Risk factors for invasive fungal infection in neonates

Invasive fungal infection is an uncommon, but increasing cause of morbidity and mortality in neonates. There are few controlled studies defining risk factors for the development of fungal infection in a contemporary neonatal population. This retrospective case-control study was undertaken to investigate antenatal, demographic and postnatal variables that may be potentially important in the development of fungal infection. Two gestation-matched controls were identified for each index case. Information about perinatal and demographic variables, as well as important neonatal outcomes, was obtained from case notes. Microbiological data collected included the presence of fungal colonization, and organisms responsible for invasive fungal infection. Over a 5-y period, 24 infants with invasive fungal infection and 48 controls were identified. Candida albicans was the organism identified in 75% of cases of fungal septicaemia, and in all cases complicated by fungal meningitis. Preceding fungal colonization, pulmonary haemorrhage and intrauterine growth restriction were factors significantly and independently associated with invasive fungal infection. Fifty-four percent of infants with invasive fungal infection died, and 82% of survivors developed chronic lung disease.

Conclusion : Some new and potentially important risk factors for the development of invasive fungal infection in a contemporary population of infants admitted to a neonatal intensive care were identified.     

早产儿侵袭性真菌感染的预防和治疗

新生儿,特别是早产儿是侵袭性真菌感染的高危人群,造成早产儿相关疾病的发病率和病死率的增加,如何预防和治疗侵袭性真菌感染,减少其对早产儿的损伤,成为新生儿科医生关注的热点.本文主要对早产儿侵袭性真菌感染的预防和治疗作重点阐述.     

Clinical spectrum and outcome of invasive filamentous fungal infections in children with Type 1 diabetes: North Indian experience

There is scarcity of data on spectrum and outcome of invasive filamentous fungal infections (IFIs) in children with Type 1 diabetes (T1D) from developing countries. A retrospective review of medical records of children with T1D hospitalized with IFI over the past decade at the Pediatric Endocrinology and Diabetes Unit of a large tertiary care hospital of North India was performed with an aim to study their clinical spectrum, hospital course and final outcome. Of the 10 patients studied, nasal/paranasal involvement was seen in 6 and pulmonary involvement in 5 patients. One patient developed disseminated disease. Majority of the identified mycoses belonged to Class Zygomycetes Order Mucorales. Early surgery along with antifungal therapy helped limit the extension of infection and achieve a good outcome in majority of patients. Two patients died; one with a late diagnosis of pulmonary mucormycosis and the other with disseminated disease. The longterm morbidity in the survivors was minimal. In conclusion, rapid diagnosis followed by a multimodal approach involving aggressive surgical debridement, appropriate antifungal therapy and control of hyperglycemic state is the key to good outcome in this otherwise lethal infection.     

儿童重症监护病房侵袭性真菌感染危险因素分析

目的 分析儿童重症监护病房(PICU)侵袭性真菌感染的特点及危险因素.方法 总结2007年至2009年我院PICU收治的35例发生侵袭性真菌感染患儿的临床资料,对真菌感染危险因素进行分析,包括危重病例评分、机械通气、导尿管和胃管置入、床旁血液净化治疗等.结果 (1)3年间PICU共收治危重患儿2 116例,其中35例发生真菌感染,发生率为1.65%(35/2 116),其中死亡7例,病死率为20.00%(7/35).(2)发生真菌感染的平均时间为人院后(10.4±8.3)d,主要表现为肺炎21例(60.0%),腹膜炎5例(14.3%),尿路感染4例(11.4%),肠道感染3例(8.6%),败血症1例(2.9%),脑膜炎1例(2.9%).(3)儿童危重病例评分低、机械通气、留置胃管及导尿管、连续性静脉血液透析滤过是引起真菌感染的危险因素.(4)致病菌以白色念珠菌为主.结论 侵袭性真菌感染已成为PICU主要的院内感染,白色念珠菌是主要致病菌.合理利用抗生素、减少不必要的侵入性操作、及时使用抗真菌药,可能是应对侵袭性真菌感染的有效策略.

