RESUMO
During surge of COVID-19-associated mucormycosis (CAM), we identified five cases of CAM where two different species of Mucorales were isolated. All had history of diabetes mellitus and presented with clinical features suggesting rhino-orbital mucormycosis. The patients grew different species from their nasal scraping/biopsy samples, Rhizopus arrhizus, R. homothallicus (n = 2); R. homothallicus, Lictheimia corymbifera (n = 1); R. arrhizus, Mucor spp (n = 1); and L. corymbifera, Apophysomyces variabilis (n = 1). All patients underwent surgical and medical (liposomal amphotericin B) treatment. All, except one growing A. variabilis and L. corymbifera survived. Mixed infection by more than one Mucorales in CAM is unique and warrants epidemiological investigation.
Assuntos
COVID-19 , Mucorales , Mucormicose , Mucormicose/diagnóstico , Mucormicose/microbiologia , Humanos , Mucorales/isolamento & purificação , Mucorales/classificação , Masculino , Pessoa de Meia-Idade , COVID-19/complicações , Feminino , Antifúngicos/uso terapêutico , Anfotericina B/uso terapêutico , Adulto , SARS-CoV-2 , IdosoRESUMO
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.
Assuntos
Sinusite , Humanos , Masculino , Tennessee , Sinusite/microbiologia , Sinusite/diagnóstico , Sinusite/parasitologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Mucormicose/diagnóstico , Mucormicose/microbiologia , Mucormicose/tratamento farmacológico , Mucorales/isolamento & purificação , Mucorales/classificação , Rinite/microbiologia , Rinite/diagnóstico , Adulto , Antifúngicos/uso terapêutico , RinossinusiteRESUMO
Fungi of the order Mucorales cause mucormycosis, a lethal infection with an incompletely understood pathogenesis. We demonstrate that Mucorales fungi produce a toxin, which plays a central role in virulence. Polyclonal antibodies against this toxin inhibit its ability to damage human cells in vitro and prevent hypovolemic shock, organ necrosis and death in mice with mucormycosis. Inhibition of the toxin in Rhizopus delemar through RNA interference compromises the ability of the fungus to damage host cells and attenuates virulence in mice. This 17 kDa toxin has structural and functional features of the plant toxin ricin, including the ability to inhibit protein synthesis through its N-glycosylase activity, the existence of a motif that mediates vascular leak and a lectin sequence. Antibodies against the toxin inhibit R. delemar- or toxin-mediated vascular permeability in vitro and cross react with ricin. A monoclonal anti-ricin B chain antibody binds to the toxin and also inhibits its ability to cause vascular permeability. Therefore, we propose the name 'mucoricin' for this toxin. Not only is mucoricin important in the pathogenesis of mucormycosis but our data suggest that a ricin-like toxin is produced by organisms beyond the plant and bacterial kingdoms. Importantly, mucoricin should be a promising therapeutic target.
Assuntos
Mucorales/patogenicidade , Mucormicose/patologia , Micotoxinas/metabolismo , Ricina/metabolismo , Animais , Antitoxinas/imunologia , Antitoxinas/farmacologia , Antitoxinas/uso terapêutico , Apoptose , Permeabilidade Capilar , Células Cultivadas , Reações Cruzadas , Humanos , Hifas/química , Hifas/patogenicidade , Lectinas/metabolismo , Camundongos , Mucorales/química , Mucorales/classificação , Mucorales/genética , Mucormicose/microbiologia , Mucormicose/prevenção & controle , Micotoxinas/química , Micotoxinas/genética , Micotoxinas/imunologia , Necrose , Interferência de RNA , Rhizopus/química , Rhizopus/genética , Rhizopus/patogenicidade , Proteínas Inativadoras de Ribossomos/metabolismo , Ricina/química , Ricina/imunologia , Virulência/efeitos dos fármacos , Virulência/genéticaRESUMO
