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1.
J Infect Dev Ctries ; 18(4): 636-639, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38728631

RESUMO

INTRODUCTION: Kodamaea ohmeri is a rare, recognized pathogen that has previously been isolated from environmental sources. The patients commonly affected by this yeast include immunocompromised as well as immunocompetent patients having several associated risk factors. METHODOLOGY: We report three cases in which K. ohmeri was isolated from blood using Bact T/ALERT. Identification was carried out by MALDI-TOF MS (Vitek-MS, BioMérieux, Marcy-l'Etoile, France) in addition to color characteristics on chromogenic media. The patients had diminished immune response on account of a multitude of comorbidities. RESULTS: K. ohmeri can be misidentified as Candida tropicalis, Candida albicans, or Candida hemolounii by conventional methods; correct and timely identification can be achieved by MALDI-TOF MS. Antifungal susceptibility breakpoints for K. ohmeri are currently not defined. An Echinocandin was added to the treatment regimen of all three of the cases. CONCLUSIONS: Identification of K. ohmeri using conventional methods is difficult and unusual yeasts should be carefully observed, especially upon prolonged incubation.


Assuntos
Antifúngicos , Hospedeiro Imunocomprometido , Saccharomycetales , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Masculino , Saccharomycetales/isolamento & purificação , Saccharomycetales/efeitos dos fármacos , Feminino , Pessoa de Meia-Idade , Idoso , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/microbiologia , Técnicas Microbiológicas
2.
J Clin Microbiol ; 62(5): e0039424, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38602412

RESUMO

Aspergillus species and Mucorales agents are the primary etiologies of invasive fungal disease (IFD). Biomarkers that predict outcomes are needed to improve care. Patients diagnosed with invasive aspergillosis and mucormycosis using plasma cell-free DNA (cfDNA) PCR were retested weekly for 4 weeks. The primary outcome included all-cause mortality at 6 weeks and 6 months based on baseline cycle threshold (CT) values and results of follow-up cfDNA PCR testing. Forty-five patients with Aspergillus and 30 with invasive Mucorales infection were retested weekly for a total of 197 tests. Using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, 30.7% (23/75), 25.3% (19/75), and 38.7% (29/75) had proven, probable, and possible IFD, respectively. In addition, 97.3% (73/75) were immunocompromised. Baseline CT increased significantly starting at week 1 for Mucorales and week 2 for Aspergillus. Aspergillosis and mucormycosis patients with higher baseline CT (CT >40 and >35, respectively) had a nonsignificantly higher survival rate at 6 weeks, compared with patients with lower baseline CT. Mucormycosis patients with higher baseline CT had a significantly higher survival rate at 6 months. Mucormycosis, but not aspergillosis patients, with repeat positive cfDNA PCR results had a nonsignificantly lower survival rate at 6 weeks and 6 months compared with patients who reverted to negative. Aspergillosis patients with baseline serum Aspergillus galactomannan index <0.5 and <1.0 had significantly higher survival rates at 6 weeks when compared with those with index ≥0.5 and ≥1.0, respectively. Baseline plasma cfDNA PCR CT can potentially be used to prognosticate survival in patients with invasive Aspergillus and Mucorales infections. IMPORTANCE: We show that Aspergillus and Mucorales plasma cell-free DNA PCR can be used not only to noninvasively diagnose patients with invasive fungal disease but also to correlate the baseline cycle threshold with survival outcomes, thus potentially allowing the identification of patients at risk for poor outcomes, who may benefit from more targeted therapies.


Assuntos
Ácidos Nucleicos Livres , DNA Fúngico , Infecções Fúngicas Invasivas , Mucormicose , Reação em Cadeia da Polimerase , Humanos , Mucormicose/diagnóstico , Mucormicose/mortalidade , Mucormicose/sangue , Mucormicose/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Ácidos Nucleicos Livres/sangue , Reação em Cadeia da Polimerase/métodos , Adulto , DNA Fúngico/genética , DNA Fúngico/sangue , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/mortalidade , Infecções Fúngicas Invasivas/microbiologia , Aspergillus/genética , Aspergillus/isolamento & purificação , Aspergilose/diagnóstico , Aspergilose/mortalidade , Aspergilose/microbiologia , Mucorales/genética , Mucorales/isolamento & purificação , Biomarcadores/sangue , Idoso de 80 Anos ou mais , Estudos Prospectivos
3.
J Infect ; 88(5): 106147, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555035