Abstract：

Objective To analyze the incidence,clinical feature and the risk factors of invasive fungal infection in pediatric intensive care unit (PICU). Methods We retrospectively summaried the invasive fungal infection in our PICU from Jan 2007 to Dec 2009 in order to analyze the incidence, clinical feature and the risk factors of invasive fungal infection in PICU. Multiple clinical data were collected such as pediatric critical illness score, mechanical ventilation, urinary drainage tube, indwelling gastric canal and continuous blood purification. Results ( 1 ) The incidence rate of invasive fungal infection was 1.65 % ( 35/2 116 ). The morbidity was 20. 00% ( 7/35 ). ( 2 ) Mean infected day was ( 10. 4 ±- 8. 3 ) d after admission. The clinical manifestations included fungal pneumonia( 60. 0% ), peritonitis ( 14. 3% ), urinary tract infection ( 11.4% ),intestinal tract infection(8. 6% ) ,sepsis(2. 9% ) and meningitis(2. 9% ). All of the patients had used broad spectrum antibiotic. (3) The risk factors of invasive fungal infection included lower pediatric critical illness score, mechanical ventilation, indwelling gastric tube, urinary drainage tube and continuous blood purification.(4) Candia albicans was the predominant pathogen in invasive fungal infection. Conclusion Invasive fungal infection has become one of the main nosocomial infection in PICU. Lung is most commonly involved and candida albicans is the major pathogen. Using antibiotics appropriately, decreasing unnecessary invasive performance,and rationally using antifungal agent mi.ght be effective strategy for invasive fungal infection in PICU.     

氟康唑预防极低出生体重儿侵袭性真菌感染疗效和安全性的Meta分析

目的 系统评价使用氟康唑预防极低出生体重儿（VLBWI）侵袭性真菌感染的疗效和安全性,为临床更好地预防性使用氟康唑提供依据。方法 计算机检索PubMed、Embase、Cochrane图书馆、万方数据库、中国科技期刊数据库（维普）和中国知网,纳入VLBWI预防性使用氟康唑的随机对照试验（RCT）研究。采用Review Manager 5.3统计软件对符合纳入标准的临床研究进行Meta分析。结果 共纳入12篇RCT研究,合计1 679例VLBWI。Meta分析结果显示：试验组（使用氟康唑）侵袭性真菌感染的发生率显著低于安慰剂对照组（RR=0.44,95% CI：0.27~0.71,P < 0.001）;真菌定植率低于对照组（RR=0.31,95% CI：0.24~0.40,P < 0.001）;住院期间病死率低于对照组（RR=0.74,95% CI：0.58~0.94,P=0.01）。使用不同预防剂量氟康唑的两组侵袭性真菌感染发生率和真菌定植率比较差异均无统计学意义（P > 0.05）;耐药情况及并发症发生率在试验组和对照组组间比较差异均无统计学意义（P > 0.05）。结论 氟康唑预防VLBWI侵袭性真菌感染有效且相对安全。小剂量给药可取得类似预防效果。     

Candida parapsilosis infection in very low birthweight infants

In a UK national surveillance study, we found that Candida parapsilosis accounted for one quarter of all cases of invasive fungal infection in very low birthweight infants. C parapsilosis was associated with fewer deep-seated infections than C albicans, but mortality was similar. Ongoing surveillance is needed to monitor the epidemiology of invasive fungal infection in very low birthweight infants.     