BACKGROUND: Lichtheimia species are emerging opportunistic fungal pathogens in the Mucorales, causing serious skin and respiratory infections in immunocompromised patients. Established agents are Lichtheimia corymbifera and L. ramosa, while L. ornata is a novel agent. Available data on a species-specific analysis of Lichtheimia infections are limited. METHODS: The first case of a fatal rhino-orbital-cerebral infection in a hematopoietic stem cell transplantation recipient caused by L. ornata is reported; the agent was identified by sequencing the ITS ribosomal region. We reviewed the literature on mucormycosis due to Lichtheimia species between 2009 and 2018, with an analysis of risk factors and epidemiological and clinical data. RESULTS: In addition to our Lichtheimia ornata case, 44 cases of human Lichtheimia were analyzed. Lichtheimia predominated in Europe (68.2%), followed by Asia (16%), and Africa (9%). The most common underlying condition was hematological malignancy (36.3%), followed by trauma/major surgery (27.3%), while diabetes mellitus was rare (11.4%). Site of infection was mostly skin and soft tissues (45.5%) and lung (25%), while relatively few cases were disseminated (13.6%) or rhinocerebral (11.4%). Mortality (36.4%) was mainly due to disseminated and rhinocerebral infections. CONCLUSION: In contrast to Rhizopus, the most common agent of mucormycosis recorded in patients with diabetes mellitus, Lichtheimia infections were primarily associated with hematological malignancies and major skin barrier damage. Given the fact that classical rhinocerebral mucormycosis remains difficult to treat, independent of causative species, timely application of amphotericin B accessory to debridement may be required for patient survival.
Assuntos
Hospedeiro Imunocomprometido , Mucorales/patogenicidade , Mucormicose/microbiologia , Adulto , Anemia Aplástica/complicações , Olho/microbiologia , Evolução Fatal , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Testes de Sensibilidade Microbiana , Mucorales/classificação , Mucorales/efeitos dos fármacos , Mucorales/isolamento & purificação , Cavidade Nasal/microbiologia , Infecções Oportunistas/microbiologia , FilogeniaRESUMO
This study describes a novel fungal species belonging to the genus Gongronella. During a previous work focusing on metalaxyl degradation by Mucorales strains, two isolates from vineyard soil samples collected in the Alentejo region, south Portugal, were identified as a putative novel species based on combined molecular and MALDI-TOF MS data. This new species is described here using a polyphasic approach that combines morphology, internal transcribed spacer of ribosomal DNA (ITS) and 28S ribosomal DNA (LSU) sequence data analysis and proteomic profiling by MALDI-TOF MS. Phenotypic and molecular data enabled this novel species to be clearly distinguished from other Gongronella species with results of combined ITS+LSU analysis showing that the Gongronella species is related to Gongronella butleri and Gongronella brasiliensis. Therefore, from the results of morphological and molecular analyses, isolates MUM 10.262 and MUM 10.263 seem to represent a new Gongronella species and the name Gongronella eborensis sp. nov. is proposed, with the ex-type strain MUM 10.262 (=CCMI 1100=CBS 128763).
Assuntos
Mucorales/classificação , Filogenia , Microbiologia do Solo , DNA Espaçador Ribossômico/genética , Mucorales/isolamento & purificação , Técnicas de Tipagem Micológica , Portugal , Proteômica , RNA Ribossômico 28S/genética , Análise de Sequência de DNA , VitisRESUMO
BACKGROUND: Limited data exist for epidemiology and outcomes of various agents causing mucormycosis in various clinical settings from developing countries like India. OBJECTIVES: To study the epidemiology and outcomes of various agents causing mucormycosis in different clinical settings in a tertiary care hospital from South India. PATIENTS AND METHODS: We reviewed details of 184 consecutive patients with culture-proven mucormycosis with consistent clinical syndrome and supporting features from September 2005 to September 2015. RESULTS: The mean age of patients was 50.42 years; 70.97% were male. Unlike developed countries, R microsporus (29/184; 15.7%) and Apophysomyces elegans (20/184; 10.8%) also evolved as important pathogens in addition to R arrhizus in our setting. Paranasal sinuses (136/184; 73.9%) followed by musculoskeletal system (28/184; 15.2%) were the common areas of involvement. Apophysomyces elegans typically produced skin and musculoskeletal disease in immune-competent individuals with trauma (12/20; 60%) and caused significantly lower mortality (P = 0.03). R microsporus was more common in patients with haematological conditions (25% vs 15.7%) and was less frequently a cause for sinusitis than R arrhizus (27.58% vs 10.9%). The overall mortality was 30.97%. Combination therapy with surgery and antifungals offered the best chance for cure. CONCLUSIONS: Agents causing mucormycosis may have unique clinical and epidemiological characteristics.
