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翁 开, 吴 椿, 庄 树, 黄 淑, 王 晓, 郑 湧. [Clinical features and prognosis of children with fungal bloodstream infection following chemotherapy for acute leukemia]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2024; 26:1086-1092. [PMID: 39467679 PMCID: PMC11527414 DOI: 10.7499/j.issn.1008-8830.2406021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 09/02/2024] [Indexed: 10/30/2024]
Abstract
OBJECTIVES To investigate the clinical features and prognosis of children with fungal bloodstream infection (BSI) following chemotherapy for acute leukemia (AL). METHODS A retrospective analysis was performed on 23 children with fungal BSI following chemotherapy for AL in three hospitals in Fujian Province, China, from January 2015 to December 2023. Their clinical features and prognosis were analyzed. RESULTS Among all children following chemotherapy for AL, the incidence rate of fungal BSI was 1.38% (23/1 668). At the time of fungal BSI, 87% (20/23) of the children had neutrophil deficiency for more than one week, and all the children presented with fever, while 22% (5/23) of them experienced septic shock. All 23 children exhibited significant increases in C-reactive protein and procalcitonin levels. A total of 23 fungal isolates were detected in peripheral blood cultures, with Candida tropicalis being the most common isolate (52%, 12/23). Caspofungin or micafungin combined with liposomal amphotericin B had a relatively high response rate (75%, 12/16), and the median duration of antifungal therapy was 3.0 months. The overall mortality rate in the patients with fungal BSI was 35% (8/23), and the attributable death rate was 22% (5/23). CONCLUSIONS Fungal BSI following chemotherapy in children with AL often occurs in children with persistent neutrophil deficiency and lacks specific clinical manifestations. The children with fungal BSI following chemotherapy for AL experience a prolonged course of antifungal therapy and have a high mortality rate, with Candida tropicalis being the most common pathogen.
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Affiliation(s)
| | - 椿萍 吴
- 福建医科大学附属协和医院小儿血液科/福建省血液病研究所/福建省血液病学重点实验室, 福建福州350001
| | - 树铨 庄
- 福建医科大学附属泉州第一医院儿科,福建泉州362000
| | | | - 晓芳 王
- 福建医科大学附属泉州第一医院儿科,福建泉州362000
| | - 湧智 郑
- 福建医科大学附属协和医院小儿血液科/福建省血液病研究所/福建省血液病学重点实验室, 福建福州350001
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Alkan A, Buyukasik Y, Uzun O, Demir AU, Coplu L. Invasive fungal infections in patients with acute leukemia: A retrospective cohort study at a tertiary-care hospital. Medicine (Baltimore) 2024; 103:e39959. [PMID: 39465746 PMCID: PMC11460920 DOI: 10.1097/md.0000000000039959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Indexed: 10/29/2024] Open
Abstract
Invasive fungal infection (IFI) is an important cause of morbidity and mortality in acute leukemia patients. In the past few decades, the incidence of IFI has dramatically increased. Nevertheless, the management of IFI has become more complicated owing to changes in the epidemiology of fungal diseases and therapeutic regimens. Therefore, it is important to establish an appropriate strategy for centers that provide the diagnosis and treatment of acute leukemia patients based on scientific data and with available resources. In this study we investigated the incidence of IFI, pathogens, the use of diagnostic methods, and risk factors for IFI in acute leukemia patients over a 17-year period. A total of 502 acute leukemia patients (male/female: 57%/43%, mean age: 57.7 ± 15.5 years) hospitalized at adult and oncology hospitals between 2003 and 2020 were reviewed retrospectively. The incidence of proven and probable IFI was 13.2% (33.1%, when possible cases were included). The most common IFI was aspergillosis (49 patients, 9.7%), followed by candidemia, mucormycosis, and Pneumocystis jirovecii pneumonia. The galactomannan antigen test was positive in the serum of 39 (23.5%) patients and in bronchoalveolar lavage (BAL) fluid in 6 (3.6%) patients. Thirteen (7.8%) sputum cultures (11 Aspergillus spp. and 2 Candida spp.) and 4 (2.4%) BAL fluid (1 Aspergillus spp., 2 Candida spp., 1 P jirovecii) were positive for a fungal pathogen. Neutropenia, intensive care unit (ICU) follow-up and mechanical ventilation (MV) increased the risk of IFI by 3.5, 2.5, and 1.8 times, respectively. The median survival was 5 (range: 1.9-8) months. ICU follow-up shortened the survival by 12 months and increased the death risk by 2.49-fold. MV shortened survival by 57 months and increased the death risk by 3.82-fold. IFI remains a significant contributor to the morbidity and mortality in acute leukemia patients. Pulmonary involvement is the most common site. Neutropenia, ICU follow-up and MV are associated with an increased risk for IFI and mortality. We recommend in the IFI approach, to be aware of IFI in patients receiving intensive chemotherapy and/or recipients of hematopoietic stem cell transplantation, and to evaluate with microbiological, serological and radiological tests during the clinical follow-up.
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Affiliation(s)
- Asli Alkan
- Ankara Etlik City Hospital, Chest Diseases Clinic, Ankara, Turkey
- Formerly Hacettepe University Faculty of Medicine, Department of Chest Diseases, Ankara, Turkey
| | - Yahya Buyukasik
- Hacettepe University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Omrum Uzun
- Hacettepe University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
| | - Ahmet Ugur Demir
- Hacettepe University Faculty of Medicine, Department of Chest Diseases, Ankara, Turkey
| | - Lutfi Coplu
- Hacettepe University Faculty of Medicine, Department of Chest Diseases, Ankara, Turkey
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Saber-Moghaddam N, Nodeh MM, Ghavami V, Rahimi H, Azimi SA, Seddigh-Shamsi M, Kamandi M, Allahyari A, Shariatmaghani SS, Elyasi S, Arasteh O. The evaluation of atorvastatin as an adjunct to fluconazole for the anti-fungal prophylaxis in acute myeloid leukemia: a multicenter, triple-blinded, randomized clinical trial. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:4355-4364. [PMID: 38095652 DOI: 10.1007/s00210-023-02892-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 12/04/2023] [Indexed: 05/23/2024]
Abstract
The development of invasive fungal infections (IFIs) is a serious complication in acute myeloid leukemia (AML) patients who undergo an induction to remission chemotherapy. Given the increased mortality in AML patients with IFI despite prophylaxis, we need to address this problem. Statins have traditionally been employed in clinical settings as agents for reducing lipid levels. Nonetheless, recent investigations have brought to light their antifungal properties in animals, as well as in vitro studies. The objective of this study was to assess the effectiveness of atorvastatin when added to the routine IFI prophylaxis regimen in patients diagnosed with AML. A randomized, multicenter, triple-blind study was conducted on 76 AML patients aged 18-70, who received either placebo or atorvastatin in addition to fluconazole. Patients were followed for 30 days in case of developing IFIs, patient survival, and atorvastatin- related adverse drug reactions. Data were analyzed with SPSS version 26.0. A level of significance of 0.05 was utilized as the threshold for all statistical tests. The data were analyzed by adjusting for the effect of age, regarding that there was a significant difference between the two groups, and showed that atorvastatin reduced the development of both probable and proven IFI (based on EORTC/MSGERC criteria) compared to placebo. IFI-free survival was also significantly better in the atorvastatin group. The incidence of developing aspergillosis did not differ between the two groups. No serious adverse events related to atorvastatin were observed. The present investigation has substantiated the antecedent in vitro and animal research on the fungicidal impact of statins and has suggested the need for additional research involving larger sample sizes and an extended duration of follow-up. Trial registration: This study was registered on the Iranian registry of clinical trials as IRCT20210503051166N1 (Date of confirmation 2021.05.03).
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Affiliation(s)
- Niloufar Saber-Moghaddam
- Department of Clinical Pharmacy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Moeini Nodeh
- Department of Hematology-Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vahid Ghavami
- Department of Epidemiology & Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Rahimi
- Department of Hematology-Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sajjad Ataei Azimi
- Department of Hematology-Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Seddigh-Shamsi
- Department of Hematology-Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mostafa Kamandi
- Department of Hematology-Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abolghasem Allahyari
- Department of Hematology-Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Sepideh Elyasi
- Department of Clinical Pharmacy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Omid Arasteh
- Department of Clinical Pharmacy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Nair KS, Alagesan M, Jose D, Yoganathan C, Saravanan R, Karthikeyan K, Divya K, Babu D, Rajan C, Pappachan JM. Clinical Profile and Factors Associated with Adverse Outcomes in Coronavirus Disease 2019-associated Mucormycosis: A Single-centre Study. TOUCHREVIEWS IN ENDOCRINOLOGY 2023; 19:73-79. [PMID: 38187078 PMCID: PMC10769467 DOI: 10.17925/ee.2023.19.2.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/04/2023] [Indexed: 01/09/2024]
Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic was associated with an increased incidence of mucormycosis globally. However, the clinical pattern, epidemiologic features and risk factors for adverse outcomes are not well established. Methods: We performed a retrospective analysis of the data from patients hospitalized with proven mucormycosis between April 2021 and August 2021. Patients were managed with a multi-disciplinary approach involving medical, surgical, and comorbidity treatment. The clinical presentation, management details, complications and outcomes, including mortality, were reviewed from clinical records. Results: The mean age of presentation was 53.7 (± 11.8) years, and 88 (84.6%) were men. Of the 104 cases with COVID-19-associated mucormycosis, 97 (93.27%) patients had diabetes, and 80.8% had a haemoglobin A1C (HbA1c) of ≥6.4% at diagnosis. Seventy percent of diabetes cases experienced steroid-induced hyperglycaemia during treatment. Even with appropriate treatment, 17 (16.35%) patients died. High HbA1c and creatinine levels, presence of chronic kidney disease (CKD), need for intensive care unit admission, and orbital evisceration were the risk factors associated with high mortality on multivariate logistic regression analysis. Cox regression analysis revealed that the overall mortality increased by a factor of 12% with each 1 percentage point increase in HbA1c ≥6.4% (hazard ratio 1.12; 95% confidence interval 0.95- 1.31). The mortality risk was even higher when diabetes was associated with CKD (hazard ratio 1.82; 95% confidence interval 0.24-14.00). Conclusion: High HbA1c and creatinine levels, intensive care unit admission, CKD, and aggressive disease requiring orbital evisceration are the predictors of mortality in patients with COVID-19-associated mucormycosis. Patients with these risk factors should be managed more actively to reduce morbidity and mortality.
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Affiliation(s)
- Krishna S Nair
- Department of General Medicine, PSG Institute of Medical Sciences and Research Center, Coimbatore, India
| | - Murali Alagesan
- Department of General Medicine, PSG Institute of Medical Sciences and Research Center, Coimbatore, India
| | - Dhanya Jose
- Department of Community Medicine, Goa Medical College, Goa, India
| | - Chidambaram Yoganathan
- Department of General Medicine, PSG Institute of Medical Sciences and Research Center, Coimbatore, India
| | | | | | - Karuppannasamy Divya
- Department of Opthalmology, PSG Institute of Medical Sciences and Research Center, Coimbatore, India
| | - Dinesh Babu
- Department of Dental Surgery, PSG Institute of Medical Sciences and Research Center, Coimbatore, India
| | - Cyril Rajan
- Department of General Medicine, PSG Institute of Medical Sciences and Research Center, Coimbatore, India
| | - Joseph M Pappachan
- Department of Medicine & Endocrinology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
- Faculty of Science, Manchester Metropolitan University, Manchester, UK
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Soldi LR, Coelho YNB, Paranhos LR, Silva MJB. The impact of antifungal prophylaxis in patients diagnosed with acute leukemias undergoing induction chemotherapy: a systematic review and meta-analysis. Clin Exp Med 2023; 23:3231-3249. [PMID: 37058186 DOI: 10.1007/s10238-023-01062-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 03/29/2023] [Indexed: 04/15/2023]
Abstract
Acute leukemias are complex diseases to treat and have a high mortality rate. The immunosuppression caused by chemotherapy also causes the patient to become susceptible to a variety of infections, including invasive fungal infections. Protocols established in many countries attempt to prevent these infections through the use of pharmacological antifungal prophylaxis. This systematic review and meta-analysis investigates the existing evidence for the use of antifungal prophylaxis in patients undergoing induction chemotherapy for acute leukemia, and how prophylaxis can affect treatment response and mortality. Through the use of a population-variable-outcome strategy, keywords were utilized to search online databases. The included studies were selected and the data was collected to develop descriptive results for all studies, and, for studies that met the criteria, a meta-analysis of the Relative Risk (RR) was analyzed for infection rates, in-hospital mortality, and complete remission. A total of 33 studies were included in this systematic review, with most studies presenting positive results (n = 28/33) from the use of antifungal prophylaxis. Using a random effects model, the pooled results of the meta-analysis presented lower invasive fungal infections in AML (RR: 0.527 (95% CI: 0.391; 0.709). p < 0.001). p < 0.001) and ALL (RR: 0.753 (95% CI: 0.574; 0.988). p = 0.041). when antifungal prophylaxis was used. No discernible difference was encountered in the rate of complete remission when using prophylaxis. Antifungal prophylaxis provides a lower risk of invasive fungal infections and in-hospital mortality in acute leukemia patients undergoing induction chemotherapy.