儿科抗真菌药物的合理使用

近20年来,随着广谱抗菌药物、免疫抑制剂、激素、抗肿瘤药物和靶向生物制剂的广泛应用以及真菌检测方法的不断改进,儿童侵袭性真菌病的发病率呈逐年上升趋势,侵袭性真菌病成为免疫低下儿童的主要死亡原因之一。除了原发性免疫缺陷、肿瘤、造血干细胞移植、实体器官移植及获得性免疫缺陷综合征病毒(HIV)感染等,婴幼儿本身也是真菌感染的高危因素。因此早期诊断、及时应用有效抗真菌药是挽救患儿生命的重要措施。儿童作为特殊人群,抗真菌药物的选择和剂量与成人不同,该文主要探讨如何选择合适的抗真菌药物来预防和治疗儿童真菌病。     

早产儿侵袭性真菌感染的防治

侵袭性真菌感染是早产儿致死和致残的重要原因,近年来,国内相关报道日益增多.该文对早产儿侵袭性真菌感染的国内外发生现状及诊断、治疗和预防方面的进展作一简要介绍.     

Strategies for the prevention of neonatal candidiasis

Invasive fungal infections represent the third-leading cause of late-onset sepsis in very-low-birth-weight infants (VLBWI) and have a high rate of infection-associated mortality. The infants at high risk for fungal sepsis are VLBWI with presence of additional risk factors that contribute to increased colonization and concentration of fungal organisms. Colonization with Candida spp. in neonates is secondary to either maternal vertical transmission or nosocomial acquisition in the nursery. Multiple sites may become colonized and a direct correlation between fungal colonization and subsequent progression to invasive candidemia was determined. Randomized, single and multiple-center, placebo-controlled trials found intravenous fluconazole prophylaxis to be effective in decreasing fungal colonization and sepsis for at-risk preterm infants <1500 g birth weight. The prophylactic use of fluconazole was found to be safe with no significant development of fungal resistance. Fluconazole prophylaxis administered to preterm neonates with birth weight <1000 g and/or 27 weeks' gestation or less has the potential of reducing and potentially eliminating invasive fungal infections and Candida-related mortality.     

Invasive fungal infection in children undergoing chemotherapy for cancer

BACKGROUND: In children with cancer, invasive fungal infection is a serious complication of anticancer therapy. Successful treatment is a major challenge for clinical oncologists. METHODS: The records of all episodes of invasive fungal infection occurring in children with cancer undergoing chemotherapy at Mackay Memorial Hospital, Taipei between January 1987 and October 2005 were reviewed. The following were documented: general characteristics, clinical presentation, predisposing factors, pathogens, antifungal treatment, association with anticancer therapy and outcome. We endeavoured to preserve renal function by administration of new antifungal agents. Anticancer therapy was given as soon as possible after diagnosis and the dose of chemotherapeutic agents was adjusted as required to prevent unduly prolonged interruption of chemotherapy and minimise the risk of leukaemia relapse. RESULTS: Twenty-six patients with 29 episodes of invasive fungal infection were reviewed. Candida species were the leading pathogens (14/29) followed by Aspergillus species (11/29). In six episodes there was both visceral dissemination and fungaemia. In 23/29 patients, antibiotic therapy preceded fungal infection with a median of 11 days. Three children died from extensive fungal infection and four from progression of malignancy; the remainder survived with a median follow-up of 40 months (range 12-233). The actuarial 12-month survival rate was 87%; in patients with invasive candidiasis and aspergillosis the rates were 75% and 100%, respectively. CONCLUSIONS: In children with cancer, most invasive fungal infections can be treated successfully. Current antifungal prophylaxis should protect patients from fungal infection.     

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]     

CT of invasive pulmonary aspergillosis in children with cancer

In treating cases of malignancy, the use of chemotherapy carries a high risk of lower respiratory tract infections, especially fungal pneumonopathy. This complication is a major cause of mortality and is often difficult to diagnose because of non-specific clinical or radiological changes, but the early recognition of invasive fungal disease is imperative. CT is an important non-invasive method for the detection and evaluation of opportunistic fungal infections. In these patients an improved survival rate can be achieved when early detection by CT leads to the prompt institution of high-dose antifungal therapy. We illustrate the spectrum of CT findings of invasive pulmonary aspergillosis encountered in children with cancer. These patients had previously been treated with highdose chemotherapy with or without bone marrow rescue, and underwent radiological examinations because of clinical evidence of pneumonopathy. Representative cases demonstrate the clinical applications of CT in the evaluation and management of invasive fungal disease.     

