Aspergillus mediastinitis following orthotopic heart transplantation: case report and review of the literature

Bacterial mediastinitis after orthotopic heart transplantation (OHT) is well described in the literature. However, little information has been published on fungal mediastinitis in this population. We describe a man with Aspergillus fumigatus mediastinitis diagnosed 10 weeks after OHT. The patient was treated with voriconazole. The literature on Aspergillus mediastinitis is also reviewed.     

Mediastinitis after cardiac surgery in Madani Heart Center, Tabriz, Iran

Post-sternotomy infections are a kind of nosocomial infection involving the mediastinum space and the sternum, with a high morbidity and mortality rate. The present study was carried out to identify the incidence of mediastinitis following cardiac surgery and the most common risk factors. Cardic patients undergoing surgery were studied for suspicious mediastinitis infection at the Madani Heart Center, Tabriz, Iran from 2004 to 2006. The most common isolated agents included the coagulase-negative staphylococci, Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacter spp. Incidence of postoperative mediastinitis after cardiac surgery was 1.2%. The mortality rate of postoperative mediastinitis was high (34.3%). Wound infection, especially mediastinitis following cardiac surgery, is rare but could be life-threatening. The most important step in the management of wound infections is prevention, and preventive measures could be strengthened by identifying the risk factors.     

Aspergillus Mediastinitis after Orthotopic Heart Transplantation: A Case Report

A 55-year-old woman was admitted for orthotopic heart transplantation. Her medical history was notable for multiple cardiovascular problems, including ischemic cardiomyopathy that necessitated circulatory support with a left ventricular assist device. Five weeks after undergoing orthotopic heart transplantation, she developed Aspergillus calidoustus mediastinitis, for which she underwent a prolonged course of antifungal treatment that comprised (in sequence) posaconazole for 11 days, voriconazole for 10 days, and amphotericin B for 42 days. During this period, she also underwent repeated mediastinal drainage and sternal débridement, followed by sternal wiring and coverage with bilateral pectoralis advancement flaps. Four months postoperatively, she was discharged from the hospital with a successfully controlled infection and a healed sternum. To our knowledge, only 3 previous cases of Aspergillus mediastinitis after orthotopic heart transplantation have been reported in the literature, none of which was Aspergillus calidoustus.     

Osteomyelitis due to Aspergillus spp. in patients with chronic granulomatous disease: comparison of Aspergillus nidulans and Aspergillus fumigatus.

OBJECTIVE: Chronic granulomatous disease (CGD) is a rare inherited disorder of NADPH oxidase in which phagocytes fail to generate reactive antimicrobial oxidants. Invasive fungal infections are an important cause of morbidity and mortality in CGD patients, with Aspergillus spp. being the most frequent fungal pathogens. We reviewed the reported cases of osteomyelitis in CGD patients due to Aspergillus nidulans and compared them with those due to Aspergillus fumigatus. METHODS: Twenty-four cases of osteomyelitis due to Aspergillus spp. in 22 male CGD patients were found in MEDLINE. RESULTS: Fourteen cases (58%) were due to Aspergillus nidulans and ten cases to Aspergillus fumigatus. No other aspergilli were reported as causes of osteomyelitis. Osteomyelitis due to Aspergillus nidulans was associated with pulmonary infection and involved 'small bones' more frequently than Aspergillus fumigatus osteomyelitis (p=0.032). Half of the CGD patients with Aspergillus nidulans osteomyelitis died compared with none of those with Aspergillus fumigatus osteomyelitis (p=0.019). In both Aspergillus nidulans and Aspergillus fumigatus cases, cure was achieved by prompt antifungal treatment combined with surgery and immunotherapy. CONCLUSION: Aspergillus nidulans causes osteomyelitis in CGD patients relatively frequently compared with Aspergillus fumigatus and may be accompanied by higher mortality. This contrasts with the low frequency with which Aspergillus nidulans causes osteomyelitis in patients with other types of immunodeficiency.     

