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Chen Z, Zhen S, Sun J, Zhou L, Zhang T, Shen Y, Guo W, Zheng Y, Zhang F, Mi Y, Qiu L, Zhu X, Jiang E, Han M, Xiao Z, Wang J, Feng S, Chen X. Clinical characteristics and treatment response of chronic disseminated candidiasis in patients with hematological disorders. Sci Rep 2025; 15:12868. [PMID: 40234627 PMCID: PMC12000619 DOI: 10.1038/s41598-025-97004-4] [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: 09/10/2024] [Accepted: 04/01/2025] [Indexed: 04/17/2025] Open
Abstract
Chronic disseminated candidiasis (CDC) is an invasive fungal infection typically affecting patients with hematological diseases and severe neutropenia, associated with increased mortality. However, there is a global shortage of clinical evidence on CDC. We retrospectively analyzed clinical data from 49 CDC patients over the past decade. Clinical characteristics of primary hematological diseases, CDC diagnosis, treatment and response evaluations were included. Clinical factors associated with CDC remission and patients' survival were analyzed. The majority of patients had hematological malignancies (n = 43, 87.8%), and 27 patients (55.1%) had persistent severe neutropenia for more than 10 days prior to CDC. CT scans revealed liver lesions in 44 patients, spleen lesions in 34 patients, and kidney lesions in 9 patients. Proven, probable and possible CDC was diagnosed in 5 (10.2%), 3 (6.1%) and 41 patients (83.7%), respectively, and treatment outcomes at 3 months included 5 complete response (CR, 10.2%), 34 partial response (PR, 69.4%) and 10 treatment failure (20.4%). Caspofungin treatment showed a trend towards improving CR/PR rate, while severe neutropenia > 20 days and proven diagnosis were significantly associated with 3-month treatment failure. Kaplan-Meier curve showed achieving CR/PR within 3 months did not significantly prolong OS compared to treatment failure patients (1197.6 days vs. 564.8 days, P = 0.074). Additionally, no patient deaths were directly attributed to CDC infection. Age > 45 years old and malignancy non-remission were prognostic factors of overall survival (OS). Furthermore, a prediction model identified severe neutropenia > 20 days, proven/probable diagnosis and concomitant bacteremia as risk factors to effectively predict treatment failure. Also, patients with a risk score < 0.203 in the model exhibited more rapid treatment response. After CDC symptoms onset, lymphocyte levels remained consistently higher in treatment failure patients, while the neutrophil-to-lymphocyte ratio was persistently higher in CR/PR patients. Our findings recommend CT scans for diagnosis and caspofungin as first-line therapy while continuing scheduled chemotherapy or bone marrow transplantation. Notably, risk factors identified by the prediction model could be used to predict treatment response.
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Affiliation(s)
- Zhangjie Chen
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Sisi Zhen
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Jiali Sun
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Lukun Zhou
- Department of Hematology, Zhongda Hospital, Southeast University, Nanjing, People's Republic of China
| | - Tingting Zhang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Yuyan Shen
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Wenjing Guo
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Yizhou Zheng
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Fengkui Zhang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Yingchang Mi
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Lugui Qiu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Xiaofan Zhu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Erlie Jiang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Mingzhe Han
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Zhijian Xiao
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Jianxiang Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China
| | - Sizhou Feng
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China.
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China.
| | - Xin Chen
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China.
- Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China.
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2
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Sedik S, Wolfgruber S, Hoenigl M, Kriegl L. Diagnosing fungal infections in clinical practice: a narrative review. Expert Rev Anti Infect Ther 2024; 22:935-949. [PMID: 39268795 DOI: 10.1080/14787210.2024.2403017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 09/02/2024] [Accepted: 09/07/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND Invasive fungal infections (IFI) present a major medical challenge, with an estimated 6.5 million cases annually, resulting in 3.8 million deaths. Pathogens such as Aspergillus spp. Candida spp. Mucorales spp. Cryptococcus spp. and other fungi species contribute to these infections, posing risks to immunocompromised individuals. Early and accurate diagnosis is crucial for effective treatment and better patient outcomes. AREAS COVERED This narrative review provides an overview of the current methods and challenges associated with diagnosing fungal diseases, including invasive aspergillosis and invasive candidiasis, as well as rare and endemic fungal infections. Various diagnostic techniques, including microscopy, culture, molecular diagnostics, and serological tests, are reviewed, highlighting their respective advantages and limitations and role in clinical guidelines. To illustrate, the need for improved diagnostic strategies to overcome existing challenges, such as the low sensitivity and specificity of current tests and the time-consuming nature of traditional culture-based methods, is addressed. EXPERT OPINION Current advancements in fungal infection diagnostics have significant implications for healthcare outcomes. Improved strategies like molecular testing and antigen detection promise early detection of fungal pathogens, enhancing patient management. Challenges include global access to advanced technologies and the need for standardized, user-friendly point-of-care diagnostics to improve diagnosis of fungal infections globally.
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Affiliation(s)
- Sarah Sedik
- Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, ECMM Excellence Center Graz, Austria
- Translational Mycology, Medical University of Graz, Graz, Austria
| | - Stella Wolfgruber
- Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, ECMM Excellence Center Graz, Austria
- Translational Mycology, Medical University of Graz, Graz, Austria
| | - Martin Hoenigl
- Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, ECMM Excellence Center Graz, Austria
- Translational Mycology, Medical University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
| | - Lisa Kriegl
- Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, ECMM Excellence Center Graz, Austria
- Translational Mycology, Medical University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
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Zhu DP, Ma R, He Y, Luo XY, Han W, Li C, Zhou JR, Liao Y, Tang BR, Longka QLT, Huang XJ, Sun YQ. [Clinical features and prognosis of hepatosplenic candidiasis in patients with hematopathy]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2024; 45:683-688. [PMID: 39231774 PMCID: PMC11388127 DOI: 10.3760/cma.j.cn121090-20231230-00347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Indexed: 09/06/2024]
Abstract
Hepatosplenic candidiasis (HSC) is a rare type of candidiasis that can occur in patients with hematologic malignancies, hematopoietic stem cell transplantation. At present, there is still a lack of studies on HSC in patients with hematologic disorders. Based on The Chinese Guidelines for the Diagnosis and Treatment of Invasive Fungal Disease in Patients with Hematological Disorders and Cancers (the 6th revision), We retrospectively analyzed the clinical characteristics and prognosis of patients with HSC treated in Peking University Institute of Hematology from 2008 to 2022. Finally, eighteen patients were included, with 1 (5.6%) proven, 2 (11.1%) probable, and 15 (83.3%) possible HSC. Among them, 3 (16.7%) patients occurred after haploid hematopoietic stem cell transplantation and 15 (83.3%) patients occurred after chemotherapy. 6 (33.3%) patients had positive blood cultures, including 4 cases of Candida tropicalis and 2 cases of Candida albicans. At 4 weeks of antifungal therapy, 10 (58.8%) patients achieved partial response (PR), At 8 weeks, 1 (6.3%) patients achieved complete response and 10 (62.5%) patients achieved PR. At 6 months after diagnosis, 3 (16.7%) patients died of hematopoietic recurrence, and none of them died of HSC. As a rare fungal infection disease, HSC has a low positive rate of microbiological and histological examinations, a persistent treat cycle, and has difficulty in remission, reminding us of the need for vigilance in patients with hematopoietic disorders and persistent fever.
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Graeter A, Lee D, Handley G, Baluch A, Klinkova O. Chronic disseminated candidiasis in a patient with acute leukemia - an illustrative case and brief review for clinicians. BMC Infect Dis 2024; 24:296. [PMID: 38448809 PMCID: PMC10916012 DOI: 10.1186/s12879-024-09172-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 02/24/2024] [Indexed: 03/08/2024] Open
Abstract
Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.
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Affiliation(s)
- Allison Graeter
- Department of Internal Medicine, University of South Florida, 17 Davis Blvd., Suite 308, 33606, Tampa, FL, USA
| | - Dasom Lee
- Division of Hematology, Stanford University, 94305, Stanford, CA, USA
| | - Guy Handley
- Department of Infectious Disease and International Medicine, 1 Tampa General Circle, 33606, Tampa, FL, USA
| | - Aliyah Baluch
- Infectious Disease Division, Moffitt Cancer Center, 12902 USF Magnolia Drive, 33612, Tampa, FL, USA
| | - Olga Klinkova
- Infectious Disease Division, Moffitt Cancer Center, 12902 USF Magnolia Drive, 33612, Tampa, FL, USA.
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Nenciarini S, Cavalieri D. Immunomodulatory Potential of Fungal Extracellular Vesicles: Insights for Therapeutic Applications. Biomolecules 2023; 13:1487. [PMID: 37892168 PMCID: PMC10605264 DOI: 10.3390/biom13101487] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 09/30/2023] [Accepted: 10/02/2023] [Indexed: 10/29/2023] Open
Abstract
Extracellular vesicles (EVs) are membranous vesicular organelles that perform a variety of biological functions including cell communication across different biological kingdoms. EVs of mammals and, to a lesser extent, bacteria have been deeply studied over the years, whereas investigations of fungal EVs are still in their infancy. Fungi, encompassing both yeast and filamentous forms, are increasingly recognized for their production of extracellular vesicles (EVs) containing a wealth of proteins, lipids, and nucleic acids. These EVs play pivotal roles in orchestrating fungal communities, bolstering pathogenicity, and mediating interactions with the environment. Fungal EVs have emerged as promising candidates for innovative applications, not only in the management of mycoses but also as carriers for therapeutic molecules. Yet, numerous questions persist regarding fungal EVs, including their mechanisms of generation, release, cargo regulation, and discharge. This comprehensive review delves into the present state of knowledge regarding fungal EVs and provides fresh insights into the most recent hypotheses on the mechanisms driving their immunomodulatory properties. Furthermore, we explore the considerable potential of fungal EVs in the realms of medicine and biotechnology. In the foreseeable future, engineered fungal cells may serve as vehicles for tailoring cargo- and antigen-specific EVs, positioning them as invaluable biotechnological tools for diverse medical applications, such as vaccines and drug delivery.
