Clinical Features and Survival Outcomes of Invasive Aspergillosis in Pediatric Patients at a Medical School in Thailand.
Suvaporn AnugulruengkittPanruethai TrinavaratPunchavit ChantranuwatSuchada SritippayawanChitsanu PancharoenThanyawee Puthanakit
8
Citation
0
Reference
10
Related Paper
Citation Trend
Abstract:
Invasive aspergillosis (IA) is a severe infection in immunocompromised patients. Recently, serum galactomannan has been widely used for diagnosis and voriconazole as an antifungal agent. The objective of this study is to describe clinical features and survival outcomes of IA.A retrospective chart review of IA in patients younger than 18 years old at King Chulalongkorn Memorial Hospital, Thailand, was conducted. Clinical definitions were based on criteria oft he European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) 2008.Between January 2006 and December 2012, 40 cases of invasive aspergillosis were identified, classified as proven (8 patients, 20%), probable (28, 70%), and possible IA (4, 10%). Median age of patients was 10 years (range, 42 days-17 years). The most common underlying disease was hematologic malignancy (60%). The major risk factor was neutropenia (65%) with median duration of 21 days (range, 4-58 days). The most common site of infection was in the lungs (80%). The most common computed tomography chest finding was nodules (71%). An air crescent sign was seen only in 11% and a halo sign was found only in 7% of patients. Serum galactomannan was positive in 78% of patients with median value of 1.34 (range 0.5-5.6). Only seven patients (17%) had microbiological confirmation, of which were Aspergillus flavus (4 cases) and Aspergillus fumigates (3 cases). Antifungal therapy included voriconazole (23 patients, 58%), amphotericin B (12, 30%), liposomal amphotericin B (3, 8%), caspofungin (1, 2%) and itraconazole (1, 2%). Two deaths related to angioinvasive complications of aspergillosis (pulmonary hemorrhage and rupture mycotic aneurysm) were reported The 3-month and 12- month survival rates after diagnosed IA were 73.7% and 56.7%, respectively. The major cause of death was new episode of sepsis found in 11 cases (52%).The 1-year survival rate was poor; however, cause of death is related to complications of the immunocompromised state not from IA.Keywords:
Galactomannan
Cite
Invasive aspergillosis (IA) is a severe infection in immunocompromised patients. Recently, serum galactomannan has been widely used for diagnosis and voriconazole as an antifungal agent. The objective of this study is to describe clinical features and survival outcomes of IA.A retrospective chart review of IA in patients younger than 18 years old at King Chulalongkorn Memorial Hospital, Thailand, was conducted. Clinical definitions were based on criteria oft he European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) 2008.Between January 2006 and December 2012, 40 cases of invasive aspergillosis were identified, classified as proven (8 patients, 20%), probable (28, 70%), and possible IA (4, 10%). Median age of patients was 10 years (range, 42 days-17 years). The most common underlying disease was hematologic malignancy (60%). The major risk factor was neutropenia (65%) with median duration of 21 days (range, 4-58 days). The most common site of infection was in the lungs (80%). The most common computed tomography chest finding was nodules (71%). An air crescent sign was seen only in 11% and a halo sign was found only in 7% of patients. Serum galactomannan was positive in 78% of patients with median value of 1.34 (range 0.5-5.6). Only seven patients (17%) had microbiological confirmation, of which were Aspergillus flavus (4 cases) and Aspergillus fumigates (3 cases). Antifungal therapy included voriconazole (23 patients, 58%), amphotericin B (12, 30%), liposomal amphotericin B (3, 8%), caspofungin (1, 2%) and itraconazole (1, 2%). Two deaths related to angioinvasive complications of aspergillosis (pulmonary hemorrhage and rupture mycotic aneurysm) were reported The 3-month and 12- month survival rates after diagnosed IA were 73.7% and 56.7%, respectively. The major cause of death was new episode of sepsis found in 11 cases (52%).The 1-year survival rate was poor; however, cause of death is related to complications of the immunocompromised state not from IA.
Galactomannan
Cite
Citations (8)
Posaconazole
Galactomannan
Allergic bronchopulmonary aspergillosis
Cite
Citations (45)
Abstract A 12‐year‐old boy in third remission of an acute lymphoblastic leukaemia developed infection of lung and paranasal sinuses with Aspergillus flavus in neutropenia. Because of the high risk of leukaemia‐relapse bone marrow transplantation (BMT) from a matched unrelated donor was carried out despite invasive pulmonary aspergillosis (IPA). It is the first reported patient with IPA, who was successfully treated by the antifungal combination therapy with voriconazole and caspofungin therapy during myeloablative BMT. Despite 6 weeks of aplasia, a dramatic decrease of lesions highly suggestive of aspergillosis was observed after BMT. Since discharge‐oral voriconazole monotherapy has been continued. Pediatr Blood Cancer 2005;44:682–685. © 2005 Wiley‐Liss, Inc.
Aplasia
Combination therapy
Cite
Citations (33)
This case-based review examines the growing literature on critical issues related to the epidemiology, diagnosis, and treatment of pediatric invasive aspergillosis. Immunocompromised children are at heightened risk for invasive aspergillosis. Children at highest risk include those with new-onset or relapsed hematologic malignancy and recipients of allogeneic stem cell transplants. Additional risk factors in stem cell transplant recipients include impaired lymphocyte engraftment and graft-versus-host disease. Pediatric invasive aspergillosis is associated with a high mortality rate (generally >50%) and requires prompt diagnosis and treatment to prevent dissemination and death. Tools available for diagnosis include radiologic examinations (primarily computed tomography), the galactomannan assay, bronchoalveolar lavage, and tissue biopsy. Age-related differences in computed tomography and galactomannan assay results have been suggested. Recommended primary therapy for pediatric invasive aspergillosis is voriconazole (7 mg/kg IV q12 hours). Currently approved alternative therapies include liposomal amphotericin B, amphotericin B lipid complex, and caspofungin. Posaconazole and itraconazole are also possibilities, but there is no established pediatric dose for posaconazole, and itraconazole dosing is difficult in children. In patients who do not benefit from initial antifungal therapy, options include switching to another agent with a different mechanism of action or combination therapy. Further research is required to better establish optimal approaches to the management of pediatric patients with invasive aspergillosis recalcitrant to initial primary therapy.
