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1.
Mycoses ; 67(5): e13730, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38712824

RESUMEN

BACKGROUND: Due to a delay in diagnosis by conventional techniques and high mortality, the development of a standardised and rapid non-culture-based technique is an unmet need in pulmonary, gastrointestinal, and disseminated forms of mucormycosis. Though limited studies have been conducted for molecular diagnosis, there are no established serologic tests for this highly fatal infection. OBJECTIVE: To develop and evaluate an indirect in-house enzyme-linked immunosorbent assay (ELISA) utilising antigens of Rhizopus arrhizus for detecting anti-Rhizopus antibodies (IgG and IgM) in sera of patients with mucormycosis. METHODS: We extracted both secretory and mycelial Rhizopus antigens using standardised protocols. Bradford assay was used for protein quantification. We then standardised an indirect ELISA using R. arrhizus mycelial and secretory antigens (10.0 µg/mL in bicarbonate buffer pH 9.2) for detecting anti-Rhizopus IgG and IgM antibodies in patient sera. We included patients with mucormycosis, other fungal infections, and healthy controls. Antibody index value (E-value) was calculated for each patient sample. RESULTS: Asparagine broth culture filtrate utilising 85% ammonium sulphate salt fractionation and mycelial homogenate grown in yeast extract peptone dextrose (YPD) broth precipitated with trichloroacetic acid (TCA) yielded a large amount of good-quality protein for the assay. We included 55 patients with mucormycosis (rhino-orbito-cerebral mucormycosis [ROCM, n = 39], pulmonary [n = 15], gastrointestinal [n = 1]), 24 with other fungal infections (probable aspergillosis [n = 14], candidiasis [n = 10]), and healthy controls (n = 16). The sensitivity of the antibody test for diagnosing mucormycosis ranged from 83.6-92.7% for IgG and 72.7-87.3% for IgM, with a specificity of 91.7-92.5% for IgG and 80-82.5% for IgM. The sera from patients with other fungal infections and healthy individuals did not show significant cross-reactivity. CONCLUSION: The detection of anti-Rhizopus IgG antibody performed significantly better in comparison to IgM-based ELISA for diagnosing both ROCM (sensitivity of 84.6% vs. 69.2%) and pulmonary cases (86.6% vs. 80.0%). More extensive studies are required to confirm our findings.


Asunto(s)
Anticuerpos Antifúngicos , Antígenos Fúngicos , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , Inmunoglobulina M , Mucormicosis , Rhizopus , Sensibilidad y Especificidad , Pruebas Serológicas , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Mucormicosis/inmunología , Humanos , Rhizopus/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Antígenos Fúngicos/inmunología , Antígenos Fúngicos/análisis , Pruebas Serológicas/métodos , Anticuerpos Antifúngicos/sangre , Inmunoglobulina M/sangre , Inmunoglobulina G/sangre , Femenino , Masculino , Persona de Mediana Edad
3.
Emerg Infect Dis ; 30(6): 1245-1248, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38782142

RESUMEN

Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for spoilage or disease but is an uncommon cause of human infection. We describe C. infundibulifera rhinosinusitis in a young man with leukemia in Tennessee, USA.


Asunto(s)
Sinusitis , Humanos , Masculino , Tennessee , Sinusitis/microbiología , Sinusitis/diagnóstico , Sinusitis/parasitología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Mucormicosis/tratamiento farmacológico , Mucorales/aislamiento & purificación , Mucorales/clasificación , Rinitis/microbiología , Rinitis/diagnóstico , Adulto , Antifúngicos/uso terapéutico , Rinosinusitis
4.
Exp Clin Transplant ; 22(4): 314-317, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38742324

RESUMEN

Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient's condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in livertransplant recipients.


