Invasive fungal infections in chronic lymphoproliferative disorders: a monocentric retrospective study.
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ABSTRACT:
SUBMITTER: Tisi MC
PROVIDER: S-EPMC5394967 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
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Invasive fungal infections in chronic lymphoproliferative disorders: a monocentric retrospective study.
Tisi Maria Chiara MC Hohaus Stefan S Cuccaro Annarosa A Innocenti Idanna I De Carolis Elena E Za Tommaso T D'Alò Francesco F Laurenti Luca L Fianchi Luana L Sica Simona S Sanguinetti Maurizio M De Stefano Valerio V Pagano Livio L
Haematologica 20161117 3
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Project description:IntroductionInvasive fungal infections (IFIs) are a significant health problem in immunocompromised patients, resulting in substantial morbidity, mortality, and healthcare costs. Micafungin is a broad-spectrum echinocandin with activity against Candida and Aspergillus spp. This was a multicenter, non-comparative, retrospective observational study that evaluated the effectiveness and tolerability of intravenously administered micafungin for treating IFIs caused by Candida and Aspergillus spp.MethodsAdult patients in China who had received at least one dose of intravenously administered micafungin were eligible. Retrospective data (May 2008-April 2015) were extracted from patients' medical files and recorded using electronic data capture. The primary endpoint was overall success rate (patients with complete or partial response). Subgroup analyses determined effectiveness according to diagnostic certainty, fungal species, type of IFI, duration of micafungin treatment, and daily dose of micafungin. Tolerability, including the incidence of adverse events (AEs), was also assessed.ResultsOverall, 2555 patients who received at least one dose of micafungin were identified. The mean duration of treatment and mean daily dose were 10.2 days and 133.0 mg, respectively. The overall success rate was 60.8%; this was significantly higher in patients who received treatment for at least 1 week (range 67.9-71.6% [mean 69.2%]) compared with less than 1 week (47.8%; P < 0.0001), and those who received 50-100 mg (65.7%) compared with other daily doses (range 42.9-60.1% [mean 59.0%]; P = 0.0011). Success rates in Candida- and Aspergillus-infected patients were similar (61.9% and 56.8%, respectively). AEs and adverse drug reactions were observed in 36.2% and 4.5% of patients, respectively. The majority of AEs were mild, while discontinuation due to AEs was low (2.3%).ConclusionMicafungin is effective and well tolerated for the treatment of patients with IFIs in China, as demonstrated in Candida- and Aspergillus-infected adults. Subgroup analyses highlighted the potential benefits of treating IFIs with micafungin for a minimum of 1 week.Trial registrationClinicalTrials.gov identifier NCT02678598.FundingAstellas Pharma Inc.
| S-EPMC6133133 | biostudies-literature
Project description:Morbidity and mortality from invasive fungal infections remain unacceptably high despite availability of new antifungal agents, underscoring the need for more effective preventative strategies. Due to our enhanced understanding of the host defense and pathogenetic mechanisms that lead to invasive fungal infections, it should be feasible to develop vaccines targeting these infections. A common immunological theme across many vaccine candidates for invasive fungal infections has been the need to activate a cell-based, pro-inflammatory, Th1 or Th17 immune response to improve phagocytic killing of the fungi. Since neutralization of virulence factor functions has not been required for many active vaccines to function, the antigenic repertoire available for testing should not be limited to virulence factors. With expansion of our fundamental understanding of the immunology of fungal infections, the biggest barrier to development of fungal vaccines is the lack of available capital to translate discoveries made at the bench into biological agents used at the bedside. Continued education on the importance and feasibility of vaccination for such infections, combined with continued development of vaccine antigens and adjuvants, is necessary.
| S-EPMC3155210 | biostudies-literature
Project description:Background and objectivesThe implications of the genetic component in the initiation and development of chronic lymphoproliferative disorders have been the subject of intense research efforts. Some of the most important genes involved in the occurrence and evolution of these pathologies are the HLA genes. The aim of this study is to analyze, for the first time, possible associations between chronic lymphoproliferative diseases and certain HLA alleles in the Romanian population.Materials and methodsThis study included 38 patients with chronic lymphoproliferative disorders, diagnosed between 2021 and 2022 at Fundeni Clinical Institute, Bucharest, Romania, and 50 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQB1/DPB1/DRB1) were investigated by doing high resolution genotyping using sequence specific primers (SSP).ResultsSeveral HLA alleles were strongly associated with chronic lymphoproliferative disorders. The most important finding was that the HLA-C*02:02 (p = 0.002, OR = 1.101), and HLA-C*12:02 (p = 0.002, OR = 1.101) have a predisposing role in the development of chronic lymphoproliferative disorders. Moreover, we identified that HLA-A*11:01 (p = 0.01, OR = 0.16), HLA-B*35:02 (p = 0.037, OR = 0.94), HLA-B*81:01 (p = 0.037, OR = 0.94), HLA-C*07:02 (p = 0.036, OR = 0.34), HLA-DRB1*11:01 (p = 0.021, OR = 0.19), and HLA-DRB1*13:02 (p = 0.037, OR = 0.94), alleles have protective roles.ConclusionsOur study indicates that HLA-C*02:02 and HLA-C*12:02 are positively associated with chronic lymphoproliferative disorders for our Romanian patients while HLA-DRB1*11:01, HLA-DRB1*13:02, and HLA-B*35:02 alleles have a protective role against these diseases.
