外科重症治疗病房中侵袭性真菌感染及耐药性分析

近年来,医院内侵袭性真菌感染（invasive fungal infection,IFI）的发生率明显增加,尤多见于免疫功能低下的患者（例如：血液恶性肿瘤、器官移植术后、ICU危重患者等）。不同疾病患者发生的侵袭性真菌感染各有其特点,外科重症治疗病房（surgical intensive care unit,SICU）中,患者多具有高龄、手术史、合并多种基础疾病或免疫功能低下等情况,真菌感染的发生率较普通病房更高^[1],病死率可高达38％-68％^[2],仅次于血液系统肿瘤患者^[3]。     

激素联合免疫抑制剂治疗高危因素的特发性膜性肾病46例疗效分析

目的：比较激素联合不同免疫抑制剂治疗高危因素特发性膜性肾病临床疗效,以探讨合理的治疗方案。方法：随机将2001年5月至2011年5月在我院确诊的46例高危因素的特发性膜性肾病患者分为3组,分别给予甲基泼尼松龙与环磷酰胺、环孢素A或霉酚酸酯中的一种联合使用,总疗程12个月,比较各组治疗方案的临床疗效。结果：（1）治疗前3组患者血压、血肌酐和24 h尿蛋白定量比较无显著性（P〉0.05）。（2）甲基泼尼松龙＋环磷酰胺、甲基泼尼松龙＋环孢素A和甲基泼尼松龙＋霉酚酸酯总缓解率分别为53.3%、80.0%和43.8%,甲基泼尼松龙＋环孢素A与其余两组比较总缓解率较高,且有显著性（P〈0.05）;甲基泼尼松龙＋环磷酰胺和甲基泼尼松龙＋霉酚酸酯两组之间总缓解率无明显差异（P〉0.05）。结论：激素联合免疫抑制剂治疗高危因素的特发性膜性肾病,可明显地提高患者的蛋白尿缓解率,其中甲基泼尼松龙＋环孢素A总缓解率较高,且优于其他免疫抑制剂,但其复发率较高,肾脏药物不良反应大,临床选用时需谨慎。     

脐带间充质干细胞治疗儿童重型免疫性血小板减少症的探索性研究

目的探讨脐带间充质干细胞（UC-MSC）输注治疗儿童重型免疫性血小板减少症（s ITP）的疗效及安全性。方法采用UC-MSC治疗儿童s ITP 3例。发病年龄为3个月至4岁,初治时血小板计数为（1-7）×10^9/L,3例均为s ITP,均出现严重出血,激素及免疫抑制剂无效或依赖。后给予2-3次（1次/周）静脉输注非血缘UC-MSC,输注细胞量为（1-2）×10^6/kg。输注后密切监测血象及肝肾功能等各项指标,观察疗效及不良反应。结果随访时间15-45个月,3例在输注细胞后渐显效：第1例在输注细胞后20 d血小板达到65×10^9/L,随访4个月,血小板均维持在1×10^11/L以上;第2例在输注细胞后41 d血小板达105×10^9/L,之后血小板一直维持正常;第3例在输注第2次细胞后血小板渐上升至2×10^11/L以上。输注过程中1例出现面色发红,1例出现血压升高,随访至今无明显不良反应。结论 UC-MSC对儿童重型ITP有一定的疗效,能提高儿童的生活质量;有必要扩大病例数,进一步研究UC-MSC治疗儿童ITP的疗效及机制。     

异基因造血干细胞移植后并发自身免疫性溶血性贫血的治疗进展

异基因造血干细胞移植（HSCT）后自身免疫性溶血性贫血（AIHA）是HSCT后并不少见的并发症,其发病率约1﹪~ 6﹪,不同于一般的AIHA,HSCT后AIHA发病机制尚未完全明确,可能与HSCT后受者体内免疫失调相关。危险因素与移植患者年龄小、非恶性疾病、使用无关供者、半相合供者移植、脐血移植、去T细胞移植及移植后并发慢性移植物抗宿主病（GVHD）等有关。皮质激素作为一线治疗,疗效有限,难以持续缓解,需联合使用利妥昔单抗（RTX）、大剂量丙种球蛋白等,甚至需要联合霉酚酸酯、环磷酰胺、西罗莫司、阿伦单抗、依库丽单抗或蛋白酶体抑制剂硼替佐米等免疫抑制剂治疗,部分患者需行血浆置换,偶有行脾切除术者。移植后AIHA总死亡率常高达50﹪,总体预后差于单纯AIHA。该综述旨在总结HSCT后并发AIHA的最新治疗进展,供临床医师参考。     