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Affiliation(s)
- Luiz Ricardo Soldi
- Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
- Tumor Biomarkers and Osteoimmunology Laboratory, Av. Pará - 1720 - Block 6T, Room 07 - District Umuarama, Uberlândia, Minas Gerais, Brazil.
- Student of the Graduate Program in Applied Immunology and Parasitology, Universidade Federal de Uberlândia, Uberlândia, Brazil.
| | - Yasmin Nascimento Bernardes Coelho
- Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
- Student of the Graduate Program in Applied Immunology and Parasitology, Universidade Federal de Uberlândia, Uberlândia, Brazil
| | - Luiz Renato Paranhos
- Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Marcelo José Barbosa Silva
- Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
- Tumor Biomarkers and Osteoimmunology Laboratory, Av. Pará - 1720 - Block 6T, Room 07 - District Umuarama, Uberlândia, Minas Gerais, Brazil
- Professor responsible for the area of Immunology at the Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, Brazil
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Weeraphon B, Nakaranurack C, Jutivorakool K, Puttilerpong C. Epidemiology and Factors Associated with Treatment Success of Invasive Fungal Infections Among Newly Hematologic Malignancy Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant in Thailand. Infect Drug Resist 2023; 16:2029-2042. [PMID: 37041985 PMCID: PMC10083034 DOI: 10.2147/idr.s405810] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 03/28/2023] [Indexed: 04/09/2023] Open
Abstract
Purpose Invasive fungal infection (IFI) causes disability/death in patients with hematologic malignancy (HM) receiving chemotherapy or hematopoietic stem cell transplant (HSCT). There is limited epidemiological data, treatment outcomes, and factors associated with IFI treatment success in Thailand. This study aimed to identify factors associated with IFI treatment success among new HM patients receiving chemotherapy or HSCT, determine IFI incidence among HM patients receiving chemotherapy or HSCT, and the IFI incidence of a breakthrough in patients receiving primary antifungal prophylaxis, and identify antifungal drugs susceptibility. Patients and Methods This study reviewed the charts of patients aged ≥ 15 years with newly HM who received chemotherapy or HSCT between January 2016 and June 2021 at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The 2020 EORTC/MSG criteria were used to diagnose IFI. IFI treatment success factors were evaluated using logistic regression. Results Ninety-two patients with 107 episodes of IFI met the inclusion criteria. IFI incidence on proven and probable cases among newly HM patients receiving chemotherapy or HSCT was 7%. Most infections (38.3%) occurred during the induction-phase chemotherapy. Aspergillosis (35.5%) was the commonest IFI, followed by candidiasis (11.2%), Pneumocystis jirovecii pneumonia (8.4%), mucormycosis (3.7%), and others, respectively. The 12-week IFI treatment success rate was 67.3%. It was associated with age < 60 years, absence of coinfection, and the receipt of appropriate empirical therapy on the first day of IFI diagnosis. The incidence of breakthrough IFI from proven and probable cases in patients receiving primary antifungal prophylaxis was 6.1%. Most fungal pathogen isolates were still highly susceptible to antifungal drugs. Conclusion The IFI treatment success in patients with HM or HSCT in our study was high. Close monitoring of coinfected patients aged ≥ 60 is recommended. Appropriate antifungal drugs are essential for clinical outcomes.
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Affiliation(s)
- Benjabhorn Weeraphon
- College of Pharmacotherapy of Thailand, Nonthaburi, Thailand
- Department of Pharmacy Practice and Pharmaceutical Care, Faculty of Pharmaceutical Science, Burapha University, Chonburi, Thailand
| | - Chotirat Nakaranurack
- Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Kamonwan Jutivorakool
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Chankit Puttilerpong
- Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Bioactive Resources for Innovative Clinical Applications, Chulalongkorn University, Bangkok, Thailand
- Correspondence: Chankit Puttilerpong, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand, Email
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Tabak C, Hyter S, Yacoub A, Byrd K, McGuirk J, Godwin AK, Abdelhakim H. Case report: Invasive fungal infection in a patient with a rare CVID-causing gene (TNFRSF13B) mutation undergoing AML treatment. Front Oncol 2023; 13:1017230. [PMID: 37007115 PMCID: PMC10050568 DOI: 10.3389/fonc.2023.1017230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 03/01/2023] [Indexed: 03/17/2023] Open
Abstract
Acute myeloid leukemia (AML) is a complex diagnosis that puts patients at a higher risk for developing infections, particularly invasive fungal infections (IFI). Mutations in TNFRSF13B have been shown to cause dysfunction in B-cell homeostasis and differentiation, making it a risk factor for developing immunodeficiency syndromes. In this case, a male patient in his 40s presented to our emergency department (ED) with symptoms leading to a diagnosis of AML with concurrent mucormycosis of the lungs and sinuses. Targeted next generation sequencing (NGS) of the patient’s bone marrow showed, among other variants, a loss of function mutation in the TNFRSF13B gene. While most patients present with fungal infections after prolonged periods of neutropenia associated with AML treatment, this case presented with IFI at diagnosis without neutropenia suggesting an immunodeficiency syndrome. The concurrent IFI and AML diagnoses create a delicate balance between treatment of the infection and the malignancy. This case highlights the risk of infection in patients receiving chemotherapy, especially those with unrecognized immunodeficiency syndromes, and emphasizes the importance of NGS for prognosis and treatment.
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Impact of revised EORTC/MSGERC 2020 criteria on diagnosis and prognosis of invasive pulmonary aspergillosis in patients with hematological malignancies undergoing bronchoscopy. J Mycol Med 2022; 32:101304. [PMID: 35738036 DOI: 10.1016/j.mycmed.2022.101304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 04/29/2022] [Accepted: 06/14/2022] [Indexed: 12/30/2022]
Abstract
INTRODUCTION The first consensus definitions for invasive fungal diseases (IFD) were published in 2002. Advances in diagnostic tests and a clear need for improvement in certain areas led to a revision of these definitions in 2008. However, growing data on Aspergillus galactomannan (GM) thresholds and the introduction of new polymerase chain reaction-based diagnostic tests resulted in a further update by EORTC and Mycoses Study Group Education and Research Consortium (MSGERC) in 2020. Compared to the 2008 version, the 2020 EORTC/MSGERC criteria have stricter definitions, especially regarding GM levels, which should lead to improved specificity. Thus, our study aimed to evaluate diagnostic changes, based on GM levels, resulting from these new definitions and ascertain the impact of the new classification on mortality rates. METHOD Patients hospitalized in a single tertiary care center with hematologic malignancies and undergoing bronchoscopy for suspected IPA between April 2004 and December 2019 were included in this retrospective study. RESULTS The study population consisted of 327 patients with 31 patients (nine patients with proven IPA and 22 patients with no IPA) excluded from the study. 194 patients were classified as probable IPA cases according to 2008 EORTC/MSG criteria. However, 53 (27.3%) of these patients were re-classified as possible IPA according to 2020 EORTC/MSGERC criteria, due to novel galactomannan cut-off levels. Compared to re-classified possible IPA patients, those remaining in the probable IPA category experienced a higher incidence of septic shock (34.0% vs 16.9%, p=0.02), and required more non-invasive (12.0% vs 0.0%, p=0.004) and invasive (44.6 vs 24.5%, p=0.01) mechanical ventilation. There was a higher in-hospital mortality rate in probable IPA patients than in the re-classified possible IPA group (42.5% vs 22.6%, p=0.01). Patients reassigned to possible IPA had similar underlying diseases, radiological features and prognosis to patients already classified as possible IPA. Independent risk factors for mortality were classification as probable IPA according to 2020 EORTC/MSGERC criteria, lack of remission from hematologic malignancy, and number of nodules in Thorax CT. CONCLUSION The use of 2020 EORTC/MSGERC criteria resulted in a 27.3% significant reduction in probable IPA diagnoses and created a more homogeneous category of patients with respect to treatment response, prognosis and mortality. Therefore, 2020 EORTC/MSGERC criteria afford more reliable mortality prediction than 2008 EORTC/MSG criteria.
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Egger M, Gornicec M, Wölfler A, Lembeck AL, Tinchon C, Maderdonner M, Prattes J. Incidence of invasive fungal infections in patients with hematological malignancies receiving ibrutinib therapy in south-east Austria. Med Mycol 2022; 60:6677974. [PMID: 36029283 DOI: 10.1093/mmy/myac061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/09/2022] [Accepted: 08/26/2022] [Indexed: 11/14/2022] Open
Abstract
Since the broad implementation of ibrutinib therapy, an increasing number of studies have been reporting on invasive fungal infections (IFI) associated with ibrutinib administration. We conducted a retrospective cohort study in three hospitals in south-east Austria in order to assess the local epidemiology of ibrutinib associated IFIs. One-hundred-thirteen patients with underlying hematological malignancy were included in the study. During the study period, a single IFI episode was observed, which corresponds to an IFI incidence of 2.3 cases per 100 person years (95% CI: 0.12-11.47). IFIs during ibrutinib therapy seem to be a rare event in case of absent additional risk factors for IFIs.
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Affiliation(s)
- Matthias Egger
- Division of Infectious Diseases, Medical University of Graz, Graz, Austria
| | - Max Gornicec
- Division of Infectious Diseases, Medical University of Graz, Graz, Austria
| | - Albert Wölfler
- Division of Hematology, Medical University of Graz, Graz, Austria
| | - Anna Lena Lembeck
- Division of Internal Medicine, Hospital of the Brothers of St. John of God, Graz, Austria
| | | | | | - Juergen Prattes
- Division of Infectious Diseases, Medical University of Graz, Graz, Austria
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Keck JM, Wingler MJB, Cretella DA, Vijayvargiya P, Wagner JL, Barber KE, Jhaveri TA, Stover KR. Approach to fever in patients with neutropenia: a review of diagnosis and management. Ther Adv Infect Dis 2022; 9:20499361221138346. [DOI: 10.1177/20499361221138346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 10/22/2022] [Indexed: 11/28/2022] Open
Abstract
Febrile neutropenia (FN) is associated with mortality rates as high as 40%, highlighting the importance of appropriate clinical management in this patient population. The morbidity and mortality of FN can be attributed largely to infectious processes, with specific concern for infections caused by pathogens with antimicrobial resistance. Expeditious identification of responsible pathogens and subsequent initiation of empiric antimicrobial therapy is imperative. There are four commonly used guidelines, which have variable recommendations for empiric therapy in these populations. All agree that changes could be made once patients are stable and/or with an absolute neutrophil count (ANC) over 500 cells/mcL. Diagnostic advances have the potential to improve knowledge of pathogens responsible for FN and decrease time to results. In addition, more recent data show that rapid de-escalation or discontinuation of empiric therapy, regardless of ANC, may reduce days of therapy, adverse effects, and cost, without affecting clinical outcomes. Antimicrobial and diagnostic stewardship should be performed to identify, utilize, and respond to appropriate rapid diagnostic tests that will aid in the definitive management of this population.
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Affiliation(s)
- J. Myles Keck
- University of Mississippi Medical Center, Jackson, MS, USA
| | | | | | | | - Jamie L. Wagner
- University of Mississippi School of Pharmacy, Jackson, MS, USA
| | - Katie E. Barber
- University of Mississippi School of Pharmacy, Jackson, MS, USA
| | | | - Kayla R. Stover
- School of Pharmacy, University of Mississippi, 2500 N State Street, Jackson, MS 39216, USA
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Abstract
Infections due to Aspergillus species are an acute threat to human health; members of the Aspergillus section Fumigati are the most frequently occurring agents, but depending on the local epidemiology, representatives of section Terrei or section Flavi are the second or third most important. Aspergillus terreus species complex is of great interest, as it is usually amphotericin B resistant and displays notable differences in immune interactions in comparison to Aspergillus fumigatus. The latest epidemiological surveys show an increased incidence of A. terreus as well as an expanding clinical spectrum (chronic infections) and new groups of at-risk patients being affected. Hallmarks of these non-Aspergillus fumigatus invasive mold infections are high potential for tissue invasion, dissemination, and possible morbidity due to mycotoxin production. We seek to review the microbiology, epidemiology, and pathogenesis of A. terreus species complex, address clinical characteristics, and highlight the underlying mechanisms of amphotericin B resistance. Selected topics will contrast key elements of A. terreus with A. fumigatus. We provide a comprehensive resource for clinicians dealing with fungal infections and researchers working on A. terreus pathogenesis, aiming to bridge the emerging translational knowledge and future therapeutic challenges on this opportunistic pathogen.