RESUMO

INTRODUCTION: Invasive mould infections (IMIs) are a leading cause of death in patients with compromised immune systems. Proven invasive mould infection requires detection of a fungus by histopathological analysis of a biopsied specimen, sterile culture, or fungal DNA amplification by PCR in tissue. However, the clinical performance of a PCR assay on blood samples taken from patients suspected of invasive mould disease has not been fully evaluated, particularly for the differential diagnosis of invasive aspergillosis (IA) and invasive Mucormycosis (IM). OBJECTIVES: To assess the diagnostic utility of our previously validated in-house real-time PCR in blood samples for diagnosis of invasive aspergillosis and mucormycosis in patients with suspected invasive mould infection. METHODS: All patients with suspected invasive mould infection were prospectively enrolled from May 2021 to July 2021. Conventional fungal diagnosis was performed using tissue and respiratory samples. In-house PCR was performed on blood samples and its diagnostic performance evaluated. RESULTS: A total of 158 cases of suspected invasive mould infection were enrolled in the study. The sensitivity and specificity of in-house PCR performed on blood samples was found to be 92.5% and 81.4% respectively for diagnosis of probable IA, and 65% and 84.62% respectively for diagnosis of proven and probable IM. It was also able to detect 3 out of 5 cases of possible IM where no other microbiological evidence of IM was obtained. CONCLUSIONS: This assay could be helpful in minimally invasive diagnosis of IMIs for patients in whom invasive sampling is not feasible, especially as a preliminary or screening test. It can help in early diagnosis, anticipating conventional laboratory confirmation by days or weeks. Possible correlation between fungal load and mortality can help in initiating aggressive treatment for patients with high initial fungal load.


Assuntos
Infecções Fúngicas Invasivas , Mucormicose , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Mucormicose/diagnóstico , Mucormicose/microbiologia , Mucormicose/sangue , Adulto , Estudos Prospectivos , Idoso , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/sangue , DNA Fúngico/sangue , DNA Fúngico/genética , Aspergilose/diagnóstico , Aspergilose/microbiologia , Aspergilose/sangue , Diagnóstico Precoce , Adulto Jovem , Idoso de 80 Anos ou mais , Diagnóstico Diferencial
4.
Expert Rev Clin Pharmacol ; 17(4): 309-321, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38379525

RESUMO

INTRODUCTION: Despite advancements, invasive fungal infections (IFI) still carry high mortality rates, often exceeding 30%. The challenges in diagnosis, coupled with limited effective antifungal options, make managing IFIs complex. Antifungal drugs are essential for IFI management, but their efficacy can be diminished by drug-drug interactions and pharmacokinetic variability. Therapeutic Drug Monitoring (TDM), especially in the context of triazole use, has emerged as a valuable strategy to optimize antifungal therapy. AREAS COVERED: This review provides current evidence regarding the potential benefits of TDM in IFI management. It discusses how TDM can enhance treatment response, safety, and address altered pharmacokinetics in specific patient populations. EXPERT OPINION: TDM plays a crucial role in achieving optimal therapeutic outcomes in IFI management, particularly for certain antifungal agents. Preclinical studies consistently show a link between therapeutic drug levels and antifungal efficacy. However, clinical research in mycology faces challenges due to patient heterogeneity and the diversity of fungal infections. TDM's potential advantages in guiding Echinocandin therapy for critically ill patients warrant further investigation. Additionally, for drugs like Posaconazole, assessing whether serum levels or alternative markers like saliva offer the best measure of efficacy is an intriguing question.