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Affiliation(s)
| | - Duccio Cavalieri
- Department of Biology, University of Florence, Via Madonna del Piano 6, Sesto Fiorentino, 50019 Florence, Italy;
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Mosleh S, Rabaia D, Zidan T. Successful Treatment of Chronic Disseminated Candidiasis Complicated by Immune Reconstitution Inflammatory Syndrome in a Child With Acute Lymphocytic Leukemia. Cureus 2023; 15:e44103. [PMID: 37750159 PMCID: PMC10518137 DOI: 10.7759/cureus.44103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/25/2023] [Indexed: 09/27/2023] Open
Abstract
Chronic disseminated candidiasis (CDC) is a severe form of disseminated fungal infection that commonly affects the liver, spleen, and kidneys. In rare cases, CDC can be further complicated by an excessive immune response known as immune reconstitution inflammatory syndrome (IRIS). This syndrome occurs during the phase of immune recovery and is characterized by a systemic inflammatory response and excessive release of cytokines. We present a case of a two-year-old female with a medical history of acute lymphocytic leukemia on chemotherapy. She was admitted with high fever refractory to conservative management that included broad-spectrum antimicrobials. Additionally, multiple skin lesions and a left-sided limp were noted. Whole-body imaging revealed multiple abscesses in the spleen, kidneys, scalp, and left lower limb. The culture of an aspirate material from skin lesions grew Candida tropicalis. Despite receiving appropriate antifungals, the patient showed no signs of improvement, leading to the diagnosis of CDC-induced IRIS. The patient was started on systemic corticosteroids, which resulted in rapid improvement in the patient's clinical status, resolution of fever, and significant reduction in inflammatory markers.
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Affiliation(s)
- Sultan Mosleh
- Pediatrics Hematology and Oncology, An-Najah National University Hospital, Nablus, PSE
| | - Dima Rabaia
- Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, PSE
| | - Thabet Zidan
- Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, PSE
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Castillo Barradas M, Flores García NC. Nonviral Infections of the Liver in Developing Countries. Clin Liver Dis (Hoboken) 2022; 19:59-62. [PMID: 35308475 PMCID: PMC8912214 DOI: 10.1002/cld.1161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Content available: Author Interview and Audio Recording.
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Affiliation(s)
- Mauricio Castillo Barradas
- GastroenterologíaInstituto Mexicano del Seguro SocialHospital de Especialidades CMN La RazaMexico CityMexico
| | - Neyelli Cointa Flores García
- GastroenterologíaDepartamento de GastroenterologíaInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityMexico
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8
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Boussen I, Lisan Q, Raffoux E, Di Blasi R, Boissel N, Oksenhendler E, Adès L, Xhaard A, Bretagne S, Alanio A, Molina JM, Denis B. Hepatosplenic candidiasis in patients with hematological malignancies: a 13-year retrospective cohort study. Open Forum Infect Dis 2022; 9:ofac088. [PMID: 35355897 PMCID: PMC8962726 DOI: 10.1093/ofid/ofac088] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 02/18/2022] [Indexed: 11/14/2022] Open
Abstract
Background Hepatosplenic candidiasis (HSC) used to be reported in patients with acute myeloid leukemia (AML) without antifungal prophylaxis. The aim was to describe the clinical features and outcomes of HSC over the last 13 years in a single French hematology center. Methods All patients diagnosed with HSC between 2008 and 2020 were included in a single-center retrospective cohort study. Data were collected from patient charts, and HSC was classified according to the 2020 European Organisation for Research and Treatment of Cancer/Mycoses Study Group definitions. Results Sixty patients were included, with 18.3% proven, 3.3% probable, and 78.3% possible HSC according to the 2020 European Organization for Research and Treatment of Cancer Mycoses Study Group classification. Among them, 19 patients were treated for acute myeloid leukemia (AML), 21 for lymphomas, and 14 for acute lymphoblastic leukemia. HSC occurred in 13 patients after autologous stem cell transplantation for lymphoma. At HSC diagnosis, 13 patients were receiving antifungal prophylaxis. Candida colonization was present in 84.2%, with prior candidemia in 36.7% of cases. β-D-glucans was positive in 55.8%, and 45.8% of tissue biopsies were contributive. First-line antifungal therapy was azoles in 61.7%, and steroids were associated in 45% of cases. At 3 months of follow-up, partial response to antifungal therapy was 94.2%. At last follow-up (mean, 22.6 months), 41 patients (68.3%) presented a complete hematological remission and 22 patients were deceased, none because of HSC. Conclusions The epidemiology of HSC has changed in the last decade, with fewer cases occurring in the AML setting. A better identification of patients at risk could lead to specific prophylaxis and improved diagnosis.
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Affiliation(s)
- I Boussen
- Department of infectious diseases, Saint Louis and Lariboisière Hospitals, APHP, Paris, France
- Université de Paris, Paris, France
| | - Q Lisan
- Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, School of Medicine, University Paris Saclay, Paris, France
| | - E Raffoux
- Department of adult hematology, Saint Louis Hospital, APHP, Paris, France
| | - R Di Blasi
- Department of hemato-oncology, Saint Louis Hospital, APHP, Paris, France
| | - N Boissel
- Department of teenagers and young adult hematology, Saint Louis Hospital, APHP, Paris, France
| | - E Oksenhendler
- Department of clinical immunology, Saint Louis Hospital, APHP, Paris, France
| | - L Adès
- Department of senior adult hematology, Saint Louis Hospital, APHP, Paris, France
| | - A Xhaard
- Department of hematology - transplantation, Saint Louis Hospital, APHP, Paris, France
| | - S Bretagne
- Université de Paris, Paris, France
- Molecular Mycology Unit, Institut Pasteur, CNRS UMR2000, Paris, France
- Department of mycology, Saint Louis Hospital, APHP, Paris, France
| | - A Alanio
- Université de Paris, Paris, France
- Molecular Mycology Unit, Institut Pasteur, CNRS UMR2000, Paris, France
- Department of mycology, Saint Louis Hospital, APHP, Paris, France
| | - J M Molina
- Department of infectious diseases, Saint Louis and Lariboisière Hospitals, APHP, Paris, France
- Université de Paris, Paris, France
| | - B Denis
- Department of infectious diseases, Saint Louis and Lariboisière Hospitals, APHP, Paris, France
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9
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Shirahige T, Tashiro M, Taguchi M, Miyazaki Y, Shibuya K, Izumikawa K. Long-term trend in serum (1,3)-β-D-glucan level in a man with chronic disseminated candidiasis treated with corticosteroids. J Infect Chemother 2021; 27:1258-1260. [PMID: 34049793 DOI: 10.1016/j.jiac.2021.05.005] [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: 11/18/2020] [Revised: 03/17/2021] [Accepted: 05/08/2021] [Indexed: 11/25/2022]
Abstract
Chronic disseminated candidiasis (CDC) is a type of invasive candidiasis. CDC commonly appears in the neutrophil recovery phase after chemotherapy in patients with hematologic malignancies, and immune reconstitution inflammatory syndrome (IRIS) is thought to play a major role in CDC development. This report describes the case of a 33-year-old man with CDC as a complication of acute myeloid leukemia. We describe the clinical course, body temperature, therapy, and (1,3)-β-D-glucan (BDG) levels over the course of 22 months. He was initially treated with antifungals, but corticosteroids were added because of a persistently elevated body temperature, which we attributed to IRIS. After starting corticosteroids, his clinical condition improved, but his BDG levels became markedly elevated. We hypothesize that the suppression of the excessive immune response by corticosteroids lead to granuloma collapse, fungal release, and hematogenous dissemination, resulting in elevated BDG levels. The patient's condition gradually improved over the course of follow-up.
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Affiliation(s)
- Tomoyuki Shirahige
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4, Sakamoto, Nagasaki, 852-8102, Japan; Medical Education Development Centre, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, 852-8102, Japan.
| | - Masato Tashiro
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4, Sakamoto, Nagasaki, 852-8102, Japan; Infection Control and Education Centre, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, 852-8102, Japan.
| | - Masataka Taguchi
- Department of Hematology, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, 852-8102, Japan.
| | - Yasushi Miyazaki
- Department of Hematology, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, 852-8102, Japan.
| | - Kazutoshi Shibuya
- Department of Surgical Pathology, School of Medicine, Toho University, Tokyo, Japan 6-11-1, Omori-nishi Ota-ku, Tokyo, 143-8541, Japan.
| | - Koichi Izumikawa
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4, Sakamoto, Nagasaki, 852-8102, Japan; Infection Control and Education Centre, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, 852-8102, Japan.
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10
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Trenker C, Dietrich CF, Klein S, Safai Zadeh E, Sohlbach K, Neubauer A, Burchert A, Görg C. [Potential of ultrasound in allogeneic stem cell transplantation and transplant-related complications]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:336-344. [PMID: 33634439 DOI: 10.1055/a-1374-4192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Allogeneic hematopoietic stem cell transplantation (HCT) is a complex therapeutic procedure causing significant morbidity and mortality, including the gastrointestinal tract. Early diagnosis and treatment of HCT-associated complications are, therefore, of utmost importance to improve overall HCT outcome. Sonography can be a powerful diagnostic tool and is easily accessible at the bedside of HCT patients. In the hands of a sonography-experienced physician, it allows for instant diagnosis and can also rule out several important transplant-associated complications. Here we review available evidence on the diagnostic and clinical value of ultrasound prior, during and after HCT.