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Blockade Of PD-1 Attenuated Postsepsis Aspergillosis Via The Activation of IFN-γ and The Dampening of IL-10. Shock 2021; 53:514-524. [PMID: 31306346 DOI: 10.1097/shk.0000000000001392] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Nosocomial aspergillosis in patients with sepsis has emerged in the past few years. Blockade of PD-1/PD-L pathway has tended to become a promising therapeutic strategy as it improved the outcome of bacterial sepsis and postsepsis secondary fungal infection. Recently, the controversial effects of PD-1 blockade on infectious diseases, including aspergillosis, have been demonstrated; therefore, the efficacy of anti-PD-1 drug still remains to be elucidated. METHODS Cecal ligation and puncture (CLP) was conducted as a mouse sepsis model. Aspergillus fumigatus spores were intravenously inoculated on day 5 post-CLP, when the immune cells succumbed to exhaustion. Amphotericin B was medicated together with or without anti-PD-1 treatment after Aspergillus infection. RESULTS Amphotericin B alone was not effective to treat the CLP-mice with secondary aspergillosis. In contrast, antifungal medication with the adjunctive anti-PD-1 treatment attenuated the fungal burdens in blood and internal organs, and improved the survival rate of the mice with secondary aspergillosis. These outcomes of PD-1 blockade were concurring with the enhanced CD86 expression on splenocytes, the augmented serum IFN-γ, and the dampened IL-10. Activated T cells from anti-PD-1-treated mice also highly increased IFN-γ and diminished IL-10 production. CONCLUSION The blockade of PD-1 on postsepsis aspergillosis presumably reinvigorated exhausted antigen-presenting cells and T cells by upregulating CD86 expression and IFN-γ production, and dampened IL-10 production, which consequently leaded to the attenuation of secondary aspergillosis. The adjunctive anti-PD-1 therapy may become a promising strategy for the advanced immunotherapy against lethal fungal infection.
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13
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Gangneux JP, Padoin C, Michallet M, Saillio E, Kumichel A, Peffault de La Tour R, Ceballos P, Gastinne T, Pigneux A. Outcomes of Antifungal Prophylaxis in High-Risk Haematological Patients (AML under Intensive Chemotherapy): The SAPHIR Prospective Multicentre Study. J Fungi (Basel) 2020; 6:jof6040281. [PMID: 33198192 PMCID: PMC7712136 DOI: 10.3390/jof6040281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/09/2020] [Accepted: 11/10/2020] [Indexed: 12/15/2022] Open
Abstract
Antifungal prophylaxis (AFP) is recommended by international guidelines for patients with acute myeloid leukaemia (AML) undergoing induction chemotherapy and allogeneic hematopoietic cell transplantation. Nonetheless, treatment of breakthrough fungal infections remains challenging. This observational, prospective, multicentre, non-comparative study of patients undergoing myelosuppressive and intensive chemotherapy for AML who are at high-risk of invasive fungal diseases (IFDs), describes AFP management and outcomes for 404 patients (65.6% newly diagnosed and 73.3% chemotherapy naïve). Ongoing chemotherapy started 1.0 ± 4.5 days before inclusion and represented induction therapy for 79% of participants. In 92.3% of patients, posaconazole was initially prescribed, and 8.2% of all patients underwent at least one treatment change after 17 ± 24 days, mainly due to medical conditions influencing AFP absorption (65%). The mean AFP period was 24 ± 32 days, 66.8% stopped their prophylaxis after the high-risk period and 31.2% switched to a non-prophylactic treatment (2/3 empirical, 1/3 pre-emptive/curative). Overall, 9/404 patients (2.2%) were diagnosed with probable or proven IFDs. During the follow-up, 94.3% showed no signs of infection. Altogether, 20 patients (5%) died, and three deaths (0.7%) were IFD-related. In conclusion, AFP was frequently prescribed and well tolerated by these AML patients, breakthrough infections incidence and IFD mortality were low and very few treatment changes were required.
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Affiliation(s)
- Jean-Pierre Gangneux
- Mycology Department, Centre Hospitalier Universitaire de Rennes, University Rennes, INSERM, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR S_1085, 35000 Rennes, France
- Correspondence: ; Tel.: +33-299-283-731
| | - Christophe Padoin
- Pharmacy Department, CHU Martinique Site P. Zobda Quitman, 97261 Fort de France, Martinique, France;
| | - Mauricette Michallet
- Clinical Haematology Department, Centre Léon Bérard (Anticancer Center), 28 Rue Laennec, 69373 Lyon, France;
| | - Emeline Saillio
- Department of Medical Affairs, MSD France, 10-12 cours Michelet, 92800 Puteaux, France;
| | - Alexandra Kumichel
- Scientific Department, ClinSearch, 110 Avenue Pierre Brossolette, 92240 Malakoff, France;
| | - Régis Peffault de La Tour
- Haematology-Bone Marrow Transplant Department, Saint-Louis Hospital APHP, 1 Avenue Claude-Vellefaux, 75010 Paris, France;
| | - Patrice Ceballos
- Clinical Haematology Department, CHRU Lapeyronie, 371 Avenue Doyen Gaston Giraud, 34295 Montpellier, France;
| | - Thomas Gastinne
- Clinical Haematology Department, CHU Nantes, 1 Place Alexis-Ricordeau, 44093 Nantes, France;
| | - Arnaud Pigneux
- Blood Diseases Department, Hospital Group Haut Leveque, Avenue de Magellan, 33604 Pessac, France;
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14
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Feng YH, Guo WW, Wang YR, Shi WX, Liu C, Li DM, Qiu Y, Shi DM. Rhinocerebral mucormycosis caused by Rhizopus oryzae in a patient with acute myeloid leukemia: A case report. World J Dermatol 2020; 8:1-9. [DOI: 10.5314/wjd.v8.i1.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 05/29/2020] [Accepted: 06/20/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Rhinocerebral mucormycosis (RCM) is a rare fatal fungal infection which is on the increase among immunocompromised hosts such as patients who have had hematological cancers, or have received immunosuppressive drugs, corticosteroids, or other T cell suppressing agents.
CASE SUMMARY We report a case of RCM caused by Rhizopus oryzae, one of the most common opportunistic pathogens, in a patient suffering from a fourth relapse of acute myeloid leukemia. The patient developed RCM after he had received long-term antibiotic agents and corticosteroids. The pathogen was isolated three times from nasal secretions collected from the deep parts of the nasal cavity and was identified by morphology and internal transcribed spacer sequencing. Blood infection was excluded by droplet digital polymerase chain reaction and blood culture. The patient was empirically treated with caspofungin and voriconazole for several days while the lesions continued to progress. The patient was given amphotericin B in combination with caspofungin after RCM was suspected, and the lesions improved over the course of treatment, which lasted several days. However, the patient eventually died of the primary disease.
CONCLUSION This case indicates that immunosuppressive drugs, including corticosteroids and antimetabolites in hematological tumor, do increase the risk of infections of this type. Early diagnosis, prompt and frequent surgical debridement, and treatment with amphotericin B without delay are all essential in combatting RCM.
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Affiliation(s)
- Ya-Hui Feng
- Department of Clinical Medicine, Jining Medical University, Jining 272067, Shandong Province, China
| | - Wen-Wen Guo
- Department of Hematology, Jining No. 1 People’s Hospital, Jining 272067, Shandong Province, China
| | - Ya-Ru Wang
- Department of Dermatology, Jining No. 1 People’s Hospital, Jining 272067, Shandong Province, China
| | - Wen-Xia Shi
- Department of Clinical Medicine, Jining Medical University, Jining 272067, Shandong Province, China
| | - Chen Liu
- Laboratory of Clinical Mycology, Jining No. 1 People’s Hospital, Jining 272067, Shandong Province, China
| | - Dong-Mei Li
- Medical Center, Georgetown University, Washington, DC 20057, United States
| | - Ying Qiu
- Department of Dermatology, Jining No. 1 People’s Hospital, Jining 272067, Shandong Province, China
| | - Dong-Mei Shi
- Laboratory of Medical Mycology, Department of Dermatology, Jining No. 1 People’s Hospital, Jining 272067, Shandong Province, China
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15
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Gründahl M, Wacker B, Einsele H, Heinz WJ. Invasive fungal diseases in patients with new diagnosed acute lymphoblastic leukaemia. Mycoses 2020; 63:1101-1106. [PMID: 32738006 DOI: 10.1111/myc.13151] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 07/20/2020] [Accepted: 07/22/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Patients with acute leukaemia have a high incidence of fungal infections. This has primarily been shown in acute myeloid leukaemia and is different for acute lymphoblastic leukaemia. Until now no benefit of mould active prophylaxis has been demonstrated in the latter population. METHODS In this retrospective single-centre study, we analysed the incidence, clinical relevance, and outcome of invasive fungal diseases (IFD) as well as the impact of antifungal prophylaxis for the first 100 days following the primary diagnosis of acute lymphoblastic leukaemia. RESULTS In 58 patients a high rate of proven, probable, and possible fungal infections could be demonstrated with a 3.4%, 8.6%, and 17.2% likelihood, respectively. The incidence might be even higher, as nearly 40% of all patients had no prolonged neutropenia for more than 10 days, excluding those from the European Organization of Research and Treatment of cancer and the Mycoses Study Group criteria for probable invasive fungal disease. The diagnosed fungal diseases had an impact on the duration of hospitalisation, which was 13 days longer for patients with proven/probable IFD compared to patients with no signs of fungal infection. Use of antifungal prophylaxis did not significantly affect the risk of fungal infection. CONCLUSION Patients with acute lymphoblastic leukaemia are at high risk of acquiring an invasive fungal disease. Appropriate criteria to define fungal infections, especially in this population, and strategies to reduce the risk of infection, including antifungal prophylaxis, need to be further evaluated.
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Affiliation(s)
- Marie Gründahl
- Department of Neurology, Klinikum Würzburg Mitte, Würzburg, Germany
| | - Beate Wacker
- Department for Internal Medicine I, Klinikum Weiden, Weiden, Germany
| | - Hermann Einsele
- Med. Clinic II, University of Würzburg Medical Center, Würzburg, Germany
| | - Werner J Heinz
- Department for Internal Medicine I, Klinikum Weiden, Weiden, Germany.,Med. Clinic II, University of Würzburg Medical Center, Würzburg, Germany
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16
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Azevedo MM, Pina-Vaz C, Baltazar F. Microbes and Cancer: Friends or Faux? Int J Mol Sci 2020; 21:ijms21093115. [PMID: 32354115 PMCID: PMC7247677 DOI: 10.3390/ijms21093115] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 04/23/2020] [Accepted: 04/26/2020] [Indexed: 02/07/2023] Open
Abstract
Cancer is one of the most aggressive and deadly diseases in the world, representing the second leading cause of death. It is a multifactorial disease, in which genetic alterations play a key role, but several environmental factors also contribute to its development and progression. Infections induced by certain viruses, bacteria, fungi and parasites constitute risk factors for cancer, being chronic infection associated to the development of certain types of cancer. On the other hand, susceptibility to infectious diseases is higher in cancer patients. The state of the host immune system plays a crucial role in the susceptibility to both infection and cancer. Importantly, immunosuppressive cancer treatments increase the risk of infection, by decreasing the host defenses. Furthermore, alterations in the host microbiota is also a key factor in the susceptibility to develop cancer. More recently, the identification of a tumor microbiota, in which bacteria establish a symbiotic relationship with cancer cells, opened a new area of research. There is evidence demonstrating that the interaction between bacteria and cancer cells can modulate the anticancer drug response and toxicity. The present review focuses on the interaction between microbes and cancer, specifically aiming to: (1) review the main infectious agents associated with development of cancer and the role of microbiota in cancer susceptibility; (2) highlight the higher vulnerability of cancer patients to acquire infectious diseases; (3) document the relationship between cancer cells and tissue microbiota; (4) describe the role of intratumoral bacteria in the response and toxicity to cancer therapy.
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Affiliation(s)
- Maria Manuel Azevedo
- Department of Microbiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- CINTESIS, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- Agrupamento de Escolas D. Maria II, 4760-067 V.N. Famalicão, Portugal
- Correspondence: ; Tel.: +351-22-551-36
| | - Cidália Pina-Vaz
- Department of Microbiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- CINTESIS, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Fátima Baltazar
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, 4835-258 Guimarães, Portugal
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17
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Clinical Spectrum, Diagnosis and Outcome of Rare Fungal Infections in Patients with Hematological Malignancies: Experience of 15-Year Period from a Single Tertiary Medical Center. Mycopathologia 2020; 185:347-355. [PMID: 32100219 DOI: 10.1007/s11046-020-00436-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 02/11/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with hematological malignancies and allogeneic hematopoietic stem-cell transplant recipients carry a high risk of rare (non-Aspergillus molds and non-Candida yeasts) invasive fungal infections (IFI). METHODS We retrospectively evaluated and described the patient profile, clinical manifestations, isolated species, treatment and outcome of patients with hematological malignancies diagnosed with these rare IFIs during 15 years in a large single hemato-oncology center. RESULTS Eighty-seven patients with hematological malignancies treated in our center had at least one positive culture or molecular identification of a rare fungus. Ninety-three isolates were considered the etiological agents of the infection. The most common underlying hematological malignancy was acute myeloid leukemia, 36 patients (41.4%). Eighty patients (91%) received chemotherapy less than 30 days prior to IFI diagnosis. The most frequent site of infection was the respiratory tract: 34 patients (39%) had pulmonary and 19 patients (22%) had a sinusal or nasopharyngeal infections. Disseminated infection, defined as positive blood cultures or parallel infection in multiple organ systems, was documented in 20 patients (23%). The most common fungal species were Fusarium (35%) and Zygomycetes (25%). Coinfection with more than one fungus was noted in 20 patients (23%). Forty-seven of 87 patients (54%) in this study died within 90 days of IFI diagnosis. CONCLUSIONS Rare IFIs in patients with hematological malignancy become increasingly frequent. Early identification with traditional and molecular methods is important in management of these patients.
