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Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Resistance to conventional antifungal drugs and the toxicity associated with high doses highlight the need for effective antifungal therapies. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed. Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 µg/mL. The doubling time was also drastically affected, going from 2.8 h to 22.5 h, which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cytotoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the potential mechanisms of A. occidentale against C. albicans on a cellular level, and might provide a promising option for the design of a new treatment for invasive candidiasis.
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BACKGROUND: Paracoccidioidomycosis is a neglected tropical disease caused by fungi of the genus Paracoccidioides. A wide range of symptoms is related to the disease; however, lungs and skin are the sites predominantly affected. The disease is mostly seen in people living in rural areas in Latin America. CASE REPORT: We present a pediatric case of severe disseminated paracoccidioidomycosis that slowly responded to the antifungal treatment. Within three months, symptoms evolved into hepatosplenomegaly, necrotic cervical and abdominal lymph nodes, and splenic abscess. Clinical response to amphotericin B deoxycholate and itraconazole was slow, resulting in pleural and peritoneal cavity effusions, heart failure and shock. Amphotericin B deoxycholate was replaced by the liposomal formulation, with no response. Subsequently, prednisone was added to the treatment, which led to improvement in the clinical response. Serological Paracoccidioides antibody titers were atypical, with very low titers in the critical phase and significant increase during the convalescence phase. The infection was finally cleared up with amphotericin B deoxycholate, liposomal amphotericin B and the use of corticosteroids. Paracoccidioidomycosis serology was non-reactive two years post-discharge. CONCLUSIONS: Due to the intense inflammatory response triggered by Paracoccidioides cells, giving low-dose prednisone for a short period of time modulated the inflammatory response and supported antifungal treatment.
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Paracoccidioidomicose , Prednisona , Humanos , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/diagnóstico , Prednisona/uso terapêutico , Masculino , Lactente , Antifúngicos/uso terapêutico , Glucocorticoides/uso terapêutico , Paracoccidioides/isolamento & purificação , Paracoccidioides/efeitos dos fármacos , Anfotericina B/uso terapêuticoRESUMO
Chitosan is a cationic polysaccharide derived from chitin deacetylation. This polysaccharide and its oligosaccharides have many biological activities and can be used in several fields due to their favorable characteristics, such as biodegradability, biocompatibility, and nontoxicity. This review aims to explore the antifungal potential of chitosan and chitooligosaccharides along with the conditions used for the activity and mechanisms of action they use to kill fungal cells. The sources, chemical properties, and applications of chitosan and chitooligosaccharides are discussed in this review. It also addresses the threat fungi pose to human health and crop production and how these saccharides have proven to be effective against these microorganisms. The cellular processes triggered by chitosan and chitooligosaccharides in fungal cells, and prospects for their use as potential antifungal agents are also examined.
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Antifúngicos , Quitosana , Fungos , Oligossacarídeos , Quitosana/química , Quitosana/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Fungos/efeitos dos fármacos , Humanos , Quitina/química , Quitina/farmacologia , Quitina/análogos & derivados , Testes de Sensibilidade MicrobianaRESUMO
Diphenyl diselenide (PhSe)2 is a stable organoselenium compound with promising in vitro antifungal activity against several fungi, including Sporothrix brasiliensis. This species is associated with feline and zoonotic sporotrichosis, an emergent mycosis in Latin America. We evaluated the activity of (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. Sixty mice were subcutaneously infected with S. brasiliensis in the footpad and treated by gavage for 30 consecutive days. The six treatment groups received: no active treatment, itraconazole (50 mg/kg), (PhSe)2 at 1, 5, and 10 mg/kg dosages, or itraconazole (50 mg/kg) + (PhSe)2 1 mg/kg, once a day, starting seven days post-inoculation. A significant reduction in the fungal burden of internal organs was achieved in the groups treated with (PhSe)2 1 mg/kg or itraconazole alone in comparison with the untreated group. Higher dosages (5 and 10 mg/kg) of (PhSe)2 increased the clinical manifestation of sporotrichosis and mortality rate. Treatment with both itraconazole and (PhSe)2 1 mg/kg was better than their activities alone (P < .001). This is the first demonstration of the potential use of (PhSe)2, alone or with the present drug of choice, in the treatment of sporotrichosis.