Assuntos
Antifúngicos/uso terapêutico , Desbridamento , Mucorales/isolamento & purificação , Mucormicose/epidemiologia , Mucormicose/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Quimioterapia Combinada/métodos , Feminino , Neoplasias Hematológicas/complicações , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Mucorales/classificação , Mucormicose/mortalidade , Mucormicose/terapia , Distribuição por Sexo , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Infecção dos Ferimentos/epidemiologia , Infecção dos Ferimentos/mortalidade , Infecção dos Ferimentos/patologia , Infecção dos Ferimentos/terapia , Ferimentos e Lesões/complicaçõesRESUMO
BACKGROUND: Invasive mucormycosis is a rare but frequently fatal fungal disease. The acute and rapidly progressive evolution causes unfavourable outcome in 22%-59% of patients and its treatment represents a clinical challenge, especially in immunocompromised patients. Current data in paediatric oncological patients are limited. OBJECTIVES: The infection Working Group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) analysed the episodes of invasive mucormycosis occurred between 2009 and 2016. PATIENTS: Fifteen cases of proven mucormycosis (male/female 8/7; median age 14.1 years, range 7.7-18.6) were reported after chemotherapy for acute leukaemia and lymphoma (12) and allogeneic stem cell transplantation (3). The aetiology was Rhizopus oryzae 4, Lichtheimia corymbifera 3 and Mucor spp. 8. RESULTS: Paranasal sinus was the primary site of infection in 14/15 patients combined with orbital involvement (9), central nervous system (8), lung (4), thyroid gland and kidney (1). All patients received liposomal Amphotericin B (L-AmB) (3-10 mg/kg), with surgical debridement in 14/15 cases. Eleven patients received maintenance treatment with posaconazole (9) or isavuconazole (2). Eight out of fifteen patients (53.3%) died, after 3-6 months. CONCLUSIONS: Mucormycosis involved mainly the sinu-orbital site and affected children >10 years. Despite aggressive treatment with high-dose L-AmB and timely surgical debridement, the mortality rate remains still high.
Assuntos
Neoplasias Hematológicas/complicações , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/patologia , Mucorales/isolamento & purificação , Mucormicose/epidemiologia , Mucormicose/patologia , Adolescente , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Itália/epidemiologia , Masculino , Mucorales/classificação , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Mucormycoses are life-threatening fungal diseases that affect a variety of patients including those with diabetes mellitus or hematological malignancies. The responsible agents, the Mucorales, are opportunistic pathogens originating from the environment such as soil or decaying organic matter. The aim of the present study was to assess the prevalence and diversity of human-pathogenic species of Mucorales in commercially available foodstuffs in France. All food samples were purchased from January 2014 to May 2015 in France. A total of 159 dried food samples including spices and herbs (n = 68), herbal tea (n = 19), cereals (n = 19), vegetables (n = 14), and other foodstuffs (n = 39) were analyzed. Each strain of Mucorales was identified phenotypically, and molecular identification was performed by ITS sequencing. From the 28 (17.6%) samples that were culture-positive for Mucorales, 30 isolates were recovered. Among the isolates, 13 were identified as Rhizopus arrhizus var. arrhizus, 10 R. arrhizus var. delemar, two Rhizopus microsporus, one Lichtheimia corymbifera, three Lichtheimia ramosa, and one Syncephalastrum racemosum. Culture-positive samples originated from different countries (Europe, Asia) and brands. The samples most frequently contaminated by Mucorales were spices and herbs (19/68, 27.9%), followed by herbal tea (2/19, 10.5%), cereals (2/19, 10.5%), other food products (5/39, 12.8%). The present study showed that human-pathogenic Mucorales were frequently recovered from commercially available foodstuffs in France with a large diversity of species. The potential danger represented by Mucorales present in food for immunocompromised patients should be further analyzed.