实体瘤患儿行自体外周血干细胞移植治疗中真菌感染情况

目的通过对31例实体瘤患儿行自体外周血干细胞移植(auto-PBSCT)治疗中真菌感染的情况进行分析,总结其临床特点、诊断与治疗经验。方法回顾性分析2006年5月-2009年12月本院儿科收治的31例实体瘤患儿行auto-PBSCT治疗过程中防治真菌感染的过程。结果 1.Ⅳ期进展期神经母细胞瘤患儿2例行自体外周血干细胞移植过程中经微生物学检查明确并肺部真菌感染,其中1例并脑、肝真菌感染;2例患儿血培养均为近平滑假丝酵母菌;4例患儿行肺部CT检查,表现为密度增高、渗出炎症阴影;1例进展期神经母细胞瘤患儿明确真菌感染后应用氟康唑、两性霉素B脂质体、伏立康唑静脉滴注抗真菌治疗有效,体温正常,度过骨髓抑制期,原发病获得部分缓解;1例进展期神经母细胞瘤患儿因存在颅内、骨骼、脊髓、肺、肝多发转移肿瘤,于自体外周血造血干细胞移植9 d后骨髓抑制期死亡。2.部分缓解期Ⅳ期神经母细胞瘤1例及进展期肝母细胞瘤1例患儿表现为发热、咳嗽、抽搐,怀疑侵袭性真菌感染,给予氟康唑、两性霉素B、伏立康唑治疗后好转度过骨髓抑制期,原发病获得部分缓解。3.余27例实体瘤患儿auto-PBSCT治疗中应用氟康唑预防真菌感染,临床未发生侵袭性真菌感染,1例进展期Ⅳ期神经母细胞瘤患儿因有多脏器转移,且有原发心脏损害,大剂量化疗后骨髓抑制期免疫耐受差,导致多脏器衰竭死亡。余26例实体瘤患儿顺利度过骨髓抑制期,病情获得缓解。结论实体瘤患儿auto-PBSCT治疗中易并真菌感染,需结合病史、血培养、G试验及CT、MRI等影像学检查做出诊断,经验性应用氟康唑、伏立康唑、两性霉素B等可防治真菌感染,原发病严重未缓解者预后差。     

急性白血病合并侵袭性曲霉病的临床治疗

目的探讨急性白血病合并侵袭性曲霉病患儿抗真菌治疗和连续强烈化疗的治疗经验。方法回顾分析我院2007年7月至2008年7月收治的4例儿童急性白血病合并侵袭性曲霉病的诊断和治疗。结果3例急性淋巴细胞白血病(ALL)诱导缓解化疗和1例急性髓细胞白血病(AML)巩固化疗的患儿合并侵袭性曲霉病,1例确诊,3例拟诊,诊断时CT表现均有晕轮征。抗霉菌初始用药首选伏立康唑或两性霉素B。治疗2～5周病灶好转,4月至1年病灶缓解。4例按计划继续强烈化疗,霉菌感染至继续化疗的平均时间为35d,无霉菌复发。结论CT晕轮征可作为早期诊断侵袭性曲霉病的指标;基于晕轮征的抢先治疗和患者免疫功能的逆转可改善侵袭性曲霉病的预后;化疗同时持续抗霉菌治疗是完成连续强烈化疗而无霉菌复发的保障。     

儿童侵袭性肺部真菌感染

近年来,儿童侵袭性肺部真菌感染病例有上升趋势,早期诊断和及时治疗对于降低病死率非常重要.本文介绍了儿童侵袭性肺部真菌感染的发生因素、临床和影像学表现、微生物检查、诊断和治疗,以期提高对本病的诊治水平.     

