Fungal infections in solid organ transplantation: An update on diagnosis and treatment

Invasive fungal infections constitute an important cause of morbidity and mortality in solid organ transplantation recipients. Since solid organ transplantation is an effective therapy for many patients with end-stage organ failure, prevention and treatment of fungal infections are of vital importance. Diagnosis and management of these infections, however, remain difficult due to the variety of clinical symptoms in addition to the lack of accurate diagnostic methods. The use of fungal biomarkers can lead to an increased diagnostic accuracy, resulting in improved clinical outcomes. The evidence for optimal prophylactic approaches remains inconclusive, which results in considerable variation in the administration of prophylaxis. The implementation of a standard protocol for prophylaxis remains difficult as previous treatment regimens, which can alter the distribution of different pathogens, affect the outcome of antifungal susceptibility testing. Furthermore, the increasing use of antifungals also contributes to incremental costs and the risk of development of drug resistance. This review will highlight risk factors, clinical manifestations and timing of fungal infections and will focus predominately on the current evidence for diagnosis and management of fungal infections.     

High-resolution computed tomographic findings of Aspergillus infection in lung transplant patients

Objective

The aim of this study was to assess high-resolution computed tomographic (HRCT) findings at presentation in lung transplant patients diagnosed with pulmonary Aspergillus infection.

Materials and methods

We retrospectively reviewed HRCT findings from 23 patients diagnosed with pulmonary aspergillosis. Imaging studies were performed 2–5 days after the onset of symptoms. The patient sample comprised 12 men and 11 women aged 22–59 years (mean age, 43.6 years). All patients had dyspnea, tachypnea, and cough. Diagnoses were established with Platelia Aspergillus enzyme immunoassays for galactomannan antigen detection in bronchoalveolar lavage and recovery of symptoms, and HRCT findings after voriconazole treatment. The HRCT scans were reviewed independently by two observers who reached a consensus decision.

Results

The main HRCT pattern, found in 65% (n = 15) of patients, was centrilobular tree-in-bud nodules associated with bronchial thickening. This pattern was described in association with areas of consolidation and ground-glass opacities in 13% (n = 3) of patients. Consolidation and ground-glass opacities were the main pattern in 22% (n = 5) of patients. The pattern of large nodules with and without the halo sign was observed in 13% (n = 3) of patients, and were associated with consolidation and ground-glass opacities in one case.

Conclusion

The predominant HRCT findings in lung transplant patients with pulmonary aspergillosis were bilateral bronchial wall thickening and centrilobular opacities with the tree-in-bud pattern. Ground-glass opacities and/or bilateral areas of consolidation were also common findings. Pulmonary nodules with the halo sign were found in only 13% of patients.     

The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis

Background and objective:   Very little is known about the response rates to or appropriateness of treatment for patients with allergic fungal diseases of the lung. This study assessed the effect of antifungal therapy in patients with severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA).
Methods:   A retrospective cohort study of 33 adult patients who fulfilled the criteria for either SAFS ( n  = 22) or ABPA ( n  = 11) was conducted. All patients had received antifungal therapy for at least 6 months. The primary study end point was the effect of antifungal therapy on patients' lung function.
Results:   Overall, total IgE values and radioallergosorbent test (RAST) for A. fumigatus markedly decreased after 6 months of therapy in both SAFS and ABPA patients ( P  = 0.004 and P  = 0.005, respectively). Reduction was seen in the eosinophil count ( P  = 0.037), dose of oral steroids ( P  = 0.043) and courses of systemic steroids required ( P  = 0.041). Lung function also improved ( P  = 0.016). Four of 10 patients discontinued oral steroids after 6 months of therapy. Reduction in IgE levels ( P  = 0.015) and RAST for A. fumigatus was also observed ( P  = 0.006) for those patients treated for at least 1 year with antifungal drugs.
Conclusions:   Both ABPA and SAFS patients benefited from oral antifungal therapy. The antifungal therapy may act by reducing the antigenic load, interacting with corticosteroids or by a direct immunological effect.     

