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1.
Invasive pulmonary aspergillosis in patients with neoplastic diseases   总被引:7,自引:0,他引:7  
Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in granulocytopenic patients. The purpose of this article is to review the current understanding of the microbiology, hospital epidemiology, clinical manifestations, diagnosis, prevention, and treatment of invasive pulmonary aspergillosis. Aspergillus conidia (spores) are inhaled from environmental sources into the paranasal sinuses and lower respiratory tract. Persistent fever, pulmonary infiltrates, and pleuritic pain in granulocytopenic patients receiving antibacterial antibiotics is a common manifestation of invasive pulmonary aspergillosis. Computerized tomographic scans of the chest often reveal characteristic peripheral nodules that also may progress to characteristic cavitary lesions. Hemoptysis may develop due either to hemorrhagic infarction during granulocytopenia or to the rupture of mycotic aneurysms during recovery from granulocytopenia. Aspergillus organisms may extend locally from the lung to involve other thoracic structures, including the heart and chest wall, and may disseminate to extrapulmonary sites, such as the brain, where focal neurological deficits ensue. Early diagnosis of invasive pulmonary aspergillosis may be difficult. Isolation of Aspergillus organisms from respiratory secretions of a persistently febrile granulocytopenic patient is usually indicative of invasive pulmonary aspergillosis and should not be dismissed as a contaminant or saprophyte. Amphotericin B is the treatment of choice; however, high dosages (1.0 to 1.5 mg/kg/day) are often necessary. Aspergillosis may develop in granulocytopenic patients who are already receiving empirical amphotericin B in lower doses (0.5 to 0.6 mg/kg/day). It is hoped that further investigation directed toward an understanding of pathogenesis, improving diagnostic methodology, and developing new therapeutic and preventive strategies will improve the outcome of this life-threatening infection.  相似文献   

2.
目的 探讨慢性阻塞性肺疾病(COPD)合并慢性肺曲霉菌病的高危因素,并分析COPD罹患不同类型慢性肺曲霉菌病的临床特征.方法 选择2015年1月至2020年5月陆军军医大学第二附属医院诊断COPD合并慢性肺曲霉菌病患者39例为观察组,选取同期COPD合并肺部感染(非曲霉非肺结核)患者39例为对照组,采集基本信息、既往病...  相似文献   

3.
BACKGROUND: Detection of methicillin-resistant Staphylococcus aureus (MRSA) carriers on admission to the intensive care unit (ICU) is an important component of strategies for controlling the spread of MRSA. METHODS: A prospective multicenter study was conducted in 14 French ICUs for 6 months. All patients were screened within 24 hours after admission, using nasal and cutaneous swabs In addition, clinical samples were obtained. Patient data collected on ICU admission included presence of immunosuppression; history of hospital stay, surgery, antimicrobial treatments, or previous colonization with MRSA; chronic health evaluation and McCabe scores; reason for admission; whether the patient was transferred from another ward; severity of illness; presence of skin lesions; and invasive procedures. Risk factors for MRSA carriage at ICU admission were estimated, and significantly associated variables were used to develop a predictive score for MRSA carriage. A cost-benefit analysis was then performed. RESULTS: Of the 2347 admissions with MRSA screening, 162 (6.9%; range, 3.7%-20.0% among ICUs) were positive for MRSA, of whom 54.3% were detected through screening specimens only. Of the 2310 first admissions (vs repeat admissions) to the ICU, 96 were newly identified MRSA carriers. Factors associated with MRSA carriage in the multivariate analysis were age older than 60 years, prolonged hospital stay in transferred patients, history of hospitalization or surgery, and presence of open skin lesions in directly admitted patients. Only universal screening detected MRSA carriage with acceptable sensitivity. A cost-benefit analysis confirmed that universal screening and preventive isolation were beneficial. CONCLUSIONS: The prevalence of MRSA carriage on admission to the ICU is high in this endemic setting. Screening for MRSA on admission is useful to identify the imported cases and should be performed in all ICU-admitted patients.  相似文献   