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18
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Shao L, Jiang L, Wu S, Yu L, Wang L, Huang X. Simultaneous occurrence of invasive pulmonary aspergillosis and diffuse large B-cell lymphoma: case report and literature review. BMC Cancer 2020; 20:15. [PMID: 31906982 PMCID: PMC6945787 DOI: 10.1186/s12885-019-6471-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 12/17/2019] [Indexed: 11/16/2022] Open
Abstract
Background Patients with lymphoma are at risk for developing pulmonary opportunistic infections due to immunocompromise. However, clinical reports of concurrent lymphoma and opportunistic infection at presentation are rare and often confined to single cases. A delayed diagnosis of either opportunistic infection or lymphoma usually occurs in this complex situation. Here, we report such a case and analyse 18 similar cases searched in the PubMed database to deepen clinicians’ understanding. Case presentation A 48-year-old man presented with a 3-month history of fever, cough and emaciation. High-resolution computed tomography revealed bilateral cavitating lesions of different sizes. Aspergillus fumigatus complex was identified from a bronchoalveolar lavage fluid culture. However, antifungal treatment combined with multiple rounds of antibacterial therapy was unsuccessful, and the patient’s lung lesions continued to deteriorate. Multiple puncture biopsies finally confirmed the coexistence of diffuse large B-cell lymphoma. Despite the initiation of combination chemotherapy, the patient died of progressive respiratory failure. Conclusions Synchronous pulmonary lymphoma and simultaneous opportunistic infection is rare and usually lacks specific clinical and imaging manifestations. Lymphoma should be considered as part of the differential diagnosis of patients with an opportunistic infection when treatment fails or other symptoms are present that could be considered “atypical” for the condition. Tissue biopsy is the gold standard, and multiple biopsies are essential for making the final diagnosis and should be performed upon early suspicion.
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Affiliation(s)
- Lianyou Shao
- Division of Pulmonary Medicine, Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Longxiang Jiang
- Division of Pulmonary Medicine, Integrated Chinese and Western Medicine Hospital of Wenzhou, Wenzhou, Zhejiang, 325000, China
| | - Siyao Wu
- Division of Pulmonary Medicine, Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Lihua Yu
- Division of Pulmonary Medicine, Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Liangxing Wang
- Division of Pulmonary Medicine, Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
| | - Xiaoying Huang
- Division of Pulmonary Medicine, Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
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19
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George B, Menon H, Bhurani D, Damodar S, Apte S, Seth T, Sharma A, Shyam R, Malhotra P, Easow J, Lakshmi KM, Agrawal N, Sengar M, Nataraj KS, Ahmed R, Sharma S, Khadwal A, Prakash G, Abraham A, Devasia A, Korula A, Mathews V. A Prospective Observational Multi-institutional Study on Invasive Fungal Infections Following Chemotherapy for Acute Myeloid Leukemia (MISFIC Study): A Real World Scenario from India. Indian J Hematol Blood Transfus 2020; 36:97-103. [PMID: 32158091 PMCID: PMC7042421 DOI: 10.1007/s12288-019-01173-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 08/13/2019] [Indexed: 12/11/2022] Open
Abstract
We performed a prospective multi-centre observational study to understand the incidence of IFI in patients with AML in India with use of anti-fungal prophylaxis. All patients with AML receiving either induction chemotherapy or salvage chemotherapy between November 2014 and February 2016 were included in this prospective observational study from 10 Indian centres. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy used, type of anti-fungal prophylaxis used, time to neutrophil recovery, incidence of IFI and survival were collected. Two hundred patients (118 male and 82 females) with a median age of 35 years (range: 2-66) were recruited. One hundred and eighty-six (93%) had newly diagnosed acute myeloid leukemia (AML) while 14 (7%) had relapsed disease. IFI occurred in 53 patients (26.5%) with proven or probable IFI occurring in 17 (8.5%). Use of posaconazole prophylaxis (p = 0.027) was the only factor found to be associated with a reduced incidence of IFI. The overall survival (OS) at 6 weeks and 3 months respectively was similar among patients who had IFI (83.0 ± 5.2%; 81.0 ± 5.4%) as compared to those without IFI (84.4 + 3.0%; 81.4 ± 3.2%). This prospective study reveals a high incidence of IFI in patients undergoing chemotherapy for AML in India. The use of posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal strategies to prevent IFI need to be studied.
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Affiliation(s)
| | | | | | | | | | - Tulika Seth
- All India Institute of Medical Sciences, New Delhi, India
| | | | | | - Pankaj Malhotra
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Jose Easow
- Apollo Specialty Hospital, Chennai, India
| | | | | | | | | | - Rayaz Ahmed
- Rajiv Gandhi Cancer Institute, New Delhi, India
| | | | - Alka Khadwal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Gaurav Prakash
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | | | - Anu Korula
- Christian Medical College, Vellore, India
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20
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Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment. Mediterr J Hematol Infect Dis 2020; 12:e2020009. [PMID: 31934319 PMCID: PMC6951355 DOI: 10.4084/mjhid.2020.009] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 12/17/2019] [Indexed: 12/11/2022] Open
Abstract
Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial, and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and even carbapenemase-producing Enterobacteriaceae (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. In this review, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.
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21
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Chien SH, Liu YC, Liu CJ, Ko PS, Wang HY, Hsiao LT, Chiou TJ, Liu JH, Gau JP. Invasive mold infections in acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2019; 52:973-982. [DOI: 10.1016/j.jmii.2018.09.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Revised: 09/14/2018] [Accepted: 09/18/2018] [Indexed: 10/28/2022]
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22
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Tavakoli M, Yazdani Charati J, Hedayati MT, Moosazadeh M, Badiee P, Seyedmousavi S, Denning DW. National trends in incidence, prevalence and disability-adjusted life years of invasive aspergillosis in Iran: a systematic review and meta-analysis. Expert Rev Respir Med 2019; 13:1121-1134. [PMID: 31426666 DOI: 10.1080/17476348.2019.1657835] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Objectives: We aimed to study the epidemiology, prevalence, incidence, clinical manifestations, underlying diseases, treatments, outcomes, and societal impact through disability-adjusted life years (DALYs) of IA in Iran. Methods: A random-effect meta-analytic model was fitted to estimate the prevalence and incidence of IA in Iran. We also calculated DALYs. Results: Out of 79 published studies during the past 25 years from Iran, 23 met the inclusion criteria. A total of 2947 patients were included, of whom 396 (13.4%) patients were diagnosed with IA according to EORTC/MSG and ICU criteria. The main underlying condition for IA was hematologic disorders (39.4%). A. flavus 86 (43%) was the most common isolate. The pooled prevalence and incidence rates were 20.5 (95% CI 12.5 to 29.9) and 4.8 (95% CI 2.3-8.2) per 100,000 population, respectively. Total DALYs was estimated 164.13 per 100,000 population. YLLs constitute the majority of IA burden compared to YLDs (162.80 YLLs/100,000 population vs 1.33 YLDs per 100,000 population). The highest YLL rates were found in people aged 45-49 (62.9 YLLs/100,000 population) and 30-34 years (45.2 YLLs/100,000 population), respectively. Conclusion: This study indicates an increasing burden of IA in Iran, despite the extensive use of prophylaxis, challenging the public health, especially immunocompromised patients.
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Affiliation(s)
- Mahin Tavakoli
- Invasive Fungi Research Center, Mazandaran University of Medical Sciences , Sari , Iran
| | - Jamshid Yazdani Charati
- Department of statistic, Faculty of Health, Mazandaran University of Medical Sciences , Sari , Iran
| | - Mohammad T Hedayati
- Invasive Fungi Research Center, Mazandaran University of Medical Sciences , Sari , Iran.,Department of Medical mycology, Mazandaran University of Medical Sciences , Sari , Iran
| | - Mahmood Moosazadeh
- Health Sciences Research center, Addiction Institute, Mazandaran University of Medical Sciences , Sari , Iran
| | - Parisa Badiee
- Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences , Shiraz , Iran
| | - Seyedmojtaba Seyedmousavi
- Invasive Fungi Research Center, Mazandaran University of Medical Sciences , Sari , Iran.,Microbiology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health , Bethesda , MD , USA
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23
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Meena JP, Gupta AK, Jana M, Seth R. Combination antifungals as an effective means of salvage in paediatric leukaemia patients with invasive fungal infections. Indian J Med Microbiol 2019; 37:109-112. [PMID: 31424020 DOI: 10.4103/ijmm.ijmm_18_157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in paediatric leukaemias. Antifungal combinations to treat these patients are being explored. Fourteen children with leukaemias and IFIs were treated with a combination of antifungal agents at our centre. The first antifungal was amphotericin-B in 13 children and voriconazole in one child. In view of no improvement and clinical deterioration, in nine patients, voriconazole was added as the second antifungal agent and in four, it was caspofungin. All patients completed 4-6 weeks of antifungal therapy. The overall mortality attributable to IFI for the cohort was 4/14 (28%).
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Affiliation(s)
- Jagdish Prasad Meena
- Department of Pediatrics, Division of Pediatric Oncology, All Institute of Medical Sciences, New Delhi, India
| | - Aditya Kumar Gupta
- Department of Pediatrics, Division of Pediatric Oncology, All Institute of Medical Sciences, New Delhi, India
| | - Manisha Jana
- Department of Radiology, All Institute of Medical Sciences, New Delhi, India
| | - Rachna Seth
- Department of Pediatrics, Division of Pediatric Oncology, All Institute of Medical Sciences, New Delhi, India
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24
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Das CK, Gogia A, Kumar L, Sharma A, Thulkar S, Xess I, Madan K. Evaluation of Pulmonary Infiltrate in Febrile Neutropenic Patients of Hematologic Malignancies. Indian J Med Paediatr Oncol 2019. [DOI: 10.4103/ijmpo.ijmpo_39_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Abstract
Background: Pulmonary infection is the major risk during neutropenia induced by chemotherapy as well as stem cell transplantation. In spite of potent new-generation antifungal and broad-spectrum antibiotics, one-third of patients usually die from infectious complications. Early diagnosis and prompt administration of appropriate therapy improve the survival. Materials and Methods: We prospectively carried out the study to identify the infectious etiology of pulmonary infiltrates in febrile neutropenia patients by imaging and bronchoscopy. Bacterial culture, fungal culture, galactomannan and molecular diagnosis for pneumocystis, and other infectious agent were carried out in the bronchoalveolar lavage (BAL) fluid and blood. Results: A total of 27 patients were evaluated. Half of the patients belonged to acute leukemia (46%). We had a diagnostic yield of 65% with the most common isolates being Gram-negative bacteria and Aspergillus species. Conclusion: Gram-negative organisms were the predominant infectious agents of pulmonary infection. Our finding emphasizes the importance of BAL in evaluating pulmonary infiltrates in neutropenic patients with hematological malignancies.
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Affiliation(s)
- Chandan K Das
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Ajay Gogia
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Lalit Kumar
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Atul Sharma
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjay Thulkar
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Immaculata Xess
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
| | - Karan Madan
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
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Paige E, Haywood P, Xie M, Worth L, Thursky K, Urbancic K, Bajel A, Slavin M. Auditing fungal disease in leukemia patients in a tertiary care center: opportunities and challenges for an antifungal stewardship program. Leuk Lymphoma 2019; 60:2373-2383. [PMID: 31096813 DOI: 10.1080/10428194.2019.1590570] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Invasive fungal disease (IFD) is responsible for significant morbidity and mortality in patients with acute leukemia. Antifungal stewardship (AFS) programs are utilized in this patient group but have been infrequently evaluated in clinical practice. Adults diagnosed with acute leukemia at an Australian tertiary center over two years were identified, with subsequent auditing of IFD prophylaxis and treatment, and identification of further opportunities for AFS activities. Proven or probable IFD occurred in 6% of cases, including 14% of acute lymphoblastic leukemia (ALL) patients and 6% of acute myeloid leukemia (AML) patients. Mold-active antifungal prophylaxis was used in 84% of cases overall, including in 94% of AML cases and 23% of ALL cases. Local auditing identified target areas for AFS in this complex patient cohort, including modification of clinical guidelines, enhanced patient screening, improved access to fungal diagnostics and therapeutic drug monitoring, and the establishment of a specialized, embedded AFS program.