Asunto(s)
Antifúngicos , Huésped Inmunocomprometido , Cirrosis Hepática Biliar , Trasplante de Hígado , Mucormicosis , Humanos , Masculino , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Mucormicosis/inmunología , Mucormicosis/tratamiento farmacológico , Mucormicosis/etiología , Persona de Mediana Edad , Trasplante de Hígado/efectos adversos , Antifúngicos/uso terapéutico , Resultado Fatal , Cirrosis Hepática Biliar/cirugía , Cirrosis Hepática Biliar/microbiología , Cirrosis Hepática Biliar/diagnóstico , Resultado del Tratamiento , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/tratamiento farmacológico , Desbridamiento , Aloinjertos , Hepatectomía , Anfotericina B/uso terapéutico , Anfotericina B/administración & dosificación , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/microbiología
5.
J Assoc Physicians India ; 72(3): 27-31, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38736113

RESUMEN

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, an increased incidence of mucormycosis infection was noted globally, the majority being from India. We aimed to study the clinical profile of the mucormycosis patients during the COVID-19 pandemic admitted at tertiary care centers. MATERIALS AND METHODS: This is a retrospective record-based observation study conducted at Gandhi Medical College, Bhopal. All suspected or laboratory-proven mucormycosis patients were included. Detailed data on demography, clinical features, risk factors, laboratory/radiological findings, and outcomes were recorded. RESULTS: A total of 288 patients were enrolled and 121(42%) showed mucormycosis on potassium hydroxide (KOH) mount. The mean age was 51.52 ± 10.88 years, male:female ratio was 2.3:1. Most common symptom was facial swelling/pain and fever. The most common risk factor was COVID-19 infection (78.5%) followed by the presence of diabetes mellitus (DM) (70.8%) out of which 152 (52.8%) patients were previously diagnosed cases and 52 (18%) patients were newly diagnosed, 159 (55.2%) had a history of corticosteroid use, 87 (30.2%) had a history of use of oxygen support and 67 (23.2%) had hypertension. Most patients had invasion limited to sinus (46.5%) but the presence of DM was associated with an increased risk of cerebral invasion. Out of 288 patients admitted with mucormycosis, 31 patients collapsed to death while the remaining 257 patients were discharged from the hospital. CONCLUSION: It is observed that during the COVID-19 pandemic, hyperglycemia and inappropriate use of corticosteroids were associated with an increased risk of development of mucormycosis in patients with or without DM. We conclude that regular blood glucose monitoring, adequate glycemic control, and judicious evidence-based use of corticosteroids and immunosuppressants in COVID-19 are recommended to reduce the emergence of mucormycosis in such circumstances.


Asunto(s)
COVID-19 , Mucormicosis , Humanos , Mucormicosis/epidemiología , Mucormicosis/diagnóstico , COVID-19/epidemiología , COVID-19/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , India/epidemiología , Adulto , Factores de Riesgo , SARS-CoV-2 , Anciano
6.
BMC Neurol ; 24(1): 151, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704555

RESUMEN

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal opportunistic viral demyelinating infectious disease of the central nervous system (CNS). There are various clinical presenting symptoms for the disease. CASE PRESENTATION: This paper presents a clinical case of PML in a patient with B-Chronic lymphocytic leukemia (B-CLL), previously treated with Chlorambucil, later complicated later with COVID-19 and mucormycosis. CONCLUSION: PML can develop in the setting of cellular immune dysfunction. Late diagnosis of this disease based on nonspecific symptoms is common, therefore when we face a neurological complication in a CLL or immunocompromised patient, we should consider PML infection. A remarkable feature of this case is the possible triggering effect of COVID-19 vaccination for emergence of PML as the disease can be asymptomatic or sub-clinical before diagnosis.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Leucemia Linfocítica Crónica de Células B , Leucoencefalopatía Multifocal Progresiva , Mucormicosis , Anciano , Humanos , Masculino , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Huésped Inmunocomprometido , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucoencefalopatía Multifocal Progresiva/etiología , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Mucormicosis/complicaciones
7.
Mycoses ; 67(5): e13745, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38767273

RESUMEN

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.


Asunto(s)
COVID-19 , Coinfección , Mucormicosis , Humanos , COVID-19/complicaciones , COVID-19/mortalidad , Mucormicosis/mortalidad , Mucormicosis/epidemiología , Mucormicosis/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Prevalencia , Coinfección/mortalidad , Coinfección/epidemiología , Coinfección/microbiología , India/epidemiología , Adulto , Aspergilosis Pulmonar/complicaciones , Aspergilosis Pulmonar/mortalidad , Aspergilosis Pulmonar/epidemiología , SARS-CoV-2 , Anciano , Estudios de Casos y Controles , Enfermedades Pulmonares Fúngicas/mortalidad , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/epidemiología
8.
JAMA ; 331(18): 1586-1587, 2024 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-38630502
9.
ACS Infect Dis ; 10(5): 1431-1457, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38682683