4.
Invasive pulmonary aspergillosis occurs predominantly in individuals who are neutropenic or who have severe defects in cell-mediated immunity. The isolation of Aspergillus from respiratory secretions of normal hosts usually signifies tracheobronchial colonization, not disease. Recent experience with three nonimmunocompromised patients who had invasive pulmonary aspergillosis, each of whom had Aspergillus isolated from respiratory secretions early in his illness, led to a reassessment of the significance of the isolation of Aspergillus from tracheobronchial secretions. Two of 10 nonimmunocompromised, nonleukopenic individuals who had pulmonary infiltrates and whose sputum yielded Aspergillus had invasive pulmonary aspergillosis, whereas two of five individuals who had pulmonary infiltrates and whose bronchial washings grew Aspergillus had invasive disease. These findings indicate that invasive pulmonary aspergillosis should be considered when Aspergillus is isolated from the respiratory secretions of anyone who has pneumonia, regardless of host defense status.  相似文献   

5.
Aspergillus infection is a rare but devastating complication following organ transplantation with high mortality rate. Aspergillus fumigatus is the most common cause of invasive aspergillosis. This fungus is present in the environment worldwide. Aspergillus infection is mainly acquired by inhalation of spores and several nosocomial infections in transplant recipient have been associated with construction work at hospitals. Risk factors for invasive aspergillosis include administration of steroid boluses, history of cytomegalovirus infection, neutropenia and prolonged antibiotic use after transplantation. Successful treatment depends on three factors: early diagnosis, aggressive antifungal therapy and decrease or removal of immunosuppression. Amphotericin deoxycholate has been the standard treatment for many years but lipid preparations for amphotericin are now used due to their significantly fewer adverse effects. A number of new antifungal drugs are now being developed including new azoles such as voriconazol and echinocandin. Invasive aspergillosis has a high mortality rate more than 95% when cerebral dissemination is demonstrated. We report the case of a 47 years old woman who received a cadaveric renal graft and developed pulmonary aspergillosis with fulminant cerebral dissemination two months later. The diagnosis of pulmonary aspergillosis was by culture isolation obtained from bronchioalveolar lavage. Removal of immunosuppresive agents and liposomal amphotericin B therapy were started shortly after admission. Brain CT scan performed on the 12th day showed cerebral dissemination. The recipient died two days later. Our patient had several risk factors such as the administration of steroid boluses and cytomegalovirus infection. Invasive aspergillosis must be always included in the differential diagnosis of fever and pulmonary disease in the renal transplant recipient.  相似文献   

6.
We investigated 120 patients suspected clinically to have pulmonary aspergillosis with different clinical manifestations "aspergilloma (Subgroup A), allergic bronchopulmonary aspergillosis (Subgroup B) and invasive pulmonary aspergillosis (Subgroup C)" and correlated between their clinical and laboratory findings and endogenous specific aflatoxin production. They were subjected to isolation of Aspergillus strains, measurement of serum total IgE and specific Aspergillus IgG by ELISA and identification of aflatoxin producing Aspergillus strains using fluorescence analysis of spectroline. Aspergillus was isolated from 45 patients (37.5%). Subgroup A had a negative statistically non-significant correlation between clinical and laboratory findings as regard total IgE and for Aspergillus IgG (only haemoptysis &weight loss had significant correlation with aspergillus IgG). Subgroup B & Subgroup C had positive, statistically significant correlation &negative statistically non significant correlation respectively as regard all clinical findings and both total IgE & serum IgG. This study also showed that 6 Aspergillus strains out of 45(13.3%) produced endogenous aflatoxin. It is concluded that a significant correlation that exists between clinical and serological findings in allergic pulmonary aspergillosis. Aflatoxins may be produced in vivo by strains of Aspergillus and may result in manifestations similar to those caused by ingestion of aflatoxin in food.  相似文献   