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Affiliation(s)
- Emma Paige
- Department of Infectious Diseases, Peter MacCallum Cancer Centre , Melbourne , Australia.,Department of Infectious Diseases, Alfred Hospital , Melbourne , Australia
| | - Peter Haywood
- Department of Haematology, Royal Melbourne Hospital , Parkville , Australia
| | - Mingdi Xie
- Department of Haematology, Royal Melbourne Hospital , Parkville , Australia
| | - Leon Worth
- Department of Infectious Diseases, Peter MacCallum Cancer Centre , Melbourne , Australia.,NHMRC National Centre for Infections in Cancer, Peter MacCallum Cancer Centre , Melbourne , Australia.,NHMRC National Centre for Antimicrobial Stewardship, Peter Doherty Institute , Melbourne , Australia
| | - Karin Thursky
- Department of Infectious Diseases, Peter MacCallum Cancer Centre , Melbourne , Australia.,NHMRC National Centre for Infections in Cancer, Peter MacCallum Cancer Centre , Melbourne , Australia.,NHMRC National Centre for Antimicrobial Stewardship, Peter Doherty Institute , Melbourne , Australia
| | - Karen Urbancic
- NHMRC National Centre for Infections in Cancer, Peter MacCallum Cancer Centre , Melbourne , Australia.,NHMRC National Centre for Antimicrobial Stewardship, Peter Doherty Institute , Melbourne , Australia.,Department of Medicine, University of Melbourne , Parkville , Australia
| | - Ashish Bajel
- Department of Haematology, Royal Melbourne Hospital , Parkville , Australia
| | - Monica Slavin
- Department of Infectious Diseases, Peter MacCallum Cancer Centre , Melbourne , Australia.,NHMRC National Centre for Infections in Cancer, Peter MacCallum Cancer Centre , Melbourne , Australia
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Qiu KY, Liao XY, Fang JP, Xu HG, Li Y, Huang K, Zhou DH. Combination antifungal treatment for invasive fungal disease after hematopoietic stem cell transplantation in children with hematological disorders. Transpl Infect Dis 2019; 21:e13066. [PMID: 30859662 DOI: 10.1111/tid.13066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 02/22/2019] [Accepted: 03/04/2019] [Indexed: 11/28/2022]
Abstract
BACKGROUND Invasive fungal disease (IFD) has a poor prognosis in children with hematological disorders after hematopoietic stem cell transplantation (HSCT). We assessed if drug combinations with different targets may improve the outcome. METHODS Retrospective study to assess the outcome of combination antifungal therapy (CAT) for proven-probable IFD (PP-IFD) in children with hematological disorders after HSCT from January 2008 to June 2018. RESULTS Over the 10-year period, 95 PP-IFD were diagnosed in pediatric recipients, median age of 5.6 years. Twenty-seven patients received combinations of caspofungin and voriconazole, 28 patients received combinations of caspofungin and amphotericin B, and 40 patients received combinations of voriconazole and amphotericin B. The overall response rate of PP-IFD was 77.9%, while the 100-day overall survival rates were 66.8%. Univariate analysis showed that factors that significantly affected the response to combination treatments were type of combination (P = 0.02), the stem cell source (P = 0.04), the donor type (P = 0.03), HLA-match (P = 0.03), aGVHD (P = 0.02), period of treatment (P = 0.044), use of corticosteroids (0.036), CD4:CD8 ratio (P = 0.014), and CMV viremia (P = 0.033). In addition, multivariate analysis demonstrated that only the type of combination remained a significant factor (odds ratio = 0.335, 95% confidence interval: 0.071-0.812, P = 0.042). Forty-three children suffered from mild and reversible adverse reactions, no serious side effects during treatment. CONCLUSION A variety of factors can affect the outcome of CAT. Combination of caspofungin with voriconazole is a safe and helpful treatment option for HSCT recipients with IFD.
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Affiliation(s)
- Kun-Yin Qiu
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xiong-Yu Liao
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jian-Pei Fang
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Hong-Gui Xu
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yang Li
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ke Huang
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Dun-Hua Zhou
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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27
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Vaughan C, Bartolo A, Vallabh N, Leong SC. A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has anything changed in the past 20 years? Clin Otolaryngol 2018; 43:1454-1464. [PMID: 29947167 DOI: 10.1111/coa.13175] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 06/22/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon yet potentially lethal fungal infection. Although most cases originate from developing countries, an ageing population and increased prevalence of chronic illness may mean some clinicians practicing in developed countries will encounter ROCM cases in their careers. Yohai et al published a systematic review of 145 case reports from 1970 to 1993 assessing prognostic factors for patients presenting with ROCM. We present an updated review of the literature and assess whether survival outcomes have changed in the two decades since that seminal paper. SEARCH STRATEGY An extensive Medline literature search was performed for case reports published between 1994 and 2015. RESULTS In total, 210 published cases were identified from the literature review, of which 175 patients from 140 papers were included in this review. Fifty-five were female, with an overall mean age of 43 years. Overall survival rate was 59.5%, which was not significantly better than the previous series reported (60%) reported by Yohai et al. Survival rates in patients with chronic renal disease had improved, from 19% to 52%, and in patients with leukaemia (from 13% to 50%). Facial necrosis and hemiplegia remained poor prognostic indicators (33% and 39% survival rates, respectively). Early commencement of medical treatment related to better survival outcomes (61% if commenced within first 12 days of presentation, compared to 33% if after 13 days). Timing of surgery had less of an effect on overall survival. However, in 28 cases that did not receive any surgical treatment, survival was only 21%. CONCLUSIONS Although overall survival rates have not improved, survival in patients with renal disease were better, potentially due to the introduction of liposomal amphotericin B which is less nephrotoxic. Prompt recognition of ROCM, reversal of predisposing co-morbidities and aggressive medical treatment remain the cornerstone of managing this highly aggressive disease.
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Affiliation(s)
- Casey Vaughan
- Department of Otorhinolaryngology - Head and Neck Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - Amanda Bartolo
- Department of Otorhinolaryngology - Head and Neck Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - Nimisha Vallabh
- Department of Otorhinolaryngology - Head and Neck Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - Samuel C Leong
- Department of Otorhinolaryngology - Head and Neck Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
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28
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Deng Q, Lv HR, Lin XM, Zhao MF, Geng L, Li YM. Empirical antifungal treatment for diagnosed and undiagnosed invasive fungal disease in patients with hematologic malignancies. Curr Med Res Opin 2018; 34:1209-1216. [PMID: 28956459 DOI: 10.1080/03007995.2017.1386167] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND Empirical antifungal therapy is effective in some patients with risk factors for invasive fungal disease (IFD) who do not qualify for the EORTC/MSG criteria for IFD, but who fail to respond to anti-bacterial and anti-viral therapy. OBJECTIVE This retrospective single-center study investigated the epidemiology of IFD and empirical antifungal therapy in patients with hematological malignancies. METHODS This study recruited 893 patients with hematologic malignancies who had failed to respond to anti-bacterial and anti-viral treatment and received antifungal therapy, but not for antifungal prophylaxis. Antifungal therapy regimens included amphotericin B, voriconazole, itraconazole and caspofungin. A total of 689 patients were diagnosed with proven, probable, or possible IFD, while 159 patients did not meet the EORTC/MSG criteria for IFD diagnosis but recovered with antifungal treatment, and 45 were excluded from having IFD. Effective treatment was defined as the disappearance or resolution of clinical symptoms of IFD. RESULTS Patients diagnosed with IFD underwent chemotherapy at a higher proportion, and had significantly higher neutrophil counts compared to those who did not qualify for the EORTC/MSG criteria for IFD but responded to antifungals. The mortality due to all causes within 3 months was significantly higher for patients diagnosed with proven IFD, compared with those who did not qualify for the EORTC/MSG criteria for IFD. There was no discontinuation reported due to adverse events of caspofungin. CONCLUSION Empirical antifungal treatment could help save the lives of some patients with severe infections who are strongly suspected of having IFD.
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Affiliation(s)
- Qi Deng
- a Department of Hematology , The First Central Hospital of Tianjin , Tianjin , China
| | - Hai-Rong Lv
- a Department of Hematology , The First Central Hospital of Tianjin , Tianjin , China
| | - Xue-Mei Lin
- a Department of Hematology , The First Central Hospital of Tianjin , Tianjin , China
| | - Ming-Feng Zhao
- a Department of Hematology , The First Central Hospital of Tianjin , Tianjin , China
| | - Li Geng
- a Department of Hematology , The First Central Hospital of Tianjin , Tianjin , China
| | - Yu-Ming Li
- a Department of Hematology , The First Central Hospital of Tianjin , Tianjin , China
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29
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Gomez SM, Caniza M, Fynn A, Vescina C, Ruiz CD, Iglesias D, Sosa F, Sung L. Fungal infections in hematopoietic stem cell transplantation in children at a pediatric children's hospital in Argentina. Transpl Infect Dis 2018; 20:e12913. [PMID: 29679436 DOI: 10.1111/tid.12913] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 12/24/2017] [Accepted: 01/07/2018] [Indexed: 12/12/2022]
Abstract
Our primary objective was to describe the incidence of proven or probable invasive fungal infections (IFIs), a devastating complication of hematopoietic stem cell transplant (HSCT), in HCST in a middle-income country. Secondary objectives were to describe factors associated with IFIs and outcomes. In this single center retrospective study, pediatric patients who underwent a first allogeneic or autologous HSCT from 1998 to 2016 were included. Of the 251 HSCT recipients: 143 transplants were allogeneic and 108 were autologous. Overall, 23 (9%) experienced an IFI, mostly due to yeasts (83%). IFIs were more common in allogeneic HSCT (18/143, 13%) than in autologous HSCT (5/108, 5%; P = .045). Of the 23 patients with IFIs, 14 (61%) died, but only 1 directly from IFI (pulmonary aspergillosis). Overall survival at 3 years was 0.42 ± 0.11 in patients with IFIs and 0.60 ± 0.37 in those without IFIs (P = .049). In Argentina, IFIs during HSCT are common. Recipients of allogeneic HSCT are at higher risk, and IFI is associated with reduced overall survival. Future work should focus on interventions to reduce and improve IFI outcomes in children undergoing transplants in low- and middle-income countries.
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Affiliation(s)
- Sergio M Gomez
- Stem Cell Transplantation Unit, Hospital de Niños Sor María Ludovica, La Plata, Argentina
| | - Miguela Caniza
- Global Pediatric Medicine, Infectious Diseases. St. Jude Children's Cancer Research Hospital, Memphis, TN, USA
| | - Alicira Fynn
- Stem Cell Transplantation Unit, Hospital de Niños Sor María Ludovica, La Plata, Argentina
| | - Cecilia Vescina
- Stem Cell Transplantation Unit, Hospital de Niños Sor María Ludovica, La Plata, Argentina
| | - Clau-Dia Ruiz
- Stem Cell Transplantation Unit, Hospital de Niños Sor María Ludovica, La Plata, Argentina
| | - Daniela Iglesias
- Stem Cell Transplantation Unit, Hospital de Niños Sor María Ludovica, La Plata, Argentina
| | - Fernanda Sosa
- Stem Cell Transplantation Unit, Hospital de Niños Sor María Ludovica, La Plata, Argentina
| | - Lillian Sung
- Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada
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30
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Infectious Risks and Complications in Adult Leukemic Patients Receiving Blinatumomab. Mediterr J Hematol Infect Dis 2018; 10:e2018029. [PMID: 29755706 PMCID: PMC5937972 DOI: 10.4084/mjhid.2018.029] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Accepted: 03/23/2018] [Indexed: 11/08/2022] Open
Abstract
Background Blinatumomab is an anti-CD19 immunotherapy approved for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) with significantly increased survival rate. While blinatumomab showed lower rates of infection, neutropenia and mucosal barrier injury versus chemotherapy, its infection risks are not well described. Methods All patients who received blinatumomab for ≥ seven days at an academic cancer center from May 2015 to April 2017 were included. Patient characteristics pertinent to infectious risks and complications were examined. Results Twenty patients with refractory (25%), relapsed (70%), or remitted (5%) B-ALL who received a total of 35 cycles were included. Ten of the 35 cycles were interrupted, none of which were due to infections. Twenty-six infections (n) were observed with lower respiratory (9), gastrointestinal (6) and bacteremia (5) being most common. Compared to patients without nodular, possible mold pneumonia (n=16), patients with nodular pneumonia (n=4) had significantly lower baseline absolute neutrophil count (ANC) (2319 v. 208/μL, p=0.011). There were no differences in baseline characteristics including ANC between bacteremic and non-bacteremic patients. One patient was discharged with no antibacterial prophylaxis since ANC recovered to >500cells/μL, but developed Pseudomonal bacteremia within a week with ANC ~100cells/μL. Conclusion Despite blinatumomab's relatively modest myelosuppression and the lack of mucotoxicity, host factors (e.g., duration and degree of neutropenia/lymphopenia) play a key role and should be considered when choosing anti-microbial prophylaxis. In relapsed/refractory disease, the ANC should be monitored closely post blinatumomab since neutropenia can unexpectedly develop after treatment which may be compounded by the underlying disease and recent chemotherapy effects.