Assuntos
Contaminação de Alimentos/análise , Microbiologia de Alimentos , Variação Genética , Mucorales/classificação , Mucorales/isolamento & purificação , Ásia , DNA Espaçador Ribossômico/genética , Grão Comestível/microbiologia , Europa (Continente) , Paris , Plantas Medicinais/microbiologia , Especiarias/microbiologia , Verduras/microbiologiaRESUMO
Mucormycosis due to Mucorales is reported at large numbers in uncontrolled diabetics across India, but systematic multicenter epidemiological study has not been published yet. The present prospective study was conducted at four major tertiary care centers of India (two in north and two in south India) during 2013-2015 to compare the epidemiology, treatment strategies and outcome of mucormycosis between the two regions. Molecular techniques were employed to confirm the identity of the isolates or to identify the agent in biopsy samples. A total of 388 proven/probable mucormycosis cases were reported during the study period with overall mortality at 46.7%. Uncontrolled diabetes (n = 172, 56.8%) and trauma (n = 31, 10.2%) were the common risk factors. Overall, Rhizopus arrhizus (n = 124, 51.9%) was the predominant agent identified, followed by Rhizopus microsporus (n = 30, 12.6%), Apophysomyces variabilis (n = 22, 9.2%) and Rhizopus homothallicus (n = 6, 2.5%). On multivariate analysis, the mortality was significantly associated with gastrointestinal (OR: 18.70, P = .005) and pulmonary infections (OR: 3.03, P = .015). While comparing the two regions, majority (82.7%) cases were recorded from north India; uncontrolled diabetes (n = 157, P = .0001) and post-tubercular mucormycosis (n = 21, P = .006) were significantly associated with north Indian cases. No significant difference was noted among the species of Mucorales identified and treatment strategies between the two regions. The mortality rate was significantly higher in north Indian patients (50.5%) compared to 32.1% in south India (P = .016). The study highlights higher number of mucormycosis cases in uncontrolled diabetics of north India and emergence of R. microsporus and R. homothallicus across India causing the disease.
Assuntos
Gerenciamento Clínico , Mucormicose/diagnóstico , Mucormicose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Complicações do Diabetes , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Mucorales/classificação , Mucorales/genética , Mucorales/isolamento & purificação , Mucormicose/mortalidade , Mucormicose/terapia , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Ferimentos e Lesões/complicações , Adulto JovemRESUMO
The diagnosis of gastrointestinal (GI) mucormycosis is always a challenge due to its non-specific clinical presentations and often diagnosed at autopsy. Recently increased number of GI mucormycosis has been reported in immunocompetent hosts and during 1948 through 2017, 200 cases of GI mucormycosis are available in literature. We could review 176 cases where case details were available. Majority (50.6%) of the cases were reported from Asia. The disease is nearly equally recorded in adults and paediatric population. The infection commonly affected the intestine (64.2%) followed by stomach (33%). A significant improvement in antemortem diagnosis was noted since 2001. Rhizopus species were the predominant (67.5%) aetiological agents. Amphotericin B was the most commonly used drug (93.4%). Despite improvement of antemortem diagnosis and therapy, the mortality was 60.5% and 67.5% in adults and children respectively. Combined medical and surgical therapy (reported in 47.8% patients) had significantly better survival rate than those receiving either of them. Analysing the clinical presentations, we propose to suspect GI mucormycosis in a malnourished/ dehydrated child (especially premature neonate) with history of exposure to broad-spectrum antibiotics or formula/spoon feeding and presenting with mass in abdomen, abdominal distension or bilious vomiting; and an adult presenting with abdominal distension, fever or GI bleed with underlying risk factors for mucormycosis.