Assuntos
Infecções Fúngicas Invasivas , Micoses , Humanos , Antifúngicos , Monitoramento de Medicamentos , Micoses/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Estado Terminal
5.
Curr Opin Pediatr ; 36(2): 136-143, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299979

RESUMO

PURPOSE OF REVIEW: Invasive fungal infection (IFI) in children is a growing problem with crescent morbidity and mortality, well recognized in developed countries, affecting mainly immunocompromised children, including neonates and children in intensive care units. The burden of IFI in South American children is less well comprehended. In addition, the current epidemiology of endemic systemic mycoses in children may have changed over time. RECENT FINDINGS: Candida spp. infections are very prevalent in South America hospitalized children, especially in neonates, in a rate far superior compared to developed countries. C. auris, has already been responsible for outbreaks in neonates and children in Venezuela and Colombia. Sporotrichosis is well established as an urban zoonosis in impoverish families. Paracoccidioidomycosis and histoplasmosis are affecting new areas of Brazil, probably due to climate change, deforestation, and human migration. SUMMARY: This review aims to unveil the real dimension of these infections in South American children. Hopefully, the awareness brought by this review will help healthcare professionals to recognize IFI more easily and it will provide support for getting more resources for IFI treatment and prevention.


Assuntos
Infecções Fúngicas Invasivas , Micoses , Criança , Recém-Nascido , Humanos , Candida , Mudança Climática , Infecções Fúngicas Invasivas/microbiologia , América do Sul/epidemiologia
6.
Infection ; 52(1): 197-208, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37656348

RESUMO

BACKGROUND: We assessed the laboratory diagnosis and treatment of invasive fungal disease (IFD) in Italy to detect limitations and potential for improvement. METHODS: The survey was available online at www.clinicalsurveys.net/uc/IFI management capacity/, and collected variables such as (a) institution profile, (b) perceptions of IFD in the respective institution, (c) microscopy, (d) culture and fungal identification, (e) serology, (f) antigen detection, (g) molecular tests, (h) susceptibility testing and (i) therapeutic drug monitoring (TDM). RESULTS: The laboratory capacity study received responses from 49 Italian centres, with an equitable geographical distribution of locations. The majority of respondents (n = 36, 73%) assessed the occurrence of IFD as moderate-high, with Aspergillus spp. being the pathogen of highest concern, followed by Candida spp. and Mucorales. Although 46 (94%) of the institutions had access to microscopy, less than half of them performed direct microscopy on clinical specimens always when IFD was suspected. Cultures were available in all assessed laboratories, while molecular testing and serology were available in 41 (83%), each. Antigen detection tests and antifungal drugs were also generally accessible (> 90%) among the participating institutions. Nevertheless, access to TDM was limited (n = 31, 63%), with a significant association established between therapeutic drug monitoring availability and higher gross domestic product per capita. CONCLUSIONS: Apart from TDM, Italy is adequately prepared for the diagnosis and treatment of IFD, with no significant disparities depending on gross domestic product. Future efforts may need to focus on enhancing the availability and application of direct microscopic methods, as well as TDM, to promote optimal treatment and better patient outcomes.


Assuntos
Infecções Fúngicas Invasivas , Laboratórios , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Antifúngicos/uso terapêutico , Candida , Aspergillus
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 44(12): 1984-1987, 2023 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-38129157

RESUMO

The WHO established the first fungal priority pathogens list (FPPL) in October 2022 to focus on and promote further research and policy interventions to strengthen the global response to fungal infections and antifungal resistance. The FPPL and its formulation process provide new significant insights for managing pathogenic fungi and invasive fungal disease (IFD) in China, necessitating the following key actions: Strengthen public health interventions for IFD. Further, it improves the ability of laboratory testing and clinical supervision for IFD and pathogenic fungi. Increase targeted investment and support for innovative research and development in IFD diagnosis, treatment, and prevention.


Assuntos
Infecções Fúngicas Invasivas , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Fungos , China/epidemiologia , Antifúngicos/uso terapêutico
9.
Artigo em Chinês | MEDLINE | ID: mdl-37805724

RESUMO

Invasive fungal infection (IFI) is one of the serious complications in burn patients. The gradual development and application of broad-spectrum antibiotics in recent years has led to a serious dysbiosis of the flora, while the widespread prophylactic use of antifungal drugs has led to an increasing number of drug-resistant fungi. The clinical treatment of IFI is difficult and the prognosis is poor. The mortality of burn patients caused by IFI is increasing year by year. This paper reviews the epidemiologic characteristics, related risk factors, diagnostic methods, and treatment progress of IFI after burns, aiming to provide new ideas and reference for the prevention and treatment of IFI after burns.