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Affiliation(s)
- Corinna Trenker
- Klinik für Hämatologie, Onkologie und Immunologie, UKGM Marburg und Philipps-Universität Marburg
| | | | - Stefan Klein
- Universitätsklinikum Mannheim, III. Medizinische Klinik
| | | | - Kristina Sohlbach
- Klinik für Hämatologie, Onkologie und Immunologie, UKGM Marburg und Philipps-Universität Marburg
| | - Andreas Neubauer
- Klinik für Hämatologie, Onkologie und Immunologie, UKGM Marburg und Philipps-Universität Marburg
| | - Andreas Burchert
- Klinik für Hämatologie, Onkologie und Immunologie, UKGM Marburg und Philipps-Universität Marburg
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11
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Candon S, Rammaert B, Foray AP, Moreira B, Gallego Hernanz MP, Chatenoud L, Lortholary O. Chronic Disseminated Candidiasis During Hematological Malignancies: An Immune Reconstitution Inflammatory Syndrome With Expansion of Pathogen-Specific T Helper Type 1 Cells. J Infect Dis 2021; 221:1907-1916. [PMID: 31879764 DOI: 10.1093/infdis/jiz688] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 12/23/2019] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Chronic disseminated candidiasis (CDC) is a rare disease that mostly occurs after chemotherapy-induced prolonged neutropenia in patients with hematological malignancies. It is believed to ensue from Candida colonization, breach of the intestinal epithelial barrier, and venous translocation to organs. Fungal blood or liver biopsy cultures are generally negative, suggesting the absence of an ongoing invasive fungal disease. METHODS To unravel the contribution of the immune system to CDC pathogenesis, we undertook a prospective multicentric exploratory study in 44 CDC patients at diagnosis and 44 matched controls. RESULTS Analysis of Candida-specific T-cell responses using enzyme-linked immunospot assays revealed higher numbers of interferon (IFN)γ-producing T cells reactive to mp65 or candidin in 27 CDC cases compared with 33 controls. Increased plasma levels of soluble CD25, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls. Neutrophilia and higher levels of CD4 and CD8 T-cell activation were found in CDC patients as well as increased proportions of CXCR3-expressing TCRγδ +Vδ2+ cells. CONCLUSIONS The expansion of Candida-specific IFNγ-producing T cells together with features of T-cell activation and systemic inflammation identified here support the view that CDC belongs to the broad spectrum of fungal-associated immune reconstitution inflammatory syndromes.
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Affiliation(s)
- Sophie Candon
- Université Paris-Descartes, Faculté de Médecine, INSERM U1151-CNRS UMR 8253, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Necker-Enfants Malades, APHP, Immunologie Biologique, Paris, France.,Université de Rouen Normandie, INSERM U1234, CHU de Rouen Normandie, Rouen, France
| | - Blandine Rammaert
- Université Paris Descartes, Faculté de Médecine, APHP, Hôpital Necker-Enfants Malades, Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, IHU Imagine, Paris, France.,Université de Poitiers, Faculté de Médecine et Pharmacie, Poitiers, France.,CHU de Poitiers, Service de Maladies Infectieuses et Tropicales, Poitiers, France
| | - Anne Perrine Foray
- Université Paris-Descartes, Faculté de Médecine, INSERM U1151-CNRS UMR 8253, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Necker-Enfants Malades, APHP, Immunologie Biologique, Paris, France
| | - Baptiste Moreira
- Université Paris-Descartes, Faculté de Médecine, INSERM U1151-CNRS UMR 8253, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Necker-Enfants Malades, APHP, Immunologie Biologique, Paris, France
| | | | - Lucienne Chatenoud
- Université Paris-Descartes, Faculté de Médecine, INSERM U1151-CNRS UMR 8253, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Necker-Enfants Malades, APHP, Immunologie Biologique, Paris, France
| | - Olivier Lortholary
- Université Paris Descartes, Faculté de Médecine, APHP, Hôpital Necker-Enfants Malades, Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, IHU Imagine, Paris, France.,Institut Pasteur, Unité de Mycologie Moléculaire, Paris, France
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12
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Moazzam Z, Yousaf A, Iqbal Z, Tayyab A, Hayat MH. Hepatic Candidiasis in an Immunocompetent Patient: A Diagnostic Challenge. Cureus 2021; 13:e13935. [PMID: 33884224 PMCID: PMC8054485 DOI: 10.7759/cureus.13935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Hepatic candidiasis is a manifestation of disseminated candidiasis, which typically presents in immunocompromised patients. Focal hepatic candidiasis in immunocompetent patients, however, is infrequent/extremely rare. We present the case of an immunocompetent female patient who presented with respiratory distress and right-sided pleural effusion. The pleural fluid tap did not grow anything, and a contrast-enhanced computed tomography (CT) scan revealed a right liver lobe subcapsular collection. CT-guided aspiration and culture resulted in Candida albicans growth. The patient responded to oral fluconazole, and a follow-up CT scan demonstrated resolution of the collection. Although hepatic candidiasis rarely occurs in immunocompetent patients, it should be included in the differential diagnosis of hepatic abscesses, as timely diagnosis and management are crucial in conferring a good prognosis.
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Affiliation(s)
| | - Amman Yousaf
- Radiology, Hamad General Hospital, Doha, QAT.,Radiology, Services Hospital, Lahore, PAK
| | - Zahid Iqbal
- Internal Medicine, Services Hospital, Lahore, PAK
| | - Ahmad Tayyab
- Internal Medicine, Services Hospital, Lahore, PAK
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13
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Abstract
Hepatosplenic candidiasis and other fungal infections of the liver are uncommon in healthy individuals; however, high index of suspicion is essential in immunocompromised patients with prolonged fever. Parasitic infections are protozoan or helminthic; their distribution and epidemiology are variable among different world regions. Clonorchiasis, opisthorchiasis, fascioliasis, and ascariasis are helminthic infections that commonly involve the biliary systems. Signs and symptoms of cholangitis require prompt management to relieve biliary obstruction; addition of antihelminthic agents is essential. Parasitic infections are mostly transmitted to humans by fecally contaminated food and water. Proper hand and food sanitation measures are essential in preventing disease transmission.
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Affiliation(s)
- Sirina Ekpanyapong
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
| | - K Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, HUP, Philadelphia, PA 19104, USA.
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14
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Candida albicans and Staphylococcus lugdunensis superinfection of liver cysts in a patient with autosomal dominant polycystic kidney disease under prednisolone treatment. CEN Case Rep 2020; 9:370-374. [PMID: 32440858 DOI: 10.1007/s13730-020-00488-4] [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: 12/19/2019] [Accepted: 05/09/2020] [Indexed: 10/24/2022] Open
Abstract
We report a case of superinfection of liver cysts caused by Candida albicans and Staphylococcus lugdunensis in a patient with autosomal dominant polycystic kidney disease. A 69-year-old man with chief complaints of headache and blurred vision was admitted to the former institution for the evaluation of suspected temporal arteritis. He was prescribed oral prednisolone (55 mg/day) as a preemptive treatment; however, he became febrile and presented with bilateral flank pain during prednisolone tapering. Blood culture revealed fungemia as a result of Candida famata infection; thus, micafungin treatment was started. Thereafter, recrudescence of the C-reactive protein level ensued. Then a cyst infection as visualized on magnetic resonance imaging led to cyst aspiration sclerotherapy. Cyst aspirate culture revealed the presence of C. albicans in one of the cysts and S. lugdunensis in two of the cysts. The patient was clinically stabilized with an additional 3 weeks of antibiotic and antifungal drug administration.
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15
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Carlesse F, Daudt LE, Seber A, Dutra ÁP, Melo ASDA, Simões B, Macedo CRD, Bonfim C, Benites E, Gregianin L, Batista MV, Abramczyk M, Tostes V, Lederman HM, Lee MLDM, Loggetto S, Galvão de Castro Junior C, Colombo AL. A consensus document for the clinical management of invasive fungal diseases in pediatric patients with hematologic cancer and/or undergoing hematopoietic stem cell transplantation in Brazilian medical centers. Braz J Infect Dis 2019; 23:395-409. [PMID: 31738887 PMCID: PMC9428207 DOI: 10.1016/j.bjid.2019.09.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Revised: 09/10/2019] [Accepted: 09/28/2019] [Indexed: 01/05/2023] Open
Abstract
In the present paper we summarize the suggestions of a multidisciplinary group including experts in pediatric oncology and infectious diseases who reviewed the medical literature to elaborate a consensus document (CD) for the diagnosis and clinical management of invasive fungal diseases (IFDs) in children with hematologic cancer and those who underwent hematopoietic stem-cell transplantation. All major multicenter studies designed to characterize the epidemiology of IFDs in children with cancer, as well as all randomized clinical trials addressing empirical and targeted antifungal therapy were reviewed. In the absence of randomized clinical trials, the best evidence available to support the recommendations were selected. Algorithms for early diagnosis and best clinical management of IFDs are also presented. This document summarizes practical recommendations that will certainly help pediatricians to best treat their patients suffering of invasive fungal diseases.
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Affiliation(s)
- Fabianne Carlesse
- Instituto de Oncologia Pediátrica, UNIFESP, São Paulo, SP, Brazil; Universidade Federal de São Paulo, Escola Paulista de Medicina (EPM), UNIFESP, São Paulo, SP, Brazil.
| | - Liane Esteves Daudt
- Universidade do Rio Grande do Sul, Hospital das Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
| | - Adriana Seber
- Hospital Samaritano de São Paulo, São Paulo, SP, Brazil; ABHH, Brazil.
| | | | | | - Belinda Simões
- Hospital das Clínicas de Ribeirão Preto-USP, São Paulo, SP, Brazil.
| | | | - Carmem Bonfim
- Hospital das Clínicas de Curitiba, Paraná, PR, Brazil.
| | | | - Lauro Gregianin
- Hospital das Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
| | - Marjorie Vieira Batista
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brazil.
| | - Marcelo Abramczyk
- Hospital Infantil Darcy Vargas, Morumbi, SP, Brazil; Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Pediatria, São Paulo, SP, Brazil.
| | - Vivian Tostes
- Pro-Imagem medicina diagnóstica Ribeirão Preto, SP, Brazil.
| | | | - Maria Lúcia de Martino Lee
- Hospital Santa Marcelina TUCA, São Paulo, SP, Brazil; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | | | | | - Arnaldo Lopes Colombo
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Disciplina de Infectologia, Brazil.