Superinfection by Aspergillus fumigatus of a pulmonary lesion caused by Mycobacterium xenopi

A 36-year-old man had a pulmonary infection with a cavity in the right upper lobe caused by Mycobacterium xenopi. A superinfection by Aspergillus fumigatus occurred 1 year later. Both organisms were found in the resected lung specimen. The patient remained asymptomatic after surgery. The superinfection of healed tuberculous lesions by 'atypical' mycobacteria or Aspergillus species is well known but the co-existence of the 2 organisms is very rare.     

Pacemaker lead infection caused by Aspergillus fumigatus

We report a case of pacemaker lead infection caused by Aspergillus fumigatus that was successfully treated by surgery and with voriconazole. This infection is rare and dangerous. When it is suspected, transesophageal echocardiography should be performed to look for lead-attached vegetations and the entire pacing system should be removed.     

A case of mediastinitis and bilateral pyothorax, following acute epiglottitis with concurrent Aspergillus infection]

Life threatening mediastinitis as a complication of acute epiglottitis is very rare. A 38-year-old male in previously good health was admitted to our hospital in a state of unconsciousness. Seven days prior to admission he had complained of a sore throat, dysphagia, high fever and dyspnea. A chest X-ray on admission showed widening of the mediastinum, mediastinal emphysema, subcutaneous emphysema and left pleural effusion. Bronchoscopy showed the swelling of supraglottic structures. He was diagnosed as having acute mediastinitis and pyothorax as a complication of acute epiglottitis, but pathogens were not identified. The blood was hyperglycemic and insulin therapy was started. Though he gradually improved by massive antibiotic therapy, steroid therapy, tracheotomy and surgical drainage of both the left thoracic cavity and the mediastinum, he died suddenly of massive hemoptysis. Autopsy revealed that the acute mediastinitis had healed, but that the Aspergillus infection was present in both lungs and the pericardium. The Aspergillus infection was not lethal in the present case, and it seemed that death had resulted from arterial hemorrhage caused by erosion of the trachea. The present case suggests the need for antifungal therapy even in non-immunocompromised patients in particular when massive doses of antibiotics and steroids are administered.     

Diagnosis of pulmonary infection caused by Aspergillus: usefulness of respiratory cultures

Aspergillus infection is often difficult to diagnose, and the usefulness of methods of culture for diagnosis has been questioned. We reviewed all respiratory cultures that yielded any species of Aspergillus and all surgical and autopsy materials suspected or diagnostic of infection with Aspergillus over a two-year period. Of 89 patients with one or more positive cultures of nonbiopsy respiratory tract specimens, eight had histologically proven disease (three had aspergillomas and five, invasive aspergillosis). All cases of disease were due to Aspergillus fumigatus or Aspergillus flavus, and eight of nine patients with two or more positive cultures of A. fumigatus or A. flavus had proven disease, versus one of 81 who were uninfected (P less than .001). Cultures from infected patients also had heavier growth and contained mixed Aspergillus species less often than did cultures from uninfected patients. We conclude that cultures of respiratory specimens are useful for diagnosis of pulmonary infection caused by Aspergillus.     

Pacemaker infection due to Aspergillus: report of two cases and literature review

BACKGROUND: Aspergillus infections of pacing systems are extremely uncommon, and most cases reported are characterized by an aggressive behavior that may lead to death of the patient. HYPOTHESIS: The study was undertaken to assess the incidence of pacemaker infection due to Aspergillus in a defined population. METHODS: A retrospective review of the case histories of all patients who underwent pacemaker implantation in the reference center for a defined population over a 13-year period was undertaken. A literature review of pacemaker infections due to Aspergillus was conducted. RESULTS: Of the 1,321 patients who required pacemaker implantation at Hospital Xeral-Calde in the Lugo region of northwestern Spain, 38 suffered a pacemaker infection. A pacemaker pocket infection due to Aspergillus fumigatus was found in two patients. Both patients had a previous history of diabetes mellitus. Cultures from pacemaker pocket inflammatory fluid yielded positive results. Following pacemaker explantation and antifungal therapy, clinical improvement was achieved. A literature review showed another five cases of pacemaker infection due to Aspergillus. However, two peculiarities were found in our patients: In both cases an etiological diagnosis was achieved prior to surgery and, to the best of our knowledge, they also constitute the first cases of pacemaker pocket infection due to Aspergillus. CONCLUSION: Although pacemaker infections due to Aspergillus species are uncommon, they should be considered in immunocompromised patients.     