Assuntos
Queimaduras , Infecções Fúngicas Invasivas , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/microbiologia , Fungos , Antifúngicos/uso terapêutico , Fatores de Risco , Queimaduras/complicações , Queimaduras/tratamento farmacológico
10.
Future Microbiol ; 18: 1095-1117, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37750748

RESUMO

Fungal infections are a serious problem affecting many people worldwide, creating critical economic and medical consequences. Fungi are ubiquitous and can cause invasive diseases in individuals mostly living in developing countries or with weakened immune systems, and antifungal drugs currently available have important limitations in tolerability and efficacy. In an effort to counteract the high morbidity and mortality rates associated with invasive fungal infections, various approaches are being utilized to discover and develop new antifungal agents. This review discusses the challenges posed by fungal infections, outlines different methods for developing antifungal drugs and reports on the status of drugs currently in clinical trials, which offer hope for combating this serious global problem.


Assuntos
Infecções Fúngicas Invasivas , Micoses , Humanos , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Micoses/microbiologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Fungos
11.
Adv Drug Deliv Rev ; 199: 114967, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37336246

RESUMO

In patients with compromised immunity, invasive fungal infections represent a significant cause of mortality. Given the limited availability and drawbacks of existing first-line antifungal drugs, there is a growing interest in exploring novel targets that could facilitate the development of new antifungal agents or enhance the effectiveness of conventional ones. While previous studies have extensively summarized new antifungal targets inherent in fungi for drug development purposes, the exploration of potential targets for novel antifungal drug delivery strategies has received less attention. In this review, we provide an overview of recent advancements in new antifungal drug delivery strategies that leverage novel targets, including those located in the physio-pathological barrier at the site of infection, the infection microenvironment, fungal-host interactions, and the fungal pathogen itself. The objective is to enhance therapeutic efficacy and mitigate toxic effects in fungal infections, particularly in challenging cases such as refractory, recurrent, and drug-resistant invasive fungal infections. We also discuss the current challenges and future prospects associated with target-driven antifungal drug delivery strategies, offering important insights into the clinical implementation of these innovative approaches.


Assuntos
Infecções Fúngicas Invasivas , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Sistemas de Liberação de Medicamentos
13.
J Antimicrob Chemother ; 78(8): 1813-1826, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37311136

RESUMO

Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/µL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug-drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.


Assuntos
Doenças Transmissíveis , Neoplasias Hematológicas , Hematologia , Infecções Fúngicas Invasivas , Humanos , Antifúngicos/uso terapêutico , Citocromo P-450 CYP3A , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/prevenção & controle , Infecções Fúngicas Invasivas/microbiologia , Doenças Transmissíveis/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Oncologia , Triazóis/uso terapêutico
14.
Sci Rep ; 13(1): 6730, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37185921

RESUMO

Isavuconazole is a triazole with broad-spectrum antifungal activity. In this post-hoc analysis of two prospective clinical trials (VITAL and SECURE), the safety and efficacy of isavuconazole in patients aged ≥ 65 years with invasive fungal diseases were evaluated. Patients were divided into two subgroups (≥ 65 and < 65 years). Adverse events (AEs); all-cause mortality; and overall, clinical, mycological, and radiological response were assessed. A total of 155 patients ≥ 65 years were enrolled in both trials. Most patients reported AEs. In the isavuconazole arm of both studies, serious AEs (SAEs) were greater in patients ≥ 65 versus < 65 years: 76.7% versus 56.9% (VITAL); 61.9% versus 49.0% (SECURE). In SECURE, SAE rates were similar in the ≥ 65 years subgroup of both treatment arms (61.9% vs 58.1%), while in the < 65 years subgroup the SAE rate was lower in the isavuconazole arm (49.0% vs 57.4%). In VITAL, all-cause mortality through day 42 (30.0% vs 13.8%) was higher, and overall response at end of treatment (27.6% vs 46.8%) was lower in patients ≥ 65 years versus < 65 years. In SECURE, all-cause mortality was similar between both subgroups, and isavuconazole (20.6% vs 17.9%) and voriconazole (22.6% vs 19.4%) treatment arms. The overall response was lower in the ≥ 65 years than the < 65 years subgroup in the isavuconazole (23.7% vs 39.0%) and voriconazole (32.0% vs 37.5%) arms. The safety and efficacy of isavuconazole were better in patients < 65 versus ≥ 65 years, and the safety profile was more favorable than that of voriconazole in both subgroups.Clinicaltrials.gov identifier NCT00634049 and NCT00412893.