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16
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Madney Y, Shalaby L, Elanany M, Adel N, Nasr E, Alsheshtawi K, Younes A, Hafez H. Clinical features and outcome of hepatosplenic fungal infections in children with haematological malignancies. Mycoses 2019; 63:30-37. [PMID: 31514231 DOI: 10.1111/myc.13002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 10/03/2019] [Accepted: 08/23/2019] [Indexed: 11/30/2022]
Abstract
Hepatosplenic fungal infection (HSFI) is a severe invasive fungal infection observed during neutrophil recovery in patients with acute leukaemia treated with intensive chemotherapy. Retrospective analysis including all paediatric haematological malignancies patients with HSC treated in Children Cancer Hospital Egypt (2013-2018). Twenty-five patients with acute leukaemia developed HSFI (19 patients diagnosed as hepatosplenic candidiasis). Most of the cases (92%) occurred during the induction phase. Organs affected were as follows: liver in 18 patients, renal in 13 patients, spleen in 12 patients, skin in four patients and retina in one patient. Five (20%) patients had proven HSC, 14 (56%) probable and six (24%) possible HSFI. Ten patients had a PET-CT for response assessment. Candida tropicalis was the most common isolated spp. from blood/tissue culture. Six (24%) patients developed HSFI on top of antifungal prophylaxis. Steroids were given in 12 (52%) patients with HSFI as immune reconstitution syndrome (IRS). Caspofungin was the first line of treatment in 14 (56%) patients, liposomal amphotericin B in six (24%) patients and azoles in five (20%) patients. HSFI was associated with delayed of intensification phase of chemotherapy (median 42 days). The success rate was reported in 24 patients with complete response (68%) and partial response in (28%) patients, while failure (death) seen in 1(4%) patient. HSC is still a major challenge in paediatric leukaemias patients with impact on treatment delay and survival outcome. PET scan, non-culture diagnostics and steroid role evidence in IRS are growing. Antifungal stewardship for screening, early detection for high-risk patients and better response assessment is challenging.
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Affiliation(s)
- Youssef Madney
- Department of Pediatric Oncology, National Cancer Institute, Cairo University, Children Cancer Hospital Egypt (CCHE), Cairo, Egypt
| | - Lobna Shalaby
- Department of Pediatric Oncology, National Cancer Institute, Cairo University, Children Cancer Hospital Egypt (CCHE), Cairo, Egypt
| | - Mervat Elanany
- Department of Clinical Microbiology, Children Cancer Hospital Egypt (CCHE), Cairo, Egypt
| | - Naglaa Adel
- Department of Clinical Pharmacology, Children Cancer Hospital Egypt (CCHE), Cairo, Egypt
| | - Eman Nasr
- Department of Radiodiagnosis, Children Cancer Hospital Egypt (CCHE), Cairo, Egypt
| | - Khaled Alsheshtawi
- Department of Clinical Research, Children Cancer Hospital Egypt (CCHE), Cairo, Egypt
| | - Alaa Younes
- Department of Surgical Oncology, Children Cancer Hospital Egypt (CCHE), Cairo, Egypt
| | - Hanafy Hafez
- Department of Pediatric Oncology, National Cancer Institute, Cairo University, Children Cancer Hospital Egypt (CCHE), Cairo, Egypt
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17
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Tang DL, Chen X, Zhu CG, Li ZW, Xia Y, Guo XG. Pooled analysis of T2 Candida for rapid diagnosis of candidiasis. BMC Infect Dis 2019; 19:798. [PMID: 31510929 PMCID: PMC6737707 DOI: 10.1186/s12879-019-4419-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 08/28/2019] [Indexed: 11/24/2022] Open
Abstract
Background The present meta-analysis examined the diagnostic accuracy of T2 Candida for candidiasis. Methods The literature databases, such as PubMed, Embase, DVIO, Cochrane library, Web of Science, and CNKI, were searched on T2 Candida detection. Results A total of 8 articles, comprising of 2717 research subjects, were included in the study. The pooled sensitivity and specificity were 0.91 (95% confidence interval (CI): 0.88–0.94) and 0.94 95% CI: 0.93–0.95), respectively. The pooled positive likelihood ratio and negative likelihood ratio was 10.16 (95% CI: 2.75–37.50) and 0.08 (95% CI: 0.02–0.35), respectively. The combined diagnostic odds ratio is 133.65 95% CI: 17.21–1037.73), and the AUC of SROC is 0.9702 [(SE = 0.0235), Q* = 0.9201(SE = 0.0381)]. Conclusions The current evidence supported that T2 Candida has high accuracy and sensitivity and is of major clinical significance in the diagnosis of Candida infection.
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Affiliation(s)
- Dong-Lan Tang
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiao Chen
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Chang-Guo Zhu
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhong-Wei Li
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yong Xia
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, Guangdong, China. .,Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. .,Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China. .,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, 510150, China.
| | - Xu-Guang Guo
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, Guangdong, China. .,Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. .,Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China. .,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, 510150, China.
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18
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Kim T, Jeon Y, Choi H, Lee JY, Kim J. Endobronchial fungal infection caused by Candida albicans with main bronchus obstruction: a case report. Oxf Med Case Reports 2019; 2019:omz055. [PMID: 31281663 PMCID: PMC6600126 DOI: 10.1093/omcr/omz055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 04/01/2019] [Accepted: 05/06/2019] [Indexed: 11/13/2022] Open
Abstract
Endobronchial fungal infection (EBFI) is a rare form of pulmonary fungal infection that especially affects immunocompromised patients. Furthermore, EBFI resulting in obstruction of the main bronchus is extremely rare. With the development of bronchoscopic techniques, rare cases of EBFI have been reported. A 68-year-old female was referred to the Department of Pulmonology for confusion and obtundation. The patient was diagnosed with septic shock due to acute pyelonephritis followed by obstructive EBFI. We performed bronchoscopic biopsy and endobronchial aspiration for culture. Biopsy showed yeast-like fungus and Candida albicans grew in the culture. EBFI has been under-recognized because of difficulties in confirming the diagnosis. Endobronchial ultrasound-guided transbronchial needle aspiration and bronchoscopy are used to improve the diagnosis of thoracic infection, such as tuberculosis. The role of bronchoscopy in the diagnosis of infectious diseases of the trachea or main bronchi is expected to widen in the future.
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Affiliation(s)
- Taeyun Kim
- Department of Pulmonology, Kosin University Gospel Hospital, Busan, South Korea
| | - Yohan Jeon
- Department of Pathology, Kosin University Gospel Hospital, Busan, South Korea
| | - Hyunji Choi
- Department of Laboratory Medicine, Kosin University Gospel Hospital, Busan, South Korea
| | - Jin Young Lee
- Department of Infectious Disease, Kosin University Gospel Hospital, Busan, South Korea
| | - Jehun Kim
- Department of Pulmonology, Kosin University Gospel Hospital, Busan, South Korea
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19
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Muñoz P, Vena A, Machado M, Gioia F, Martínez-Jiménez MC, Gómez E, Origüen J, Orellana MÁ, López-Medrano F, Fernández-Ruiz M, Merino P, González-Romo F, Frías I, Pérez-Granda MJ, Aguado JM, Fortún J, Bouza E. T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study. J Antimicrob Chemother 2019; 73:iv6-iv12. [PMID: 29608751 DOI: 10.1093/jac/dky047] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objectives We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy. Methods Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome). Results Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14 (57.1%) versus 17/35 (48.6%), P = 0.75] results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome [5/14 (35.7%) versus 0/35 (0.0%) P = 0.0001]. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome from those with good clinical evolution. Conclusions T2MR may be of significant utility to identify patients who may benefit from maintaining antifungal therapy.
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Affiliation(s)
- Patricia Muñoz
- Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain.,Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.,CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain
| | - Antonio Vena
- Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain.,Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.,Infectious Diseases Clinic, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata, Udine, Italy
| | - Marina Machado
- Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Francesca Gioia
- Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | - Elia Gómez
- Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Julia Origüen
- Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), Universidad Complutense, Madrid, Spain
| | - María Ángeles Orellana
- Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), Universidad Complutense, Madrid, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), Universidad Complutense, Madrid, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), Universidad Complutense, Madrid, Spain
| | - Paloma Merino
- Clinical Microbiology Department, Hospital Universitario Clinico San Carlos, Madrid, Spain
| | - Fernando González-Romo
- Clinical Microbiology Department, Hospital Universitario Clinico San Carlos, Madrid, Spain
| | - Isabel Frías
- Postsurgical Intensive Care Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - María-Jesús Pérez-Granda
- Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), Universidad Complutense, Madrid, Spain
| | - Jesús Fortún
- Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Emilio Bouza
- Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain.,Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.,CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain
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20
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Yi P, Yang X, Yang M, Zhang Y, Li L. Multifocal muscle candidiasis of the legs in a patient with acute myeloid leukemia: A case report. Medicine (Baltimore) 2019; 98:e14580. [PMID: 30813175 PMCID: PMC6408043 DOI: 10.1097/md.0000000000014580] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
RATIONALE Opportunistic infections frequently develop in immunocompromised patients, such as those with hematological malignancies, causing significant mortality. Early diagnosis of invasive fungal infections is often important and difficult due to the difficult nature of confirming infection using cytologic and histologic findings. However, we report the first case of candidal infection leading to muscle abscesses in the legs of a patient with leukemia. PATIENT CONCERNS A 60-year-old man with acute myeloid leukemia (AML) presented with multifocal muscle abscesses of the legs. DIAGNOSES Multifocal muscle candidiasis of the legs was confirmed by fine-needle aspiration biopsy of 2 of the calf lesions. INTERVENTIONS After treatment with amphotericin B and flucytosine for 1 month, the patient was administered intravenous caspofungin for 3 months. OUTCOME A CT scan of the abdomen and an MRI of the lower calves showed significant improvement. LESSONS This case highlights that fungal infection should be considered when patients present with multiple abscesses, emphasizing the value of early biopsy to confirm diagnosis and facilitate precision treatment.