环孢素A对难治性免疫性血小板减少性紫癜的辅助治疗

目的探讨环孢素A辅助治疗难治性免疫性血小板减少性紫癜(ITP)的临床疗效及对患者血小板计数和细胞因子的影响。方法选择2013年1月至2016年12月期间浙江省金华市人民医院收治的难治性ITP患者78例。按照随机数字表分为观察组39例与对照组39例。对照组患者给予利妥昔单抗治疗,观察组在对照组基础上结合环孢素A辅助治疗,两组患者疗程均为3个月。比较两组患者的疗效,治疗前后血小板计数变化,血小板恢复正常时间,治疗前后细胞因子变化及不良反应发生情况。结果观察组患者治疗总有效率(92.31%)高于对照组(69.23%),差异有统计学意义(χ2=6.6857,P0.05);两组患者治疗后血小板计数增加,观察组患者治疗后血小板计数高于对照组、血小板恢复正常时间低于对照组,差异均有统计学意义(t=20.6717、8.1189,P0.05);两组患者治疗后IFN-γ水平较治疗前降低,IL-4、IL-10水平升高,差异有统计学意义(观察组:t=22.9522、11.7500、11.9032,对照组:t=9.8537、7.2250、6.7012,P0.05),且治疗后观察组患者IFN-γ水平低于对照组,IL-4、IL-10水平高于对照组,差异有统计学意义(t=13.0096、3.8277、4.7989,P0.05);两组患者不良反应发生率比较差异无统计学意义(χ2=0.0000,P0.05)。结论环孢素A辅助治疗难治性ITP患者疗效显著,且可增加患者血小板数量,降低IFN-γ水平,增加IL-4、IL-10水平,提高患者免疫力。     

激素治疗大疱性疾病引起真菌感染回顾性分析

目的研究糖皮质激素治疗大疱性疾病患者发生医院真菌感染的病原菌分类、危险因素和防治对策。方法收集67例大疱性类天疱疮和38例天疱疮患者糖皮质激素治疗的临床资料,计算医院真菌感染率,分析相关危险因素。结果大疱性疾病患者糖皮质激素治疗出现医院真菌感染率达32.38%,口腔真菌感染率为27.61%,肺部真菌感染率为13.33%,主要病原菌分别为白念珠菌(69.77%),热带念珠菌(11.63%)和近平滑念珠菌(6.98%)。糖皮质激素剂量、免疫抑制剂、抗生素、住院日及糖尿病病史明显增加真菌感染危险,其中免疫抑制剂、抗生素和糖尿病病史为独立危险因素。结论糖皮质激素治疗大疱性疾病患者院内真菌感染发生率高,免疫抑制剂、抗生素和糖尿病病史是其主要危险因素。     

难治性抑郁症治疗前后血浆单胺类神经递质代谢产物的变化

目的：探讨难治性抑郁症患者抗抑郁剂治疗前后的单胺类神经递质代谢产物的改变。方法：随机入组30例难治性抑郁症患者,进行汉密尔顿抑郁量表（HAMD）的临床评定。用酶联免疫吸附方法对这30例患者进行5-HIAA,MHPG检测,并与随机选取的经汉密尔顿抑郁量表（HAMD）临床评定的30名普通抑郁症患者进行比较。综合治疗8周后对难治性抑郁症患者进行治疗前后对比。结果：难治性抑郁症组治疗前血浆5-HIAA,MHPG浓度低于普通对照组（p〈0.05）,经5-羟色胺重摄取抑制剂治疗的难治性抑郁症患者,5-HIAA和MHPG含量与治疗前比较均有所升高,差异有显著性（p〈0.05）;结论：难治性抑郁症患者存在中枢5-羟色胺和去甲肾上腺素功能低下;个体化合理使用SSRIs类药物辅以心理治疗能有效地提高难治性抑郁症患者的外周单胺类递质水平,减轻患者的抑郁程度。     