Assuntos
Aspergilose , Infecções Fúngicas Invasivas , Idoso , Humanos , Antifúngicos/efeitos adversos , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Nitrilas/efeitos adversos , Estudos Prospectivos , Triazóis/efeitos adversos , Voriconazol/efeitos adversos
15.
Mycoses ; 66(8): 723-731, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37059587

RESUMO

BACKGROUND: Invasive fungal disease (IFD) is associated with high morbidity and mortality. Data are lacking regarding physicians' perspectives on the diagnosis and management of IFD in China. OBJECTIVES: To evaluate physicians' perspectives on the diagnosis and management of IFD. METHODS: Based on current guidelines, a questionnaire was designed and administered to 294 physicians working in haematology departments, intensive care units, respiratory departments and infectious diseases departments in 18 hospitals in China. RESULTS: The total score and subsection scores for invasive candidiasis, invasive aspergillosis (IA), cryptococcosis and invasive mucormycosis (IM) were 72.0 ± 12.2 (maximum = 100), 11.1 ± 2.7 (maximum = 19), 43.0 ± 7.8 (maximum = 57), 8.1 ± 2.0 (maximum = 11) and 9.8 ± 2.3 (maximum = 13), respectively. Although the perspectives of the Chinese physicians were in good overall agreement with guideline recommendations, some knowledge gaps were identified. Specific areas in which the physicians' perspectives and guideline recommendations differed included use of the ß-D-glucan test to facilitate the diagnosis of IFD, relative utility of the serum galactomannan test and bronchoalveolar lavage fluid galactomannan test in patients with agranulocytosis, use of imaging in the diagnosis of mucormycosis, risk factors for mucormycosis, indications for initiating antifungal therapy in patients with haematological malignancies, when to start empirical therapy in mechanically ventilated patients, first-line drugs for mucormycosis and treatment courses for IA and IM. CONCLUSION: This study highlights the main areas that could be targeted by training programs to improve the knowledge of physicians treating patients with IFD in China.


Assuntos
Aspergilose , Candidíase Invasiva , Infecções Fúngicas Invasivas , Mucormicose , Humanos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Aspergilose/diagnóstico , Candidíase Invasiva/diagnóstico , Fatores de Risco
16.
Med Mycol ; 61(5)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37120735

RESUMO

Posaconazole (PSC) delayed-release tablet prophylaxis is the standard of care for preventing invasive fungal infection (IFI) in patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. The clinical features, risk factors, and PSC profiles of breakthrough IFI (bIFI) in patients receiving PSC tablet prophylaxis were investigated. A single-center retrospective cohort study was conducted, including adult patients with myeloid malignancy who received prophylactic PSC tablets while undergoing chemotherapy from June 2016 to June 2021. Logistic regression analysis was used to identify risk factors for bIFI. A receiver operating characteristic curve was used to predict the relationship between PSC trough level at steady state and bIFI. A total of 434 patients with myeloid malignancy who received PSC tablets were screened. A total of 10 patients with bIFI were compared with 208 non-IFI patients. There were four proven and six probable IFI cases, nine due to Aspergillus, and one due to Fusarium species. The bIFI patients had higher in-hospital mortality (30.0%) than the non-IFI patients (1.9%; P < 0.001). History of allogeneic hematopoietic stem cell transplantation (odds ratio [OR] 6.27; 95% confidence interval [CI] 1.63-24.09), prolonged neutropenia ≥28 days (OR 4.33; 95% CI 1.20-15.70), and low plasma PSC concentration <0.7 µg/ml (OR 16.33; 95% CI 4.15-64.26) were risk factors for bIFI. The optimal cutoff value of plasma PSC concentration predicting bIFI was 0.765 µg/ml (sensitivity, 60.0%; specificity, 91.3%; area under the curve, 0.746). bIFI was not uncommon in patients with myeloid malignancy receiving PSC tablet prophylaxis and associated with poor outcomes. Therapeutic drug monitoring may still be necessary, even in patients receiving PSC tablets.