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Affiliation(s)
- Ping Yi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University
| | - Xiang Yang
- Shu Lan (Hangzhou) Hospital, Hangzhou, China
| | - MeiFang Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University
| | - Yan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University
- Shu Lan (Hangzhou) Hospital, Hangzhou, China
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21
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Jang YR, Kim MC, Kim T, Chong YP, Lee SO, Choi SH, Kim YS, Woo JH, Hong JY, Yoon DH, Suh C, Lee JH, Lee JH, Lee KH, Kim SH. Clinical characteristics and outcomes of patients with chronic disseminated candidiasis who need adjuvant corticosteroid therapy. Med Mycol 2018; 56:782-786. [PMID: 29228331 DOI: 10.1093/mmy/myx110] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 10/07/2017] [Indexed: 01/05/2023] Open
Abstract
We performed a retrospective study involving 21 patients with chronic disseminate candidiasis (CDC) and 38 patients with candidemia. Neutropenia of >2 weeks' duration was more common in those with CDC (71%) than in those with candidemia (26%, P < .001), and the azole-resistant rate in patients with CDC (5%) was lower than that in those with candidemia (29%, P = .03). Of the 21 patients with CDC, five (24%) needed adjuvant corticosteroid therapy due to persistent debilitating fever (median, 19 days). Rapid defervescence (median, 5 days) occurred after adjuvant corticosteroid therapy. However, there were no significant differences in 90-day mortality between CDC patients with and without corticosteroid therapy. Further prospective data are needed to define the role of steroids in this setting.
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Affiliation(s)
- Young-Rock Jang
- Department of Infectious Diseases.,Division of Infectious Disease, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea
| | | | - Taeeun Kim
- Department of Infectious Diseases.,Division of Infectious Diseases, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea
| | | | | | | | | | | | | | | | | | - Jung-Hee Lee
- Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Je-Hwan Lee
- Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kyoo-Hyung Lee
- Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Response of Symptomatic Persistent Chronic Disseminated Candidiasis to Corticosteroid Therapy in Immunosuppressed Pediatric Patients: Case Study and Review of the Literature. Pediatr Infect Dis J 2018; 37:686-690. [PMID: 29140934 DOI: 10.1097/inf.0000000000001844] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Chronic disseminated candidiasis (CDC) is a severe invasive fungal infection principally observed during neutrophil recovery in patients with acute leukemia treated with intensive chemotherapy. Its pathophysiology remains unclear. We describe the management of 6 children with symptomatic CDC who did not respond to antifungal therapy. METHODS The databases of the hematology-oncology departments of 2 tertiary pediatric medical centers were searched for all patients diagnosed with CDC from 2003 to 2015, who responded to corticosteroids after failing antifungal therapy. Clinical, laboratory and radiologic data were collected. RESULTS Six patients (3 women, 3 men; 9-18 years of age) met the study criteria. Underlying diseases were acute lymphoblastic leukemia (n = 3) and large B-cell lymphoma, acute myeloid leukemia and severe aplastic anemia (n = 1 each). Presenting symptoms/signs of CDC were fever in all cases, with abdominal or chest pain, and/or mucositis. Candida infection was identified in blood cultures in 4 patients and in bronchoalveolar lavage fluid in one. In the absence of response to antifungal agents (4-50 days from CDC diagnosis), prednisone 2 mg/kg/day or equivalent was administered. CDC-attributable clinical symptoms resolved in 4 patients within 6-19 days; one patient required an additional nonsteroidal anti-inflammatory agent. Abnormalities on imaging decreased or disappeared within 5 months to 2 years in 4 patients. CONCLUSIONS In children with persistent symptomatic CDC, despite adequate antifungal therapy, administration of corticosteroids may yield rapid resolution of symptoms and decreased inflammatory markers. In patients who do not respond to steroids, the addition of a nonsteroidal anti-inflammatory drug should be considered.
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Yeoh SF, Lee TJ, Chew KL, Lin S, Yeo D, Setia S. Echinocandins for management of invasive candidiasis in patients with liver disease and liver transplantation. Infect Drug Resist 2018; 11:805-819. [PMID: 29881298 PMCID: PMC5985852 DOI: 10.2147/idr.s165676] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Candida species remains one of the most important causes of opportunistic infections worldwide. Invasive candidiasis (IC) is associated with considerable morbidity and mortality in liver disease (LD) patients if not treated promptly. Echinocandins are often recommended as a first-line empirical treatment for managing IC and can especially play a critical role in managing IC in LD patients. However, advanced LD patients are often immunocompromised and critically ill. Hence altered pharmacokinetics, drug interactions as well as tolerance issues of antifungal treatments are a concern in these patients. This comprehensive review examines the epidemiology, risk factors and diagnosis of IC in patients with LD and evaluates differences between three available echinocandins for treating this group of patients.
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Affiliation(s)
- Siang Fei Yeoh
- Department of Pharmacy, National University Health System, Singapore, Singapore
| | - Tae Jin Lee
- Department of Pharmacy, National University of Singapore, Singapore, Singapore
| | - Ka Lip Chew
- Department of Laboratory Medicine, National University Hospital, Singapore, Singapore
| | - Stephen Lin
- Global Medical Affairs, Asia-Pacific region, Pfizer, Hong Kong, People’s Republic of China
| | - Dennis Yeo
- Medical Affairs, Pfizer Pte. Ltd., Singapore, Singapore
| | - Sajita Setia
- Medical Affairs, Pfizer Pte. Ltd., Singapore, Singapore
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24
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Shinozaki M, Tochigi N, Sadamoto S, Yamagata Murayama S, Wakayama M, Nemoto T. [Histopathological Diagnosis of Invasive Fungal Infections in Formalin-Fixed and Paraffin-Embedded Tissues in Conjunction with Molecular Methods]. Med Mycol J 2018; 59:E7-E18. [PMID: 29491339 DOI: 10.3314/mmj.17-00016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The main objective of this study was to evaluate the relationship between histopathology, polymerase chain reaction (PCR), and in situ hybridization (ISH) for the identification of causative fungi in formalin-fixed and paraffin-embedded (FFPE) tissue specimens. Since pathogenic fungi in tissue specimens can be difficult to identify morphologically, PCR and ISH have been usually employed as auxiliary procedures. However, little comparison has been made on the sensitivity and specificity of PCR and ISH using FFPE specimens. Therefore, to compare and clarify the reproducibility and usefulness of PCR and ISH as auxiliary procedures for histological identification, we performed histopathological review, PCR assays, and ISH to identify pathogenic fungi in 59 FFPE tissue specimens obtained from 49 autopsies. The following are the main findings for this retrospective review: i) even for cases classified as "mold not otherwise specified" (MNOS), two cases could be identified as Aspergillus species by molecular methods; ii) all cases classified as non-zygomycetes mold (NZM) were Aspergillus species and were not identified by molecular methods as other fungi; iii) all 3 cases classified as zygomycetes mold (ZM) could be identified by molecular methods as Mucorales; iv) except for 1 case identified by molecular methods as Trichosporon spp., 5 cases were originally identified as dimorphic yeast (DY). As a measure of nucleic acid integrity, PCR and ISH successfully detected human and fungal nucleic acids in approximately 60% of the specimens. Detection of Aspergillus DNA by nested PCR assay and by ISH against the A. fumigatus ALP gene were similarly sensitive and significant (p<0.01). Thus, our findings demonstrated the potential risk of error in the classification of fungi based on pathological diagnosis. Combining molecular methods such as ISH and PCR on FFPE specimens with pathological diagnosis should improve diagnostic accuracy of fungal infection.
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Affiliation(s)
- Minoru Shinozaki
- Department of Pathology, Toho University Graduate School of Medicine
| | - Naobumi Tochigi
- Department of Pathology, Toho University Graduate School of Medicine.,Department of Surgical Pathology, Toho University School of Medicine
| | - Sota Sadamoto
- Department of Pathology, Toho University Graduate School of Medicine.,Department of Surgical Pathology, Toho University School of Medicine
| | | | - Megumi Wakayama
- Department of Pathology, Toho University Graduate School of Medicine.,Department of Surgical Pathology, Toho University School of Medicine
| | - Tetsuo Nemoto
- Department of Surgical Pathology, Toho University School of Medicine
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25
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Clancy CJ, Pappas PG, Vazquez J, Judson MA, Kontoyiannis DP, Thompson GR, Garey KW, Reboli A, Greenberg RN, Apewokin S, Lyon GM, Ostrosky-Zeichner L, Wu AHB, Tobin E, Nguyen MH, Caliendo AM. Detecting Infections Rapidly and Easily for Candidemia Trial, Part 2 (DIRECT2): A Prospective, Multicenter Study of the T2Candida Panel. Clin Infect Dis 2018; 66:1678-1686. [DOI: 10.1093/cid/cix1095] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 12/20/2017] [Indexed: 12/18/2022] Open
Affiliation(s)
| | | | - Jose Vazquez
- Medical College of Georgia, Augusta University, New York
| | | | | | | | | | - Annette Reboli
- Cooper Medical School of Rowan University and Cooper University Healthcare, Camden, New Jersey
| | | | | | | | | | | | - Ellis Tobin
- St. Peters Healthcare System, Albany, New York
| | - M Hong Nguyen
- University of Pittsburgh Medical Center, Pennsylvania
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26
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27
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Posch W, Heimdörfer D, Wilflingseder D, Lass-Flörl C. Invasive candidiasis: future directions in non-culture based diagnosis. Expert Rev Anti Infect Ther 2017; 15:829-838. [PMID: 28829207 DOI: 10.1080/14787210.2017.1370373] [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] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Delayed initial antifungal therapy is associated with high mortality rates caused by invasive candida infections, since accurate detection of the opportunistic pathogenic yeast and its identification display a diagnostic challenge. diagnosis of candida infections relies on time-consuming methods such as blood cultures, serologic and histopathologic examination. to allow for fast detection and characterization of invasive candidiasis, there is a need to improve diagnostic tools. trends in diagnostics switch to non-culture-based methods, which allow specified diagnosis within significantly shorter periods of time in order to provide early and appropriate antifungal treatment. Areas covered: within this review comprise novel pathogen- and host-related testing methods, e.g. multiplex-PCR analyses, T2 magnetic resonance, fungus-specific DNA microarrays, microRNA characterization or analyses of IL-17 as biomarker for early detection of invasive candidiasis. Expert commentary: Early recognition and diagnosis of fungal infections is a key issue for improved patient management. As shown in this review, a broad range of novel molecular based tests for the detection and identification of Candida species is available. However, several assays are in-house assays and lack standardization, clinical validation as well as data on sensitivity and specificity. This underscores the need for the development of faster and more accurate diagnostic tests.
