Pulmonary Aspergillosis In Neutropenic Patients Research Articles

Invasive aspergillosis in neutropenic patients during hospital renovation: effectiveness of mechanical preventive measures in a prospective cohort of 438 patients.

Aspergillus species are the main cause of invasive fungal disease for patients with severe and prolonged neutropenia. Building or renovation works have been shown as one of the major causes of outbreaks of aspergillosis. This study aimed to assess the effectiveness of introduction and adaptation by air sampling of mechanical preventive measures on the incidence of invasive pulmonary aspergillosis in neutropenic patients during hospital renovation. All of the patients admitted for prolonged and severe neutropenia during a renovation period from 2003 to 2008 were prospectively enrolled. Invasive pulmonary aspergillosis (IPA) cases were classified as possible, probable, and proven, according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group criteria. The effectiveness of preventive measures was determined by air sampling. We recorded 705 hospitalizations for neutropenia concerning 438 patients. The majority of hospitalized neutropenic patients was treated for acute leukemia (38.3 %), followed by patients suffering from non-Hodgkin and Hodgkin lymphomas (33 %). The total cumulative incidence of probable and proven IPA was 4.1 %. Risk factors for developing IPA were underlying disease, treatment course at the time of hospitalization, and the mean duration of hospitalization and of neutropenia. In this prospective study, the incidence of invasive pulmonary aspergillosis did not increase in neutropenic patients during a renovation period because of efficient mechanical preventive measures systematically adjusted using the results of air sampling.

Pandemic 2009 influenza A(H1N1) virus infection coinciding with invasive pulmonary aspergillosis in neutropenic patients

SIn patients receiving anti-neoplastic chemotherapy, the impact of influenza on the incidence of invasive pulmonary aspergillosis (IPA) remains unknown. We matched data of the Cologne Cohort of Neutropenic Patients (CoCoNut) with records from the Institute for Virology and compared the findings to historical data. During the pandemic, we diagnosed influenza A(H1N1) in five patients with malignancies and febrile neutropenia refractory to antibiotic therapy. Probable IPA was diagnosed in three of these patients on the grounds of typical computed tomography morphology and microbiological results. Three of five patients receiving remission-induction chemotherapy for acute myeloid leukaemia developed aspergillosis although receiving posaconazole prophylaxis. In the 3 years before the influenza pandemic, only 2/77 patients of this group developed infection. Infection with influenza A(H1N1) may increase the risk for invasive aspergillosis in neutropenic patients. Pulmonary aspergillosis is an important additional differential diagnosis in neutropenic influenza patients with pneumonia.

Invasive pulmonary aspergillosis in neutropenic patients: Early diagnosis by thoracic high-resolution CT scan.

e19713 Background: The aim of this study was to determine the utility of thoracic high resolution CT scan (HRCT) in the characterization of lung infiltrates for the early diagnosis of invasive pulmonary aspergillosis (IPA) in febrile neutropenic patients. Methods: We included hematology patients (acute leukemia/aplastic anemia) with febrile neutropenia in this study. We took chest x-rays at admission and at onset of fever or development of respiratory signs/symptoms. We did HRCT scan of the chest when fever had lasted for more than 4 days of antibiotic therapy or if the patient had signs/symptoms suggestive of pulmonary involvement or when chest X- ray showed abnormalities. Patterns of parenchymal infiltrates and the presence of nodular lesions, halo sign, cavitation, air crescent sign and fungal ball were noted. IPA was classified as proven, probable or suspected as per EORTC case definitions [excluding radiological criteria]. Calculation of sensitivity and specificity of HRCT in diagnosing IPA was based on these groups. Results: We studied 76 febrile episodes. Chest x-ray abnormalities were seen in 49 (61%) patients.HRCT scan of the chest showed abnormalities in 63 (84%) patients. Normal chest x-ray with abnormal CT was seen in 19(24%) patients. Typical CT findings included nodules in 24 (43%), nodules with halo sign in 19 (34%), segmental consolidation in 34 (61%), cavitation/air crescent sign in 9 (16%), fungal ball in 4(7%), pleural effusion in 11(20%) and hilar/paratracheal lymphadenopathy in 7 (13%). Multiple abnormalities were seen in 36 (47) % of cases. There were 32 cases of suspected IPA and 1 probable IPA. The overall sensitivity and specificity of HRCT for diagnosing IPA was 96% and 65% respectively. The sensitivity and specificity of the halo sign was 39% and 81% and that of the air crescent sign was 27% and 94%. Some of the larger nodules and consolidations in patients with suspected IPA showed a central hypodensity on non-contrast CT (‘hypodense sign’). These radiological findings were useful in the early institution of anti-fungal therapy in these patients. Conclusions: High resolution CT scan is superior to conventional chest x-ray for the early diagnosis of IPA in neutropenic patients.