Invasive fungal infections increase mortality in acute myeloid leukemia patients. This study investigated breakthrough invasive fungal infection cases in patients receiving posaconazole tablet prophylaxis. Our results will contribute to improving the outcome of patients with myeloid malignancy.


Assuntos
Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Animais , Antifúngicos/uso terapêutico , Estudos Retrospectivos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/prevenção & controle , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/veterinária , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/veterinária , Comprimidos/uso terapêutico , Fatores de Risco
17.
Curr Opin Pulm Med ; 29(3): 149-159, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36917216

RESUMO

PURPOSE OF REVIEW: The burden of invasive fungal infection is increasing worldwide, largely due to a growing population at-risk. Most serious human fungal pathogens enter the host via the respiratory tract. Early identification and treatment of invasive fungal respiratory infections (IFRIs) in the immunocompromised host saves lives. However, their accurate diagnosis is a difficult challenge for clinicians and mortality remains high. RECENT FINDINGS: This article reviews IFRIs, focussing on host susceptibility factors, clinical presentation, and mycological diagnosis. Several new diagnostic tools are coming of age including molecular diagnostics and point-of-care antigen tests. As diagnosis of IFRI relies heavily on invasive procedures like bronchoalveolar lavage and lung biopsy, several novel noninvasive diagnostic techniques are in development, such as metagenomics, 'volatilomics' and advanced imaging technologies. SUMMARY: Where IFRI cannot be proven, clinicians must employ a 'weights-of-evidence' approach to evaluate host factors, clinical and mycological data. Implementation studies are needed to understand how new diagnostic tools can be best applied within clinical pathways. Differentiating invasive infection from colonization and identifying antifungal resistance remain key challenges. As our diagnostic arsenal expands, centralized clinical mycology laboratories and efforts to ensure access to new diagnostics in low-resource settings will become increasingly important.


Assuntos
Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas , Infecções Respiratórias , Humanos , Biópsia , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/imunologia , Infecções Fúngicas Invasivas/microbiologia , Micoses/diagnóstico , Micoses/imunologia , Micoses/microbiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/imunologia , Infecções Respiratórias/microbiologia , Lavagem Broncoalveolar , Líquido da Lavagem Broncoalveolar/microbiologia , Pulmão/microbiologia , Pulmão/patologia
18.
Med Mycol ; 61(3)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36906282

RESUMO

Since COVID-19 spread worldwide, invasive fungal rhinosinusitis (IFRS) has emerged in immunocompromised patients as a new clinical challenge. In this study, clinical specimens of 89 COVID-19 patients who presented clinical and radiological evidence suggestive of IFRS were examined by direct microscopy, histopathology, and culture, and the isolated colonies were identified through DNA sequence analysis. Fungal elements were microscopically observed in 84.27% of the patients. Males (53.9%) and patients over 40 (95.5%) were more commonly affected than others. Headache (94.4%) and retro-orbital pain (87.6%) were the most common symptoms, followed by ptosis/proptosis/eyelid swelling (52.8%), and 74 patients underwent surgery and debridement. The most common predisposing factors were steroid therapy (n = 83, 93.3%), diabetes mellitus (n = 63, 70.8%), and hypertension (n = 42, 47.2%). The culture was positive for 60.67% of the confirmed cases, and Mucorales were the most prevalent (48.14%) causative fungal agents. Different species of Aspergillus (29.63%) and Fusarium (3.7%) and a mix of two filamentous fungi (16.67%) were other causative agents. For 21 patients, no growth was seen in culture despite a positive result on microscopic examinations. In PCR-sequencing of 53 isolates, divergent fungal taxons, including 8 genera and 17 species, were identified as followed: Rhizopus oryzae (n = 22), Aspergillus flavus (n = 10), A. fumigatus (n = 4), A. niger (n = 3), R. microsporus (n = 2), Mucor circinelloides, Lichtheimia ramosa, Apophysomyces variabilis, A. tubingensis, A. alliaceus, A. nidulans, A. calidoustus, Fusarium fujikuroi/proliferatum, F. oxysporum, F. solani, Lomentospora prolificans, and Candida albicans (each n = 1). In conclusion, a diverse set of species involved in COVID-19-associated IFRS was observed in this study. Our data encourage specialist physicians to consider the possibility of involving various species in IFRS in immunocompromised and COVID-19 patients. In light of utilizing molecular identification approaches, the current knowledge of microbial epidemiology of invasive fungal infections, especially IFRS, may change dramatically.