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Affiliation(s)
- Wilfried Posch
- a Division of Hygiene and Medical Microbiology , Medical University of Innsbruck , Innsbruck , Austria
| | - David Heimdörfer
- a Division of Hygiene and Medical Microbiology , Medical University of Innsbruck , Innsbruck , Austria
| | - Doris Wilflingseder
- a Division of Hygiene and Medical Microbiology , Medical University of Innsbruck , Innsbruck , Austria
| | - Cornelia Lass-Flörl
- a Division of Hygiene and Medical Microbiology , Medical University of Innsbruck , Innsbruck , Austria
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28
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Katragkou A, Fisher BT, Groll AH, Roilides E, Walsh TJ. Diagnostic Imaging and Invasive Fungal Diseases in Children. J Pediatric Infect Dis Soc 2017; 6:S22-S31. [PMID: 28927203 DOI: 10.1093/jpids/pix055] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Invasive fungal disease (IFD) is a life-threatening condition, especially in immunocompromised children. The role of diagnostic imaging in children at risk for an IFD is multifactorial, including initially detecting it, evaluating for dissemination of infection beyond the primary site of disease, monitoring the response to antifungal therapy, and assessing for potential relapse. The objective of this review was to synthesize the published literature relevant to the use of various imaging modalities for the diagnosis and management of IFD in children.
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Affiliation(s)
- Aspasia Katragkou
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Nationwide Children's Hospital and Ohio State University, Columbus
| | - Brian T Fisher
- Division of Infectious Diseases and Center for Pediatric Clinical Effectiveness Research, Children's Hospital of Philadelphia, Pennsylvania.,Departments of Pediatrics and Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Andreas H Groll
- Infectious Disease Research Program, Department of Pediatric Hematology and Oncology and Center for Bone Marrow Transplantation, University Children's Hospital Muenster, Germany
| | - Emmanuel Roilides
- Infectious Diseases Section, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Thessaloniki, Greece
| | - Thomas J Walsh
- Transplantation-Oncology Infectious Diseases Program and Departments of Medicine, Pediatrics, Microbiology and Immunology, Weill Cornell Medicine of Cornell University and New York Presbyterian Hospital
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29
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van Prehn J, Menke-van der Houven van Oordt CW, de Rooij ML, Meijer E, Bomers MK, van Dijk K. Hepatosplenic Candidiasis Without Prior Documented Candidemia: An Underrecognized Diagnosis? Oncologist 2017; 22:989-994. [PMID: 28469041 PMCID: PMC5553951 DOI: 10.1634/theoncologist.2017-0019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 02/16/2017] [Indexed: 11/27/2022] Open
Abstract
Hepatosplenic candidiasis (HSC) often occurs without prior documented candidemia. Underrecognized HSC can be mistaken for metastases and can have serious consequences for patients, especially when additional, inappropriate treatment, such as surgery and chemo‐ or immunotherapy, is initiated. To emphasize the importance of diagnosing HSC without prior documented candidemia, three illustrative cases and a review of the literature on HSC and candidemia are presented. Introduction. Patients with a history of chemotherapy or stem cell transplantation (SCT) and prolonged neutropenia are at risk for hepatic and/or splenic seeding of Candida. In our experience, hepatosplenic candidiasis (HSC) without documented candidemia often remains unrecognized. Case presentations. We describe three cases of HSC without documented candidemia and the challenges in establishing the diagnosis and adequately treating this condition. The first patient had a history of SCT for treatment of breast cancer and was scheduled for hemihepatectomy for suspected liver metastasis. A second opinion at our institute resulted in the diagnosis of hepatic candidiasis without prior documented candidemia, for which she was treated successfully with fluconazole. The second case demonstrates the limitations of (blood and tissue) cultures and the value of molecular methods to confirm the diagnosis. Case 3 illustrates treatment challenges, with ongoing dissemination and insufficient source control despite months of antifungal therapy, eventually resulting in a splenectomy. Literature review. A structured literature search was performed for articles describing any patient with HSC and documented blood culture results. Thirty articles were available for extraction of data on candidemia and HSC. Seventy percent (131/187) of patients with HSC did not have documented candidemia. The majority of HSC events were described in hematologic patients, although some cases were described in patients with solid tumors treated with SCT (n = 1) or chemotherapy and a history of leukopenia (n = 2). Current guidelines and practices for diagnosis and treatment are described. Conclusion. Clinicians should be aware that HSC most often occurs without documented candidemia. In case of persistent or unexplained fever or lesions in the liver and/or spleen, a history of neutropenia should place disseminated candidiasis in the differential diagnosis. HSC is not limited to hematological patients and may occur in patients with solid tumors treated with bone marrow‐suppressing chemotherapy or SCT. In the latter group, HSC as alternative diagnosis for hepatic metastasis should be considered when lesions are not typical for metastasis. This might prevent unnecessary surgery or inappropriate treatment. Implications for Practice. Timely diagnosis of hepatosplenic candidiasis (HSC) is challenging, but can prevent further complications and dissemination, and may even prevent unnecessary invasive procedures. Clinicians should realize that HSC often occurs without documented candidemia and that sensitivity of blood cultures for candidemia is limited. HSC is not strictly limited to hematologic patients and might also occur in patients with solid tumors treated with intensive chemotherapy or stem cell transplantation. Increased awareness for HSC in patients with any history of neutropenia is of importance to increase detection and prevent serious sequelae.
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Affiliation(s)
- Joffrey van Prehn
- Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands
| | | | - Madelon L de Rooij
- Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
| | - Ellen Meijer
- Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands
| | - Marije K Bomers
- Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
| | - Karin van Dijk
- Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands
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30
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Norimatsu Y, Morii D, Kogure A, Hamanaka T, Kuwano Y, Yokozawa T, Oda T. A case of breakthrough Candida parapsilosis fungemia during micafungin therapy for a Candida glabrata bloodstream infection. Med Mycol Case Rep 2017; 16:1-3. [PMID: 28377868 PMCID: PMC5369859 DOI: 10.1016/j.mmcr.2017.03.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 02/28/2017] [Accepted: 03/21/2017] [Indexed: 11/25/2022] Open
Abstract
We describe a case of breakthrough Candida parapsilosis fungemia in an 80-year-old woman with pyoderma gangrenosum and rheumatoid arthritis. C. parapsilosis was detected in blood culture while the patient was treated with micafungin for a Candida glabrata bloodstream infection. The breakthrough infection was successfully treated with liposomal amphotericin B.
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Affiliation(s)
- Yuta Norimatsu
- Department of Infectious Diseases, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira, Tokyo 187-8510, Japan
| | - Daiichi Morii
- Department of Infectious Diseases, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira, Tokyo 187-8510, Japan; Department of Infection Control and Prevention Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan
| | - Asako Kogure
- Department of Dermatology, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira, Tokyo 187-8510, Japan
| | - Taeko Hamanaka
- Department of Dermatology, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira, Tokyo 187-8510, Japan
| | - Yoshihiro Kuwano
- Department of Dermatology, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira, Tokyo 187-8510, Japan
| | - Takayuki Yokozawa
- Department of Clinical Laboratory, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira, Tokyo 187-8510, Japan
| | - Toshimi Oda
- Department of Infectious Diseases, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira, Tokyo 187-8510, Japan
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31
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Marchetti O, Tissot F, Calandra T. Infections in the Cancer Patient. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00079-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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32
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Kaaniche FM, Allela R, Cherif S, Algia NB. Invasive candidiasis in critically ill patients. TRENDS IN ANAESTHESIA AND CRITICAL CARE 2016. [DOI: 10.1016/j.tacc.2016.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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33
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Albano D, Bosio G, Bertoli M, Petrilli G, Bertagna F. Hepatosplenic Candidiasis Detected by (18)F-FDG-PET/CT. ASIA OCEANIA JOURNAL OF NUCLEAR MEDICINE & BIOLOGY 2016; 4:106-8. [PMID: 27408899 PMCID: PMC4938872 DOI: 10.7508/aojnmb.2016.02.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hepatosplenic candidiasis is a fungal infection, which mostly affects patients with hematologic malignancies such as leukemia. The pathogenesis of this infection is not clear yet, and the liver is the most commonly affected organ. Diagnosis of hepatosplenic candidiasis can be only established via biopsy, since computed tomography (CT) scan, ultrasonography, and magnetic resonance imaging (MRI) yield non-specific results. The role of fluorine-18 fluorodeoxyglucose positron emission tomography /computed tomography (18F-FDG PET/CT) in diagnosis of hepatosplenic candidiasis remains undetermined, considering a few evidences in the literature. In this case report, we present the case of a 47-year-old patient, affected by acute myeloid leukemia, which was treated with three cycles of chemotherapy, resulting in the development of neutropenia and fever following the last cycle. The 18F-FDG PET/CT scan showed some foci of intense FDG uptake in the liver and spleen. The subsequent diagnostic investigations (i.e., abdominal CT scan and biopsy) were suggestive of hepatosplenic candidiasis. The patient was started on antifungal treatment with fluconazole. After one month, the clinical conditions were resolved, and the subsequent abdominal CT scan was negative.
