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Microbiology Spectrum Jun 2022A diagnostic-driven (DD) treatment strategy has proven successful for treating invasive fungal infections (IFIs) caused by Aspergillus. However, uptake of this treatment...
Real-World Financial and Clinical Impact of Diagnostic-Driven and Empirical-Treatment Strategies in High-Risk Immunocompromised Patients with Suspected Aspergillus Infection in the United Kingdom.
A diagnostic-driven (DD) treatment strategy has proven successful for treating invasive fungal infections (IFIs) caused by Aspergillus. However, uptake of this treatment strategy is not fully embraced. This study compares the economic and clinical impact of DD and empirical-treatment (ET) strategies used within hospitals. Methods: a decision-analytic model was developed to compare costs and clinical outcomes associated with ET or a DD strategy of identifying infections caused by Aspergillus via galactomannan-antigen testing or Aspergillus polymerase chain reaction (PCR) in neutropenic patients with unexplained fever. Patients were treated prophylactically with antifungal treatments as seen in United Kingdom (UK) hospitals. The IFI incidence, response, mortality, resource use, and adverse events were obtained from meta-analyses and other clinical studies. Analyses were performed from the U.K. hospital perspective, and costs were obtained from standard costing sources. Although diagnostic-testing costs increased, total cost and length of stay were reduced by £1,121 and 1.54 days when treating via a DD strategy. Intensive care and general ward days accounted for > 40% of total costs and > 58% of the cost reduction came from reduced antifungal costs. Treating with a DD strategy reduced the number of patients being treated with antifungal agents while survival was increased. Thus, a DD strategy was cost savings (-£136,787 cost per death avoided) compared with an ET strategy. Conclusion: this study suggests that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever. Patients at risk of invasive fungal infections (IFIs), such as Aspergillus spp., tend to be immunocompromised and usually take several medications which may generate many side effects. Prescribing is further complicated by comorbidities, drug interactions and challenges accessing diagnostics. Therefore, adding another agent may be neither straightforward nor the best option for these types of patients. A diagnostic-driven (DD) treatment strategy has proven successful for treating IFIs. However, uptake of this treatment strategy is not fully embraced in clinical practice perhaps because this strategy is thought to be more costly and/or to result in higher mortality relative to treating empirically. We developed a decision-analytic model to examine the impact of these 2 strategies on costs and health outcomes. This study indicates that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever.
Topics: Antifungal Agents; Aspergillosis; Aspergillus; Humans; Immunocompromised Host; Invasive Fungal Infections; Mycoses; United Kingdom
PubMed: 35532266
DOI: 10.1128/spectrum.00425-22 -
Veterinary Medicine and Science Jan 2023The ubiquitous environmental fungus Aspergillus flavus is also a life-threatening avian pathogen.
BACKGROUND
The ubiquitous environmental fungus Aspergillus flavus is also a life-threatening avian pathogen.
OBJECTIVES
This study aimed to assess the genetic diversity and population structure of A. flavus isolated from turkey lung biopsy or environmental samples collected in a poultry farm.
METHODS
A. flavus isolates were identified using both morphological and ITS sequence features. Multilocus microsatellite genotyping was performed by using a panel of six microsatellite markers. Population genetic indices were computed using FSTAT and STRUCTURE. A minimum-spanning tree (MST) and UPGMA dendrogram were drawn using BioNumerics and NTSYS-PC, respectively.
RESULTS
The 63 environmental (air, surfaces, eggshells and food) A. flavus isolates clustered in 36 genotypes (genotypic diversity = 0.57), and the 19 turkey lung biopsies isolates clustered in 17 genotypes (genotypic diversity = 0.89). The genetic structure of environmental and avian A. flavus populations were clearly differentiated, according to both F-statistics and Bayesian model-based analysis' results. The Bayesian approach indicated gene flow between both A. flavus populations. The MST illustrated the genetic structure of this A. flavus population split in nine clusters, including six singletons.
CONCLUSIONS
Our results highlight the distinct genetic structure of environmental and avian A. flavus populations, indicative of a genome-based adaptation of isolates involved in avian aspergillosis.
Topics: Animals; Aspergillus flavus; Bayes Theorem; Farms; Aspergillosis; Birds; Turkeys; Genetic Structures
PubMed: 36445341
DOI: 10.1002/vms3.1015 -
Journal of Infection and Public Health Feb 2014The incidence of invasive Aspergillus infections in the Middle East continues to rise with the increase in the number of immunocompromised patients, and carries... (Review)
Review
The incidence of invasive Aspergillus infections in the Middle East continues to rise with the increase in the number of immunocompromised patients, and carries significant morbidity and mortality. A panel of experts analysed the evidence from the most recent international guidelines and relevant published literature to reach consensus and develop clear clinical practice guidelines to aid diagnosis and treatment of invasive Aspergillus infections in the Middle East. Disease-specific recommendations were provided for the management of invasive aspergillosis. The expert panel acknowledged that these guidelines should be followed as closely as possible but used alongside clinical judgement.