血清半乳甘露聚糖检测诊断侵袭性肺曲霉病的实验研究

目的评价血清半乳甘露聚糖（GM）检测对侵袭性肺曲霉病（IPA）的诊断价值。方法清洁级健康成年SD大鼠90只，按随机区组设计分为烟曲霉感染组、白假丝酵母菌感染组、毛霉感染组、肺炎链球菌感染组、烟曲霉口咽定植组，每组18只。气管插管滴人法建立大鼠侵袭性肺部真菌感染和细菌感染动物模型。经鼻腔和口咽滴人法建立烟曲霉口咽定植动物模型。分别于接种完成后第3天、第7天、第12天处死大鼠，取心脏血，采用Platelia Aspergillus（法国Bio—Rad公司）试剂盒检测血清GM，取肺组织行组织病理学检查。多组间比较采用单因素方差分析，实验数据经SPSS统计软件处理。结果除曲霉定植组外，光镜下各组大鼠肺组织均见明显炎症反应，真菌感染大鼠在肺组织中可见真菌菌丝或孢子。烟曲霉、白假丝酵母菌、毛霉、肺炎链球菌感染组和烟曲霉口咽定植组大鼠血清GM的吸光度指数均值分别为1．69±0．29、0．89±0．46、0．87±0．39、0．77±0．34和0．90±0．49，烟曲霉感染组与其他4组分别比较，差异明显。以吸光度指数为1．5作为诊断阈值诊断IPA的敏感性、特异性、阳性预测值和阴性预测值分别为78．6％、87．5％、57．9％和94．9％；以吸光度指数为1．5时，第3天、第7天和第12天血清GM检测诊断IPA的敏感性分别为60％、80％和100％。结论GM检测可区分IPA与白假丝酵母菌感染、毛霉感染、肺炎链球菌感染和烟曲霉口咽定植；GM检测诊断IPA的敏感性随感染时间的延长而增加；以吸光度指数为1．5作为诊断阈值诊断IPA的敏感性、特异性较理想。     

TLR2对曲霉感染支气管上皮细胞时Dectin-1表达的影响

目的 探讨烟曲霉感染人支气管上皮（HBE）细胞时Toll样受体2（TLR2）对树突状细胞植物血凝素-1 （Dectin-1）表达的影响.方法 建立烟曲霉感染HBE细胞模型,通过PCR、Western blot方法分别在mRNA、蛋白水平检测Dectin-1和TLR2的表达情况;沉默TLR2,复制感染模型,应用Western blot及流式细胞技术评价Dectin-1的表达变化.结果 ①烟曲霉感染后HBE细胞TLR2表达水平虽然有所升高,并在感染18h达到峰值,但与静息状态表达水平的差异无统计学意义（P＞0.05）.②沉默TLR2,在烟曲霉感染HBE细胞后18 h时Dectiin1的蛋白表达受到显著抑制（P＜0.05）.结论 HBE细胞静息状态下能够表达TLR2,在烟曲霉感染早期,随着时间的延长其表达有逐步增高的趋势;HBE细胞启动Dectin-1的表达可能是建立在TLR2对烟曲霉早期识别的基础上,通过下游信号通路的激活来实现的。     

Invasive pulmonary aspergillosis due to a multi-azole resistant Aspergillus fumigatus

A patient with invasive pulmonary aspergillosis due to an azole-resistant Aspergillus fumigatus is described. Despite treatment change from voriconazole to amphotericin B as soon as the resistance data were available, the patient died. Azole resistance is an emerging problem, which significantly complicates the management of A. fumigatus infections. It should be considered in every patient with an invasive A. fumigatus infection who is not responding to voriconazole therapy.     