We evaluated the activity of diphenyl diselenide (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. This is the first demonstration of the potential use of (PhSe)2, alone or in an association against sporotrichosis.
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Doenças do Gato , Sporothrix , Esporotricose , Animais , Gatos , Camundongos , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Esporotricose/microbiologia , Esporotricose/veterinária , Testes de Sensibilidade Microbiana/veterinária , Antifúngicos/farmacologia , Antifúngicos/uso terapêuticoRESUMO
Coccidioidomycosis (CM) and paracoccidioidomycosis (PCM) are systemic mycoses that are highly endemic in Latin America and have recently been included on the World Health Organization (WHO) Fungal Priority Pathogens List. Coccidioides immitis and Coccidioides posadasii are recognized as etiological agents of CM, with peculiarities in their geographic distribution. The genus Paracoccidioides now includes Paracoccidioides lutzii and the Paracoccidioides brasiliensis complex, which encompasses four phylogenetic species. In both diseases, pulmonary signs and symptoms are the main reasons for patients to seek medical assistance, and they are frequently misdiagnosed as tuberculosis. In this paper, we present a critical view of the strategies for diagnosis and clinical management of CM and PCM. Over the past few decades, there has been an increase in the number of reports of endemic fungal infections in areas previously thought to be "non-endemic" due to climate change and increased travel, among other factors. Learning to recognize their main epidemiological aspects and clinical manifestations is crucial so that clinicians can include them in the differential diagnosis of lung disease and avoid late diagnosis.
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Cryptococcosis is a global fungal infection caused by the Cryptococcus neoformans/Cryptococcus gattii yeast complex. This infection is acquired by inhalation of propagules such as basidiospores or dry yeast, initially causing lung infections with the possibility of progressing to the meninges. This infection mainly affects immunocompromised HIV and transplant patients; however, immunocompetent patients can also be affected. This review proposes to evaluate cryptococcosis focusing on studies of this mycosis in Brazilian territory; moreover, recent advances in the understanding of its virulence mechanism, animal models in research are also assessed. For this, literature review as realized in PubMed, Scielo, and Brazilian legislation. In Brazil, cryptococcosis has been identified as one of the most lethal fungal infections among HIV patients and C. neoformans VNI and C. gattii VGII are the most prevalent genotypes. Moreover, different clinical settings published in Brazil were described. As in other countries, cryptococcosis is difficult to treat due to a limited therapeutic arsenal, which is highly toxic and costly. The presence of a polysaccharide capsule, thermo-tolerance, production of melanin, biofilm formation, mechanisms for iron use, and morphological alterations is an important virulence mechanism of these yeasts. The introduction of cryptococcosis as a compulsory notification disease could improve data regarding incidence and help in the management of these infections.