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Affiliation(s)
| | - Giovanni Bosio
- Nuclear Medicine, Spedali Civili di Brescia, Brescia, Italy
| | - Mattia Bertoli
- Nuclear Medicine, Spedali Civili di Brescia, Brescia, Italy
| | - Giulia Petrilli
- Department of Molecular and Translational Medicine, Anatomic Pathology Section, Spedali Civili di Brescia, Brescia, Italy
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34
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Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, Zaoutis TE, Sobel JD. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 62:e1-50. [PMID: 26679628 PMCID: PMC4725385 DOI: 10.1093/cid/civ933] [Citation(s) in RCA: 2138] [Impact Index Per Article: 237.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 11/02/2015] [Indexed: 02/06/2023] Open
Abstract
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
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Affiliation(s)
| | - Carol A Kauffman
- Veterans Affairs Ann Arbor Healthcare System and University of Michigan Medical School, Ann Arbor
| | | | | | - Kieren A Marr
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | | | | | | | - Thomas J Walsh
- Weill Cornell Medical Center and Cornell University, New York, New York
| | | | - Jack D Sobel
- Harper University Hospital and Wayne State University, Detroit, Michigan
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35
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Chen SC, Sorrell TC, Chang CC, Paige EK, Bryant PA, Slavin MA. Consensus guidelines for the treatment of yeast infections in the haematology, oncology and intensive care setting, 2014. Intern Med J 2015; 44:1315-32. [PMID: 25482743 DOI: 10.1111/imj.12597] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Pathogenic yeast forms are commonly associated with invasive fungal disease in the immunocompromised host, including patients with haematological malignancies and patients of haemopoietic stem cell transplants. Yeasts include the Candida spp., Cryptococcus spp., Pneumocystis jirovecii and some lesser-known pathogens. Candida species remain the most common cause of invasive yeast infections (and the most common human pathogenic fungi). These guidelines present evidence-based recommendations for the antifungal management of established, invasive yeast infections in adult and paediatric patients in the haematology/oncology setting. Consideration is also given to the critically ill patient in intensive care units, including the neonatal intensive care unit. Evidence for 'pre-emptive' or 'diagnostic-driven antifungal therapy' is also discussed. For the purposes of this paper, invasive yeast diseases are categorised under the headings of invasive candidiasis, cryptococcosis and uncommon yeast infections. Specific recommendations for the management of Pneumocystis jirovecii are presented in an accompanying article (see consensus guidelines by Cooley et al. appearing elsewhere in this supplement).
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Affiliation(s)
- S C Chen
- Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR - Pathology West, Westmead, New South Wales; Department of Infectious Diseases, Westmead Hospital, Westmead, New South Wales; Sydney Medical School, The University of Sydney, Sydney, New South Wales
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36
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Raggam RB, Fischbach LML, Prattes J, Duettmann W, Eigl S, Reischies F, Wölfler A, Rabensteiner J, Prueller F, Krause R, Hoenigl M. Detection of (1→3)-β-D-glucan in same-day urine and serum samples obtained from patients with haematological malignancies. Mycoses 2015; 58:394-8. [PMID: 25959065 DOI: 10.1111/myc.12328] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Revised: 04/03/2015] [Accepted: 04/05/2015] [Indexed: 11/28/2022]
Abstract
Serum 1,3-beta-d-glucan (BDG) testing is an established diagnostic marker for invasive fungal infections (IFI) among patients with haematological malignancies. In contrast limited data exist regarding the application of urine BDG testing. Same-day midstream urine and serum screening samples were collected in adult patients with underlying haematological malignancies. A total of 80 urine samples from 46 patients were investigated: Twenty-six had positive corresponding serum BDG >120 pg ml(-1), 27 intermediate (60-80 pg ml(-1)), and 27 negative serum BDG (<25 pg ml(-1)). A significant positive correlation between BDG in serum and urine samples was observed (P = 0.025; r = 0.252). Sensitivity, specificity, positive predictive value and negative predictive value (compared with same-day serum results) were: 42%, 76%, 46%, 73% when using an 80 pg ml(-1) urine cut-off, and 35%, 96%, 82%, 75% for a 250 pg ml(-1) cut-off. Urine BDG seemed to be higher in samples obtained from patients with probable IFI (n = 13, median 145, IQR 22-253) compared to those from patients without IFI (n = 56, median 24, IQR 15-88) but the difference was not significant (P = 0.069). Overall correlation of same-day urine BDG and serum BDG was moderate. However, urine BDG testing may warrant further investigation in larger studies, as high-positive urine results correlated with high-positive corresponding serum levels and clinical performance was comparable to serum BDG.
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Affiliation(s)
- Reinhard B Raggam
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Lara M L Fischbach
- Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria
| | - Juergen Prattes
- Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria
| | - Wiebke Duettmann
- Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria.,Division of Haematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Susanne Eigl
- Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria.,Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Frederike Reischies
- Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria
| | - Albert Wölfler
- Division of Haematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Jasmin Rabensteiner
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Florian Prueller
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Robert Krause
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Martin Hoenigl
- Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria.,Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.,Division of Infectious Diseases, Department of Medicine, University of California, San Diego, San Diego, USA
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37
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Kunze G, Staritz M, Köhler M. Contrast-enhanced ultrasound in different stages of pyogenic liver abscess. ULTRASOUND IN MEDICINE & BIOLOGY 2015; 41:952-959. [PMID: 25701525 DOI: 10.1016/j.ultrasmedbio.2014.12.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Revised: 10/20/2014] [Accepted: 12/02/2014] [Indexed: 06/04/2023]
Abstract
To enable sonographic classification of different stages of pyogenic liver abscesses, sonographic findings in 86 patients with 113 pyogenic liver abscesses were retrospectively analyzed and compared with established pathomorphologic descriptions of the disease. The typical findings in contrast-enhanced ultrasound were sub-segmental hyperemia (93/113, 82%) and necrosis with a hyperemic margin (109/113, 96%) in the arterial phase and a washout of liver tissue surrounding necrosis in the late phase (101/113, 89%). Four different sonomorphologic stages of pyogenic liver abscess were identified. Stage I was defined by focal inflammation without necrosis (n = 2); stage II by focal clusters of micro-abscesses appearing to coalesce (n = 41); and stage III by a single cavity with or without capsule (n = 64). Stage IV was defined as numerous small abscesses scattered all over the liver (n = 6). The results indicate that contrast-enhanced ultrasound is suitable for classifying different stages of pyogenic liver abscesses. Knowledge of the described morphologic patterns influences therapeutic decisions and helps distinguish abscesses from other liver masses.
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Affiliation(s)
- Georg Kunze
- Department for Internal Medicine and Gastroenterology, Schwarzwald-Baar Klinikum Villingen-Schwenningen, Villingen-Schwenningen, Germany.
| | | | - Michael Köhler
- Department for Internal Medicine and Gastroenterology, Schwarzwald-Baar Klinikum Villingen-Schwenningen, Villingen-Schwenningen, Germany
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Kelly MS, Benjamin DK, Smith PB. The epidemiology and diagnosis of invasive candidiasis among premature infants. Clin Perinatol 2015; 42:105-17, viii-ix. [PMID: 25677999 PMCID: PMC4328135 DOI: 10.1016/j.clp.2014.10.008] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Invasive candidiasis is a leading infectious cause of morbidity and mortality in premature infants. Improved recognition of modifiable risk factors and antifungal prophylaxis has contributed to the recent decline in the incidence of this infection among infants. Invasive candidiasis typically occurs in the first 6 weeks of life and presents with nonspecific signs of sepsis. Definitive diagnosis relies on the growth of Candida in blood culture or cultures from other normally sterile sites, but this may identify fewer than half of cases. Improved diagnostics are needed to guide the initiation of antifungal therapy in premature infants.
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Affiliation(s)
- Matthew S. Kelly
- Duke Clinical Research Institute, Durham, North Carolina
- Department of Pediatrics, Duke University, Durham, North Carolina
| | - Daniel K. Benjamin
- Duke Clinical Research Institute, Durham, North Carolina
- Department of Pediatrics, Duke University, Durham, North Carolina
| | - P. Brian Smith
- Duke Clinical Research Institute, Durham, North Carolina
- Department of Pediatrics, Duke University, Durham, North Carolina
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39
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Badiee P, Amirghofran AA, Ghazi Nour M. Evaluation of noninvasive methods for the diagnosis of fungal endocarditis. Med Mycol 2014; 52:530-6. [DOI: 10.1093/mmy/myu017] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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40
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Okawa T, Ono T, Endo A, Takagi M, Nagasawa M. Chronic disseminated candidiasis complicated with a ruptured intracranial fungal aneurysm in ALL. World J Hematol 2014; 3:44-48. [DOI: 10.5315/wjh.v3.i2.44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Revised: 12/11/2013] [Accepted: 01/20/2014] [Indexed: 02/05/2023] Open
Abstract
An 11-year-old boy with acute lymphocytic leukemia (ALL) contracted disseminated candidiasis during induction therapy, which was complicated with rupture of a fungal cranial aneurysm. Ventricular drainage and coil embolization of a residual aneurysm in combination with intensive antifungal therapy rescued the patient. Although clinical improvement was achieved, high fever and elevated levels of C-reactive protein and β-D-glucan continued for more than 10 mo. One year later, the ALL relapsed during maintenance therapy with methotrexate and 6-mercaptopurine. After salvage chemotherapy, the patient received unrelated bone marrow transplantation (BMT) in a non-complete remission condition and survived. During subsequent chemotherapy and BMT, no recurrence of the fungal infection was observed under the prophylactic anti-fungal therapy with micafungin.