RESUMEN

Mucormycosis, a rare but deadly fungal infection, was an epidemic during the COVID-19 pandemic. The rise in cases (COVID-19-associated mucormycosis, CAM) is attributed to excessive steroid and antibiotic use, poor hospital hygiene, and crowded settings. Major contributing factors include diabetes and weakened immune systems. The main manifesting forms of CAM─cutaneous, pulmonary, and the deadliest, rhinocerebral─and disseminated infections elevated mortality rates to 85%. Recent focus lies on small-molecule inhibitors due to their advantages over standard treatments like surgery and liposomal amphotericin B (which carry several long-term adverse effects), offering potential central nervous system penetration, diverse targets, and simpler dosing owing to their small size, rendering the ability to traverse the blood-brain barrier via passive diffusion facilitated by the phospholipid membrane. Adaptation and versatility in mucormycosis are facilitated by a multitude of virulence factors, enabling the pathogen to dynamically respond to various environmental stressors. A comprehensive understanding of these virulence mechanisms is imperative for devising effective therapeutic interventions against this highly opportunistic pathogen that thrives in immunocompromised individuals through its angio-invasive nature. Hence, this Review delineates the principal virulence factors of mucormycosis, the mechanisms it employs to persist in challenging host environments, and the current progress in developing small-molecule inhibitors against them.


Asunto(s)
Antifúngicos , Inteligencia Artificial , COVID-19 , Mucormicosis , Factores de Virulencia , Mucormicosis/tratamiento farmacológico , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Factores de Virulencia/antagonistas & inhibidores , Factores de Virulencia/metabolismo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/patogenicidad
10.
J Clin Microbiol ; 62(5): e0039424, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38602412

RESUMEN

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.


Asunto(s)
Ácidos Nucleicos Libres de Células , ADN de Hongos , Infecciones Fúngicas Invasoras , Mucormicosis , Reacción en Cadena de la Polimerasa , Humanos , Mucormicosis/diagnóstico , Mucormicosis/mortalidad , Mucormicosis/sangre , Mucormicosis/microbiología , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Ácidos Nucleicos Libres de Células/sangre , Reacción en Cadena de la Polimerasa/métodos , Adulto , ADN de Hongos/genética , ADN de Hongos/sangre , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/mortalidad , Infecciones Fúngicas Invasoras/microbiología , Aspergillus/genética , Aspergillus/aislamiento & purificación , Aspergilosis/diagnóstico , Aspergilosis/mortalidad , Aspergilosis/microbiología , Mucorales/genética , Mucorales/aislamiento & purificación , Biomarcadores/sangre , Anciano de 80 o más Años , Estudios Prospectivos
12.
J Med Virol ; 96(4): e29601, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38597375

RESUMEN

Coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) was reported predominantly from India during the second wave of COVID-19  and has a high mortality rate. The present study aims to understand the fungal community composition of the nasopharyngeal region of CAM-infected individuals and compare it with severe COVID-19 patients and healthy controls. The fungal community composition was decoded by analyzing the sequence homology of the internal transcribed spacer-2-(ITS-2) region of metagenomic DNA extracted from the upper respiratory samples. The alpha-diversity indices were found to be significantly altered in CAM patients (p < 0.05). Interestingly, a higher abundance of Candida africana, Candida haemuloni, Starmerella floris, and Starmerella lactiscondensi was observed exclusively in CAM patients. The interindividual changes in mycobiome composition were well supported by beta-diversity analysis (p < 0.05). The current study provides insights into the dysbiosis of the nasal mycobiome during CAM infection. In conclusion, our study shows that severe COVID-19 and CAM are associated with alteration in mycobiome as compared to healthy controls. However, the sequential alteration in the fungal flora which ultimately leads to the development of CAM needs to be addressed by future studies.