Endemic and epidemic aspergillosis associated with in-hospital replication of Aspergillus organisms

When a new hospital opened in 1983, environmental culturing for Aspergillus organisms and surveillance for nosocomial aspergillosis cases were begun to characterize the relationship between environmental contamination and infection. Monthly air sampling demonstrated increasing concentrations of Aspergillus flavus and Aspergillus fumigatus to mean levels greater than 1 cfu/m3 during 1986-1987, accompanied by a progressive increase in incidence of aspergillosis to 1.2% in immunocompromised patients. This prompted an inspection that revealed heavy growth of Aspergillus organisms on air filters. Subsequent inspections of hospital wards showed small foci of A. flavus growth on other materials. Removal of the contaminated filters and improved environmental maintenance were associated with reduction in A. flavus and A. fumigatus to 0.01 cfu/m3 and a fourfold decline in aspergillosis incidence during the next 2 years. These findings, together with laboratory studies that showed aspergilli could proliferate on common hospital materials when moistened, indicate a need for careful environmental maintenance.     

Vaccination of corticosteroid immunosuppressed mice against invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis is an emerging devastating infection in the immunocompromised host that is treated with corticosteroids for neoplastic disease or for organ transplantation. By use of a model of invasive pulmonary aspergillosis in corticosteroid-treated CF-1 mice, prior infection and 2 Aspergillus fumigatus vaccine preparations (sonicate and filtrate) administered intranasally and subcutaneously were tested for efficacy in protecting against subsequent lethal A. fumigatus infection. The mortality rates were as follows: control subjects, 100%; prior infection, 12.5%; sonicate administered intranasally, 29%; sonicate given subcutaneously, 0%; filtrate given intranasally, 75%; and filtrate given subcutaneously, 50%. Prior infection and A. fumigatus sonicate vaccine administered by 2 routes protected corticosteroid-treated animals against subsequent lethal invasive pulmonary aspergillosis. The sonicate vaccine was more protective, but the subcutaneous route was more effective.     

Characterization of antigens from Aspergillus fumigatus. III. Comparison of antigenic relationships of clinically important aspergilli.

Antigenic relationships between strains of Aspergillus fumigatus, Aspergillus fumigatus var. elipticus, Aspergillus phialiseptus, Aspergillus flavus, and Aspergillus niger were analyzed by fused rocket immunoelectrophoresis and by skin tests. Seventy-three to 89 % of the numbers of antigens detected between strains and species of the A. fumigatus series were shared. The degree of sharing between antigens of A. flavus, A. fumigatus series, and A. niger was much lower and ranged from 19 to 35 %. In reciprocal skin tests in sensitized guinea pigs, similar relationships were shown. Three fractions of A. fumigatus extract proved to be markedly specific for this species. Cross reactivity was associated primarily with carbohydrate and glycoprotein fractions.     

Aspergillus osteochondritis after median sternotomy. Combined operative treatment and drug therapy with amphotericin B

A case of Aspergillus fumigatus osteochondritis after median sternotomy for open heart surgery is presented. To the best of our knowledge, it is the second well documented case that has been reported in the literature. Successful healing was obtained with combined operative treatment (consisting of a large resection of the 8th, 9th and 10th right costal cartilages and surrounding soft tissues), and systemic drug therapy with Amphotericin B. Repeated serologic studies and bone scans were used for both the diagnosis and monitoring of the evolution of the infection; these 2 tools are recommended in cases of mycotic infections in that area.     

Pumonary aspergillosis during hospital renovation.

