17例,46%）,病原以白色假丝酵母菌为主 （9例,53%）。49例患儿均存在至少一项感染高危因素,主要为抗生素使用、长时间住院以及侵袭性操作。行G试验检查的24例中17例阳性 （71%）。49例患儿均接受抗真菌治疗,37例 （75%） 治愈,3例 （6%） 仍在治疗中,5例 （10%） 死亡,4例 （8%） 失访。结论 对于无基础疾病的IFD患儿,新型隐球菌、念珠菌为其主要病原,肺部感染最为多见。长期大量使用抗生素是较突出危险因素。无基础疾病的IFD患儿对于抗真菌药物敏感,预后较好。     

新生儿血液近平滑假丝酵母菌感染的临床特点及药敏分析

目的 了解新生儿血液近平滑假丝酵母菌感染的临床特点和药敏结果,为临床预防和诊治提供参考.方法 对8例新生儿血培养中分离出的近平滑假丝酵母菌进行药敏分析,并回顾性分析感染患儿的临床特点.血培养采用BD9120血培养仪,沙保罗培养基分离培养,科玛嘉(CHROMagar)酵母菌显色培养基及API20C真菌鉴定板,药敏试验采用FUNGUS3微量稀释版.结果 近平滑假丝酵母菌抗真菌药敏结果分别为5-氟胞嘧啶≤4 μg/ml,两性霉素B≤0.5 μg/mL,氟康唑≤1～2.0μg/ml,伊曲康唑≤0.125～0.125 μg/ml,伏立康唑≤0.06～0.06 μg/ml.7例为早产儿(低出生体重或超低出生体重儿),1例足月先天幽门闭锁术后患儿.8例患儿血培养前均应用广谱抗生素和静脉营养治疗,均曾留置中心静脉导管,3例曾应用机械通气.4例用氟康唑,3例氟康唑联合两性霉素B脂质体,1例先用氟康唑后用威凡,8例患儿全部治愈.结论 近平滑假丝酵母菌已成为早产、低出生体重儿血液真菌感染的主要病原菌之一,对5种常用抗真菌药物体外药敏试验均敏感,及早发现和治疗愈后较好.     

新生儿侵袭性真菌感染67例临床分析

目的 探讨新生儿侵袭性真菌感染的临床特点.方法 选取2009年1月至2010年12月收治的67例侵袭性真菌感染新生儿病例,分析其病原、高危因素、临床特点、实验室检查及转归情况.结果 67例患儿均为念珠菌属感染,以白色念珠菌感染最为常见,占47.7%,其次为光滑假丝酵母菌,占43.3%;早产儿占所有病例的91.0%,其中50%以上的早产儿胎龄≤ 32周,9例存在先天性消化道畸形,11例合并有巨细胞病毒感染;25例患儿真菌感染前经外周中心静脉插管(PICC)置管时间≥ 14 d,16例气管插管机械通气治疗时间＞ 7 d;35例(52.2%)患儿白细胞计数＜ 10 × 109 /L,46例(68.7%)患儿有血小板下降,其中33例持续≥ 7 d;24例患儿伴有器官受累,包括中枢神经系统、眼及关节;47例(70.1%)经抗真菌治疗后病情好转或治愈,15例(22.4%)患儿死亡.结论 新生儿侵袭性真菌感染的病原主要为念珠菌属,尤以白色念珠菌及光滑假丝酵母菌为多见.中枢神经系统、眼及关节为常见受累器官.侵袭性真菌感染的发生、严重程度及转归与患儿的机体状态、原发病及并发症密切相关.     

恶性实体瘤患儿化疗并发口腔真菌感染25例临床分析

目的探讨实体瘤患儿口腔真菌感染的临床表现、病原菌、药物敏感性以及抗真菌治疗效果。方法回顾性分析2013年1月—2015年12月北京同仁医院儿科收治的化疗后合并口腔真菌感染的25例实体瘤患儿的临床资料。结果实体瘤患儿口腔真菌感染的发病率为1.11%,发病时患儿均处于化疗后骨髓抑制期,多伴有发热、食欲差、呕吐、腹泻、咳嗽等表现;实验室检查可有外周血白细胞计数异常、贫血、血小板下降,C反应蛋白不同程度升高。常见口腔真菌感染病原菌为白色念珠菌、光滑念珠菌、白色假丝酵母菌、近光滑假丝酵母菌,部分患儿真菌血培养阳性。应用碳酸氢钠联合氟康唑外用或口服、两性霉素B雾化治疗口腔真菌感染4～7天后好转。结论实体瘤患儿骨髓抑制期口腔真菌感染率较高,易于反复,化疗后加强口腔护理,局部早期应用氟康唑、两性霉素B抗真菌治疗效果较好,治愈率高。     