Asunto(s)
COVID-19 , Mucormicosis , Micobioma , Humanos , Mucormicosis/epidemiología , Nariz , India/epidemiología
13.
Dtsch Med Wochenschr ; 149(10): 569-578, 2024 May.
Artículo en Alemán | MEDLINE | ID: mdl-38657596

RESUMEN

The first patients positive for SARS-CoV-2 were registered in December 2019. In March 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a global pandemic, the beginning of a worldwide health crisis that revealed numerous medical challenges for healthcare systems and pandemic emergency strategies.Among these challenges, mucormycosis, a typically rare fungal infection, gained global attention. With an average global incidence of about 2 per 1 million people, mucormycosis is considered a very rare disease, an opportunistic infection mostly affecting the lungs or skin and soft tissues in immunocompromised patients. Poorly controlled diabetes mellitus is one of the leading risk factors for rhino-orbital mucormycosis. Countries with a high prevalence of diabetes and limited healthcare resources have higher mucormycosis rates, with India and Pakistan being among the nations with particularly high incidences.During the second wave of the COVID-19 pandemic in India, mucormycosis rates surged dramatically within a few weeks, with over 47,500 cases of COVID-19-associated mucormycosis (CAM) reported between May and August 2021. Mucormycosis is characterized by a high mortality rate of up to 90%, especially when the diagnosis is delayed, and treatment commences late. There were concerns about a potentially global threat.In this article, we explore the risk factors and mechanisms leading to this viral-fungal coinfection. We present global distribution patterns, clinical presentation, and challenges in the diagnosis and treatment of COVID-19-associated mucormycosis.


Asunto(s)
COVID-19 , Mucormicosis , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Mucormicosis/epidemiología , Mucormicosis/diagnóstico , Mucormicosis/terapia , Factores de Riesgo , SARS-CoV-2 , Antifúngicos/uso terapéutico , Pandemias
14.
Biomedica ; 44(1): 10-15, 2024 03 31.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38648346

RESUMEN

Mucormycosis is an invasive opportunistic fungal infection with high mortality, mainly detected in people with COVID-19, especially those with underlying diseases such as diabetes mellitus. Mucormycosis prevalence is 0.005 to 1.7 cases per million inhabitants, and it has been increasing in countries like India and Pakistan. This mycosis can affect different organs, and clinical manifestations reflect the transmission mechanism. Frequent forms are rhino-orbital-cerebral and pulmonary. This disease should be suspected in patients with necrotic injuries on mucous membranes or skin. We present a case of a patient with diabetes mellitus and diagnosed with oral mucormycosis associated with COVID-19.


La mucormicosis es una infección fúngica oportunista e invasiva, con una elevada tasa de mortalidad. Se ha detectado principalmente en pacientes con COVID-19, especialmente en personas con enfermedades concomitantes como la diabetes mellitus. La prevalencia de las mucormicosis es de 0,005 a 1,7 casos por millón de habitantes y ha ido en aumento en países como India y Pakistán; puede afectar diferentes órganos y su forma clínica refleja el mecanismo de transmisión. Entre las formas frecuentes están la rino-orbital-cerebral y la pulmonar, por ello, debe sospecharse mucormicosis en los pacientes con lesiones necróticas en mucosas o piel. Se presenta el caso de un paciente con antecedentes de diabetes mellitus que fue diagnosticado con mucormicosis oral asociada a la COVID-19.


Asunto(s)
COVID-19 , Mucormicosis , Humanos , Mucormicosis/complicaciones , Mucormicosis/epidemiología , Mucormicosis/diagnóstico , COVID-19/complicaciones , COVID-19/epidemiología , Masculino , Enfermedades de la Boca/microbiología , Complicaciones de la Diabetes , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Antifúngicos/uso terapéutico
16.
Indian J Tuberc ; 71(2): 225-231, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38589128

RESUMEN

Pulmonary mucormycosis is a rare but highly lethal fungal infection, usually affecting immunocompromised patients. Pulmonary mucormycosis was also a critical problem that complicated the later part of the clinical course of COVID-19 in India. Early diagnosis of the disease, combined with aggressive treatment, is crucial for patient survival. Fibreoptic bronchoscopy is a useful procedure for diagnosis of pulmonary mucormycosis, but image-guided percutaneous biopsy efficiently samples lesions abutting the chest wall. Biopsy is more yielding than cultures and imaging guided biopsy is required for lesions that cannot be microbiologically confirmed by fibreoptic bronchoscopy. We present a case series of four patients of pulmonary mucormycosis in whom ultrasound guided biopsy clinched the diagnosis. All the four patients were poor surgical candidates and underwent medical management with antifungal agents, and had successful clinical recovery and radiological resolution. Our case series illustrates the utility of ultrasound guided percutaneous biopsy as a diagnostic tool for sampling cavitatory disease due to pulmonary mucormycosis, when fibreoptic bronchoscopy failed to yield a diagnosis and the beneficial role antifungal agents as salvage therapy in poor surgical candidates.