特发性血小板减少性紫癜与巨细胞病毒、EB病毒感染相关性

目的：探讨小儿特发性血小板减少性紫癜（ITP）与巨细胞病毒、EB病毒感染的关系。方法：实验组：48例确诊断为ITP患儿,对照组：44例同期呼吸道感染患儿,应用酶联免疫吸附法（ELISA）对两组小儿外周血进行巨细胞病毒IgM抗体（HCMV-IgM）、EB病毒感染IgM抗体（EB-IgM）检测。结果：48例ITP患儿中HCMV-IgM抗体阳性者20例,阳性率为41.67%,明显高于对照组,两组之间差异有显著性（P〈0.01）;EBV-IgM抗体阳性者14例,阳性率为29.17%,明显高于正常对照组,两组之间差异有显著性（P〈0.05）。结论：1、巨细胞病毒感染是引起特发性血小板减少性紫癜的重要原因之一,且通过临床观察巨细胞病毒感染引起的ITP患儿病情重,病程长,治疗时间长,转为慢性ITP的可能性大;2、EB病毒感染可能是引起特发性血小板减少性紫癜的原因之一,并且EB病毒感染引起的特发性血小板减少性紫癜病情也偏重。     

重组人血小板生成素治疗血小板减少性紫癜

目的:分析重组人血小板生成素(rh TPO)治疗血小板减少性紫癜(ITP)的临床疗效。方法:选取100例难治性ITP患者为研究对象,随机分作两组,即观察组50例,采用rh TPO治疗;对照组50例,采用达那唑治疗。比较两组疗效及不良反应。结果:观察组总有效率90%优于对照组72%,差异明显有统计学意义(P<0.05);输注rh TPO之后,有7例患者出现不良反应,主要包括血清丙氨酸氨基转移酶升高、乏力、头晕以及注射处疼痛等,症状较轻且自行缓解。结论:在难治性ITP的临床治疗中,rh TPO具有诸多优势,不仅安全,而且有效,临床疗效优于达那唑,能够实现对出血症状的理想控制,表现出了比较良好的临床应用价值以及前景。     

国产伏立康唑治疗侵袭性真菌感染6例临床观察

目的观察国产伏立康唑治疗恶性血液病患者侵袭性真菌感染（IFI）的临床疗效和安全性。方法以国产伏立康唑治疗6例发生于恶性血液病患者的侵袭性真菌感染,观察疗效及不良反应。结果6例患者中,有效4例,其中完全反应3例,部分反应1例。1例用药第6天出现低钾血症。结论国产伏立康唑是治疗恶性血液病患者侵袭性真菌感染的安全有效的药物,     

Posaconazole Salvage Treatment for Invasive Fungal Infection

Invasive fungal infection (IFI) is an important cause of morbidity and mortality. Posaconazole is a second generation triazole with a broad spectrum, and it may be suitable for salvage antifungal treatment although posaconazole is not usually considered to be as first-line antifungal therapy for IFI. The purpose of this study was to assess the utility of posaconazole salvage treatment for IFI. We conducted a retrospective review of patients with salvage antifungal treatment with posaconazole for IFI at our institution between December 2007 and July 2012. A total of ten patients received posaconazole salvage IFI. Etiology of IFI was consisting of mucormycosis (four patients), Paecilomyces variotii (one patient), and unspecified IFI etiology (five patients). Causes of posaconazole treatment were following; intolerance of previous antifungal therapy in five patients, refractory IFI on previous antifungal therapy in four patients, and both intolerance of previous antifungal therapy and refractory IFI on previous antifungal therapy in one patient. Duration of posaconazole salvage treatment ranged from 15 to 355 days with median 47 days. The overall successful posaconazole salvage treatment response rate was 80.0 % (8 of 10 patients). There were three patients who died during the study period. However, only one death was attributed to the progression of IFI. Two patients discontinued posaconazole due to adverse events. Posaconazole salvage treatment was effective antifungal therapy for IFI. Further studies are needed to define the optimal therapeutic strategy.     