早产儿院内真菌感染72例病原菌及耐药性分析

目的 了解早产儿院内真菌感染病原菌分布特点及抗生素耐药情况,为早产儿院内真菌感染的防治提供依据.方法 对发生院内真菌感染的72例早产儿的临床资料进行回顾性分析.结果 我院早产儿真菌感染前3位的病原菌分别为菌假丝酵母菌38株(52.8％,38/72),白假丝酵母菌10株(13.9％,10/72),近平滑假丝酵母菌9株(12.5％,9/72).72例院内真菌感染早产儿的体重均在2000 g以下,其中以极低出生体重儿为主；胎龄以27～30周居多,其中27 ～ 28周占36.1％(26/72),29～30周占34.7％(25/72),各组病原菌均以菌假丝酵母菌为主.分离出的72株真菌未见对两性霉素B耐药,对氟康唑耐药率为1.4％(1/72)、对伏立康唑耐药率为4.2％(3/72)、对伊曲康唑耐药率为2.8％(2/72),后3者耐药率间差异无统计学意义(x2=1.02,P＞0.05)；对5-氟胞嘧啶耐药者占59.7％(43/72),与上述4种药物耐药率间的差异有统计学意义(x2=57.73,P＜0.005)；而两性霉素B与氟康唑间耐药率差异无统计学意义(x2 =1.01,P＞0.05).结论 对有院内真菌感染高危因素的早产儿可预防性应用氟康唑,对明确真菌感染的早产儿首选静脉给予氟康唑治疗尤其是合并中枢神经系统真菌感染时,必要时可联合应用两性霉素B.     

新生儿真菌性败血症23例临床分析

目的探讨新生儿真菌性败血症的高危因素、病原谱、药物敏感性以及抗菌药物治疗效果。方法回顾性分析2009年5月至2013年8月收治的新生儿真菌性败血症患者的临床资料。结果共收治23例新生儿真菌性败血症,培养出真菌36株,其中近平滑假丝酵母菌20株(55.6%)、白色假丝酵母菌11株(30.6%)。药敏试验显示,真菌对两性霉素、五氟尿嘧啶敏感性最高,总有效率在69.4%~77.8%。23例新生儿均有早产、低出生体质量、应用广谱抗生素、有创操作等真菌性败血症的高危因素。抗真菌治疗后预后良好(存活或好转出院)15例(65.2%),预后不良(放弃或死亡)8例(34.8%)。预后良好组的平均抗真菌治疗时间高于预后不良组,差异有统计学意义(t=2.982,P0.05)。抗真菌治疗前及治疗后2周内,新生儿的肝肾功能及外周血白细胞变化不明显;血小板在抗真菌治疗开始后1周内即升高,与治疗前差异有统计学意义(P0.05)。结论新生儿真菌败血症病原菌以假丝酵母菌为主,对两性霉素敏感性较高;足疗程抗真菌治疗可提高治愈率。     

儿科重症监护病房院内侵袭性真菌血流感染21例临床分析

目的 提高对侵袭性真菌感染（invasive fungal infection,IFI）的认识,帮助早期诊断、早期治疗,积极改善预后。方法　选取2012年1月至2018年1月于中国医科大学附属盛京医院儿科重症监护病房（PICU）住院,临床诊断IFI血流感染的21例患儿为研究对象,回顾性分析其临床特点、高危因素及预后。结果　临床诊断IFI血流感染的21例患儿中,真菌感染的发生与年龄性别无明显相关性,致病菌以白色念珠菌及近平滑假丝酵母菌为主,近平滑假丝酵母菌病死率较高（80%）;21例真菌血流感染的患儿,28 d随访存活8例,死亡13例,病死率高达61.90%;原发病以呼吸系统（14.29%）、消化系统疾病（23.81%）居多,其中重症肺炎4例,消化道穿孔4例;高危因素主要以广谱抗生素联合应用、侵入性操作（气管插管、中心静脉置管、导尿及留置胃管等）、长期ICU住院等为著,均在85%以上。真菌感染多表现为不典型发热（80.95%）,白细胞异常升高或降低（47.62%）,C反应蛋白多升高（80.95%）,G试验的阳性率可达到42.86%;存活组的8例患儿诊断真菌感染前75%预防性应用抗真菌治疗,死亡组预防用药率为53.85%。结论　长期ICU住院、大量广谱抗生素的长期及联合应用、侵入性操作、自身免疫缺陷等因素的存在增加了真菌感染的风险,对于临床原发病基础上出现不典型难治感染,要警惕真菌感染,应积极完善相关微生物学检查。     