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31
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Fites JS, Gui M, Kernien JF, Negoro P, Dagher Z, Sykes DB, Nett JE, Mansour MK, Klein BS. An unappreciated role for neutrophil-DC hybrids in immunity to invasive fungal infections. PLoS Pathog 2018; 14:e1007073. [PMID: 29782541 PMCID: PMC5983859 DOI: 10.1371/journal.ppat.1007073] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 06/01/2018] [Accepted: 05/03/2018] [Indexed: 12/15/2022] Open
Abstract
Neutrophils are classically defined as terminally differentiated, short-lived cells; however, neutrophils can be long-lived with phenotypic plasticity. During inflammation, a subset of neutrophils transdifferentiate into a population called neutrophil-DC hybrids (PMN-DCs) having properties of both neutrophils and dendritic cells. While these cells ubiquitously appear during inflammation, the role of PMN-DCs in disease remains poorly understood. We observed the differentiation of PMN-DCs in pre-clinical murine models of fungal infection: blastomycosis, aspergillosis and candidiasis. Using reporter strains of fungal viability, we found that PMN-DCs associate with fungal cells and kill them more efficiently than undifferentiated canonical neutrophils. During pulmonary blastomycosis, PMN-DCs comprised less than 1% of leukocytes yet contributed up to 15% of the fungal killing. PMN-DCs displayed higher expression of pattern recognition receptors, greater phagocytosis, and heightened production of reactive oxygen species compared to canonical neutrophils. PMN-DCs also displayed prominent NETosis. To further study PMN-DC function, we exploited a granulocyte/macrophage progenitor (GMP) cell line, generated PMN-DCs to over 90% purity, and used them for adoptive transfer and antigen presentation studies. Adoptively transferred PMN-DCs from the GMP line enhanced protection against systemic infection in vivo. PMN-DCs pulsed with antigen activated fungal calnexin-specific transgenic T cells in vitro and in vivo, promoting the production of interferon-γ and interleukin-17 in these CD4+ T cells. Through direct fungal killing and induction of adaptive immunity, PMN-DCs are potent effectors of antifungal immunity and thereby represent innovative cell therapeutic targets in treating life-threatening fungal infections.
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Affiliation(s)
- J. Scott Fites
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
| | - Michael Gui
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
| | - John F. Kernien
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
| | - Paige Negoro
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Zeina Dagher
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - David B. Sykes
- Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Jeniel E. Nett
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
| | - Michael K. Mansour
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Bruce S. Klein
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
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32
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Agha Kuchak Afshari S, Rahimi H, Hashemi SJ, Daie Ghazvini R, Badali H, Aghaei Gharehbolagh S, Rezaie S. Evaluation of PCR-reverse line blot hybridization assay for simultaneous identification of medically important saprophytic fungi. J Mycol Med 2017; 28:173-179. [PMID: 29100947 DOI: 10.1016/j.mycmed.2017.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Revised: 09/05/2017] [Accepted: 09/11/2017] [Indexed: 11/29/2022]
Abstract
BACKGROUND In immunocompromised patients suffering from invasive fungal infections, rapid identification of fungal species is important since the appropriate treatment is usually related to the responsible species. We describe here, an assay based on combination of PCR and reverse line blot hybridization (PCR/RLB) for differentiation causative agent of fungal infections. MATERIALS AND METHODS We performed PCR/RLB assay on 10 reference strains, which include Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, and A. clavatus), Mucor circnelloides, Rhizopus oryzae, Alternaria alternata, Cladosporium herbarum, and Fusarium solani. Besides, twenty-two clinical specimens from patients with proven fungal infections were analyzed for the identification of species. The obtained results were then compared with the results of culture and sequence analysis. RESULTS The fungal species-specific oligonucleotide probes were able to distinguish between all species represented in this study with the exception of cross-reactivity between A. niger and A. fumigatus species. Two specimens, which were represented as mixed fungi in culture, were identified properly by this method. Results of the RLB assay were concordant with the culture and ITS sequencing results. CONCLUSION Our result demonstrate that the RLB assay potentially is suitable for rapid and simultaneous identification of variety fungal pathogens directly from culture as well as from clinical specimens.
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Affiliation(s)
- S Agha Kuchak Afshari
- Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - H Rahimi
- Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - S J Hashemi
- Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - R Daie Ghazvini
- Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - H Badali
- Department of Medical Mycology and Parasitology, Antimicrobial Resistance Research Center (ARRC), Mazandaran University of Medical Science, Sari, Iran
| | - S Aghaei Gharehbolagh
- Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - S Rezaie
- Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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33
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Korula A, Abraham A, Abubacker FN, Viswabandya A, Lakshmi KM, Abraham OC, Rupali P, Varghese GM, Michael JS, Srivastava A, Mathews V, George B. Invasive fungal infection following chemotherapy for acute myeloid leukaemia-Experience from a developing country. Mycoses 2017; 60:686-691. [PMID: 28736936 DOI: 10.1111/myc.12646] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 05/19/2017] [Accepted: 05/24/2017] [Indexed: 12/28/2022]
Abstract
The incidence of invasive fungal infections (IFI) is believed to be higher in patients with acute myeloid leukaemia (AML) undergoing chemotherapy in non-HEPA-filtered rooms. The aim of this study is to review the incidence of IFI in a large cohort of patients with AML treated at a single centre in India. Two hundred and twenty-two patients with AML treated with either induction chemotherapy or salvage chemotherapy between 2008 and 2013 were studied retrospectively. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy, prophylactic strategies, engraftment (ANC>500), the presence of IFI and survival were collected. IFI was diagnosed in 86 patients (38.7%) with proven IFI in 12 (5.4%). Use of posaconazole prophylaxis (P=.001) was the only factor associated with reduced incidence of IFI. Survival in patients with proven IFI was lower than those without proven IFI, but not statistically significant (59.4% vs 78.5%; P=.139). There is a high incidence of IFI during induction chemotherapy for acute myeloid leukaemia in developing countries. Posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal yet cost-effective strategies for prevention and early diagnosis of IFI are required to improve survival in patients undergoing chemotherapy for AML.
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Affiliation(s)
- Anu Korula
- Department of Haematology, Christian Medical College, Vellore, India
| | - Aby Abraham
- Department of Haematology, Christian Medical College, Vellore, India
| | | | - Auro Viswabandya
- Department of Haematology, Christian Medical College, Vellore, India
| | - Kavitha M Lakshmi
- Department of Haematology, Christian Medical College, Vellore, India
| | - O C Abraham
- Department of Infectious Diseases, Christian Medical College, Vellore, India
| | - Priscilla Rupali
- Department of Infectious Diseases, Christian Medical College, Vellore, India
| | - George M Varghese
- Department of Infectious Diseases, Christian Medical College, Vellore, India
| | - Joy S Michael
- Department of Microbiology and Mycology, Christian Medical College, Vellore, India
| | - Alok Srivastava
- Department of Haematology, Christian Medical College, Vellore, India
| | - Vikram Mathews
- Department of Haematology, Christian Medical College, Vellore, India
| | - Biju George
- Department of Haematology, Christian Medical College, Vellore, India
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Young AY, Leiva Juarez MM, Evans SE. Fungal Pneumonia in Patients with Hematologic Malignancy and Hematopoietic Stem Cell Transplantation. Clin Chest Med 2017; 38:479-491. [PMID: 28797490 DOI: 10.1016/j.ccm.2017.04.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Fungal pneumonias cause unacceptable morbidity among patients with hematologic malignancies (HM) and recipients of hematopoietic stem cell transplantation (HSCT). The high incidence of fungal pneumonias in HM/HSCT populations arises from their frequently severe, complex, and persistent immune dysfunction caused by the underlying disease and its treatment. The cytopenias, treatment toxicities, and other immune derangements that make patients susceptible to fungal pneumonia frequently complicate its diagnosis and increase the intensity and duration of antifungal therapy. This article addresses the host factors that contribute to susceptibility, summarizes diagnostic recommendations, and reviews current guidelines for management of fungal pneumonia in patients with HM/HSCT.
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Affiliation(s)
- Alisha Y Young
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The University of Texas Health Sciences Center, 6431 Fannin Street, MSB 1.434, Houston, TX 77030, USA
| | - Miguel M Leiva Juarez
- Division of Internal Medicine, Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1100, Houston, TX 77030, USA
| | - Scott E Evans
- Division of Internal Medicine, Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1100, Houston, TX 77030, USA.
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van de Peppel RJ, von dem Borne PA, le Cessie S, de Boer MGJ. A new time-dependent approach for assessment of the impact of invasive aspergillosis shows effect on short- but not on long-term survival of patients with AML or high-risk MDS. Bone Marrow Transplant 2017; 52:883-888. [PMID: 28504663 DOI: 10.1038/bmt.2017.71] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 02/21/2017] [Accepted: 03/03/2017] [Indexed: 12/13/2022]
Abstract
Invasive aspergillosis (IA) has been reported to yield high mortality rates. Patients with an unfavourable prognostic haematological disease not only have a higher probability of developing IA but are also more likely to die due to causes directly related to the underlying disease. This complexity of risk mechanisms confounds the causal interpretation of IA occurrence and mortality. Full consideration of the changing patient characteristics over time is necessary to obtain reliable estimates of the correlation of IA with mortality. We studied the effect of IA on mortality in 167 consecutive patients starting with remission-induction therapy for AML or of whom most patients continued to haematopoietic stem cell transplantation (HSCT). No standard antifungal prophylaxis was administered in the period before HSCT. Survival analyses were performed to determine risk estimates of IA for different phases of treatment before and after HSCT. Time-dependent adjustment for confounding variables was performed using Cox proportional hazards models. In 55 of 167 enroled patients, IA was diagnosed. Before HSCT, adjusted hazard ratios and 95% confidence intervals on mortality after the diagnosis of IA were 3.5 (1.7-7.5), 2.0 (0.69-5.9), 2.3 (0.79-6.8) and 0.80 (0.49-1.4) within 30 days, between 30 and 60 days, between 60 and 90 days or more than 90 days, respectively. A similar pattern was observed after HSCT. The occurrence of IA did not significantly influence the decision to follow through with HSCT. The results provide new insights in short- and long-term survival of patients diagnosed with IA. A significantly increased mortality risk was only observed in the first month after diagnosis of IA. No unfavourable association with mortality was observed in the later course of treatment. The occurrence of IA did not affect the probability of attaining HSCT in our population.
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Affiliation(s)
- R J van de Peppel
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - P A von dem Borne
- Department of Haematology, Leiden University Medical Center, Leiden, The Netherlands
| | - S le Cessie
- Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
| | - M G J de Boer
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
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Fischer M, Müller JP, Spies-Weisshart B, Gräfe C, Kurzai O, Hünniger K, Hochhaus A, Scholl S, Schnetzke U. Isoform localization of Dectin-1 regulates the signaling quality of anti-fungal immunity. Eur J Immunol 2017; 47:848-859. [PMID: 28303575 DOI: 10.1002/eji.201646849] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 02/08/2017] [Accepted: 03/14/2017] [Indexed: 01/06/2023]
Abstract
Dectin-1 is recognized as a major receptor for fungal ß-glucans and contributes to anti-fungal immunity. Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site. Here, we analyzed the expression of both isoforms in human monocyte-derived cells. The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy. Intracellular protein signaling and cytokine production were analyzed by immunoblotting and cytometric bead array, respectively. Monocyte-derived cells showed cell type-specific expression of the two isoforms. Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly. Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells. Differential isoform specific cytokine secretion was observed by cytometric bead array. We show here that n-glycosylation of Dectin-1 is crucial for its cell surface expression and consequently signal transduction. Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
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Affiliation(s)
- Mike Fischer
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany
| | - Jörg P Müller
- Institut für Molekulare Zellbiologie, CMB, Universitätsklinikum Jena, Jena, Germany
| | - Bärbel Spies-Weisshart
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany
| | - Christine Gräfe
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany
| | - Oliver Kurzai
- Septomics Research Center, Friedrich Schiller University Jena, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knoell-Institute, Jena, Germany
| | - Kerstin Hünniger
- Septomics Research Center, Friedrich Schiller University Jena, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knoell-Institute, Jena, Germany
| | - Andreas Hochhaus
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany
| | - Sebastian Scholl
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany
| | - Ulf Schnetzke
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany
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de León-Borrás R, DelPilar-Morales E, Rivera-Pérez N, Pallens-Feliciano M, Tirado-Gómez M, González-Sepúlveda L, Bertrán-Pasarell J. Factors Associated to Invasive Fungal Infection in Hispanic Patients with Hematological Malignancies. BOLETIN DE LA ASOCIACION MEDICA DE PUERTO RICO 2017; 109:43-48. [PMID: 29861498 PMCID: PMC5980240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Fungal infections represent a serious complication for immunosuppressed patients resulting in an increased morbidity and mortality. A non-concurrent prospective study was performed to evaluate the factors associated to invasive fungal infection (IFI) in patients with hematological malignancies admitted to the University Hospital in San Juan, Puerto Rico from January 1st, 2011 through June 15th, 2014. The medical records of 84 patients were evaluated. Fifty-nine patients with IFI and twenty-five without IFI. The majority were men between 35 to 55 years old. The main hematological diagnosis was acute myelogenous leukemia (AML) followed by acute lymphoblastic leukemia (ALL). Seventy-percent developed IFI. The most common fungi were C. albicans followed by non-albicans species, Fusarium and, Aspergillus species, respectively. About 63% of the patients with AML and 81% without AML had IFI. Those who received steroids were more likely to develop IFI. After adjusting for AML and age, the odds of IFI among patients using steroids were 3.33 higher than those not using steroids. Patients who were exposed to different antifungal medication had 72% lower odds to develop IFI.