Asunto(s)
Mucormicosis , Humanos , Antifúngicos/uso terapéutico , Biopsia , Broncoscopía , Biopsia Guiada por Imagen , Mucormicosis/diagnóstico por imagen , Mucormicosis/tratamiento farmacológico , Ultrasonografía Intervencional
17.
Swiss Med Wkly ; 154: 3730, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38579310

RESUMEN

AIMS OF THE STUDY: Invasive mould infections are life-threatening complications in patients with haematologic cancer and chemotherapy-induced neutropenia. While invasive aspergillosis represents the main cause of invasive mould infections, non-Aspergillus mould infections, such as mucormycosis, are increasingly reported. Consequently, their local epidemiology should be closely monitored. The aim of this study was to investigate the causes of an increased incidence of non-Aspergillus mould infections in the onco-haematology unit of a Swiss tertiary care hospital. METHODS: All cases of proven and probable invasive mould infections were retrospectively identified via a local registry for the period 2007-2021 and their incidence was calculated per 10,000 patient-days per year. The relative proportion of invasive aspergillosis and non-Aspergillus mould infections was assessed. Factors that may affect invasive mould infections' incidence, such as antifungal drug consumption, environmental contamination and changes in diagnostic approaches, were investigated. RESULTS: A significant increase of the incidence of non-Aspergillus mould infections (mainly mucormycosis) was observed from 2017 onwards (Mann and Kendall test p = 0.0053), peaking in 2020 (8.62 episodes per 10,000 patient-days). The incidence of invasive aspergillosis remained stable across the period of observation. The proportion of non-Aspergillus mould infections increased significantly from 2017 (33% vs 16.8% for the periods 2017-2021 and 2007-2016, respectively, p = 0.02). Building projects on the hospital site were identified as possible contributors of this increase in non-Aspergillus mould infections. However, novel diagnostic procedures may have improved their detection. CONCLUSIONS: We report a significant increase in non-Aspergillus mould infections, and mainly in mucormycosis infections, since 2017. There seems to be a multifactorial origin to this increase. Epidemiological trends of invasive mould infections should be carefully monitored in onco-haematology units in order to implement potential corrective measures.


Asunto(s)
Aspergilosis , Hematología , Mucormicosis , Humanos , Mucormicosis/epidemiología , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Estudios Retrospectivos , Incidencia , Antifúngicos/uso terapéutico , Aspergilosis/epidemiología , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología
18.
Antimicrob Agents Chemother ; 68(5): e0154523, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38557112

RESUMEN

Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer ß-(1,3)-D-glucan by inhibiting the enzyme glucan synthase. We evaluated the in vivo efficacy of ibrexafungerp against pulmonary mucormycosis using an established murine model. Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Ibrexafungerp was as effective as LAMB or PSC in prolonging median survival (range: 15 days to >21 days) and enhancing overall survival (30%-65%) vs placebo (9 days and 0%; P < 0.001) in mice infected with R. delemar. Furthermore, median survival and overall percent survival resulting from the combination of ibrexafungerp plus LAMB were significantly greater compared to all monotherapies (P ≤ 0.03). Similar survival results were observed in mice infected with M. circinelloides. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis.


Asunto(s)
Anfotericina B , Antifúngicos , Glicósidos , Mucormicosis , Neutropenia , Triterpenos , Animales , Anfotericina B/uso terapéutico , Anfotericina B/farmacología , Mucormicosis/tratamiento farmacológico , Ratones , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Triterpenos/farmacología , Triterpenos/uso terapéutico , Neutropenia/tratamiento farmacológico , Neutropenia/complicaciones , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Rhizopus/efectos de los fármacos , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/microbiología , Mucor/efectos de los fármacos , Triazoles/uso terapéutico , Triazoles/farmacología
20.
Microbiol Spectr ; 12(4): e0361423, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38426765

RESUMEN

Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when A. fumigatus (Af293) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae, and Rhizopus microsporus but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus, indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant A. fumigatus. The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus. Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis. IMPORTANCE: Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various Aspergillus spp. and several Mucorales in vitro and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA.


Asunto(s)
Aspergilosis , Mucormicosis , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Aspergillus fumigatus , Mucormicosis/tratamiento farmacológico , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Hongos , Aspergillus
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