Relevancia de la anfotericina B liposomal en el tratamiento de las infecciones fúngicas invasoras en pacientes oncohematológicos

Liposomal amphotericin B (L-AmB) has been a key cornerstone for the management of invasive fungal infections (IFI) caused by a wide array of molds and yeasts during the last three decades. Multiple studies performed over this period have generated a large body of evidence on its efficacy and safety, becoming the main antifungal agent in the management of IFI in patients with hematologic malignancies in several not mutually exclusive clinical settings. First, L-AmB is the most commonly used antifungal agent in patients undergoing intensive chemotherapy for acute leukemia and high-risk myelodysplastic syndrome, as well as in hematopoietic stem cell transplant recipients. Additionally, due to the administration of newer targeted therapies (such as monoclonal antibodies or small molecule inhibitors), opportunistic mold infections are increasingly being reported in patients with hematologic malignancies usually considered low-risk for IFI. These agents usually have a high drug-drug interaction potential, being triazoles, commonly used for antifungal prophylaxis, included. Finally, patients developing breakthrough IFI because of either subtherapeutic concentrations of antifungal prophylactic drugs in blood or selection of resistant strains, require broad spectrum antifungal therapy, usually with an antifungal of a different class. In both situations, L-AmB remains as the best option for early antifungal therapy.     

Tratamiento antifúngico individualizado en el paciente crítico con infección fúngica invasora

Invasive candidiasis (IC) is the most common invasive fungal infection (IFI) affecting critically ill patients, followed by invasive pulmonary aspergillosis (IPA). International guidelines provide different recommendations for a first-line antifungal therapy and, in most of them, echinocandins are considered the first-line treatment for IC, and triazoles are so for the treatment of IPA. However, liposomal amphotericin B (L-AmB) is still considered a second-line therapy for both clinical entities. Although in the last decade the management of IFI has improved, several controversies persist. The antifungal drugs currently available may have a suboptimal activity, or be wrongly used in certain IFI involving critically ill patients. The aim of this review is to analyze when to provide individualized antifungal therapy to critically ill patients suffering from IFI, emphasizing the role of L-AmB. Drug-drug interactions, the clinical status, infectious foci (peritoneal candidiasis is discussed), the fungal species involved, and the need of monitoring the concentration of the antifungal drug in the patient are considered.     

β-D-glucan Surveillance with Preemptive Anidulafungin for Invasive Candidiasis in Intensive Care Unit Patients: A Randomized Pilot Study

Background

Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.

Methods

Patients admitted to the ICU for ≥3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3∶1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.

Results

Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

Conclusions

BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.

Trial Registration

Clinical Trials.gov {"type":"clinical-trial","attrs":{"text":"NCT00672841","term_id":"NCT00672841"}}NCT00672841     

Particularidades clínicas del paciente crítico con infección fúngica invasora

BackgroundInvasive fungal infection (IFI) is an entity that encompasses different types of infections caused by different types of those fungi pathogenic for humans. In the setting of critically ill patients with multiple and oftenconcurrent risk factors and comorbidities the most common are those caused by the Candida and Aspergillus species. Among the characteristics of IFI in critically ill patients, three aspects can be highlighted: those related to the host (e.g.: risk factors, clinical severity), those related with the pathogen (sensitivity, virulence), or those concerning antifungal treatment (spectrum, features PK / PD, safety, interactions). The fungus that most often causes an IFI in critically ill patients is Candida; the most common type infections are candidemia, Candida peritonitis and catheter-related infections. In recent years new antifungal treatments have expanded the therapeutic options, with echinocandins as a clear choice, often the first in the latest guidelines in critically ill patients with IFI.Case reportWe report the case of a critically ill patient having the most common risk factors, multiple organ dysfunction and development of an IFI. The complexity of establishing an antifungal treatment from the moment of its inception, its setting, and the considerations of the different therapeutic possibilities according to organ dysfunction of the patient are discussed. The antifungal treatment options mentioned in the current guidelines and recommendations are also evaluated.ConclusionsThe most common fungal infection in critically ill patients is invasive candidiasis, with candidemia or candida peritonitis being the most frequent clinical presentations. Candins have brought new possibilities for treating these complex patients due to their good safety profile and clinical efficacy.     