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Affiliation(s)
- Rafael de León-Borrás
- Division of Infectious Diseases, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
| | - Esteban DelPilar-Morales
- Division of Infectious Diseases, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
| | - Nicole Rivera-Pérez
- Division of Infectious Diseases, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
| | - Mara Pallens-Feliciano
- Division of Infectious Diseases, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
| | - Maribel Tirado-Gómez
- Division of Hematology Oncology, Department of Medicine, University of Puerto Rico School of Medicine, San Juan Puerto Rico
| | | | - Jorge Bertrán-Pasarell
- Division of Infectious Diseases, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
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SOYER N, KİPER ÜNAL HD, VURAL F, ŞAHİN F, TÖBÜ M, DÖNMEZ A, TOMBULOĞLU M, ARDA B, SAYDAM G. Epidemiology and analysis of invasive fungal infections in patients withhematological malignancies: a single-center real-life experience. Turk J Med Sci 2017; 47:1535-1542. [DOI: 10.3906/sag-1611-90] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
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Badiee P, Hashemizadeh Z, Ramzi M, Karimi M, Mohammadi R. Non-Invasive Methods to Diagnose Fungal Infections in Pediatric Patients with Hematologic Disorders. Jundishapur J Microbiol 2016; 9:e41573. [PMID: 28138379 PMCID: PMC5240159 DOI: 10.5812/jjm.41573] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Revised: 10/08/2016] [Accepted: 10/09/2016] [Indexed: 12/15/2022] Open
Abstract
Background Invasive fungal infection (IFIs) is a major infectious complication in immunocompromised patients. Early diagnosis and initiation of antifungal therapy is important to achieve the best outcome. Objectives The current study aimed to investigate the incidence of IFIs and evaluate the diagnostic performance of non-invasive laboratory tests: serologic (β-D-glucan, galactomannan) and molecular (nested polymerase chain reaction) tests to diagnose fungal infections in hematologic pediatric patients. Patients and Methods In a cross-sectional study from October 2014 to January 2015, 321 blood samples of 62 pediatric patients with hematologic disorders and at high risk for fungal infections were analyzed. Non-invasive tests including the Platelia Aspergillus enzyme immunoassay (EIA) to detect galactomannan antigen, Glucatell for β–D–glucan and nested PCR to detect Candida and Aspergillus species-specific DNA were used in a weekly screening strategy. Results Twenty six patients (42%) were considered as proven and probable IFIs, including 3 (5%) proven and 23 (37%) probable cases. Eighteen patients (29%) were considered as possible cases. The sensitivity, specificity, positive and negative predictive values for galactomannan test in 26 patients with proven and probable fungal infections were 94.4%, 100%, 100% and 94.7%; for β-D-glucan test 92.3%, 77.7%, 85%, 87.5% and for nested-PCR were 84.6%, 88.8%, 91.7% and 80%, respectively. Conclusions The rate of IFIs in pediatric patients with hematologic disorders is high, and sample collection from the sterile sites cannot be performed in immunocompromised patients. Detection of circulating fungal cell wall components and DNA in the blood using non-invasive methods can offer diagnostic help in patients with suspected IFIs. Their results should be interpreted in combination with clinical, radiological and microbiological findings.
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Affiliation(s)
- Parisa Badiee
- Prof Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Hashemizadeh
- Prof Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Corresponding author: Zahra Hashemizadeh, PhD of Mycology, Prof Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Tel: +98-36474303, Fax: +98-36474304, E-mail:
| | - Mani Ramzi
- Hematology Research Center, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Karimi
- Prof Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Rasoul Mohammadi
- Department of Medical Parasitology and Mycology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Discrimination of Aspergillosis, Mucormycosis, Fusariosis, and Scedosporiosis in Formalin-Fixed Paraffin-Embedded Tissue Specimens by Use of Multiple Real-Time Quantitative PCR Assays. J Clin Microbiol 2016; 54:2798-2803. [PMID: 27605714 DOI: 10.1128/jcm.01185-16] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 09/01/2016] [Indexed: 12/24/2022] Open
Abstract
In a retrospective multicenter study, 102 formalin-fixed paraffin-embedded (FFPE) tissue specimens with histopathology results were tested. Two 4- to 5-μm FFPE tissue sections from each specimen were digested with proteinase K, followed by automated nucleic acid extraction. Multiple real-time quantitative PCR (qPCR) assays targeting the internal transcribed spacer 2 (ITS2) region of ribosomal DNA, using fluorescently labeled primers, was performed to identify clinically important genera and species of Aspergillus, Fusarium, Scedosporium, and the Mucormycetes The molecular identification was correlated with results from histological examination. One of the main findings of our study was the high sensitivity of the automated DNA extraction method, which was estimated to be 94%. The qPCR procedure that was evaluated identified a range of fungal genera/species, including Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus niger, Fusarium oxysporum, Fusarium solani, Scedosporium apiospermum, Rhizopus oryzae, Rhizopus microsporus, Mucor spp., and Syncephalastrum Fusarium oxysporum and F. solani DNA was amplified from five specimens from patients initially diagnosed by histopathology as having aspergillosis. Aspergillus flavus, S. apiospermum, and Syncephalastrum were detected from histopathological mucormycosis samples. In addition, examination of four samples from patients suspected of having concomitant aspergillosis and mucormycosis infections resulted in the identification of two A. flavus isolates, one Mucor isolate, and only one sample having both R. oryzae and A. flavus Our results indicate that histopathological features of molds may be easily confused in tissue sections. The qPCR assay used in this study is a reliable tool for the rapid and accurate identification of fungal pathogens to the genus and species levels directly from FFPE tissues.
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Hites M, Goicoechea Turcott EW, Taccone FS. The role of galactomannan testing to diagnose invasive pulmonary aspergillosis in critically ill patients. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:353. [PMID: 27761457 PMCID: PMC5066040 DOI: 10.21037/atm.2016.08.32] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Accepted: 07/20/2016] [Indexed: 12/15/2022]
Affiliation(s)
- Maya Hites
- Department of Infectious Diseases, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | | | - Fabio Silvio Taccone
- Department of Intensive Care Unit, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium
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Biehl LM, Vehreschild JJ, Liss B, Franke B, Markiefka B, Persigehl T, Bücker V, Wisplinghoff H, Scheid C, Cornely OA, Vehreschild MJGT. A cohort study on breakthrough invasive fungal infections in high-risk patients receiving antifungal prophylaxis. J Antimicrob Chemother 2016; 71:2634-41. [DOI: 10.1093/jac/dkw199] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 04/26/2016] [Indexed: 12/15/2022] Open
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Abstract
Diagnostic tools for invasive fungal infections have continuously improved within the last decades. Nowadays, cultural methods, antigen testing, and molecular tests, such as polymerase chain reaction, are widely used. These methods, however, are accompanied with different limitations as various availability, various turnaround time or high costs. A new generation of point-of-care test has shown promising results in various studies and may overcome some of these limitations. We therefore reviewed the literature for the most promising new point-of-care tests for invasive aspergillosis (Aspergillus-specific lateral-flow device test, Aspergillus proximity ligation antigen assay), cryptococcosis (cryptococcal lateral-flow assay), and for histoplasmosis (loop-mediated isothermal amplification assay).
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44
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Pham AN, Bubalo JS, Lewis JS. Comparison of posaconazole serum concentrations from haematological cancer patients on posaconazole tablet and oral suspension for treatment and prevention of invasive fungal infections. Mycoses 2016; 59:226-233. [PMID: 26742659 DOI: 10.1111/myc.12452] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 12/03/2015] [Accepted: 12/03/2015] [Indexed: 12/18/2022]
Abstract
Posaconazole tablet formulation (PTF) was developed to optimise bioavailability. This study compared posaconazole levels between patients on the PTF and oral suspension formulation (OSF). We also examined factors that may impact posaconazole levels. The primary and secondary objectives were analysed by comparing trough levels and attainment of target level between the formulation groups. For the 86 patients on PTF and 176 on OSF, the mean first levels was 1.32 μg ml-1 (SD = 0.69) and 0.81 μg ml-1 (SD = 0.59), P < 0.0001 respectively. PTF group was more likely to achieve levels ≥0.7 μg ml-1 than OSF group (OR 7.97 [95 CI; 3.75-16.93], P < 0.0001). Levels from patients on PTF and with presence of acid suppression, GI GVHD, mucositis or diarrhoea were not statistically different from those without these factors. For PTF, no correlation was found between patient's weight (kg) and levels (R2 = 0.0536, P = 0.035). The incidences of elevation in ALT/AST or Tbili were similar between the formulation groups. In conclusion, PTF should be considered the preferred formulation because it demonstrated better absorption than the OSF. Patients on PTF for prophylaxis are more likely to attain target level and may not routinely require therapeutic drug monitoring during prophylaxis.
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Affiliation(s)
- Aaron N Pham
- Department of Pharmacy Services, Oregon Health & Science University Hospital and Clinics, Portland, OR, USA
| | - Joseph S Bubalo
- Department of Pharmacy Services, Oregon Health & Science University Hospital and Clinics, Portland, OR, USA
| | - James S Lewis
- Department of Pharmacy Services, Oregon Health & Science University Hospital and Clinics, Portland, OR, USA
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45
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Han SB, Kim SK, Lee JW, Yoon JS, Chung NG, Cho B, Jeong DC, Kang JH, Kim HK, Lee DG, Lee HS, Im SA. Serum galactomannan index for early prediction of mortality in immunocompromised children with invasive pulmonary aspergillosis. BMC Infect Dis 2015; 15:271. [PMID: 26168914 PMCID: PMC4501281 DOI: 10.1186/s12879-015-1014-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 07/06/2015] [Indexed: 11/24/2022] Open
Abstract
Background Invasive pulmonary aspergillosis (IPA) is the most common invasive fungal disease in immunocompromised patients, and it has a 30 % mortality rate despite appropriate antifungal therapy. This retrospective study was performed to determine risk factors for mortality in immunocompromised children with IPA. Methods Medical records of 45 probable/proven IPA cases diagnosed in children with hematologic/oncologic diseases were reviewed. Selected cases were divided into the survival (n = 30) and fatality (n = 15) groups based on survival at 12 weeks after antifungal therapy. Clinical characteristics and serum galactomannan indices (GMIs) were compared between the two groups. Results Significantly more children in the fatality group were male (p = 0.044), not in complete remission of the underlying malignancies (p = 0.016), and had received re-induction/salvage or palliative chemotherapy (p = 0.035) than those in the survival group. However, none of these factors was significantly associated with mortality in a multivariate analysis. Serum GMIs were higher in the fatality group than in the survival group during the entire period of antifungal therapy, and serum GMI at 1 week after antifungal therapy was most significantly associated with mortality. A serum GMI > 1.50 at 1 week after antifungal therapy exhibited a sensitivity and specificity of 61.5 % and 89.3 %, respectively, in predicting mortality within 12 weeks after antifungal therapy. Conclusions Higher serum GMI in the early phase of antifungal therapy was associated with mortality in immunocompromised children with IPA. These children should receive more intensive care for IPA than others.
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Affiliation(s)
- Seung Beom Han
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Seong Koo Kim
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Jae Wook Lee
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Jong-Seo Yoon
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Nack-Gyun Chung
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Bin Cho
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,Department of Pediatrics, Seoul St. Mary's Hospital, 222, Banpo-daero, Seocho-gu, Seoul, 137-701, Republic of Korea.
| | - Dae Chul Jeong
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Jin Han Kang
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Hack-Ki Kim
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Dong-Gun Lee
- The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. .,Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Hyun Sil Lee
- Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Soo Ah Im
- Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Gedik H, Şimşek F, Yıldırmak T, Kantürk A, Arıca D, Aydın D, Demirel N, Yokuş O. Novel antifungal drugs against fungal pathogens: do they provide promising results for treatment? Indian J Hematol Blood Transfus 2015; 31:196-205. [PMID: 25825558 PMCID: PMC4375158 DOI: 10.1007/s12288-014-0370-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Accepted: 03/06/2014] [Indexed: 01/19/2023] Open
Abstract
The febrile neutropenia episodes of hematological patients and their outcomes were evaluated with respect to fungal pathogens and antifungal therapy in this retrospective study. All patients, who were older than 14 years of age and developed at least one neutropenic episode after chemotherapy due to hematological cancer from November 2010 to November 2012, were included into the study. We retrospectively collected demographic, treatment, and survival data of 126 patients with neutropenia and their 282 febrile episodes. The mean Multinational Association for Supportive Care in Cancer score was 17.18 ± 8.27. Systemic antifungal drugs were initiated in 22 patients with 30 culture-proven invasive fungal infections (IFIs), 25 attacks of 19 patients with probable invasive pulmonary aspergillosis (IPA), 42 attacks of 38 patients with possible IPA, and 31 attacks of 30 patients with suspected IFI. Voriconazole (VOR), caspofungin and liposomal amphotericin B were used to treat 72 episodes of 65 patients, 45 episodes of 37 patients and 34 episodes of 32 patients as a first-line therapy, respectively. Unfavorable conditions of our hematology ward are thought to increase the number of cases with invasive pulmonary aspergillosis and VOR use. It should be taken into consideration that increased systemic and per oral VOR usage predisposes patients to colonization and infection with azole-resistant fungal strains. Catheters should be removed in cases where patients' conditions are convenient to remove it. Acute myeloblastic leukemia cases that are more likely to develop invasive fungal infections should be monitored closely for early diagnosis and timely initiation of antifungal drugs which directly correlates with survival rates.