Invasive fungal rhinosinusitis (IFRS) may infect people with diabetes, cancer, or COVID-19. In this study, various types of fungi were identified from COVID-19-associated-IFRS, encouraging physicians to consider specific treatments.


Assuntos
COVID-19 , Fungos , Infecções Fúngicas Invasivas , Sinusite , COVID-19/complicações , COVID-19/microbiologia , Sinusite/complicações , Sinusite/epidemiologia , Sinusite/microbiologia , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/patologia , Infecções Fúngicas Invasivas/cirurgia , Fatores de Risco , Reação em Cadeia da Polimerase , DNA Fúngico/genética , Irã (Geográfico)/epidemiologia , Humanos , Masculino , Feminino , Biodiversidade
19.
Mycoses ; 66(5): 405-411, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36670539

RESUMO

BACKGROUND: Invasive fungal diseases (IFD) are life-threatening and demand timely and appropriate treatment. Research showed that isavuconazole treatment positively affects clinical outcome and length of hospital stay (LOS). OBJECTIVES: The aim of this study was to assess the hospital costs of patients diagnosed with IFD and treated with isavuconazole using real-world data from a German cancer centre. PATIENTS/METHODS: Data and LOS collected from Jan-2016 to Jun-2021 at Department I of Internal Medicine, University Hospital Cologne were retrieved. Case-related resources consumed during the hospital stay across isavuconazole routes of administration (oral, parenteral, and mixed administration) were identified, quantified, valued and compared via a cost analysis that adopted the healthcare payer perspective. RESULTS: In total, 101 cases with isavuconazole treatment were identified (oral: n = 22, 21.8%; parenteral: n = 59, 58.4%; mixed: n = 20, 19.8%). Median total LOS was greater in the mixed group (46.5 days; p = .009). Median ICU LOS and ventilation duration were both longest in the parenteral-only group (16 days, p = .008; 224 h, p = .003). Invasive aspergillosis was the most frequent isavuconazole indication (n = 86, 85.2%). Average hospital costs were highest in the mixed group (€ 101,226). The median overall costs of cases treated with isavuconazole was € 52,050. CONCLUSIONS: Treating IFD is resource intensive, often requires intensive care and implies high rates of in-hospital mortality. Our study emphasises the high hospital treatment costs and thus the need for reimbursement systems to enable live-saving costly treatments.


Assuntos
Aspergilose , Infecções Fúngicas Invasivas , Neoplasias , Humanos , Antifúngicos/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Triazóis/uso terapêutico , Nitrilas/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia
20.
Med Mycol ; 60(9)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36073757

RESUMO

Invasive fungal infections (IFIs) and medical mycology receive little attention in Ghana. However, the present evolution of biomarker assays for IFIs, offers an opportunity for an increased access to fungal laboratory testing in resource-limited settings, and probably make a case for availability of essential antifungal agents. Using surveys and personal communications, the state of medical mycology and IFI in Ghana were highlighted. Inadequate awareness and insufficient access to fungal diagnostics and therapeutics were identified as the key challenges, the establishment of the Ghana Medical Mycology Society was discussed, and recommendations were made to improve the status quo.


Invasive fungal infections (IFIs) receive little attention in Ghana, despite its growing relevance globally. Using surveys and personal communications, the main challenges were identified, and the formation of the Ghana Medical Mycology Society was discussed as a tool to improve the status quo.


Assuntos
Infecções Fúngicas Invasivas , Micologia , Animais , Antifúngicos/uso terapêutico , Gana , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/veterinária , Inquéritos e Questionários
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