肝衰竭患者侵袭性肺曲霉病的临床特点及治疗分析

目的提高对肝衰竭患者并发侵袭性肺曲霉病（invasive pulmonary aspergillosis IPA）的认识,探讨其临床特点及其对策。方法回顾性分析2005年11月至2007年9月间收治的341例肝功能衰竭并发肺部感染患者的临床资料。结果病理学明确诊断的侵袭性肺曲霉病11例和临床诊断3例。绝大多数患者有发热,6例患者无明显呼吸道症状。IPA主要诱发因素是长期应用广谱抗生素和糖皮质激素治疗。其临床症状和影像学变化呈非特异性。肺曲霉病85．7％（12／14）患者白细胞计数和中性粒细胞百分比明显升高。及时诊断并使用卡泊芬净治疗,可以降低IPA患者的病死率。结论在肝衰竭患者,高度怀疑有IPA时,如能早期诊断,及时予卡泊芬净治疗可明显改善肝衰竭患者并发侵袭性肺曲霉病的预后。     

曲霉菌病性痛性眼肌麻痹

目的:讨论导致痛性眼肌麻痹的曲霉菌病的病例特点及诊断。方法:对1例患者进行临床相关资料分析和文献复习。结果:曲霉菌病是痛性眼肌麻痹的原因之一,导致痛性眼肌麻痹的曲霉菌病起病急骤,病变进展迅速,可累及海绵窦、鼻窦、眶尖、颈内动脉,而出现眼肌麻痹,眶后、眶周疼痛,视力障碍,偏瘫等临床表现。活检可确诊曲霉菌病。结论:导致痛性眼肌麻痹的曲霉菌病容易误诊,通过病史及体格检查,并结合CT、MRI、活检可以确诊。     

继发于肺癌的侵袭性气管支气管曲霉病临床分析（附8例报告）

目的探讨侵袭性气管支气管曲霉病(ITBA)的临床特点。方法回顾性分析2016年11月-2018年11月苏州大学附属第一医院呼吸与危重症医学科经病理确诊的8例继发于肺癌的ITBA患者的临床资料,包括病因、临床表现、胸部CT表现、气管镜下表现、感染部位、血清和灌洗液半乳甘露聚糖(galactomannan,GM)试验、治疗过程和预后。结果①8例ITBA患者均接受过全身化疗,7例接受过放疗(包括后装放疗及I125粒子植入),2例行气道内支架置入;②ITBA主要症状:咳嗽咳痰8例(100.0%)、胸闷5例(62.5%)、痰中带血2例(25.0%),发热1例(12.5%);胸部CT表现:无明显变化4例(50.0%)、病变部位气管壁增厚或管腔狭窄2例(25.0%)、阻塞性肺不张2例(25.0%);气管镜下表现:伪膜型3例(37.5%)、阻塞型2例(25.0%)、溃疡型3例(37.5%);GM试验:血清GM试验阳性率为28.6%(2/7),平均值(0.37±0.21);灌洗液GM试验阳性率为100.0%(7/7),平均值(4.27±2.14),灌洗液GM试验阳性率和平均值均高于血清(2=7.78,P=0.005;t=4.79,P=0.003);③经伏立康唑等抗曲霉菌治疗后,1例痊愈,7例死亡,总生存时间为(4.07±3.31)个月。结论①肺癌、化疗、放疗、气道支架置入均可能成为ITBA的高危因素;②ITBA临床及影像学表现缺乏特异性、诊断困难、预后差,纤维支气管镜在ITBA的诊断及治疗过程中仍具有不可替代的作用;③灌洗液GM试验在诊断ITBA方面较血清具有更高的敏感性,值得进一步研究。     

Environmental Aerobiological Studies in Allergic Bronchopulmonary Aspergillosis

An aerobiological pilot study was undertaken to measure airborne concentrations of Aspergillus spores in and around the dwellings of two patients with allergic bronchopulmonary aspergillosis (ABPA). The aim of the investigation was 1) to find a specific source of Aspergillus antigen, and 2) to find out whether disease activity, or exacerbation, paralleled Aspergillus spore prevalence. In the environment of the first patient heavy spore contaminated air was found in a cow-shed, and the adjacent hayloft and scullery. The patient experienced no typical exacerbation during the study period, probably because she now scrupulously avoided this source. The environment of the second patient contained lower spore concentrations in and around the house, and the patient had no typical exacerbation, possibly due to low-intensity exposure. Both patients, however, had increased bronchial obstruction during periods with high Aspergillus spore content in the outside air. The results suggest that avoidance of Aspergillus spore sources and low overall exposure may play a major role in preventing exacerbation of the disease.     

Case report: successful interdisciplinary treatment of cerebrally disseminated invasive pulmonal aspergillosis in a child with acute myeloid leukemia

Invasive pulmonary aspergillosis (IPA) is a life-threatening infection in immunocompromised patients. Mortality rates of cerebrally disseminated IPA approach 100%. We report on a case of a 9-year-old girl with acute myeloid leukemia, who acquired cerebrally disseminated IPA during chemotherapy-induced leukopenia. Longtime survival was achieved by left pneumonectomy and neurosurgical resection of the intracerebral lesion combined with systemic application of itraconazole and liposomal amphotericin B. A review of literature revealed 7 other cases of cerebrally disseminated IPA with survival of more than 12 months.