儿童176株假丝酵母菌血流感染的临床特征和耐药性分析

目的 分析本院儿科假丝酵母菌血流感染的临床分布、菌种分布和耐药性,为临床有效预防和治疗提供参考依据.方法 收集2009年1月至2015年12月儿科住院患者的血液标本,经BacT/ALERT 3D全自动血培养仪培养,沙保罗培养基分离培养,柯玛嘉显色培养基,API 20CAUX酵母样真菌鉴定板和VITEK-2 compact YST卡进行菌种鉴定,药敏试验采用ATB FUNGUS 3微量稀释板,总结并分析患儿的临床资料.结果 分离出的176株假丝酵母菌中,来自新生儿92株(52.3％),来自PICU 46株(26.1％).新生儿组中早产儿85株,其中低和极低出生体重儿37株、新生儿肺炎20株、新生儿呼吸窘迫综合征9株;PICU以重症感染患儿为主,年龄2d～13岁,平均11个月.176株假丝酵母菌中,白假丝酵母菌71株(40.3％),近平滑假丝酵母菌62株(35.2％),光滑假丝酵母菌16株(9.1％),热带假丝酵母菌9株(5.1％),其他假丝酵母菌18株(10.2％).结论 假丝酵母菌血流感染可发生于各年龄段,以早产儿和PICU重症感染患儿为主;菌种以白假丝酵母菌为主,近平滑假丝酵母菌次之,除光滑假丝酵母菌外,其他菌种对氟康唑等常用抗真菌药物敏感率＞93％,临床上选择抗真菌治疗时要考虑假丝酵母菌的菌种类别.     

Prospective evaluation of Candida antigen and antibody assays for detection of Candida infections in children with malignant disease

The clinical efficacy of assays for Candida albicans antigens by latex agglutination and for antibodies by indirect haemagglutination were prospectively evaluated in the diagnosis of invasive Candida infections in 38 children suffering from acute leukaemia or other malignant disease. The controls were 74 other patients without any malignancy; 72 of these had no signs or symptoms of fungal infections, but 2 had an invasive C. albicans infection. During a period of 21 months, 302 serum samples were tested by both assays, and the results were compared with clinical and other microbiological data. Invasive fungal infection was diagnosed on clinical grounds in 2 of the immunocompromised children, and periodic gut colonization was demonstrated in 11 of 36 (31 %) children in this group. Positive Candida antigen was detected in 14 patients (37%) and a positive antibody titre in 7 patients (18%). Colonization was not correlated with antigen or antibody titre. Compared with the presence of invasive fungal infection, the antibody assay detected all four infections, whereas the antigen assay detected one of the two C. albicans septicaemias. Although the Candida antibody assay performed well, a detectable change in antibody titres appeared only slowly. Thus it was of no clinical help when antifungal treatment was to be considered. Follow-up of antibody titres, however, gave confirmation of the presence of fungal infection as well as the response to antifungal treatment.     

Candida dubliniensis fungemia and vascular access infection

Candida dubliniensis is a newly recognized species of yeast, which may have been forrmerly identified as Candida albicans, that has been rarely isolated from invasive fungal infections among humans. The authors document a C. dubliniensis fungemia that occurred during the course of a vascular access infection in a 2-year-old who was undergoing active therapy for neuroblastoma. Presumptive C. albicans isolates from an 18-year period were reassessed, and it was found that C. dubliniensis is a rare cause of fungemia among pediatric patients (0.5% of all such isolates).     

The Spanish Society of Paediatric Infectious Diseases (SEIP) recommendations on the diagnosis and management of invasive candidiasis

Candida yeasts are ubiquitous commensals, which can cause opportunistic infection in any location of the body. The source of infection may be both endogenous and exogenous. Invasive candidiasis encompasses different entities ranging from invasive candidiasis to disseminated multiorgan infection. Invasive candidiasis is the third leading cause of nosocomial bloodstream infection and the fourth of all nosocomial infections. It is also the most common invasive fungal infection in non-neutropenic critically ill patients, with a remarkable increase in the last 20 years owing to the increased survival of these patients and to more complex diagnostic, therapeutic and surgical procedures. Its incidence in infants, according to recent reviews, stands at 38.8 cases/100,000 children younger than 1 year. Candida albicans remains the most frequent isolate in invasive infections, although infections caused by other species have risen in the last years, such as C. kruzsei, C. glabrata and C. parapsilosis; the latter causing invasive candidiasis mainly associated with central venous catheter management, especially in neonatal units. The overall mortality of invasive candidiasis is high, with 30-day mortality reaching 20-44% in some series involving paediatric patients. This report provides an update on incidence, epidemiology, clinical presentation, diagnosis, treatment and outcome of invasive infection by Candida spp. in the paediatric patient.     

