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1.
Ann Agric Environ Med ; 26(4): 665-668, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31885243

RESUMO

A case is presented of mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson's disease. A 58-year-old female was admitted to the Department of Haematology with deterioration of her general condition, loss of appetite, tiredness and difficulty with mental contact for a few days. Blood and urine cultures for bacteria and fungus, galactomannan antigen were negative. Whole body computed tomography demonstrated bilateral hilar lymphadenopathy with necrotic lesions: splenomegaly with a hypodensive lesion 13 × 20 × 19 mm and lower pulmonary infiltrates suggested fungal etiology. Magnetic resonance imaging of the brain showed thickened meninges. Finally, mucormycosis was diagnosed. Treatment with amphotericin B lipid complex was started, resulting in an partial improvement of the general condition and decreased level of inflammatory markers. However, the patient's condition continued to deteriorate, with sepsis etiology Escherichia coli, and despite the intensive managements she eventually died.


Assuntos
Degeneração Hepatolenticular/cirurgia , Leucemia Mieloide Aguda/complicações , Transplante de Fígado/efeitos adversos , Mucormicose/etiologia , Complicações Pós-Operatórias/etiologia , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Evolução Fatal , Feminino , Degeneração Hepatolenticular/complicações , Humanos , Pessoa de Meia-Idade , Mucormicose/diagnóstico , Mucormicose/diagnóstico por imagem , Mucormicose/tratamento farmacológico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/tratamento farmacológico
2.
Zhonghua Nei Ke Za Zhi ; 58(11): 861-864, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31665870

RESUMO

Mucor infection is rarely reported in non-immunocompromised population, especially in isolated gastrointestinal tracts. IgG(4)-related diseases (IgG(4)-RD) have been recognized in recent years, but secondary causes of IgG(4) elevation should be differentiated. We reported a young man with duodenal mass and ulcer and high serum IgG(4) level. Histological biopsy of the mass revealed positive mucor mycelium and infiltration of IgG(4) positive plasma cells. Serum IgG(4) decreased to normal range after surgical resection and systemic antifungal treatment. This case suggests that isolated mucor mycosis infection can develop in the digestive tract and mimics as IgG(4)-related disease.


Assuntos
Antifúngicos/uso terapêutico , Úlcera Duodenal/patologia , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Imunoglobulina G/sangue , Mucor/isolamento & purificação , Mucormicose/tratamento farmacológico , Biópsia , Úlcera Duodenal/cirurgia , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/efeitos dos fármacos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/microbiologia , Masculino , Mucor/efeitos dos fármacos , Mucormicose/microbiologia , Resultado do Tratamento
3.
Transplant Proc ; 51(7): 2498-2500, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31405737

RESUMO

INTRODUCTION: Mucormycosis is a severe infection in renal transplant recipients. Here, we report a case of maxillary sinus mucormycosis in a patient who presented with a facial pain complaint. CASE: A 51-year-old female patient with renal transplantation due to autosomal dominant, polycystic kidney disease and diabetic nephropathy was admitted to our hospital with facial pain and minimal edema of the left half of her face on the 8th month of transplantation. On physical examination, there was only tenderness and slight edema on the left half of the face. On the paranasal computed tomography, extensive soft tissue densities involving septations, filling the left maxillary sinus, extending to the nasal cavity, and obliterating the left osteometeal unit were observed. Because facial pain was not relieved by antibiotics and several, potent analgesic drugs on the second day, mucormycosis infection with bone involvement was suspected. A left maxillary sinus excision was performed. Microscopic examination of the debridement specimen revealed necrotic bone interspersed with fungal hyphae, and culture isolated Rhizopus oryzae. Liposomal amphotericin B was started. The patient was on tacrolimus, prednisolone, and mycophenolate mofetil. Tacrolimus was switched to cyclosporine to regulate serum glucose levels. The left maxillary sinus was washed with liposomal amphoterin B daily and curetted with intervals. The patient started dialysis because of severe renal function loss. The patient was discharged on the 96th day of liposomal amphotericin B. CONCLUSION: It should be kept in mind that mucormycosis may be present in the sinuses even if there is no evidence for nasal, oral, and dental examination in renal transplant patients with facial pain.