Posaconazole
Galactomannan
Cite
Citations (63)
Hematology
Posaconazole
Cite
Citations (4)
Posaconazole
Aspergillus niger
Anidulafungin
Cite
Citations (39)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct damage to the pulmonary epithelium, enabling Aspergillus invasion. Rapid progression and high mortality of invasive aspergillosis have been reported. In the present study, we report a rare case of possible COVID-19-associated pulmonary aspergillosis (CAPA) caused by A. niger in a Greek patient. Diagnosis was based on ECMM/ISHAM specific criteria and the new algorithm “BM-AspICU” for the invasive pulmonary aspergillosis diagnostic strategy. The fungal isolate was recovered in a non-bronchoalveolar lavage (non-BAL) sample and its identification was performed by standard macroscopic and microscopic morphological studies. MALDI-TOF analysis confirmed the identification of A. niger. In addition, galactomannan antigen and Aspergillus real-time PCR testing were positive in the non-BAL sample, while in serum they proved negative. The A. niger isolate showed an MIC for fluconazole ≥128 μg/mL, for itraconazole and posaconazole 0.25 μg/mL, for voriconazole 0.5 μg/mL, for flucytosine 4 μg/mL, for amphotericin B 1 μg/mL, and for all echinocandins (caspofungin, anidulafungin, micafungin) >8 μg/mL. The patient was initially treated with voriconazole; amphotericin B was subsequently added, when a significant progression of cavitation was demonstrated on chest computed tomography. A. niger was not isolated in subsequent samples and the patient’s unfavorable outcome was attributed to septic shock caused by a pandrug-resistant Acinetobacter baumannii strain.
Anidulafungin
Posaconazole
Aspergillus niger
Galactomannan
Acinetobacter baumannii
Cite
Citations (4)
Abstract: Historically, treatment of invasive fungal infections (IFI) has consisted of amphotericin B. However, new therapeutic agents have recently been introduced. At the same time, the relatively low incidence of IFI and the progress in the diagnostic accuracy of IFI have made routine use of empirical antifungal therapy questionable. Objectives and methods: With the aim to define the present trends in the use of antifungal agents for the treatment of IFI, we prospectively observed type, safety, and efficacy of given antifungal treatment in patients with hematological malignancies during a recent 18‐month period. We also analyzed the impact of restricted use of empirical antifungal therapy on IFI‐related mortality. Results: A total of 279 episodes of neutropenia and fever following the chemotherapy were recorded. Treatment of IFI was given during the management of 41 (14%) episodes. Voriconazole (27 episodes) and caspofungin (14 episodes) were the only antifungal agents used as initial therapy. The rate of antifungal therapy success outcome was 78%. The overall 4‐week mortality rate was 8%. Two patients died of invasive pulmonary aspergillosis. Empirical antifungal therapy was given in 13 episodes with persistent febrile neutropenia (PFN) and resulted in successful outcome in 92% of cases. In general, antifungal agents were well tolerated and only two patients had to discontinue treatment because of severe adverse event. In 127 episodes of PFN, antifungal therapy was deemed unnecessary and accordingly was not administered. In this subgroup of patients, no IFI‐related mortality occurred. Conclusion: A better tolerability and efficacy of voriconazole and caspofungin together with the availability of an oral formulation of voriconazole most probably contributed to the observed shift in the use of antifungal agents. A restricted use of empirical antifungal therapy was, in this setting, not associated with an increased IFI‐related mortality.
Amphotericin B deoxycholate
Tolerability
Cite
Citations (12)
Echinocandins
Galactomannan
Medical microbiology
Cite
Citations (103)
Summary Persistent or recurrent fever of unexplained origin (PFUO) in neutropenic patients receiving antibiotic therapy is commonly treated with empirical antifungal therapy (EAFT). EAFT was established as an adequate management of PFUO around 20 years ago with conventional amphotericin B deoxycholate (c‐AmB), despite its high rate of infusional and systemic toxicities. In recent years, EAFT trials for PFUO have used less toxic agents, such as the lipid formulations of AmB, the new azoles, and the echinocandin, caspofungin. In clinical trials, the lipid formulations of AmB [especially liposomal AmB (L‐AmB)] provided similar efficacy with lower toxicity but at a much higher cost. Although rarely used in clinical practice, fluconazole is equivalent to c‐AmB, provided patients at high risk of Aspergillus infections are excluded. Intravenous itraconazole was shown to be equivalent to c‐AmB, with a lower toxicity. Voriconazole did not meet non‐inferiority criteria when compared with L‐AmB. Caspofungin was shown to be non‐inferior to L‐AmB and more effective in treating baseline invasive fungal infections. To date, alternatives to AmB have shown less toxicity, but improved efficacy is less clear. This is probably because of the weakness of the indication and to the consequent difficulty in establishing objective and reproducible endpoints for comparisons. The new challenge for physicians in this field is probably presumptive antifungal therapy, an approach based on patient risk‐group stratification for developing invasive candidiasis or aspergillosis and/or the use of new diagnostic techniques to identify patients at a very early stage of infection.
Echinocandins
Amphotericin B deoxycholate
Cite
Citations (52)