7.
Aspergillosis in the acquired immunodeficiency syndrome   总被引:2,自引:0,他引:2  
A Klapholz  N Salomon  D C Perlman  W Talavera 《Chest》1991,100(6):1614-1618
The role of Aspergillus species as a pathogen in acquired immunodeficiency syndrome (AIDS) has not been clearly defined. From 1984 to 1989, more than 2,000 AIDS patients were seen at Beth Israel Medical Center, New York. Aspergillus was isolated in ten patients; seven had invasive disease and three had noninvasive disease. Invasive pulmonary aspergillosis (IPA) was diagnosed in six patients and invasive renal aspergillosis was found in one patient. Five were homosexual men and two were intravenous drug users. At presentation, all ten had fever, seven had cough, eight had dyspnea, and five had pleuritic chest pain. Chest roentgenograms revealed focal infiltrates in six patients, bilateral interstitial infiltrates in two patients, and bilateral pneumothoraces in one patient. Predisposing conditions included corticosteroid therapy in four, granulocytopenia (less than 1,000/cu m) in two, and broad-spectrum antibiotic therapy in five. Three of the four patients receiving corticosteroids received them as adjuvant therapy for Pneumocystis carinii pneumonia (PCP). Aspergillus was identified antemortem in eight patients, in bronchoalveolar lavage (BAL) fluid in six, in transbronchial biopsy specimen in three, in open lung biopsy specimen in one, and postmortem in one patient. Six of seven patients had at least one concomitant pulmonary process. Six underwent necropsy and findings showed IPA in three, disseminated aspergillosis in two, and PCP in one. Invasive aspergillosis, although significant, is uncommon in AIDS. When Aspergillus is isolated in the setting of corticosteroid therapy, antibiotics, or granulocytopenia, one must suspect invasive disease.  相似文献   

8.
From January 1981 to December 1990, 2180 patients underwent orthotopic liver transplantation at the University of Pittsburgh. Thirty-two patients (1.5%) were identified with invasive aspergillosis (29 lung, 2 intraabdominal, 1 meningitis). Of 29 patients with invasive lung disease, only 23 (79%) had positive culture (Aspergillus fumigatus, 20; Aspergillus flavus, 3). Forty-eight variables were analyzed and compared in 23 patients with invasive disease with positive cultures and 9 patients with colonization only. The variables associated with pulmonary invasive disease, by univariate analysis, were surgical time (P = .03), presence of laparotomies (P = .02), higher creatinine level at time of Aspergillus isolation (P = .01), and use of OKT3 (P = .02). However, in a multivariate analysis, only the last two (creatinine, OKT3) were associated with invasive lung aspergillosis. Of 4 patients with positive abdominal wound culture, 2 had local invasive aspergillosis. Therefore, positive cultures of Aspergillus organisms from respiratory secretions and wound drainage may represent invasive disease and should not be ignored.  相似文献   

9.
Two blinded, controlled trials were done to evaluate the usefulness of fungal antigen detection for the diagnosis of invasive aspergillosis. Detection of Aspergillus fumigatus carbohydrate by radioimmunoassay was compared with antibody detection by an enzyme-linked immunosorbent assay and with diagnostic microbiologic and histopathologic procedures. In the first trial, antigenemia was detected in 4 of 6 leukemic patients with invasive pulmonary aspergillosis, but not in 8 acute leukemic controls or in 24 normal controls. Fungal antigenemia persisted for 8 to 75 days in 4 patients and seroconversion occurred at the onset of pulmonary infiltrates in 3. Antibody to A. fumigatus was detected in 2 of the 6 patients with aspergillosis, but also in 2 leukemic controls and 6 normal controls. Aspergillus species were identified in four of seven bronchoscopies done in 5 patients with invasive pulmonary aspergillosis. Prospective nasal cultures grew Aspergillus species in 4 of the 6 patients with invasive aspergillosis, but in only 1 patient was this information available before a histologic diagnosis was made. In a second trial, antigenemia was detected in 2 patients with invasive aspergillosis, and in 1 with possible invasive aspergillosis, but not in 9 controls. This study indicates that the radioimmunoassay for A. fumigatus antigen is a highly specific and moderately sensitive serodiagnostic test for invasive pulmonary aspergillosis. Prospective nasal cultures grew Aspergillus species in 4 of the 6 patients with invasive aspergillosis, but in only 1 patient was this information available before a histologic diagnosis was made. In a second trial, antigenemia was detected in 2 patients with invasive aspergillosis, and in 1 with possible invasive aspergillosis, but not in 9 controls. This study indicates that the radioimmunoassay for A. fumigatus antigen is a highly specific and moderately sensitive serodiagnostic test for invasive pulmonary aspergillosis.  相似文献   