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Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Infecções por HIV , Animais , Brasil/epidemiologia , Criptococose/epidemiologia , Criptococose/microbiologia , Cryptococcus gattii/genética , Cryptococcus neoformans/genética , Humanos , Saccharomyces cerevisiaeRESUMO
Background: Mortality rates among adults with candidemia vary widely in different geographical settings. Studies directly comparing epidemiology and clinical practices between countries are scarce and could bring insights into improving clinical outcomes. Methods: Retrospective cohort including adults with candidemia diagnosed in five tertiary hospitals from Brazil and Spain between 2010-2018. Adequate therapeutic management included appropriate antifungal therapy and central-venous-catheter (CVC) removal within 48 h of fungemia. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors associated with 30-day mortality. Findings: Overall, 720 patients were included, being 323 from Spain. Spanish patients received echinocandins more often (52·5% vs. 39·3%, p = 0.001), initiated antifungals earlier [2 (0-7) vs. 2 days (0-16), p<0.001], and had faster CVC-removal [1 (0-42) vs. 2 days (0-38), p = 0.012]. Mortality was higher among Brazilians at 14 days (35·8% vs. 20·1%, p<0.001), and at 30 days (51·9% vs. 31·6%, p < 0.001). Factors associated with mortality included: age [OR 1·02, 95%CI (1·008-1·032), p = 0·001], neutropenia [OR 3·24, 95%CI (1·594-6·585), p = 0·001], chronic pulmonary disease [OR 2·26, 95%CI (1·495-3·436), p < 0·001], corticosteroids [OR 1·45, 95%CI (1·018-2·079), p = 0·039], Pitt-Score>1 [OR 2·56, 95%CI (1·776-3·690), p < 0·001], and inadequate therapeutic management [OR 2·84, 95%CI (1·685-4·800), p < 0·001]. Being from Spain [OR 0·51, 95%CI (0·359-0·726), p < 0·001] and C. parapsilosis [OR 0·36, 95%CI (0·233-0·568), p < 0·001] were protective. Interpretation: Higher mortality rates were observed in Brazil. Factors associated with 30-day mortality included mainly epidemiological characteristics and inadequate therapeutic management. Thus, effective and prompt antifungals combined with CVC-removal still need to be emphasized in order to improve the prognosis of adults with candidemia. Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2017/02203-7); CAPES Foundation (PDSE 88881.187981/2018-01).
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Nowadays, the HIV pandemic is far from controlled. HIV+/AIDS patients show a serious risk of developing resistance to HIV antiretroviral drugs and to be orally colonized by albicans and non-albicans Candida strains resistant to antifungals. As a consequence, new drugs that possess anti-candidal and anti-HIV effects would represent an alternative in the comprehensive treatment of HIV+/AIDS patients. The present study evaluates the possible anti-HIV and anti-Candida effects of a methanolic extract from Heteropterys brachiata (Hb MeOH), an American tropical plant. The anti-HIV effect of Hb MeOH was tested using a non-radioactive colorimetric method (Lenti RT® Activity Assay; Cavidi Tech) that uses reverse transcriptase of HIV-1 enzyme as enzymatic target. The anti-candidal effect of HbMeOH extract was evaluated by following a standardized test protocol of microdilution for yeast using the Candida albicans strain ATCC® 90028. The Hb MeOH at 1 mg/mL concentration shows 38.5% RT-HIV inhibition, while Hb MeOH at 10 mg/mL concentration produced 98% C. albicans growth inhibition. Our findings show that the Hb MeOH possesses a strong anti-candidal activity and moderate anti-HIV effect and suggests that the plant extract could be considered as a potential candidate for HIV/AIDS treatment.
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Candida , Metanol , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologiaRESUMO
Fungal infections have increased in recent years due to host factors, such as oncohaematological and transplant-related disorders, immunosuppressive therapy, and AIDS. Additionally, molecular and proteomic facilities have become available to identify previously unrecognizable opportunists. For these reasons, reports on less-known and recalcitrant mycoses, such as those caused by black fungi, hyaline filamentous fungi, coelomycetes, Mucorales, and non-Candida yeasts have emerged. In this review, novel taxonomy in these groups, which often are multi-resistant to one or several classes of antifungals, is discussed. Clinical presentations, diagnosis and current treatment of some major groups are summarised.
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Mucorales , Micoses , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Humanos , Micoses/diagnóstico , Micoses/tratamento farmacológico , ProteômicaRESUMO
Sporotrichosis zoonotic transmission by cats has obtained hyperendemic magnitude in Rio de Janeiro, Brazil. Atypical cases, relapses, and reinfections as well as reduced diagnostic sensitivity of conventional methods have been reported. Previously, the anti-SsCBF enzyme-linked immunosorbent assay (ELISA) test was shown to be useful as a diagnostic tool for human sporotrichosis. Effective diagnosis and treatment are critical to interrupt the chain of transmission of this major pathogen in Brazilian Public Health. To evaluate its applicability for feline sporotrichosis diagnosis and/or therapeutic follow-up, 15 domestic cats from Rio de Janeiro were clinically and laboratory monitored by cytopathology, culture, Sporothrix genotyping, and anti-SsCBF IgG levels. Subsequently, animals were divided into satisfactory and non-satisfactory therapeutic responders. Averages of antibody serum levels obtained for diagnosis (first consultation) compared with the levels found after follow-up (last consultation) were significantly different in both groups (p = 0.0002 and p = 0.038, respectively). We conclude that the SsCBF ELISA test can predict feline sporotrichosis therapeutic responses even for animals with distinct clinical evolutions.