Assuntos
Gastroenteropatias/epidemiologia , Mucorales/isolamento & purificação , Mucormicose/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Antifúngicos/administração & dosagem , Criança , Pré-Escolar , Feminino , Gastroenteropatias/microbiologia , Gastroenteropatias/patologia , Gastroenteropatias/terapia , Saúde Global , Humanos , Lactente , Intestinos/microbiologia , Intestinos/patologia , Masculino , Pessoa de Meia-Idade , Mucorales/classificação , Mucormicose/microbiologia , Mucormicose/patologia , Mucormicose/terapia , Fatores de Risco , Estômago/microbiologia , Estômago/patologia , Procedimentos Cirúrgicos Operatórios/métodos , Resultado do Tratamento , Adulto JovemRESUMO
Mucormycosis is an emerging infectious disease with high rates of associated mortality and morbidity. Little is known about the characteristics of mucormycosis or entomophthoromycosis occurring in Mexico. A search strategy was performed of literature published in journals found in available databases and theses published online at Universidad Nacional Autónoma de México (UNAM) library website reporting clinical cases or clinical case series of mucormycosis and entomophthoromycosis occurring in Mexico between 1982 and 2016. Among the 418 cases identified, 72% were diabetic patients, and sinusitis accounted for 75% of the reported cases. Diabetes mellitus was not a risk factor for entomophthoromycosis. Mortality rate was 51% (125/244). Rhizopus species were the most frequent isolates (59%, 148/250). Amphotericin B deoxycholate was used in 89% of cases (204/227), while surgery and antifungal management as combined treatment was used in 90% (172/191). In diabetic individuals, this combined treatment approach was associated with a higher probability of survival (95% vs 66%, OR = 0.1, 95% CI, 0.02-0.43' P = .002). The most common complications were associated with nephrotoxicity and prolonged hospitalization due to IV antifungal therapy. An algorithm is proposed to establish an early diagnosis of rhino-orbital cerebral (ROC) mucormycosis based on standardized identification of warning signs and symptoms and performing an early direct microbiological exam and histopathological identification through a multidisciplinary medical and surgical team. In summary, diabetes mellitus was the most common risk factor for mucormycosis in Mexico; combined antifungal therapy and surgery in ROC mucormycosis significantly improved survival.
Assuntos
Complicações do Diabetes/diagnóstico , Complicações do Diabetes/epidemiologia , Gerenciamento Clínico , Mucormicose/diagnóstico , Mucormicose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Desbridamento , Complicações do Diabetes/mortalidade , Complicações do Diabetes/terapia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Mucorales/classificação , Mucorales/isolamento & purificação , Mucormicose/mortalidade , Mucormicose/terapia , Prevalência , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Benjaminiella poitrasii, a dimorphic non-pathogenic zygomycetous fungus, exhibits a morphological yeast (Y) to hypha (H) reversible transition in the vegetative phase, sporangiospores (S) in the asexual phase and zygospores (Z) in the sexual phase. To study the gene expression across these diverse morphological forms, suitable reference genes are required. In the present study, 13 genes viz. ACT, 18S rRNA, eEF1α, eEF-Tu,eIF-1A, Tub-α, Tub-b, Ubc, GAPDH, Try, WS-21, NADGDH and NADPGDH were evaluated for their potential as a reference, particularly for studying gene expression during the Y-H reversible transition and also for other asexual and sexual life stages of B. poitrasii. Analysis of RT-qPCR data using geNorm, normFinder and BestKeeper software revealed that genes such as Ubc, 18S rRNA and WS-21 were expressed at constant levels in each given subset of RNA samples from all the morphological phases of B. poitrasii. Therefore, these reference genes can be used to elucidate the role of morpho-genes in B. poitrasii. Further, use of the two most stably expressed genes (Ubc and WS-21) to normalize the expression of the ornithine decarboxylase gene (Bpodc) in different morphological forms of B. poitrasii, generated more reliable results, indicating that our selection of reference genes was appropriate.
Assuntos
Genes Fúngicos , Mucorales/classificação , Mucorales/genética , Reação em Cadeia da Polimerase em Tempo Real , AMP Cíclico/metabolismo , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Estágios do Ciclo de Vida , Mucorales/citologia , Mucorales/crescimento & desenvolvimento , NADP/metabolismo , Esporos Fúngicos , TranscriptomaRESUMO
Mucormycosis is a deadly invasive fungal infection and mainly affects immunocompromised patients. To investigate the clinical features of patients who developed mucormycosis and to determine the parameters, which influenced the outcome following mycotic infection. The current investigation retrospectively evaluated the demographic characteristics, clinical features, therapeutic data, as well as the outcomes of treatment in all cases of proven and probable mucormycosis diagnosed from 2002 until 2016 in our hospital. A total of thirty cases were recorded. Rhizopus spp. was the predominant pathogen among the identified Mucorales (26.7%). Diabetes mellitus (46.7%) and haematological malignancy (40%), were the most common underlying diseases. With regard to predisposing factors, neutropenia (43.3%) and chemotherapy (40%) were the leading concomitant parameters. The most frequent sites of infection were lung (30%) and sinus (26.7%), whereas disseminated infection was also found in nine of 30 patients (30%). Neutropenia remained the only independent factor associated with mortality (Relative Risk=3.557, 95% CI=1.365-9.271, P=.009). Diagnostic delay -either due to delayed presentation of patients to our centre or insufficient awareness about invasive fungal infection among our clinicians- is a likely explanation for such a high mortality rate in our series.