Assuntos
Hospedeiro Imunocomprometido , Transplante de Rim/efeitos adversos , Sinusite Maxilar/imunologia , Mucormicose/imunologia , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Dor Facial/etiologia , Feminino , Humanos , Sinusite Maxilar/complicações , Sinusite Maxilar/microbiologia , Pessoa de Meia-Idade , Mucormicose/complicações , Mucormicose/tratamento farmacológico , Rhizopus/isolamento & purificação
5.
World Neurosurg ; 130: 206-210, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31279104

RESUMO

BACKGROUND: Mucormycosis of the central nervous system is an uncommon infection caused by saprophytic or parasitic fungi of the subphylum Mucormycotina and order Mucorales viz. Rhizopus, Mucor, and Rhizomucor. Isolated, chronic involvement of the central nervous system is a rare occurrence. To the best of our knowledge, isolated chronic ventricular involvement in an infant has not been reported previously. Isolated intracerebral mucormycosis is a disease of the immunocompromised patient, and to date only 6 cases have been reported in immunocompetent patients, including 2 pediatric cases. CASE DESCRIPTION: We present the case of an immunocompetent infant presenting with features of increased intracranial tension. He underwent cerebrospinal fluid diversion and was found to harbor mucormycosis on histopathologic examination of intraventricular debris. We also present a brief review of the relevant literature. CONCLUSIONS: Although mucormycosis is an acute fulminant infection, chronic isolated cerebral cases are known in the immunocompetent patient. Patients also may present with isolated hydrocephalus, and hence fungal infection must be ruled out in all, especially if a shunt is warranted.


Assuntos
Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido/imunologia , Ventrículos Laterais/diagnóstico por imagem , Mucormicose/diagnóstico , Encéfalo/diagnóstico por imagem , Doença Crônica , Humanos , Lactente , Masculino , Mucormicose/líquido cefalorraquidiano , Mucormicose/tratamento farmacológico , Rhizopus/patogenicidade
6.
Mycoses ; 62(9): 730-738, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31192488

RESUMO

Mucormycosis is a rare but important invasive fungal disease that most often affects immunocompromised hosts. The incidence of mucormycosis appears to be increasing worldwide, as risk factors such as the use of immunosuppressive therapies become more common. We report the results of a literature review of 143 mucormycosis cases reported in South America between 1960 and 2018. The number of reported cases has increased by decade, from 6 in the 1960s to 51 in the 2010s. The most common underlying conditions associated with mucormycosis in South America were diabetes mellitus (42.0%) and penetrating trauma/burns (20.0%). Underlying conditions involving immunosuppression, including treatment of haematologic malignancy, solid organ transplant, and corticosteroid use, also accounted for a large proportion of cases (45.5%). Between 1960 and 2018, cases of mucormycosis associated with conditions involving immunosuppression accounted for the highest mortality rate (58.5%), followed by diabetes mellitus (45.0%), and penetrating trauma/burns (37.9%). Overall mortality decreased from 100% to 39.4% during this period, mainly driven by the increasing availability and use of antifungal therapies and surgical intervention. However, these treatments are not yet universally utilised across the region in the treatment of mucormycosis; efforts to improve availability of effective treatments would be likely to improve outcomes.


Assuntos
Infecções Fúngicas Invasivas/epidemiologia , Mucormicose/sangue , Mucormicose/epidemiologia , Antifúngicos/uso terapêutico , Complicações do Diabetes , Neoplasias Hematológicas/complicações , Humanos , Hospedeiro Imunocomprometido , Imunossupressão/efeitos adversos , Infecções Fúngicas Invasivas/tratamento farmacológico , Mucormicose/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , América do Sul/epidemiologia
7.
Mycoses ; 62(10): 893-907, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31173415

RESUMO

BACKGROUND: Mucormycosis portends a poor prognosis with mortality rates ranging from 50% to 70% in pulmonary mucormycosis (PM) and up to 95% in disseminated disease. However, detailed outcomes data have been lacking. It remains unknown how to identify patients who would benefit from surgical resection. OBJECTIVES: We present our experience with patients undergoing surgical resection for PM, including an analysis of factors affecting postoperative survival. We also describe a thoracic surgeon's approach through illustrative cases. PATIENTS/METHODS: We conducted a single-centre retrospective study of all adult patients with PM who received antifungal therapy and underwent surgical resection or who received antifungal therapy alone at Stanford between January 2004 and June 2018. RESULTS: Twelve patients received antifungal therapy and underwent surgical resection and 13 patients received antifungal therapy alone. From infection onset to death (or right-censoring if still alive), patients who underwent surgical resection had a median survival of 406 days (mean, 561.3; range, 22-2510), and patients who received antifungal therapy alone had a median survival of 28 days (mean, 66.7; range, 8-447). In patients who underwent surgical resection, median postoperative survival time was 154 days (range, 11-2495), in-hospital mortality was 16.7%, and 1-year mortality was 50.0%. Age, primary disease, ASA status, extrapulmonary dissemination, laterality, multilobar involvement, number of lesions, largest lesion size, platelet count, surgical approach, type of resection or extent of resection were not significantly associated with postoperative survival. CONCLUSIONS: Surgical resection significantly increases survival and should be strongly considered for selected patients with PM.