10.
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.  相似文献   

11.
Invasive aspergillosis is a well-known complication in immunocompromised patients. There are only a few reports of invasive aspergillosis in non-immunocompromised patients. We describe a 72-year-old female patient with clinical signs of spondylodiskitis occurring 4 months after what had appeared to be successful treatment of pulmonary aspergillosis. The patient used inhalation corticosteroids on a daily basis because of chronic obstructive pulmonary disease (COPD). Spondylodiskitis of the intervertebral disc Th11 and Th12 with involvement of both adjacent vertebral bodies was confirmed by magnetic resonance imaging. Histopathological examination revealed the presence of septate hyphae, indicative of Aspergillus species. Subsequently, evidence of Aspergillus spondylodiskitis was obtained by amplification of Aspergillus-DNA with a specific polymerase chain reaction method. Aspergillus spondylodiskitis after pulmonary aspergillosis is only very rarely encountered. Patients with COPD, managed with short-term courses of systemic corticosteroids or with high-dose corticosteroid inhalation therapies, are considered non-immunocompromised but might be at risk of developing invasive aspergillosis.  相似文献   

12.
目的 分析重症患者气道分泌物曲霉培养阳性的危险因素及其临床意义.方法 收集2007年1-12月在北京协和医院ICU住院的、怀疑肺部真菌感染的患者,每周进行3次气道分泌物培养,根据培养结果分为真菌培养阴性、念珠菌培养阳性和曲霉培养阳性三组,分析与曲霉阳性相关的危险因素,同时针对曲霉培养阳性的患者,按照诊断标准划分为确诊、临床诊断和定植,比较感染组(确诊和临床诊断)与定植组的临床特征,分析由定植到感染的危险因素.采用SPSS12.0软件处理数据,计量资料用x±s表示,采用Students't检验(正态分布)或秩和检验(非正态分布).计数资料采用x2检验.多组计量资料比较采用单因素方差分析.采用logistic凹归进行多因素分析.结果 160例中,男82例,女78例,年龄28~81岁,平均(64.5±17.2)岁.气道分泌物曲霉培养阳性45例,念珠菌阳性63例,真菌培养阴性52例,三组患者的病死率依次为48.9%(22/45)、23.8%(15/63)和7.7%(4/52),曲霉阳性者病死率高于念珠菌阳性者及真菌培养阴性者.曲霉阳性的45例中,28例为感染(2例确诊,26例临床诊断),曲霉培养阳性预测感染的比例为62%(28/45).多元回归分析结果显示,自身免疫性疾病(OR=3.3,95%CI为1.7~12.2,x2=4.82,P<0.01)、肝功能不全(OR=8.1,95%CI为1.7~15.2,x2=19.2,P<0.01)、糖皮质激素治疗(OR=4.6,95%CI为2.6~13.7,x2=8.92,P<0.01)、肾脏替代治疗(OR=5.1,95%CI为2.6~11.5,x2=11.4,P<0.01)是曲霉分离阳性的独立危险因素.曲霉感染组较定植组的急性生理与慢性健康Ⅱ评分(APACHE Ⅱ;25±6和14±8,t=2.75,P<0.01)及感染性休克的发生率高(57%和27%,x2=3.56,P<0.01),抗生素使用时间长(15.9 d和9.2 d,t=2.49,P<0.01).结论 重症患者气道分泌物曲霉培养阳性者较阴性者病死率高.自身免疫性疾病、肝功能不全、应用糖皮质激素及肾脏替代治疗与气道分泌物曲霉分离阳性有关.当患者合并严重疾病状态时,气道分泌物曲霉阳性对预测感染有较高的价值.  相似文献   