儿童实体瘤合并侵袭性真菌感染3例临床分析

目的总结实体瘤患儿合并侵袭性真菌感染的诊断与治疗经验。方法回顾性分析3例实体瘤患儿于化疗过程中合并侵袭性真菌感染的临床特点及诊治经过。结果 3例实体瘤患儿均于多疗程化疗后发生肺部真菌感染,其中1例合并其他部位感染。3例患儿均有发热、中性粒细胞缺乏,曾使用广谱抗生素、激素治疗。3例患儿血真菌培养均为阳性,其中近平滑假丝酵母菌2例,白色念珠菌1例,1-3-β-D葡聚糖检测结果明显升高。3例患儿肺部CT均表现为密度增高、渗出炎症阴影。2例患儿治疗后好转存活,1例经治疗好转后,因肿瘤多发转移而死亡。结论肺部真菌感染为儿童实体瘤合并侵袭性真菌感染的常见表现形式,多发生于多次化疗后骨髓抑制期;临床表现缺乏特异性,需结合病史、实验室及影像学检查作出诊断;可疑侵袭性真菌感染时应及时进行经验性治疗。[临床儿科杂志,2012,30(5):425-427]     

儿童重症监护病房侵袭性真菌感染38例临床分析

目的：探讨儿童重症监护病房（PICU）侵袭性真菌感染（IFI）的临床特征,为其有效防治提供依据。方法：回顾性分析38例IFI患儿的临床特征及治疗转归情况。结果：38例患儿中,以呼吸道感染最多见（89%）;感染前均有较严重的基础疾病,且使用过多种抗生素,其中碳青霉烯类抗生素使用率高达95%;47%患儿曾全身激素治疗;所有患儿均有侵入性操作史,其中47%患儿接受过气管插管及机械通气治疗;所有患儿临床症状及体征不典型,影像学检查无特异性。真菌培养共检出致病真菌56株,以白色念珠菌为主（41%）,其次为曲霉菌（25%）和毛霉菌（20%）;所有患儿及时予以高效抗真菌药物治疗,治愈15例,好转16例,有效率为82%,不良反应发生率为16%。结论：呼吸道为最常见IFI感染部位;白色念珠菌为主要病原;多数患儿有严重基础疾病、广谱抗生素及糖皮质激素的使用史和侵入性操作史;早期诊断、及时使用高效抗真菌药物可改善预后。     

Invasive Candida infections in children: the clinical characteristics and species distribution and antifungal susceptibility of Candida spp

The aims of the study were to examine the distribution of Candida spp. isolated from sterile body sites, the antifungal susceptibility of the isolates to amphotericin B, fluconazole, voriconazole, and caspofungin, and factors affecting mortality with invasive Candida infections in children. Thirty-five children with invasive candidiasis between January 2004 and January 2008 were evaluated retrospectively. The antifungal susceptibility of isolated Candida species was studied by Etest. Of the invasive Candida infections, 65.7% were due to C. albicans. The second most common isolated species was C. parapsilosis (11.4%). The rates of resistance to fluconazole, amphotericin B and voriconazole were 8.5%, 2.8% and 5.7%, respectively. Caspofungin was the most effective antifungal agent. 22.8% of the patients died in the first 30 days. In univariate analyses, increased mortality was associated with stay in the intensive care unit, the presence of central venous catheter (CVC), failure to remove CVC, and mechanical ventilation.     

乌鲁木齐市多中心儿童侵袭性念珠菌病临床特征及其血流感染的危险因素分析

目的了解儿童侵袭性念珠菌病的临床特征,探讨念珠菌血流感染的危险因素。方法选取2010年1月至2015年12月乌鲁木齐市5家三级医院确诊或临床诊断的134例侵袭性念珠菌病患儿为研究对象。采用多中心、回顾性研究方法,检测患儿真菌感染类型及构成比,比较念珠菌血流感染组及非血流感染组患儿的临床资料,并应用logistic多因素回归分析探讨念珠菌血流感染的危险因素。结果 134例患儿中分离出134株念珠菌菌株,其中非白色念珠菌占53.0%。侵袭性念珠菌病在PICU及非PICU病区的发生率分别为41.8%、48.5%。血流感染为主(68例,50.7%),其次为尿路感染(45例,33.6%)。念珠菌血流感染组与非血流感组在年龄及广谱抗生素使用率、慢性肾功能不全发生率、心力衰竭发生率、留置尿管率及非白色念珠菌感染率比较中差异有统计学意义(P0.05)。多因素logistic回归分析显示,年龄(1~24个月)(OR=6.027)、非白色念珠菌感染(OR=1.020)是念珠菌血流感染的独立危险因素。结论侵袭性念珠菌病在儿科ICU及非ICU病区发生率基本相同;感染菌株以非白色念珠菌为主;血流感染为最常见的念珠菌感染形式;年龄1~24个月及非白色念珠菌感染患儿发生念珠菌血流感染的风险增加。     

Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

AIM: The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. METHODS: We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998-2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. RESULTS: Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235-4.432, p = 0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). CONCLUSIONS: Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.