Assuntos
Pneumopatias Fúngicas/cirurgia , Mucormicose/cirurgia , Procedimentos Cirúrgicos Pulmonares/métodos , Adulto , Idoso , Antifúngicos/uso terapêutico , Terapia Combinada/métodos , Feminino , Humanos , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mucormicose/tratamento farmacológico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
9.
Mycoses ; 62(9): 716-729, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254420

RESUMO

Breakthrough invasive fungal infections (IFIs) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed and circulated to all members of the two organisations for comment and suggestions. The authors addressed comments received and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non-response to treatment. Relapsed IFI occurs after treatment and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.


Assuntos
Infecções Fúngicas Invasivas/diagnóstico , Micoses/diagnóstico , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Aspergilose/sangue , Aspergilose/tratamento farmacológico , Ensaios Clínicos como Assunto , Europa (Continente) , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Mucormicose/sangue , Mucormicose/tratamento farmacológico , Fatores de Risco , Falha de Tratamento
10.
Mycoses ; 62(9): 739-745, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31044442

RESUMO

Mediastinal mucormycosis is an uncommon but lethal infection associated with an 83% mortality. We describe a case of fatal Rhizopus microsporus mediastinitis despite three exploratory mediastinal surgeries and complementary systemic and mediastinal irrigation with liposomal amphotericin B. We further review the literature on surgical and antifungal management of mediastinal mucormycosis.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Doenças do Mediastino/diagnóstico , Doenças do Mediastino/microbiologia , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Adulto , Evolução Fatal , Feminino , Humanos , Doenças do Mediastino/tratamento farmacológico , Doenças do Mediastino/cirurgia , Rhizopus/efeitos dos fármacos , Irrigação Terapêutica
11.
Internist (Berl) ; 60(7): 684-689, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31119309

RESUMO

BACKGROUND: Invasive aspergillosis, mucormycosis, and cryptococcosis are severe opportunistic infections in patients with long phases of neutropenia and also after allogeneic stem cell and organ transplantation. Due to the late appearance of clinical signs and the often poor outcome, these diseases require special attention and proactive interventions. MATERIAL AND METHODS: Published guidelines and selected current literature were reviewed for this article. RESULTS: Invasive aspergillosis and mucormycosis are typically observed in the upper and lower airways of severely immunocompromized patients. When invasive fungal diseases are suspected, sectional imaging and, if possible, serological testing should be performed as soon as possible. If imaging or serological tests confirm the suspected diagnosis, pre-emptive antimycotic treatment should be started and further confirmation of the diagnosis sought via microbiological and/or histological investigations. Treatment depends on comedication, comorbidity and risk factors, primarily with voriconazole, isavuconazole and liposomal amphotericin B. With the advent of antiretroviral treatment, a decrease of cryptococcosis cases in people with human immunodeficiency virus was observed; however, increasing cases have been reported in patients with new forms of immunosuppression. Cryptococcus spp. predominantly cause central nervous system infections but also pneumonia and bloodstream infections. Diagnostics include blood and cerebrospinal fluid cultures and antigen tests. First line treatment consists of a combination therapy with amphotericin B and flucytosine. CONCLUSION: An interdisciplinary approach with microbiologists, infectious diseases specialists and radiologists is needed for diagnostics and treatment of invasive fungal diseases.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose , Mucormicose , Micoses/tratamento farmacológico , Infecções Oportunistas , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Humanos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Micoses/diagnóstico , Neutropenia
12.
Pediatr Blood Cancer ; 66(9): e27834, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31131954

RESUMO

Mucormycosis in pediatric oncology patients is a rare invasive fungal infection associated with significant morbidity and mortality. We describe five patients diagnosed with mucormycosis during induction chemotherapy for acute lymphoblastic leukemia at our institution. All of the patients in our series survived, some in spite of having disseminated disease. Most of the patients' chemotherapy was modified with the aim of controlling their leukemia while minimizing immunosuppression until their fungal infection was under control. Although mucormycosis is frequently fatal, rapid diagnosis and a multidisciplinary approach can lead to excellent outcomes, even in patients undergoing intensive chemotherapy.