13.
Six hundred sixteen sera from 79 hematology patients admitted on 152 occasions were analyzed for validation of the Aspergillus fumigatus antigen radioimmunoassay (RIA). Invasive aspergillosis developed on 24 admissions of 22 patients. Maximal antigenic activity was significantly higher in patients with invasive aspergillosis than in controls (P less than .0005). At the level of antigenic activity selected as the cutoff value, the sensitivity of the RIA was 74%, the specificity 90%, the positive predictive value 82%, and the negative predictive value 85%. Antigen was detected before invasive aspergillosis was suspected during 30% of admissions and before pathological or even preliminary microbiological evidence for disease in 46%. In 17 (77%) of the 22 episodes of pulmonary aspergillosis, the RIA would have been the first positive diagnostic test for aspergillosis or would have confirmed a diagnosis established by other means. Overall, the test would have been of clinical usefulness in diagnosis, management, and prognosis in 80% of 16 fatal cases.  相似文献   

14.
Invasive pulmonary aspergillosis, a serious opportunistic infection in adult patients with acute leukemia, is difficult to diagnose antemortem. To identify patients with invasive pulmonary aspergillosis without reliance on invasive diagnostic procedures, a discriminant scorecard for invasive pulmonary aspergillosis based on clinical parameters was evaluated in a three-phase study. In phase I, the records of 62 patients, including 15 with invasive pulmonary aspergillosis, were reviewed. Eleven clinical parameters distinguished patients with invasive pulmonary aspergillosis from control subjects. These parameters were combined into a discriminant scorecard. In phase II, the discriminant scorecard was validated by a blinded, retrospective review of 94 consecutive admissions. The discriminant scorecard score was highly associated with the clinical outcome (p less than 0.0005). The sensitivity of the discriminant scorecard was calculated as a range from 62.9 to 92.8 percent and the specificity as a range from 87.5 to 98.3 percent. In phase III, the clinical utility of the discriminant scorecard was determined by its prospective application to 49 consecutive patient admissions. The discriminant scorecard identified patients with invasive pulmonary aspergillosis at an average of 4.1 days prior to clinical recognition of the disease and initiation of amphotericin B therapy. The discriminant scorecard outperformed a complex function based on multiple linear regressions, was easy to use, and did not require difficult calculations. Thus, for this patient population, the discriminant scorecard was an accurate, useful noninvasive screening test for invasive pulmonary aspergillosis. The scorecard allows more rapid clinical identification of patients with this infection and could lead to improved patient survival through earlier diagnostic and therapeutic intervention.  相似文献   

15.
ObjectiveTo explore the clinical and epidemiological characteristics of chronic obstructive pulmonary disease (COPD) patients with Aspergillus spp. isolation from respiratory samples, and to identify which factors may help us to distinguish between colonisation and infection.MethodsA retrospective cohort study was performed. All patients with COPD and respiratory isolation of Aspergillus spp. over a 12-year period were included. Patients were assigned to 2 categories: colonisation and pulmonary aspergillosis (PA), which includes the different clinical forms of aspergillosis. A binary logistic regression model was performed to identify the predictive factors of PA.ResultsA total of 123 patients were included in the study: 48 (39.0%) with colonisation and 75 (61.0%) with PA: 68 with probable invasive pulmonary aspergillosis and 7 with chronic pulmonary aspergillosis. Spirometric stages of the GOLD classification were not correlated with a higher risk of PA. Four independent predictive factors of PA in COPD patients were identified: home oxygen therapy (OR: 4.39; 95% CI: 1.60-12.01; P = .004), bronchiectasis (OR: 3.61; 95% CI: 1.40-9.30; P = .008), hospital admission in the previous three months (OR: 3.12; 95% CI: 1.24-7.87; P = .016) and antifungal therapy against Candida spp. in the previous month (OR: 3.18; 95% CI: 1.16-8.73; P = .024).ConclusionsContinuous home oxygen therapy, bronchiectasis, hospital admission in the previous three months and administration of antifungal medication against Candida spp. in the previous month were associated with a higher risk of pulmonary aspergillosis in patients with COPD.  相似文献   