| S-EPMC10972167 | biostudies-literature
Project description:Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening neoplasms after organ transplantation. Because of their rarity and multiple grades of malignancy, the incidence, outcomes, and clinicopathological features affecting patient survival after liver transplantation (LT) remain unclear. We reviewed 1954 LTs in 1849 recipients (1990-2020), including 886 pediatric (<18 years of age) and 963 adult recipients. The following clinicopathological factors were studied: age, sex, liver etiologies, malignancy grades, Epstein-Barr virus status, performance status (PS), Ann Arbor stage, international prognostic index, and histopathological diagnosis. Of 1849 recipients, 79 PTLD lesions (4.3%) were identified in 70 patients (3.8%). After excluding 3 autopsy cases incidentally found, 67 (45 pediatric [5.1%] and 22 adult [2.3%]) patients were finally enrolled. Comorbid PTLDs significantly worsened recipient survival compared with non-complicated cases (P < 0.001). The 3-year, 5-year, and 10-year overall survival rates after PTLD diagnosis were 74%, 66%, and 58%, respectively. The incidence of PTLDs after LT (LT-PTLDs) was significantly higher (P < 0.001) with earlier onset (P = 0.002) in children, whereas patient survival was significantly worse in adults (P = 0.002). Univariate and multivariate analyses identified the following 3 prognostic factors: age at PTLD diagnosis ≥18 years (hazard ratio [HR], 11.2; 95% confidence interval [CI], 2.63-47.4; P = 0.001), PS ≥2 at diagnosis (HR, 6.77; 95% CI, 1.56-29.3; P = 0.01), and monomorphic type (HR, 6.78; 95% CI, 1.40-32.9; P = 0.02). A prognostic index, the "LT-PTLD score," that consists of these 3 factors effectively stratified patient survival and progression-free survival (P = 0.003 and <0.001, respectively). In conclusion, comorbid PTLDs significantly worsened patient survival after LT. Age ≥18 years and PS ≥2 at PTLD diagnosis, and monomorphic type are independent prognostic factors, and the LT-PTLD score that consists of these 3 factors may distinguish high-risk cases and guide adequate interventions.
| S-EPMC8453854 | biostudies-literature
Project description:Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined.Articles were retrieved form PubMed covering the years 2000-2012. Various search terms were used. Then the articles were clustered in different types like 'review,' 'pharmacokinetics,' 'case reports' and others.From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed.The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at ClinicalTrials.gov has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics.The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.
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Project description:Few data are available on infectious complications in critically ill patients with different viral infections. We performed a retrospective monocentric study including all of the patients admitted to the intensive care unit (ICU) with confirmed COVID-19 (as of 13 March 2020) or Influenza A and/or B infections (as of 1 January 2015) until 20 April 2020. Coinfection and secondary infections (occurring within and after 48 h from admission, respectively) were recorded. Fifty-seven COVID-19 and 55 Influenza patients were included. Co-infections were documented in 13/57 (23%) COVID-19 patients vs. 40/55 (73%) Influenza patients (p < 0.001), most of them being respiratory (9/13, 69% vs. 35/40, 88%; p = 0.13) and of bacterial origin (12/13, 92% vs. 29/40, 73%; p = 0.25). Invasive aspergillosis infections were observed only in Influenza patients (8/55, 15%). The COVID-19 and Influenza patients presented 1 (0–4) vs. 0 (0–4) secondary infections (p = 0.022), with comparable sites being affected (lungs: 35/61, 57% vs. 13/31, 42%; p = 0.16) and causative pathogens occurring (Gram-negative bacteria: 51/61, 84% vs. 23/31, 74%; p > 0.99). The COVID-19 patients had longer ICU lengths of stay (15 (–65) vs. 5 (1–89) days; p = 0.001), yet the two groups had comparable mortality rates (20/57, 35% vs. 23/55, 41%; p = 0.46). We report fewer co-infections but more secondary infections in the ICU COVID-19 patients compared to the Influenza patients. Most of the infectious complications were respiratory and of bacterial origin.