Invasive pulmonary aspergillosis in neutropenic patients and the influence of hospital renovation

To evaluate the effects of airborne Aspergillus contamination during and after the renovation work of a Florentine haematology unit, we conducted (November 2003-January 2005) a strict programme of environmental fungal surveillance. Air samples were taken from patients' rooms, along the corridors inside the wards, along the corridor between wards and outside the building. The concentration of Aspergillus fumigatus was high along the corridor between the two haematology wards (2.98 CFU m(-3)), lower in the non-neutropenic patients' rooms and outside the hospital building (1.53 and 1.42 CFU m(-3), respectively), very low in the neutropenic patients' rooms (0.09 CFU m(-3)). During this period, three proven cases (A. fumigatus), two probable ones and two possible cases of invasive pulmonary aspergillosis were documented in 97 patients with acute leukaemia (7%). The three cases of proven aspergillosis coincided with the period of renovation work and with the period in which we have found the maximum concentration of A. fumigatus along the corridor. These data suggest a possible relationship between environmental fungal contamination and the incidence of invasive aspergillosis, and underline the importance of environmental surveillance.

Lung Resection for Invasive Pulmonary Aspergillosis in Neutropenic Patients with Hematologic Malignancies: Long Term Results in Thirty Two Cases.

Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in neutropenic patients. Despite adequate medical treatments, such as amphotericin B or voriconazole, the prognosis of IPA remains poor. Nevertheless, recent studies suggest that the outcome of IPA is improving due to early diagnosis (CT scan, antigenemia), use of new antifungal agents (Azols and Echinocandins), and possibly in some cases to early surgical resection. We here report a retrospective one center study of 32 cases of IPA treated by surgical treatment from 1988 to 2005.Between 1988 and December 2005, thirty-seven consecutive patients underwent lung resection for suspected IPA. They were 22 men and 15 women, with a median age of 49.2 years (15 – 74). The underlying diseases were AML, ALL, aggressive lymphoma and myeloma in 26, 7, 2 and 2 cases, respectively. Surgery was planned after hematologic recovery from the last course of chemotherapy during which IPA was diagnosed, either possible in 18 cases, probable in 18 cases or proven in 1 case (Ascioglu, CID 2002). Surgery consisted in 1 pneumectomy, 6 bilobectomies, 18 lobectomies, 8 wedge resections and 4 lobectomies with wedge resections. No perioperative deaths occurred and the median duration of post surgical hospitalisation was 13 days. Six patients presented surgery related complications: three patients required prolonged pleural drainage, one had a section of the phrenic nerve, one presented a major bleeding and last patient had a pneumopathy. The diagnosis of definite IPA was confirmed in 32 cases. Immediately after surgery, 26 of the 32 patients were able to receive subsequent intensive chemotherapy courses, including 15 stem cell transplant (SCT), either auto (5) or allogenic (10). In all cases, patients subsequently received parenteral antifungal therapy. During these new intensive chemotherapy courses, recurrent aspergillosis was observed in only 2 cases, inducing 1 death from brain localization. Overall, with a median follow-up of 8.3 years (1–18), 40.5% of the patients are alive and the main cause of mortality was relapse, but not IPA.In conclusion, early surgical resection together with antifungal therapy allows definite diagnosis of IPA, prevents from IPA recurrence and early death due to hemotysis, with very few peri-operative complications. All the more, it allows subsequent high-dose chemotherapy to treat the underlying hematologic disease. Surgery might be a treatment of choice to a define group of patient.

Indications, complications and prediction of outcome of lung resection for invasive pulmonary aspergillosis in neutropenic patients

PURPOSE: Despite new antifungal agents mortality of invasive pulmonary aspergillosis (IPA) in neutropenic patients remains high. Only few centres perform lung resection for IPA in this patient group. Most centres fear intra- and perioperative complications especially infections because of neutropenia and bleeding because of thrombopenia. We assessed the complication rate and possible prediction of outcome of lung resection for suspected IPA in a large number of hematologic patients.

Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients.

Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in neutropenic patients. Microbiological and serological tests are of limited value. The diagnosis should be considered in neutropenic patients with fever not responding to antibiotics, and typical findings on thoracic computed tomography scan. Whenever possible, diagnosis should be confirmed by tissue examination. Newer techniques, such as polymerase chain reaction may change the current diagnostic approach. Therapeutic strategies consist of prophylaxis in risk groups and the early application of antifungal agents in suspected or probable disease. Amphotericin B as desoxycholate or lipid formulation is the current standard medication in invasive infection, although it has major side effects. Its role is challenged by the new azole derivates, such as itraconazole and voriconazole, and the new echinocandins. Additional therapies with cytokines, such as granulocyte macrophage colony stimulating factor and interferon-gamma, and with granulocyte transfusions are under evaluation. In selected cases lung resection is of proven diagnostic and therapeutic value. This paper analyses the current understanding of the pathogenesis and epidemiology of invasive aspergillosis and reviews the actual diagnostic and therapeutic strategies for invasive pulmonary aspergillosis in neutropenic patients.

Role of early diagnosis and aggressive surgery in the management of invasive pulmonary aspergillosis in neutropenic patients

Invasive pulmonary aspergillosis (IPA) occurs mostly in immunocompromised hosts and especially in neutropenic patients. Improved prognosis for IPA requires early diagnosis. We report our experience in the management of IPA in patients with hematological malignancies. In prolonged neutropenia (> 10 days), thoracic CT scanning seems to be the best choice for the diagnosis of IPA (with CT halo or air-crescent signs). Its systematic use allows a dramatic reduction in the time to achieve the diagnosis, if there is evidence of a halo sign. The systematic screening for the detection of Aspergillus antigenemia with an ELISA test is helpful for early diagnosis. The detection of Aspergillus antigen (with the less sensitive latex agglutination test) on bronchoalveolar lavage (BAL) fluid may also be as useful. The treatment of IPA relies on amphotericin B (or its lipid formulations) or on azole antifungal agents. Pulmonary surgical resection should be considered either as an emergency procedure (despite persistent neutropenia) to avoid massive hemoptysis, or as an elective or diagnostic procedure. This global strategy for the management of IPA is associated with a 75-80% success rate in hematological patients. Nevertheless, the control of underlying malignancy remains a major prognostic factor.

Lung resection for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases.

Invasive pulmonary aspergillosis (IPA) is associated with a high mortality. In 27 consecutive neutropenic patients who underwent lung resection for suspected IPA, we analyzed preoperative diagnostic evaluation, operative procedure, perioperative management, histological findings, outcome concerning recurrence of aspergillosis, and survival to evaluate the morbidity and mortality of a surgical treatment of IPA. Seventeen patients with hematologic diseases had previously undergone high-dose chemotherapy and four stem cell transplantation. Six patients with aplastic anemia were treated with antilymphocyte globulin. IPA was suspected if localized infiltrates developed on thoracic CT scan, and fever persisted under antibiotic therapy in neutropenic patients. In only one case a diagnosis of IPA could be made preoperatively. Twenty patients underwent lobectomy and seven wedge resection. At day of surgery the neutrophil count was below 500 x 10(9)/L in 78% of patients, and the platelet count below in 50 x 10(9)/L in 58% of patients. Invasive fungal infection was confirmed histologically in 22 of 27 patients (81.5%); in five patients no fungal infection was documented. The median duration of surgery was 120 min. Postoperatively, patients stayed one night in the intensive care unit, and chest tubes were removed after 2 d. Within 7 d a median of four erythrocyte packs and two platelet packs per patient were replaced. Major surgical complications occurred in two patients (bronchial dehiscence; pleural aspergillosis). Minor surgical complications included prolonged chest tube drainage (recurrent pneumothorax, n = 2; air leakage, n = 1; hematothorax, n = 1), pleural effusion (n = 4), and seroma (n = 2). Postoperatively, two patients suffered from histologically proven disseminated aspergillosis (pleural aspergillosis, renal aspergilloma) and another patient from suspected orbital aspergillosis. At 30 d postoperative mortality was 11% and 3-mo survival was 77%. After lung resection, seven patients underwent stem cell transplantation without recurrence of IPA. In conclusion, we suggest lung resection is a therapeutic option for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases and is associated with a low surgery-related morbidity and mortality.