Assuntos
Mucorales/isolamento & purificação , Mucormicose/diagnóstico , Mucormicose/patologia , Idoso , Feminino , Hospitais Universitários , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Mucorales/classificação , Mucormicose/tratamento farmacológico , Mucormicose/mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
Abstract Mucorales comprises fungi commonly isolated as saprobes from soil, dung, stored grains and plants. Although these fungi have been studied in several countries, there are relatively a few reports of them in semi-arid areas. Therefore, the aims of the present study were to assess and compare the Mucorales communities in dung from different species and breeds of herbivores in the semi-arid of Pernambuco, based on the frequency of occurrence and species richness of these fungi. Samples of dung collected in the cities of Arcoverde, Serra Talhada and Sertânia were incubated in moist chambers in triplicate. Altogether, 24 taxa of Mucorales distributed in the genera Absidia, Circinella, Cunninghamella, Lichtheimia, Mucor, Pilobolus, Rhizopus and Syncephalastrum were identified. The highest species richness was found in sheep excrement. Mucor circinelloides f. griseo-cyanus was the most common taxon, followed by M. ramosissimus. The similarity of the composition of Mucorales species was greatest between the excrements of Guzerá and Sindi breeds (bovine). All mucoralean species isolated are being cited for the first time from animal dung found in Caatinga and a new species of Mucor was recorded. An identification key for species of Mucorales from dung in the semi-arid region of Brazil is provided.
Assuntos
Animais , Microbiologia Ambiental , Mucorales , Brasil , Bovinos , Ovinos , Análise por Conglomerados , Biodiversidade , Herbivoria , Mucorales/classificaçãoRESUMO
OBJECTIVE: To review the current literature for the pathogenesis of mucormycosis, discuss diagnostic strategies, and evaluate the efficacy of polyenes, triazoles, and echinocandins as pharmacological treatment options. DATA SOURCES: An electronic literature search was conducted in PubMed using the MESH terms Rhizopus, zygomycetes, zygomycosis, Mucorales and mucormycosis, with search terms amphotericin B, micafungin, anidulafungin, caspofungin, extended infusion amphotericin B, liposomal amphotericin B, combination therapy, triazole, posaconazole, isavuconazole, diagnosis, and clinical manifestations. STUDY SELECTION AND DATA EXTRACTION: Studies written in the English language from January 1960 to March 2016 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. DATA SYNTHESIS: Mucormycosis is a rare invasive fungal infection with an exceedingly high mortality and few therapeutic options. It has a distinct predilection for invasion of endothelial cells in the vascular system, which is likely important in dissemination of disease from a primary focus of infection. Six distinct clinical syndromes can occur in susceptible hosts, including rhino-orbital-cerebral, pulmonary, gastrointestinal, cutaneous, widely disseminated, and miscellaneous infection. CONCLUSION: Diagnosis of mucormycosis is typically difficult to make based on imaging studies, sputum culture, bronchoalveolar lavage culture, or needle aspirate. Surgical debridement prior to dissemination of infection improves clinical outcomes. Surgery combined with early, high-dose systemic antifungal therapy yields greater than a 1.5-fold increase in survival rates. The Mucorales are inherently resistant to most widely used antifungal agents. Amphotericin B is appropriate for empirical therapy, whereas posaconazole and isavuconazole are best reserved for de-escalation, refractory cases, or patients intolerant to amphotericin B.