儿童侵袭性肺部真菌感染

近年来,儿童侵袭性肺部真菌感染病例有上升趋势,早期诊断和及时治疗对于降低病死率非常重要.本文介绍了儿童侵袭性肺部真菌感染的发生因素、临床和影像学表现、微生物检查、诊断和治疗,以期提高对本病的诊治水平.     

急性白血病合并侵袭性曲霉病的临床治疗

目的:探讨急性白血病合并侵袭性曲霉病患儿抗真菌治疗和连续强烈化疗的治疗经验。方法:回顾分析我院2007年7月至2008年7月收治的4例儿童急性白血病合并侵袭性曲霉病的诊断和治疗。结果:3例急性淋巴细胞白血病（ALL）诱导缓解化疗和1例急性髓细胞白血病(AML)巩固化疗的患儿合并侵袭性曲霉病,1例确诊,3例拟诊,诊断时CT表现均有晕轮征。抗霉菌初始用药首选伏立康唑或两性霉素B。治疗2~5周病灶好转,4月至1年病灶缓解。4例按计划继续强烈化疗,霉菌感染至继续化疗的平均时间为35 d,无霉菌复发。结论: CT晕轮征可作为早期诊断侵袭性曲霉病的指标;基于晕轮征的抢先治疗和患者免疫功能的逆转可改善侵袭性曲霉病的预后;化疗同时持续抗霉菌治疗是完成连续强烈化疗而无霉菌复发的保障。［中国当代儿科杂志,2009,11（11）：901-904］     

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.     

Invasive fungal infections in pediatric oncology patients: 11-year experience at a single institution

The purpose of this study was to determine the incidence of fungal infections in pediatric hematology and oncology (PHO) patients and to describe variations regarding site of infection, organisms, and mortality. The records of 1,052 patients presenting to the UCLA PHO service with various malignancies from 1991 to 2001 were retrospectively reviewed. No patient received invasive antifungal prophylaxis. Transplant patients were excluded. The 11-year incidence of fungal infections in this pediatric oncology cohort was 4.9%. There was a linear increase in the incidence of fungal infections from 2.9% to 7.8% between 1996 and 2001 (P = 0.001). Patients with acute leukemia represented 36% of the population but had a disproportionate incidence (67%) of fungal infections. Adolescents had twice the expected incidence of infection (P < 0.0001). Overall, Candida sp. was the major pathogen. Over time, a trend of fewer infections caused by Candida and more due to Aspergillus was noted. Blood-borne infections decreased over time, while those in the urinary and respiratory tracts increased (P = 0.04). Sixty-two percent of infections occurred in neutropenic patients. PHO patients had an overall mortality of 21%, but those with fungal infections experienced a 2.6-fold higher mortality that was not attributable to infections alone. Empiric antifungal therapy had no effect on mortality rates. Concurrent nonfungal infections did not increase mortality rates. The incidence of fungal infections increased over time, possibly as a result of advances in antibacterial and chemotherapeutic regimens. Adolescents and patients with leukemia were especially at risk. Fungal infections are a poor prognostic factor, independent of fungal-related mortality. New diagnostic methods allowing for early detection and treatment as well as more effective therapies are needed.     

Respiratory muscle testing in children

The range of techniques available to assess respiratory muscles weakness has greatly expanded over recent years. Respiratory muscle tests can be divided into non-invasive tests, such as lung function parameters, maximal static pressures and sniff nasal pressure and invasive tests, such as transdiaphragmatic pressures during crying, maximal static pressures and magnetic stimulation of the phrenic nerves. Sniff nasal pressure and magnetic stimulation should have increasing relevance in children in the coming years. However, probably the most important message is to arrange for the evaluation of respiratory muscles in children with unexplained or disproportionate breathlessness such as in patients with neuromuscular diseases. Improvements are needed to evaluate respiratory muscle endurance in children, which is more difficult but complementary to the assessment of respiratory muscle strength.