Antifungal therapy in 'bone marrow failure'.

Antifungal therapy in 'bone marrow failure'.

Surgical Management of Invasive Pulmonary Aspergillosis in Neutropenic Patients

The aim of our study was to clarify the indications for operation in invasive pulmonary aspergillosis. Nineteen patients with hematologic malignancy, in whom invasive pulmonary aspergillosis developed during the course of neutropenia, had operations. Neutropenia lasted 28 days (range, 15 to 45 days). The preoperative diagnosis of invasive pulmonary aspergillosis was based on computed tomographic scan findings (halo or air crescent signs). Eight patients underwent emergency operations, before marrow recovery, for prevention of massive hemoptysis. The criterion for operation was an aspergillosis lesion that contacted the pulmonary artery on computed tomography. A lobectomy was performed in all cases. A sleeve resection of the pulmonary artery was necessary on two occasions. There was one postoperative death due to extensive aspergillosis. The length of hospitalization after operation was 13 days (range, 6 to 18 days). Seven patients were treated by elective resection of a residual mass (before hematologic therapy in 6 cases). The types of resection performed were lobectomy (n = 4), lingulectomy (n = 1), and wedge resection (n = 2). There were no postoperative deaths. The average length of stay before discharge from the hospital was 11 days (range, 7 to 20 days). The surgical resection was performed as a diagnostic procedure in the 4 remaining patients after an allotted time of 14 days (range, 4 to 24 days) from initiation of antifungal therapy. The combination of antifungal agents and surgical resection is an efficient strategy for the treatment of invasive pulmonary aspergillosis in patients with hematologic malignancy.

Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery.

The prognosis of invasive pulmonary aspergillosis (IPA) occurring in neutropenic patients remains poor. We studied whether new strategies for early diagnosis could improve outcome in these patients. Twenty-three histologically proven and 14 highly probable IPAs in 37 hematologic patients (neutropenic in 36) were analyzed retrospectively. The most frequent clinical signs associated with IPA were cough (92%), chest pain (76%), and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32 cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL fluid. Since October 1991, early thoracic computed tomographic (CT) scans were systematically performed in febrile neutropenic patients with pulmonary x-ray infiltrates. This approach allowed us to recognize suggestive CT halo signs in 92% of patients, compared with 13% before this date, and the mean time to IPA diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable patients, 10 failed to respond (amphotericin B [AmB] plus fluorocytosyne, n = 2; itraconazole + AmB, n = 8) and died of aspergillosis. Twenty-six patients were cured or improved by antifungal treatment (itraconazole with or without AmB, n = 22; voriconazole, n = 4). In 15 of 16 cases, surgical resection was combined successfully with medical treatment. Achievement of hematologic response, early diagnosis, unilateral pulmonary involvement, and highest level of fibrinogen value < 9 g/L were associated with better outcome. In febrile neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early antifungal treatment, combined with surgical resection if necessary, improves IPA prognosis dramatically in these patients.

Itraconazole as Salvage Therapy in Invasive Pulmonary Aspergillosis Occurring during Amphotericin B Therapy in Neutropenic Patients

Amphotericin B is commonly used as prophylactic therapy in addition to broad-spectrum antibiotics in febrile neutropenic patients with leukaemia. Despite amphotericin B therapy, invasive pulmonary aspergillosis commonly occurs in such patients. This abstract reports 15 cases of invasive pulmonary aspergillosis occurring in neutropenic patients previously treated with intravenous amphotericin B, 0.89 mg/kg/day (range, 0.5-1.5 mg/kg/day) for a mean of 16.1 days (range, 5-70 days). The results are summarized in table 1. Seven patients achieved a complete haematological response with chemotherapy, and 8 patients did not achieve a complete haematological response and were considered to have progressive haematological disease. Deaths from invasive pulmonary aspergillosis occurred in 2/7 patients with a complete haematological response and in 3/8 patients with progressive haematological disease. Of 13 patients treated with itraconazole, 300-600 mg/day for a mean duration of 138 days (range, 74-225 days), 10 (77%) were improved. Among these 13 patients, the mean duration of neutropenia had a prognostic value for the outcome of itraconazole treatment failure (* p = 0.05, Mann-Whitney non-parametric test; see table 1). Itraconazole thus seems to be an effective treatment for invasive pulmonary aspergillosis in neutropenic patients, even after failure of amphotericin B.