Assuntos
Antifúngicos/uso terapêutico , Mucorales/efeitos dos fármacos , Mucormicose/tratamento farmacológico , Anfotericina B/administração & dosagem , Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Anidulafungina , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Caspofungina , Desbridamento , Farmacorresistência Fúngica , Equinocandinas/administração & dosagem , Equinocandinas/efeitos adversos , Equinocandinas/uso terapêutico , Humanos , Lipopeptídeos/administração & dosagem , Lipopeptídeos/efeitos adversos , Lipopeptídeos/uso terapêutico , Masculino , Micafungina , Pessoa de Meia-Idade , Mucorales/classificação , Mucorales/isolamento & purificação , Mucorales/patogenicidade , Mucormicose/microbiologia , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Triazóis/uso terapêutico , VirulênciaRESUMO
Mucormycosis is associated with significant morbidity and mortality. We reviewed patients with mucormycete isolated at Alfred Health, Australia. A retrospective review of 66 patients with mucormycete(s) identified, between 1 April 2008 and 30 June 2014. Baseline demographic, microbiological, radiological, treatment/outcome data were recorded. Site of isolation was sinopulmonary in 77% and skin/soft tissue in 21%. A total of 32% of cases were proven-IFD, 12% probable-IFD and 56% were defined as no-IFD (or colonisation). Rhizopus spp. was identified in 48%. Comparing probable/proven-IFD with no-IFD/colonisation, more patients were postallogeneic stem cell transplantation (28% vs. 0%, P < 0.01) and were receiving immunosuppressive therapy (59% vs. 24%, P < 0.01) including prednisolone >20 mg daily (24% vs. 5%, P = 0.04). A total of 93% of patients with proven/probable IFD received treatment while 30% of no-IFD/colonisation were treated. A total of 72% of patients with proven/probable IFD and 92% of those with colonisation had no further mucormycete isolated. Thirty day mortality was higher in the proven/probable-IFD cohort (24%) compared with no-IFD/colonisation (3%) (P = 0.02). Mucormycosis remains uncommon, with 56% of cases not associated with clinical infection. Immunosuppressive therapy remains strongly associated with mucormycosis. Mortality remains high in those with proven/probable IFD.
Assuntos
Mucorales/classificação , Mucormicose/epidemiologia , Estudos de Coortes , Feminino , Humanos , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Mucorales/isolamento & purificação , Mucormicose/mortalidade , Mucormicose/terapia , Seios Paranasais/microbiologia , Estudos Retrospectivos , Fatores de Risco , Pele/microbiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/mortalidade , Centros de Atenção Terciária , Resultado do Tratamento , Vitória/epidemiologiaRESUMO
A case report of cutaneous mucormycosis and obstacles to early diagnosis is presented. A 38-year-old male was involved in a car accident that led to amputation of both lower limbs. Subsequently, he developed fungal wound infection of the left lower limb stump. The infection was detected very early, although the diagnosis was difficult because only a small area was affected and histopathological examination was initially negative. The infection was proven by microscopy, culture and histopathology. The isolate was identified by sequencing of the rDNA ITS region gene (internal transcribed spacer region of ribosomal DNA) as Lichtheimia corymbifera. Liposomal amphotericin B and surgery were successful in management of the disease.