肺隐球菌病12例临床分析

目的 提高对隐球菌病的认识.方法 对确诊为肺隐球菌病的12例病例的临床资料进行回顾性分析.结果 12例病例中,男性8例,女性4例,年龄31～68岁,平均年龄(51.8±12.6)岁,6例伴有基础疾病,但无1例有鸟类接触史;有临床症状者10例,其中咳嗽8例,咯痰3例,胸痛4例,发热2例,有体征者仅2例;胸部影像表现为:1...     

自身免疫性大疱病合并侵袭性肺曲霉病:3例报告

目的通过典型病例回顾探讨自身免疫性大疱病糖皮质激素治疗过程中合并肺曲霉病的诊断和治疗情况。方法报告3例自身免疫性大疱病合并侵袭性肺曲霉病病例。3例病例均行痰镜检、培养、抗原检测、胸部CT或者坏死组织病理检查。分离病原菌经形态学和分子生物学鉴定为烟曲霉、黄曲霉和刺孢裸胞壳。结果 3例病例证实为侵袭性肺曲霉病。进行以伏立康唑为主的综合治疗后均治愈。结论自身免疫性大疱病糖皮质激素治疗过程中应警惕肺曲霉病的发生。多种实验室检查可以帮助早期诊断,提高疗效。     

国产两性霉素B抢先治疗血液病患者肺部侵袭性真菌感染的疗效与安全性分析

目的观察国产两性霉素B抢先治疗血液病患者侵袭性肺部真菌感染(以下简称IFI)的疗效与不良反应。方法回顾性分析我院2004年12月～2008年12月间,45例免疫功能低下IFI患者接受国产两性霉素B治疗的临床资料。结果 45例患者均应用两性霉素B治疗两周以上,最长应用时间为14周,中位数6周。总有效率为86.7%,不良反应主要有低钾血症、发热、转氨酶升高、肾功损害、胃肠道反应,根据WHO药物毒性分级标准均为I～II级毒性。结论国产两性霉素B对于血液病患者IFI临床诊断的抢先治疗疗效肯定,不良反应可耐受。     

Low Rate of Invasive Fungal Infections During Induction and Consolidation Chemotherapy for Adults with De Novo Acute Myeloid Leukemia Without Anti-mold Prophylaxis: Single-Center 2002–2018 Empirical/Pre-emptive Approach

Broad-spectrum antifungal prophylaxis is currently considered the standard of care for adults with de novo AML for the prevention of invasive fungal infections (IFIs), especially invasive pulmonary aspergillosis (IPA). Because fluconazole has been used in our center as anti-yeast prophylaxis, we sought to analyze in detail the incidence of IFIs over a 17-year period, as well as their impact on outcome. A standardized protocol of patient management, including serum galactomannan screening and thoracic CT-guided diagnostic-driven antifungal therapy, was used in all patients. A total of 214 consecutive adults with de novo AML who were treated in 3 CETLAM (Grupo Cooperativo para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias) protocols from 2002 to 2018 were included. The 90-day incidence of any IFI (including possible cases) was 11% (95% CI 4–15%), most cases occurred during induction chemotherapy (8%, 95% CI 4–12%), and most cases were probable/proven IPA (8%, 95% CI 3–13%). Developing an IFI during induction and consolidation had no impact on 1-year survival. A case–control study with 23 cases of IPA and 69 controls identified induction/re-induction chemotherapy, chronic pulmonary disease and age?>?60 years/poor baseline performance status as potential pretreatment risk factors. The current study proves that inpatient induction and consolidation chemotherapy for de novo AML can be given in areas with “a priori” high-burden of airborne molds with fluconazole prophylaxis, while the selective use of anti-mold prophylaxis in patients at very high risk may further reduce the incidence of IFI in this specific clinical scenario.