Assuntos
Quimioterapia de Indução/efeitos adversos , Mucormicose , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mucormicose/induzido quimicamente , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Estudos Retrospectivos
14.
Transplant Proc ; 51(2): 551-555, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879588

RESUMO

Pulmonary coinfection with Mucor and Aspergillus species has not been reported in organ transplant recipients. Here, we report a rare case of pulmonary coinfection with invasive fungal species in a renal transplant recipient with delayed graft function. The patient was first treated with a regime containing voriconazole, but the infection only worsened. Then, bronchoalveolar lavage fluid culture and internal transcribed spacer region sequencing were performed, and simultaneous pulmonary infection by Lichtheimia ramosa and Aspergillus fumigatus was clearly diagnosed. Susceptibility testing determined that the fungi were sensitive to amphotericin B and posaconazole. Therefore, a therapeutic regime containing posaconazole and amphotericin B liposome, which are less toxic to the kidney, was planned and resulted in resolution of the infectious symptoms. The present case demonstrates the importance of identifying fungal pathogens early and definitively, determining the effective anti-fungal medications, and administering the properly planned therapeutic regime in a timely manner to treat cases of coinfection in transplant recipients.


Assuntos
Aspergilose/imunologia , Hospedeiro Imunocomprometido , Transplante de Rim/efeitos adversos , Mucormicose/imunologia , Infecções Respiratórias/imunologia , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Aspergillus fumigatus , Coinfecção , Função Retardada do Enxerto , Humanos , Masculino , Mucorales , Mucormicose/tratamento farmacológico , Infecções Respiratórias/microbiologia , Triazóis/uso terapêutico
15.
Mycoses ; 62(9): 746-760, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30830980

RESUMO

Mucormycosis mostly affects immunocompromised patients and is associated with a high morbidity and mortality despite currently available treatments. In that context, combination therapy might be the key to a better outcome for these patients. Purpose of this review is to summarise and to discuss the current combination data obtained in vitro, in vivo in animal models of mucormycosis, and in patients. In vitro combination studies showed that most of the interactions between antifungal drugs were indifferent, even though that some synergistic interactions were achieved for the combination of echinocandins with either azoles or amphotericin B. Importantly, antagonism was never observed. Animal models of mucormycosis focused on infections caused by Rhizopus arrhizus, neglecting most other species responsible for human disease. In these experimental animal models, no strong interactions have been demonstrated, although a certain degree of synergism has been reported in some instances. Combinations of antifungals with non-antifungal drugs have also been largely explored in vitro and in animal models and yielded interesting results. In patients with ketoacidosis and rhino-orbito-cerebral infection, combination of polyene with caspofungin was effective. In contrast, despite promising experimental data, adjunctive therapy with the iron chelator deferasirox was unfavourable and was associated with a higher mortality than monotherapy with liposomal amphotericin B. More combinations have to be tested in vitro and a much larger panel of Mucorales species has to be tested in vivo to give a valuable statement if antifungal combination therapy could be an effective treatment strategy in patients with mucormycosis.


Assuntos
Antifúngicos/uso terapêutico , Mucorales/efeitos dos fármacos , Mucormicose/tratamento farmacológico , Anfotericina B/uso terapêutico , Animais , Azóis/uso terapêutico , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Hospedeiro Imunocomprometido , Lipopeptídeos/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Mucormicose/microbiologia , Mucormicose/mortalidade
16.
Med Mycol ; 57(Supplement_2): S245-S256, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30816980

RESUMO

Fungi of the basal lineage order Mucorales are able to cause infections in animals and humans. Mucormycosis is a well-known, life-threatening disease especially in patients with a compromised immune system. The rate of mortality and morbidity caused by mucormycosis has increased rapidly during the last decades, especially in developing countries. The systematic, phylogenetic, and epidemiological distributions of mucoralean fungi are addressed in relation to infection in immunocompromised patients. The review highlights the current achievements in (i) diagnostics and management of mucormycosis, (ii) the study of the interaction of Mucorales with cells of the innate immune system, (iii) the assessment of the virulence of Mucorales in vertebrate and invertebrate infection models, and (iv) the determination of virulence factors that are key players in the infection process, for example, high-affinity iron permease (FTR1), spore coat protein (CotH), alkaline Rhizopus protease enzyme (ARP), ADP-ribosylation factor (ARF), dihydrolipoyl dehydrogenase, calcineurin (CaN), serine and aspartate proteases (SAPs). The present mini-review attempts to increase the awareness of these difficult-to-manage fungal infections and to encourage research in the detection of ligands and receptors as potential diagnostic parameters and drug targets.


Assuntos
Interações Hospedeiro-Patógeno , Leucócitos/imunologia , Mucorales/imunologia , Mucorales/patogenicidade , Mucormicose/epidemiologia , Mucormicose/patologia , Fatores de Virulência/metabolismo , Animais , Gerenciamento Clínico , Modelos Animais de Doenças , Humanos , Hospedeiro Imunocomprometido , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico
17.
BMC Infect Dis ; 19(1): 134, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30744563

RESUMO

BACKGROUND: Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden. METHODS: The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs. RESULTS: The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%. CONCLUSIONS: This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective.