Assuntos
Mucorales/isolamento & purificação , Mucormicose/diagnóstico , Infecção dos Ferimentos/diagnóstico , Ferimentos e Lesões/complicações , Acidentes de Trânsito , Adulto , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , DNA Fúngico/química , DNA Fúngico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Desbridamento , Diagnóstico Precoce , Histocitoquímica , Humanos , Masculino , Microscopia , Mucorales/classificação , Mucorales/genética , Mucormicose/microbiologia , Mucormicose/patologia , Análise de Sequência de DNA , Resultado do Tratamento , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologiaRESUMO
Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the Order Mucorales and class of Mucormycetes. We conducted a prospective study of 38 patients who were diagnosed as having mucormycosis in a tertiary care hospital during January 2010 to June 2011. The cases were analyzed regarding the site of involvement, underlying disease and species of fungi isolated, antifungal susceptibility pattern of the isolates, and outcome of therapy. The mean age of the patients was 40.43 years, with 72% male. Rhino-orbital mucormycosis (61.5%) was the most common presentation followed by cutaneous manifestations (31%), gastrointestinal symptoms (5%), and pulmonary (2.5%). Diabetes mellitus (56%) was the significant risk factor in rhino-orbito-cerebral presentation (OR = 7.55, P = 0.001). Among 23 culture isolates, Rhizopus arrhizus (37.5%) was the most common, followed by Apophysomyces variabilis (29.2%), Lichtheimia ramosa (16.7%), Rhizopus microsporus (4.2%), Rhizomucor pusillus (4.2%), and Apophysomyces elegans (4.2%). Rhizopus arrhizus was most commonly isolated from rhino-orbito-cerebral mucormycosis and Apophysomyces species were generally obtained from cutaneous mucormycosis. In vitro antifungal susceptibility showed that 16 isolates were sensitive to amphotericin B (MIC less than 1 µg/ml), while in contrast, all isolates were found to be resistant to voriconazole (MIC- 0.25 to >8), fluconazole (MIC > 32), flucytosine (MIC > 32). Treatment regimens included antifungal therapy, reversal of underlying predisposing risk factors, and surgical debridement. Combination of surgery and medical treatment with amphotericin B was significantly better (OR = 0.2, P < 0.04) than amphotericin B alone (61.5% vs. 10.3% patient survival). The awareness of fungal diseases amongst clinicians is required to decrease the fatal outcome of disease.
Assuntos
Mucorales/isolamento & purificação , Mucormicose/epidemiologia , Mucormicose/patologia , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Criança , Desbridamento , Feminino , Humanos , Índia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Mucorales/classificação , Mucormicose/microbiologia , Mucormicose/terapia , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
Mucormycosis has emerged as a relatively common severe mycosis in patients with haematological and allogeneic stem cell transplantation. Source of transmission is from unidentified sources in the environment. Early diagnosis of infection and its source of contamination are paramount for rapid and appropriate therapy. In this study, rolling circle amplification (RCA) is introduced as a sensitive, specific and reproducible isothermal DNA amplification technique for rapid molecular identification of six of the most virulent species (Rhizopus microsporus, R. arrhizus var. arrhizus, R. arrhizus var. delemar, Mucor irregularis, Mucor circinelloides, Lichtheimia ramosa, Lichtheimia corymbifera). DNAs of target species were successfully amplified, with no cross reactivity between species. RCA can be considered as a rapid detection method with high specificity and sensitivity, suitable for large screening.
Assuntos
DNA Fúngico/isolamento & purificação , Mucorales/isolamento & purificação , Mucormicose/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Diagnóstico Precoce , Humanos , Mucor/classificação , Mucor/crescimento & desenvolvimento , Mucor/isolamento & purificação , Mucorales/classificação , Mucorales/crescimento & desenvolvimento , Rhizopus/classificação , Rhizopus/crescimento & desenvolvimento , Rhizopus/isolamento & purificação , Sensibilidade e EspecificidadeRESUMO
Mucormycosis is increasingly common in patients with risk factors such as diabetes mellitus, neutropenia, and corticosteroid therapy. However, mucormycosis seems to be less common in patients with human immunodeficiency virus (HIV) infection compared to patients with other risk factors. Despite their lower virulence, Lichtheimia species should be regarded as emerging pathogens among Mucoralean fungi. We report a fatal case of pulmonary mucormycosis due to Lichtheimia ramosa in a 52-year-old man with an end-stage HIV infection. He had a cachectic appearance and his CD4 count was 8 cells/mm(3). The fungal infection was diagnosed based on a positive sputum culture with histopathologic confirmation. The fungus was resistant to caspofungin, anidulafungin, and voriconazole [minimum inhibitory concentration (MCI) >32 µg/ml], whereas the E test MIC values of itraconazole, posaconazole, and amphotericin B were 0.38, 0.38, and 0.5 µg/ml, respectively. Although intravenous drug use is the main risk factor for the development of mucormycosis in HIV-infected patients, it may also develop in patients with low CD4 count, opportunistic infections and/or additional diseases, such as Kaposi's sarcoma or severe immunodeficiency, as in our case.