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Affiliation(s)
- Habip Gedik
- />Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Okmeydanı Training and Research Hospital, S. B. Okmeydanı Eğitim ve Araştırma Hastanesi Şişli, Istanbul, Turkey
| | - Funda Şimşek
- />Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Okmeydanı Training and Research Hospital, S. B. Okmeydanı Eğitim ve Araştırma Hastanesi Şişli, Istanbul, Turkey
| | - Taner Yıldırmak
- />Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Okmeydanı Training and Research Hospital, S. B. Okmeydanı Eğitim ve Araştırma Hastanesi Şişli, Istanbul, Turkey
| | - Arzu Kantürk
- />Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Okmeydanı Training and Research Hospital, S. B. Okmeydanı Eğitim ve Araştırma Hastanesi Şişli, Istanbul, Turkey
| | - Deniz Arıca
- />Department of Hematology, Ministry of Health Okmeydanı Training and Research Hospital, S. B. Okmeydanı Eğitim ve Araştırma Hastanesi Şişli, Istanbul, Turkey
| | - Demet Aydın
- />Department of Hematology, Ministry of Health Okmeydanı Training and Research Hospital, S. B. Okmeydanı Eğitim ve Araştırma Hastanesi Şişli, Istanbul, Turkey
| | - Naciye Demirel
- />Department of Hematology, Ministry of Health Okmeydanı Training and Research Hospital, S. B. Okmeydanı Eğitim ve Araştırma Hastanesi Şişli, Istanbul, Turkey
| | - Osman Yokuş
- />Department of Hematology, Ministry of Health Okmeydanı Training and Research Hospital, S. B. Okmeydanı Eğitim ve Araştırma Hastanesi Şişli, Istanbul, Turkey
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Hsu LY, Lee DG, Yeh SP, Bhurani D, Khanh BQ, Low CY, Norasetthada L, Chan T, Kwong YL, Vaid AK, Alejandria I, Mendoza M, Chen CY, Johnson A, Tan TY. Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study. Clin Microbiol Infect 2015; 21:594.e7-11. [PMID: 25749561 DOI: 10.1016/j.cmi.2015.02.019] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Revised: 01/12/2015] [Accepted: 02/22/2015] [Indexed: 12/15/2022]
Abstract
We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality.
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Affiliation(s)
- L Y Hsu
- National University Hospital, National University Health System, Singapore.
| | - D G Lee
- Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - S P Yeh
- China Medical University Hospital, Taiwan
| | - D Bhurani
- Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - B Q Khanh
- National Institute of Hematology and Blood Transfusion, Hanoi, Viet Nam
| | - C Y Low
- Singapore General Hospital, Singapore
| | | | - T Chan
- Queen Mary Hospital, Hong Kong Special Administrative Region, China
| | - Y L Kwong
- Queen Mary Hospital, Hong Kong Special Administrative Region, China
| | - A K Vaid
- Maedanta Medicity, Gurgaon, India
| | - I Alejandria
- National Kidney and Transplant Institute, Quezon City, Philippines
| | - M Mendoza
- National Kidney and Transplant Institute, Quezon City, Philippines
| | - C Y Chen
- National Taiwan University Hospital, Taiwan
| | - A Johnson
- International Health Management Associates, Inc., Schaumburg, IL, USA
| | - T Y Tan
- Changi General Hospital, Singapore
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Taccone FS, Van den Abeele AM, Bulpa P, Misset B, Meersseman W, Cardoso T, Paiva JA, Blasco-Navalpotro M, De Laere E, Dimopoulos G, Rello J, Vogelaers D, Blot SI. Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2015; 19:7. [PMID: 25928694 PMCID: PMC4344741 DOI: 10.1186/s13054-014-0722-7] [Citation(s) in RCA: 274] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 12/15/2014] [Indexed: 12/20/2022]
Abstract
Introduction Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting. Methods An observational study including all patients with a positive Aspergillus culture during ICU stay was performed in 30 ICUs in 8 countries. Cases were classified as proven IA, putative IA or Aspergillus colonization according to recently validated criteria. Demographic, microbiologic and diagnostic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. Results A total of 563 patients were included, of whom 266 were colonized (47%), 203 had putative IA (36%) and 94 had proven IA (17%). The lung was the most frequent site of infection (94%), and Aspergillus fumigatus the most commonly isolated species (92%). Patients with IA had higher incidences of cancer and organ transplantation than those with colonization. Compared with other patients, they were more frequently diagnosed with sepsis on ICU admission and more frequently received vasopressors and renal replacement therapy (RRT) during the ICU stay. Mortality was 38% among colonized patients, 67% in those with putative IA and 79% in those with proven IA (P < 0.001). Independent risk factors for death among patients with IA included older age, history of bone marrow transplantation, and mechanical ventilation, RRT and higher Sequential Organ Failure Assessment score at diagnosis. Conclusions IA among critically ill patients is associated with high mortality. Patients diagnosed with proven or putative IA had greater severity of illness and more frequently needed organ support than those with Aspergillus spp colonization.
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Affiliation(s)
- Fabio Silvio Taccone
- Department of Intensive Care Erasme Hospital, Free University of Brussels, Route de Lennik 808, 1070, Brussels, Belgium.
| | | | - Pierre Bulpa
- Department of Intensive Care Mont-Godinne University Hospital, Catholic University of Louvain, Avenue G.Thérasse 1, 5530, Yvoir, Belgium.
| | - Benoit Misset
- Department of Intensive Care Foundation Hospital Saint-Joseph, Paris-Descartes University, 185 Rue Raymond Losserand, 75014, Paris, France.
| | - Wouter Meersseman
- Medical Intensive Care Unit, University Hospital Leuven, Herestraat 49, 3000, Leuven, Belgium.
| | - Teresa Cardoso
- Department of Intensive Care, Santo Antonio Hospital, Largo Prof. Abel Salazar, 4099-001, Porto, Portugal.
| | - José-Artur Paiva
- Department of Emergency and Intensive Care, Hospital Centre S. Joao and University of Porto Medical School Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
| | - Miguel Blasco-Navalpotro
- Department of Intensive Care, University Hospital Severo Ochoa, Avenida de Orellana, s/n 28911, Leganés, Madrid, Spain.
| | - Emmanuel De Laere
- Department of Microbiology, General Hospital Delta, Brugsesteenweg 90, 8800, Roeselare, Belgium.
| | - George Dimopoulos
- Department of Critical Care Medicine, Attikon University Hospital, University of Athens Medical School, 1 Rimini Street, Haidari, 124 62, Athens, Greece.
| | - Jordi Rello
- Hospital Universitari Vall d'Hebron, Vall D'Hebron, Institute of Research, CIBERES, Autonomous University of Barcelona, Passeig Vall d'Hebron, 119-129, 08035, Barcelona, Spain.
| | - Dirk Vogelaers
- Department of Internal Medicine Faculty of Medicine & Health Science, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
| | - Stijn I Blot
- Department of Internal Medicine Faculty of Medicine & Health Science, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium. .,Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Herston (Brisbane), 4006, Queensland, Australia.
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49
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Liu M, Li Y, Zhang Y, Zhao X, Zhai B, Zhang Q, Wang L, Zhao Y, Li H, Wang Q, Gao C, Huang W, Yu L. Secondary antifungal prophylaxis in hematological malignancy patients with previous invasive fungal disease: a retrospective analysis. PLoS One 2014; 9:e115461. [PMID: 25531544 PMCID: PMC4274009 DOI: 10.1371/journal.pone.0115461] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2014] [Accepted: 11/23/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Invasive fungal disease (IFD) causes morbidity and mortality in patients with hematological malignancy. Recurrence of IFD after chemotherapy or hematopoietic stem cell transplantation (HSCT) is associated with poor prognosis. The present study aimed to investigate the efficacy of different strategies of secondary antifungal prophylaxis (SAP) for IFD and choose an appropriate SAP regimen. METHODS Clinical data of patients with previous IFD who underwent chemotherapy or HSCT between Jan 2008 and Jun 2013 were retrospectively reviewed and followed up to 180 days post-chemotherapy or HSCT. The clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IFD. The efficacy of different strategies for SAP and risk factors influencing the failure of SAP were evaluated. RESULTS Of the 164 patients enrolled, 121 patients received SAP regimen (73.78%), and IFD recurred in 40 patients: 16.5% (20/121) in SAP group and 46.5% (20/43) in non-SAP group. In SAP group, 58 received SAP agents which were proven effective for their previous IFD, while other 63 patients received other broad-spectrum antifungal agents. There was no significant difference in the recurrence rates between these two subgroups (13.8% (8/58) vs 19.0% (12/63), P = 0.437). The IFD recurrence rates were statistically significant between patients with allogeneic HSCT and chemotherapy or autologous HSCT (25% vs 8.2%, P = 0.013). Multivariate analysis indicated that allogeneic HSCT was the independent risk factor of IFD recurrence after SAP. CONCLUSIONS Secondary antifungal prophylaxis is necessary to prevent IFD recurrence in patients with hematological malignancy, especially for patients in the setting of allogeneic HSCT.
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Affiliation(s)
- Mingjuan Liu
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
- Department of Hematology, the 309th Hospital of Chinese People's Liberation Army, 17 Heishanhu Road, Beijing 100091, China
| | - Yan Li
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
- Department of Hematology, Hainan Branch of Chinese PLA General Hospital, Linwang Street of Sanya City, Hainan province, 572013, China
| | - Yongqing Zhang
- Department of Hematology, the 309th Hospital of Chinese People's Liberation Army, 17 Heishanhu Road, Beijing 100091, China
| | - Xiaoli Zhao
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | - Bing Zhai
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | - Qingyi Zhang
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | - Lijun Wang
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | - Yu Zhao
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | - Honghua Li
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | - Quanshun Wang
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | - Chunji Gao
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | - Wenrong Huang
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
- Department of Hematology, Hainan Branch of Chinese PLA General Hospital, Linwang Street of Sanya City, Hainan province, 572013, China
- * E-mail: (LY); (WRH)
| | - Li Yu
- Department of Hematology and BMT center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
- * E-mail: (LY); (WRH)
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50
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Babouee Flury B, Weisser M, Prince SS, Bubendorf L, Battegay M, Frei R, Goldenberger D. Performances of two different panfungal PCRs to detect mould DNA in formalin-fixed paraffin-embedded tissue: what are the limiting factors? BMC Infect Dis 2014; 14:692. [PMID: 25518949 PMCID: PMC4272807 DOI: 10.1186/s12879-014-0692-z] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Accepted: 12/09/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Detection of fungal DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is challenging due to degradation of DNA and presence of PCR inhibitors in these samples. We analyzed FFPE samples of 26 patients by panfungal PCR and compared the results to the composite diagnosis according to the European Organization for Research and Treatment of Cancer (EORTC) criteria. Additionally we analyzed the quality of human and fungal DNA and their level of age-dependent degradation, as well as the existence of PCR inhibition in these tissue samples. METHODS We evaluated two 45-cycle panfungal PCR tests that target the internal transcribed spacer 2 (ITS2) as well as the ITS1-5.8S-ITS2 (ITS1-2) region. The PCRs were applied to 27 FFPE specimens from 26 patients with proven invasive fungal disease (IFD), and one patient with culture and histologically negative but PCR-positive fungal infection collected at our institution from 2003 to 2010. Quality of DNA in FFPE tissue samples was evaluated using fragments of the beta-globin gene for multiplex PCR, inhibition of PCR amplification was evaluated by spiking of C. krusei DNA to each PCR premix. RESULTS In 27 FFPE samples the ITS2 PCR targeting the shorter fragment showed a higher detection rate with a sensitivity of 53.8% compared to the ITS1-2 fragment (sensitivity 38%). Significant time-dependent degradation of human DNA in FFPE sample extracts was detected based on partial beta-globin gene amplification which was not in correlation to successful panfungal PCR identification of fungal organisms. The analytical sensitivity of both assays compared with culture was 60 CFU/ml of a Candida krusei reference strain. The performance of the two tests in an Aspergillus proficiency panel of an international external quality assessment programme showed considerable sensitivity. CONCLUSION Panfungal diagnostic PCR assays applied on FFPE specimens provide accurate identification of molds in highly degraded tissue samples and correct identification in samples stored up to 7 years despite sensitivity limitations, mainly caused by partial PCR inhibition and DNA degradation by formalin.
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Affiliation(s)
- B Babouee Flury
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, Basel, 4031, Switzerland.
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