Assuntos
Antifúngicos/economia , Aspergilose/economia , Infecções Fúngicas Invasivas/economia , Nitrilos/economia , Piridinas/economia , Triazóis/economia , Voriconazol/economia , Adulto , Anfotericina B , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Estudos de Casos e Controles , Análise Custo-Benefício , Árvores de Decisões , Feminino , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Mucormicose/tratamento farmacológico , Mucormicose/economia , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Suécia , Triazóis/uso terapêutico , Voriconazol/uso terapêutico
18.
PLoS Genet ; 15(2): e1007957, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742617

RESUMO

Mucormycosis-an emergent, deadly fungal infection-is difficult to treat, in part because the causative species demonstrate broad clinical antifungal resistance. However, the mechanisms underlying drug resistance in these infections remain poorly understood. Our previous work demonstrated that one major agent of mucormycosis, Mucor circinelloides, can develop resistance to the antifungal agents FK506 and rapamycin through a novel, transient RNA interference-dependent mechanism known as epimutation. Epimutations silence the drug target gene and are selected by drug exposure; the target gene is re-expressed and sensitivity is restored following passage without drug. This silencing process involves generation of small RNA (sRNA) against the target gene via core RNAi pathway proteins. To further elucidate the role of epimutation in the broad antifungal resistance of Mucor, epimutants were isolated that confer resistance to another antifungal agent, 5-fluoroorotic acid (5-FOA). We identified epimutant strains that exhibit resistance to 5-FOA without mutations in PyrF or PyrG, enzymes which convert 5-FOA into the active toxic form. Using sRNA hybridization as well as sRNA library analysis, we demonstrate that these epimutants harbor sRNA against either pyrF or pyrG, and further show that this sRNA is lost after reversion to drug sensitivity. We conclude that epimutation is a mechanism capable of targeting multiple genes, enabling Mucor to develop resistance to a variety of antifungal agents. Elucidation of the role of RNAi in epimutation affords a fuller understanding of mucormycosis. Furthermore, it improves our understanding of fungal pathogenesis and adaptation to stresses, including the evolution of drug resistance.


Assuntos
Farmacorresistência Fúngica Múltipla/genética , Mucor/efeitos dos fármacos , Mucor/patogenicidade , Antifúngicos/farmacologia , Epigênese Genética , Genes Fúngicos , Humanos , Mucor/genética , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Mutação , Orotato Fosforribosiltransferase/genética , Ácido Orótico/análogos & derivados , Ácido Orótico/farmacologia , Orotidina-5'-Fosfato Descarboxilase/genética , Interferência de RNA , RNA Fúngico/genética , Sirolimo/farmacologia , Tacrolimo/farmacologia
19.
Mycopathologia ; 184(2): 309-313, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30666543

RESUMO

We report a case of eczema-like cutaneous mucormycosis caused by Rhizopus arrhizus. A 4-year-old child was presented to our hospital with a history of gradually enlarging papule and plaque in the periumbilical area for nearly 4 years since 2 weeks after his birth, and it has been misdiagnosed as eczema for nearly 3 years. Based on histopathology examination, the fungus culture test and DNA sequencing, it was revealed that R. arrhizus should be the responsible fungus for skin infection. The patient was successfully cured by combination of intravenous drip and percutaneous injection amphotericin B for nearly 3 months, and no recrudescence was seen during a follow-up of 6-month observation.


Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Dermatomicoses/diagnóstico , Dermatomicoses/patologia , Mucormicose/diagnóstico , Mucormicose/patologia , Rhizopus/isolamento & purificação , Pré-Escolar , Dermatomicoses/tratamento farmacológico , Eczema/patologia , Histocitoquímica , Humanos , Infusões Intravenosas , Injeções , Masculino , Técnicas Microbiológicas , Mucormicose/tratamento farmacológico , Análise de Sequência de DNA , Resultado do Tratamento
20.
Trop Doct ; 49(2): 153-155, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30691355

RESUMO

Mucormycosis is a potentially fatal fungal infection with high prevalence in poor-resource settings. Besides being an extremely expensive disease to treat, the challenges range from lack of experienced mycologists or mycology department to knowledge and availability of treatment regimes.


Assuntos
Países em Desenvolvimento , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Antifúngicos/uso terapêutico , Serviços de Laboratório Clínico/normas , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoal de Laboratório Médico/educação , Mucormicose/economia , Mucormicose/epidemiologia , Prevalência
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