During a 4-week period, Aspergillus fumigatus caused disease in 2 patients and colonized a third patient in a renal transplant ward. Our investigation indicated that increased exposure of these patients to spores probably occurred during renovation of the ward one floor above it. Cases were significantly clustered (P = 0.014) during the period when work overhead caused dust to filter down through pores in the acoustical tiles of the false ceiling of the renal transplant ward. Swab cultures demonstrated A. fumigatus in the dust, and air samples showed heavy contamination with A. fumigatus and other fungi at and below a renovation site, but not on 2 distant wards. We concluded that dust can be an important source of aspergilli and that release of dust and spores during activities such as renovation may increase the risk of nosocomial Aspergillus infection in exposed, immunosuppressed patients.     

Anaerobic wound infection: Bacteroides mediastinitis after cardiovascular surgery

A case of postoperative anaerobic mediastinitis after coronary artery bypass grafting is reviewed. One of the causative organisms, Bacteroides oralis, has never previously been described as a pathogen causing mediastinitis after median sternotomy incision. There was associated Bacteroides fragilis bacteremia. Only three cases of Bacteroides species mediastinitis after open heart surgery have been reported. This anaerobic bacterium remains a rare pathogen in median sternotomy infections despite the increasing number of cases of mediastinitis seen in association with the burgeoning number of patients undergoing cardiac surgery. Multiple risk factors may contribute to mediastinal infections, which occur in about 2% of patients undergoing coronary artery surgery. When infection occurs, aerobic and anaerobic wound cultures should be made and appropriate antimicrobial and surgical therapy instituted.     

Significance of isolation of Aspergillus from the respiratory tract in diagnosis of invasive pulmonary aspergillosis. Results from a three-year prospective study

The isolation of Aspergillus species from respiratory secretions has been regarded as being of limited usefulness in the antemortem diagnosis of invasive pulmonary aspergillosis. One hundred and eight consecutive patients were evaluated in whom Aspergillus species were isolated from respiratory secretions. Invasive aspergillosis was not demonstrated in non-immunosuppressed patients or in patients with solid tumors in the absence of neutropenia. Lung tissue was examined in 17 patients with leukemia and/or neutropenia; all had invasive aspergillosis. Tissue examination was not performed in 20 neutropenic patients; of 17 not receiving antifungal therapy, 16 died. Multivariate statistical analysis showed that neutropenia and absence of cigarette smoking were significant predictors of invasive aspergillosis in patients with respiratory tract cultures yielding Aspergillus. All cases of invasive aspergillosis were associated with A. fumigatus or A. flavus. The isolation of A. fumigatus or A. flavus from the respiratory tract of a patient with leukemia and/or neutropenia is highly predictive of invasive infection. Empiric amphotericin B therapy, without the necessity for tissue diagnosis, should be considered in this patient subgroup.     

Aortic bypass graft infection due to Aspergillus: report of a case and review.

Aspergillus is a rare cause of aortic graft infection. A recent case is reported and a review of seven other cases described in the literature since 1966 is presented. Infections of both thoracic and abdominal aortic grafts have been reported. Infection occurred from 5 weeks to 3 years after surgery. Underlying immunosuppressive disorders were not present. The most common presenting symptoms were back pain, fever, and embolic phenomena. Pseudoaneurysm of the vascular prosthesis with contiguous vertebral osteomyelitis was frequently seen. Blood cultures were always negative. Laboratory findings were nonspecific. The diagnosis was not anticipated in any case. Aspergillus was isolated in culture of specimens of the vertebral bone, excised graft, or peripheral emboli. Aspergillus fumigatus was the species most frequently isolated. Infection may have occurred intraoperatively as a result of contamination with airborne fungal spores. Optimal treatment included early removal of the graft with extraanatomical bypass plus prolonged antifungal therapy. Delayed surgical intervention and medical therapy alone were associated with high mortality rates. Aspergillar vascular infection should be suspected in patients with aortic grafts who develop persistent back pain, fever, or arterial embolization, and whose blood cultures are sterile.