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41
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Novak DA, Lauwers GY, Kradin RL. Bacterial, parasitic, and fungal infections of the liver. LIVER DISEASE IN CHILDREN 2014:673-693. [DOI: 10.1017/cbo9781139012102.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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42
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Mousset S, Buchheidt D, Heinz W, Ruhnke M, Cornely OA, Egerer G, Krüger W, Link H, Neumann S, Ostermann H, Panse J, Penack O, Rieger C, Schmidt-Hieber M, Silling G, Südhoff T, Ullmann AJ, Wolf HH, Maschmeyer G, Böhme A. Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2013; 93:13-32. [PMID: 24026426 PMCID: PMC3889633 DOI: 10.1007/s00277-013-1867-1] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 07/29/2013] [Indexed: 11/28/2022]
Abstract
The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient's risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.
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Affiliation(s)
- Sabine Mousset
- Interdisziplinäres Zentrum für Palliativmedizin, Agaplesion Markus Krankenhaus, Wilhelm Epstein-Straße 4, 60431, Frankfurt, Germany,
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43
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Alothman AF, Al-Musawi T, Al-Abdely HM, Salman JA, Almaslamani M, Yared N, Butt AA, Raghubir N, Morsi WE, Al Thaqafi AO. Clinical practice guidelines for the management of invasive Candida infections in adults in the Middle East region: Expert panel recommendations. J Infect Public Health 2013; 7:6-19. [PMID: 24035607 DOI: 10.1016/j.jiph.2013.08.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Revised: 08/05/2013] [Accepted: 08/12/2013] [Indexed: 11/26/2022] Open
Abstract
Invasive Candida infections contribute to significant morbidity and mortality in patients with healthcare-associated infections. They represent a major burden on the public health system, and are challenging to diagnose and treat. A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for the management of invasive Candida infections in the Middle East. Based on diagnosis, recommendations were provided for the management of Candida infections in non-neutropenic and neutropenic patients. Polyenes (amphotericin B-deoxycholate [AmB-d] and lipid formulations amphotericin B [LFAmB]), triazoles (fluconazole, itraconazole and voriconazole), echinocandins (caspofungin, anidulafungin, and micafungin) and flucytosine are the recommended categories of antifungal agents for treatment of Candida infections. Echinocandins are preferred for treatment of proven and suspected Candida infections, especially in critically ill patients or those with previous exposure to azoles. Recommendations were also provided for infections caused by specific Candida species as well as management of different disease conditions. The experts highlighted that the guidelines should be used along with clinical judgment. Given the paucity of published data from the region, research in the form of randomized clinical trials should be given priority.
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Affiliation(s)
- Adel F Alothman
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
| | | | - Hail M Al-Abdely
- King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
| | | | - Muna Almaslamani
- Hamad Medical Corporation (HMC), Weill Cornell Medical College, Qatar, State of Qatar.
| | - Nadine Yared
- Lebanese University, Faculty of Medical Sciences, Beirut, Lebanon.
| | - Adeel A Butt
- Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.
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Abstract
Invasive fungal infections are an increasingly frequent etiology of sepsis in critically ill patients causing substantial morbidity and mortality. Candida species are by far the predominant agent of fungal sepsis accounting for 10% to 15% of health-care associated infections, about 5% of all cases of severe sepsis and septic shock and are the fourth most common bloodstream isolates in the United States. One-third of all episodes of candidemia occur in the intensive care setting. Early diagnosis of invasive candidiasis is critical in order to initiate antifungal agents promptly. Delay in the administration of appropriate therapy increases mortality. Unfortunately, risk factors, clinical and radiological manifestations are quite unspecific and conventional culture methods are suboptimal. Non-culture based methods (such as mannan, anti-mannan, β-d-glucan, and polymerase chain reaction) have emerged but remain investigational or require additional testing in the ICU setting. Few prophylactic or pre-emptive studies have been performed in critically ill patients. They tended to be underpowered and their clinical usefulness remains to be established under most circumstances. The antifungal armamentarium has expanded considerably with the advent of lipid formulations of amphotericin B, the newest triazoles and the echinocandins. Clinical trials have shown that the triazoles and echinocandins are efficacious and well tolerated antifungal therapies. Clinical practice guidelines for the management of invasive candidiasis have been published by the European Society for Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of North America.
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Affiliation(s)
- Julie Delaloye
- Infectious Diseases Service; Department of Medicine; Centre Hospitalier Universitaire Vaudois and University of Lausanne; Lausanne, Switzerland
| | - Thierry Calandra
- Infectious Diseases Service; Department of Medicine; Centre Hospitalier Universitaire Vaudois and University of Lausanne; Lausanne, Switzerland
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Dang AT, Johnson MA, Bundle DR. Synthesis of a Candida albicans tetrasaccharide spanning the β1,2-mannan phosphodiester α-mannan junction. Org Biomol Chem 2013; 10:8348-60. [PMID: 22996034 DOI: 10.1039/c2ob26355f] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The cell wall phosphomannan of Candida species is a complex N-linked glycoprotein with a glycan chain containing predominantly an α-linked mannose backbone with α-mannose branches. A minor β-mannan component is attached to the branches either via a glycosidic bond (acid stable β-mannan) or a phosphodiester bond (acid-labile β-mannan). The α-mannan residues of the cell wall phosphomannan do not afford protective antibody, while the β-mannan portion is a protective antigen and has become an attractive target as the key epitope of a conjugate vaccine. We report the first synthesis of a tetrasaccharide 1 consisting of a β1,2-mannopyranosyl trisaccharide linked via a phosphodiester to methyl α-mannopyranoside. This encompasses the attachment site of the acid labile β-mannan to the α-mannan component of the cell wall phosphomannan. The trisaccharide was formed by an iterative process to first create a β-glucopyranoside linkage and then epimerize the C-2 center via an oxidation-reduction sequence. The phosphate diester linkage was accessed via an anomeric H-phosphonate. The binding of phosphomannan fragment 1 with the protective antibody C3.1 has been evaluated and compared with a β-mannotrioside in hapten inhibition experiments. The observed activities are rationalized with a model for docked in the binding site of C3.1.
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Affiliation(s)
- Anh-Thu Dang
- Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, Canada
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Sugawara Y, Nakase K, Nakamura A, Ohishi K, Sugimoto Y, Fujieda A, Monma F, Suzuki K, Masuya M, Matsushima Y, Wada H, Nobori T, Katayama N. Clinical utility of a panfungal polymerase chain reaction assay for invasive fungal diseases in patients with haematologic disorders. Eur J Haematol 2013; 90:331-9. [PMID: 23360173 DOI: 10.1111/ejh.12078] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/15/2013] [Indexed: 12/28/2022]
Abstract
OBJECTIVES Invasive fungal diseases (IFDs) are life-threatening events in patients with haematologic disorders, and the spectrum of the aetiological pathogens continues to expand. This study aimed to evaluate the clinical utility of a panfungal polymerase chain reaction (PCR) assay for the management of IFDs in such patients. METHODS We prospectively analysed 273 consecutive blood samples from 64 risk episodes in 51 patients with haematologic disorders at high risk for IFD who were treated at our hospital between April 2007 and October 2010. RESULTS PCR-positive results were obtained in 18 of 64 risk episodes (35.3%). IFD was documented in 14 episodes (21.9%, 9 probable IFDs and 5 possible IFDs) according to the revised criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group. PCR was positive in all of these 14 episodes, and in 4 of the 50 episodes with no IFD category. Sensitivity, specificity, positive predictive value, and negative predictive value of our assay were 100%, 92%, 78% and 100% respectively. A considerable number of fungi (44.4%) that are less common than Aspergillus and Candida species were positive by PCR. Molecular diagnoses of Cunninghamella species, Aspergillus ustus, Fusarium species, Scedosporium apiospermum, Rhodotorula species and Rhizopus species were beneficial in selecting suitable treatments. CONCLUSIONS Our panfungal PCR approach allows for the highly sensitive and specific detection and identification of a wide spectrum of fungal pathogens, which provides indispensable information for managing IFDs, especially refractory or breakthrough IFDs during antifungal therapy in high-risk patients with haematologic disorders.
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Affiliation(s)
- Yumiko Sugawara
- Department of Hematology and Oncology, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, Japan
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Clancy CJ, Nguyen MH. Finding the “Missing 50%” of Invasive Candidiasis: How Nonculture Diagnostics Will Improve Understanding of Disease Spectrum and Transform Patient Care. Clin Infect Dis 2013; 56:1284-92. [DOI: 10.1093/cid/cit006] [Citation(s) in RCA: 424] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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48
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Fleischhacker M, Schulz S, Jöhrens K, von Lilienfeld-Toal M, Held T, Fietze E, Schewe C, Petersen I, Ruhnke M. Diagnosis of chronic disseminated candidosis from liver biopsies by a novel PCR in patients with haematological malignancies. Clin Microbiol Infect 2012; 18:1010-6. [DOI: 10.1111/j.1469-0691.2011.03713.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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49
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Lipinski T, Wu X, Sadowska J, Kreiter E, Yasui Y, Cheriaparambil S, Rennie R, Bundle DR. A β-mannan trisaccharide conjugate vaccine aids clearance of Candida albicans in immunocompromised rabbits. Vaccine 2012; 30:6263-9. [DOI: 10.1016/j.vaccine.2012.08.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2011] [Revised: 08/01/2012] [Accepted: 08/05/2012] [Indexed: 02/07/2023]
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50
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Infections in Leukemia and Hematopoietic Stem Cell Transplantation. LEUKEMIA AND RELATED DISORDERS 2012. [PMCID: PMC7178857 DOI: 10.1007/978-1-60761-565-1_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Infections are one of the most common complications in patients diagnosed with leukemia and serve as a major obstacle to treatment. Through the early 1970s, infections were the most common cause of death in patients diagnosed with acute leukemia, but improvement in treatment and supportive care over the past few decades, coupled with expanded prophylaxis and prevention regimens, have led to reduction in both the frequency and severity of infections. Regardless, due in part to an aging cancer population and the diversity of cancer treatments and procedures, infectious diseases remain a major cause of morbidity and mortality in patients with leukemia.
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