| S-EPMC9219538 | biostudies-literature
Project description:ObjectiveInvasive sino-orbital fungal infections in immunocompetent patients are a rare clinical entity; the diagnosis and management of which is challenging. We present a large case series of invasive sino-orbital fungal granulomas in patients without pre-existing systemic immunocomprimising condition.DesignRetrospective case series.ParticipantsTwenty cases of invasive sino-orbital/naso-orbital fungal granulomas in immunocompetent individuals.MethodsWe retrospectively analyzed all patients with orbital fungal granuloma who were treated at a tertiary referral eye center in South India between January 2005 and December 2012. Histopathologic confirmation of tissue invasion by fungal elements and presence of granulomatous inflammation was established in all cases included in the study.Main outcome measuresRelief of patient symptoms, resolution/no progression of disease on orbital imaging, ocular, and vision salvage were the treatment outcomes studied.ResultsTwenty patients (11 male and 9 female) were studied. Mean age of patients was 47.4 years ranging from 24-65 years. Aspergillus was the causative fungus in 18 cases while 2 were cases of mucormycosis. Surgical debulking of the orbital disease was performed in 7 patients. Exenteration was performed in 2 patients to prevent spread to the CNS. Medical therapy consisted of oral itraconazole in all patients and intravenous amphotericin B was administered in 2 patients. Average duration of medical therapy required to achieve relief from symptoms was 6-8 months. Recurrences are common and long-term follow-up is essential.ConclusionsOrbital fungal infections are challenging in terms of both diagnosis and treatment. Debulking along with prolonged antifungal therapy seems to be effective in controlling the infection.
| S-EPMC6707179 | biostudies-literature
Project description:Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug-drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA) or mucormycosis. Similar to amphotericin B and posaconazole, isavuconazole exhibits a broad spectrum of in vitro activity against yeasts, dimorphic fungi, and molds. Isavuconazole is available in both oral and intravenous formulations, exhibits a favorable safety profile (notably the absence of QTc prolongation), and reduced drug-drug interactions (relative to voriconazole). Phase 3 studies have evaluated the efficacy of isavuconazole in the management of IA, mucormycosis, and invasive candidiasis. Based on the results of these studies, isavuconazole appears to be a viable treatment option for patients with IA as well as those patients with mucormycosis who are not able to tolerate or fail amphotericin B or posaconazole therapy. In contrast, evidence of isavuconazole for invasive candidiasis (relative to comparator agents such as echinocandins) is not as robust. Therefore, isavuconazole use for invasive candidiasis may initially be reserved as a step-down oral option in those patients who cannot receive other azoles due to tolerability or spectrum of activity limitations. Post-marketing surveillance of isavuconazole will be important to better understand the safety and efficacy of this agent, as well as to better define the need for isavuconazole serum concentration monitoring.
| S-EPMC4977098 | biostudies-other
Project description:More antifungal agents have reached clinical use in the past two decades than at any other time. The echinocandins have been a welcome addition to this group, with the latest being anidulafungin. There are several lines of evidence to support anidulafungin's role as primary therapy for the treatment of invasive candidiasis in non-neutropenic patients, and as alternative therapy to fluconazole in patients with esophageal candidiasis with azole intolerance or triazole-resistant Candida. Pharmacokinetic-pharmacodynamic studies in animals have demonstrated superior efficacy, defined as maximal microbial kill, when compared to fluconazole, regardless of the fluconazole susceptibility of the Candida species. These studies, as well as dose-effect studies in patients, also support the currently recommended dose of anidulafungin. A well designed randomized controlled trial has demonstrated anidulafungin's efficacy in patients with invasive candidiasis. In this paper, we argue that anidulafungin may be preferable to fluconazole for the treatment of candidemia. However, as of yet, the difference between anidulafungin and the other two licensed echinocandins as first-line therapy for invasive candidiasis is unclear. On the other hand, there is insufficient evidence as of yet to support first-line use of anidulafungin in patients with neutropenia or aspergillosis.
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Project description:Granulocyte transfusions have a long history of being used in patients with neutropenia or neutrophil dysfunction to prevent and treat invasive fungal infections. However, there are limited and conflicting data concerning its clinical effectiveness, considerable variations in current granulocyte transfusion practices, and uncertainties about its benefit as an adjunct to modern antifungal therapy. In this review, we provide an overview on granulocyte transfusions and summarize the evidence on their role in the prevention and treatment of invasive fungal infections.
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