16.
This case describes a 61-year-old apparently immunocompetent female with invasive pulmonary aspergillosis (IPA) and eosinophilia who demonstrated spontaneous clinical and radiological recovery. The patient had a history of asthma and had been corticosteroid dependent until 2 months prior to her presentation. This report explores the role of PCR in confirming the diagnosis of invasive aspergillosis in circumstances where only histological data are available and highlights the fact that invasive infections with Aspergillus spp. can occur without profound immunological deficiency. The case also documents the resolution of IPA without specific therapy.  相似文献   

17.
The occurrence of invasive pulmonary aspergillosis is unusual during the course of AIDS. Patients at risk have a CD4 T-lymphocyte count under 50 cells/mm(3) combined with other risk factors in 50% of the cases. Positive diagnosis is based on chest CT scan imaging and isolation of Aspergillus in broncho-alveolar fluid. Detection of galactomannan antigen in serum and broncho-alveolar lavage fluid (BALF) is a reliable complementary tool in assessing the diagnosis. The first line therapy is Voriconazole. The prognosis, often severe, depends on prompt initiation of the appropriate antifungal treatment. We report two cases of invasive pulmonary aspergillosis in AIDS patients.  相似文献   

18.
The efficacy of inhaled amphotericin B in prevention of invasive aspergillosis in patients with granulocytopenia (granulocytes less than 0.5 X 10(9)/l for greater than 10 days) was investigated over a 12-month period. Amphotericin B prophylaxis was administered twice daily for the period of granulocytopenia to 34 patients who were at risk during 144 episodes of granulocytopenia. The cohort at risk was compared with historical controls. In the 2 years prior to institution of prophylaxis, 14 patients (11.4% of those at risk) developed invasive aspergillosis. All cases occurred whilst the patients were nursed on the open wards. Aspergillosis did not develop in 25 granulocytopenic patients nursed in single rooms with HEPA filtration. Since institution of prophylaxis, there have been no cases of invasive aspergillosis. These data suggest that nebulized amphotericin B may be useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients, especially those nursed on the open wards, and warrants further investigation.  相似文献   

19.
Ninety-one patients with documented invasive infections due to an Aspergillus species were identified at Memorial Sloan-Kettering Cancer Center from July 1, 1971, through December 31, 1976. Of the 29 patients in whom the diagnosis was made during life, 10 had successful treatment and survived the Aspergillus infection by two to 17 months. An immunodiffusion test was useful in the early diagnosis of invasive aspergillosis, and in 11 patients in whom the diagnosis was supported by seroconversion and who underwent treatment, the survival rate was 64 percent. Cultures of respiratory secretions were not reliable because they often reflected only colonization. In one year, only 9 percent of the patients with Aspergillus species isolated from the sputum had an invasive infection. The lung was the commonest site of involvement, 91 percent of the patients having pulmonary lesions. The most frequently affected extrapulmonary organ was the brain (18.3 percent). Eight patients had nonpulmonary aspergillosis as the only manifestation of this infection. Most of the 91 patients had hematologic neoplasms as the underlying disease, and neutropenia and antibacterial therapy preceded the diagnosis of aspergillosis in the majority of cases.  相似文献   

20.
The clinical significance of Aspergillus fungaemia in the setting of a deep-seated aspergillosis has not been clearly established. Among 107 microbiologically documented Aspergillus infections in patients with haematological diseases observed over a 17-year period, blood cultures grew Aspergillus species from 10 cases. Aspergillus fungaemia was documented in 9 out of 89 (10.1%) patients with pulmonary aspergillosis at a median of 5 d from the onset of clinical signs of infection, and in one patient with central venous catheter focal infection. Five (50%) patients died as a result of fungal infection a median of 12 d (range 4--48) from the documentation of Aspergillus fungaemia. A comparison between cases of invasive aspergillosis with or without fungaemia showed that fungaemic patients were similar to those without positive blood cultures regarding clinical presentation, risk factors, clinical course and outcome. The diagnostic role of Aspergillus fungaemia in the setting of a deep-seated infection is limited because blood cultures become positive when a microbiological or clinical diagnosis of aspergillosis has already been performed. Aspergillus fungaemia does not necessarily seem to be correlated with a disseminated infection or a poorer prognosis.  相似文献   

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