Topics: Adult; Aspergillosis; Humans; Middle East; Practice Guidelines as Topic
PubMed: 24029495
DOI: 10.1016/j.jiph.2013.08.003 -
Clinical Microbiology and Infection :... Jul 2009Patterns of invasive fungal infections are changing in many ways. Although yeast infections appear to have reached a stable incidence, the number of infections as a... (Review)
Review
Patterns of invasive fungal infections are changing in many ways. Although yeast infections appear to have reached a stable incidence, the number of infections as a result of Aspergillus species appears to be increasing. Especially for mould infection, the diagnosis remains difficult and the detection and identification of clinically relevant isolates to the species level requires new validated techniques. Diagnostic tests are becoming more accurate, with biological markers such as PCR, galactomannan and 1,3 beta-D-glucan undergoing clinical validation. This is of importance because an early diagnosis is associated with increased survival. Correct diagnosis and in vitro susceptibility testing are becoming imperative for guidance of therapy in the context of changing epidemiology and the emergence of acquired resistance to antifungal drugs, as is insight into host factors that increase susceptibility to invasive mould infection and into the risks associated with new treatment modalities of underlying diseases. Despite improvements in the survival rates of patients with invasive fungal infection in recent years, continued research is required to meet the challenges associated with changes in epidemiology and resistance development.
Topics: Antifungal Agents; Aspergillosis; Aspergillus; Fungi; Genetic Predisposition to Disease; Humans; Mycoses
PubMed: 19673973
DOI: 10.1111/j.1469-0691.2009.02929.x -
Revista Da Associacao Medica Brasileira... 2023The aim of this study was to evaluate the demographic data, molecular epidemiology, and in vitro antifungal susceptibility results of patients with Aspergillus isolated...
OBJECTIVE
The aim of this study was to evaluate the demographic data, molecular epidemiology, and in vitro antifungal susceptibility results of patients with Aspergillus isolated from various clinical specimens.
METHODS
A total of 44 Aspergillus strains were studied. The definition of invasive aspergillosis in patients was made according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Strains were phenotypically and molecularly identified. Demographic characteristics of patients and genotypes of strains were evaluated. Phylogenetic analysis was done by the The Unweighted Pair-Group Method with Arithmetic Mean (UPGMA). Antifungal susceptibility of strains was determined according to The Clinical and Laboratory Standards Institute (CLSI)-M61-Ed2 and The European Committee on Antimicrobial Susceptibility Testing (EUCAST).
RESULTS
A total of 11 patients were classified as proven and 33 as probable invasive aspergillosis. There was a statistically significant difference in age groups, subdisease, neutropenic, and receiving chemotherapy between groups. A total of 23 strains were identified as Aspergillus fumigatus, 12 as Aspergillus niger, 6 as Aspergillus flavus, and 3 as Aspergillus terreus. Phylogenetic analysis revealed five different genotypes. No statistical difference was found in the comparisons between patients groups and genotype groups. There was a statistically significant difference between genotype groups and voriconazole, posaconazole, and itraconazole Minimum Inhibition Concentration (MIC).
CONCLUSION
Accurate identification of strains and antifungal susceptibility studies should be performed due to azole and amphotericin B resistance. Genotyping studies are important in infection control due to identifying sources of infection and transmission routes.
Topics: Humans; Antifungal Agents; Molecular Epidemiology; Phylogeny; Aspergillosis; Aspergillus; Invasive Fungal Infections
PubMed: 36820712
DOI: 10.1590/1806-9282.20220441 -
PLoS Pathogens Aug 2021Aspergillus fumigatus is a saprophytic, filamentous fungus found in soils and compost and the causative agent of several pulmonary diseases in humans, birds, and other... (Review)
Review
Aspergillus fumigatus is a saprophytic, filamentous fungus found in soils and compost and the causative agent of several pulmonary diseases in humans, birds, and other mammals. A. fumigatus and other filamentous fungi grow as networks of filamentous hyphae that have characteristics of a classic microbial biofilm. These characteristics include production of an extracellular matrix (ECM), surface adhesion, multicellularity, and increased antimicrobial drug resistance. A. fumigatus biofilm growth occurs in vivo at sites of infection, highlighting the importance of defining mechanisms underlying biofilm development and associated emergent properties. We propose that there are 3 distinct phases in the development of A. fumigatus biofilms: biofilm initiation, immature biofilm, and mature biofilm. These stages are defined both temporally and by unique genetic and structural changes over the course of development. Here, we review known mechanisms within each of these stages that contribute to biofilm structure, ECM production, and increased resistance to contemporary antifungal drugs. We highlight gaps in our understanding of biofilm development and function that when addressed are expected to aid in the development of novel antifungal therapies capable of killing filamentous fungal biofilms.
Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Biofilms; Disease Progression; Drug Resistance, Fungal; Humans; Microbial Viability
PubMed: 34437655
DOI: 10.1371/journal.ppat.1009794 -
Japanese Journal of Infectious Diseases Mar 2023Invasive aspergillosis (IA) is a major cause of morbidity and mortality. This study aimed to present our 10-year IA experience at a single center. Fifty-nine pediatric...
Invasive aspergillosis (IA) is a major cause of morbidity and mortality. This study aimed to present our 10-year IA experience at a single center. Fifty-nine pediatric patients with IA were included in this study. The male-to-female ratio was 42/17. The median age was 8.75 years. Hematologic malignancy was present in the majority of the patients (40/59, 68%). The mean neutropenia duration was 18.5 days. Cytosine arabinoside was the most common immunosuppressive therapy directed at T cells during IA diagnosis. IA cases were categorized as proven (27%), probable (51%), or possible (22%) according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. The lungs (78%) were the most common site of IA, and nodules were the most frequent radiological findings (75.5%). In 38 patients (64.4%) receiving antifungal prophylaxis, prophylactic agents included fluconazole (30.5%), liposomal amphotericin B (23.7%), posaconazole (8.5%), and voriconazole (1.7%). Initial treatment was most commonly administered as monotherapy (69.5%). The median antifungal treatment duration was 67 days. Eleven deaths (18.6%) were due to aspergillosis. With the increased use of corticosteroids, biological agents, and intensive immunosuppressive chemotherapy, IA will most likely continue to occur frequently in pediatric patients.
Topics: Humans; Male; Child; Female; Antifungal Agents; Retrospective Studies; Aspergillosis; Voriconazole; Invasive Fungal Infections
PubMed: 36450573
DOI: 10.7883/yoken.JJID.2022.346 -
Annals of Clinical Microbiology and... Jun 2021Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT). (Review)
Review
BACKGROUND
Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT).
METHODS
Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline.
RESULTS
Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%).
CONCLUSION
CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.
Topics: Antifungal Agents; Asia; Aspergillosis; Central Nervous System; Databases, Factual; Europe; Female; Humans; Leukemia; Male; Stem Cell Transplantation; Voriconazole
PubMed: 34130699
DOI: 10.1186/s12941-021-00452-9 -
BMC Infectious Diseases Jan 2019The preventive effect of laminar air flow (LAF) on aspergillosis has been observed in patients with hematological malignancies. However, the short follow-up period...
BACKGROUND
The preventive effect of laminar air flow (LAF) on aspergillosis has been observed in patients with hematological malignancies. However, the short follow-up period limits the interpretation of study results.
METHODS
To assess the preventive effect of long-term LAF use on aspergillosis in its long-term use, we retrospectively analyzed 124 acute leukemia patients at our hospital between January 2005 and March 2016. We compared the incidence of aspergillosis before (May 2008) and during the construction of a new building (June 2008-January 2010) and in the early (February 2010-March 2014) and late (April 2014-March 2016) periods after moving to a new hematology ward with an LAF system. The 2008 European Organization for Research and Treatment of Cancer and Mycosis Study Group criteria were used for the diagnosis of aspergillosis.
RESULTS
Fourteen patients were diagnosed with possible, probable, or definite aspergillosis. Cumulative incidence rates of aspergillosis at day 180 were 12.4, 24.9, 9.3, and 25.1% before construction, during construction, in the early period after moving to a new ward, and in the late period after moving to a new ward, respectively (p = 0.106). Multivariate analysis showed that the LAF system tended to reduce the risk of aspergillosis in the early period (before construction vs. early period; hazards ratio (HR) = 1.97, p = 0.463 and during construction vs. early period;HR = 3.42, p = 0.184), but the risk increased in the late period (late vs. early period, HR = 5.65, p = 0.035).
CONCLUSIONS
Building construction might increase the risk of aspergillosis. Short-term LAF use might reduce aspergillosis risk, but its long-term use is inadequate, although we could not exclude the possibility of increased risks in the recent period due to continued improvements in the different areas of our hospital. Strict maintenance, more effective LAF system, and optimization of aspergillosis prophylaxis may be necessary.
Topics: Aspergillosis; Environment, Controlled; Hospital Design and Construction; Hospitalization; Humans; Incidence; Leukemia, Myeloid, Acute; Retrospective Studies
PubMed: 30626352
DOI: 10.1186/s12879-018-3665-9 -
Medicine Jul 2000
Topics: Antifungal Agents; Aspergillosis; Diagnosis, Differential; Humans; Immunocompromised Host; Prognosis
PubMed: 10941357
DOI: 10.1097/00005792-200007000-00009