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Doenças do Gato/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Sporothrix/efeitos dos fármacos , Esporotricose/veterinária , Animais , Anticorpos Antifúngicos/sangue , Brasil/epidemiologia , Doenças do Gato/sangue , Doenças do Gato/epidemiologia , Doenças do Gato/microbiologia , Gatos , Sporothrix/classificação , Sporothrix/genética , Sporothrix/fisiologia , Esporotricose/tratamento farmacológico , Esporotricose/epidemiologia , Esporotricose/microbiologiaRESUMO
The treatment of feline sporotrichosis is a challenge for veterinary clinicians since refractory cases may occur, due either to patient and/or to pharmacological management errors or due to the development of antifungal resistance. Thus, we aimed to describe the therapeutic history of feline cases infected by itraconazole-resistant Sporothrix brasiliensis in an endemic region of Southern Brazil. Medical records of cats attended at the Veterinary Clinic Hospital (Pelotas/RS, Brazil) between 2016 and 2017 were reviewed. Twelve cases of infection by S. brasiliensis with that showed high minimum inhibitory concentration (MIC) values (≥ 4 µg/mL) to itraconazole by M38-A2 of CLSI were selected. At the hospital consultation, disseminated (cats 1-l0, 12) and localized (cat 11) skin lesions remained in the cats, even after treatment with fluconazole, ketoconazole (02/12), and itraconazole (ITZ, 09/12) performed before this study. High doses (25-100 mg/kg/day) of ITZ for up to 4 months (03/12, cats 2, 6, 12) or over 12 months (05/12, cats 1, 5, 7, 8, 11) did not provide a clinical cure, except for the association of ITZ plus potassium iodide (01/12, cat 12) for 3 months, which proved useful in infections with itraconazole-resistant S. brasiliensis. However, the combined issues of abandonment of therapy by owners for financial reasons, difficulties surrounding therapy administration (03/12, cats 6, 11, 12), and the inappropriate choice of medication (01/12, cat 6), together reflect the reality of this endemic region, which greatly compromises clinical healing. This study highlighted the occurrence of refractory cases by itraconazole-resistant S. brasiliensis in cats from Southern Brazil, as well as the abandonment of treatment and therapeutic errors. We warn of the need for antifungal susceptibility tests to adapt therapeutic protocols in feline sporotrichosis.
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Antifúngicos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Farmacorresistência Fúngica , Itraconazol/uso terapêutico , Sporothrix/efeitos dos fármacos , Esporotricose/veterinária , Animais , Brasil , Doenças do Gato/microbiologia , Gatos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Sporothrix/fisiologia , Esporotricose/tratamento farmacológico , Esporotricose/microbiologiaRESUMO
BACKGROUND: Cyst infection is a prevalent complication in autosomal dominant polycystic kidney disease (ADPKD) patients, however therapeutic and diagnostic approaches towards this condition remain unclear. The confirmation of a likely episode of cyst infection by isolating the pathogenic microorganism in a clinical scenario is possible only in the minority of cases. The available antimicrobial treatment guidelines, therefore, might not be appropriate to some patients. CASE PRESENTATION: We describe two unique cases of kidney cyst infection by Candida albicans, a condition that has not been previously described in literature. Both cases presented clear risk factors for Candida spp. infection. However, since there was no initial indication of cyst aspiration and culture, antifungal therapy was not immediately started and empirical treatment was initiated as recommended by the current guidelines. Antifungal treatment was instituted in both cases along the clinical course, according to their specificities. CONCLUSION: Our report highlights the possibility of Candida spp. cyst infection. Failure of clinical improvement with antibiotics should raise the suspicion of a fungal infection. Identification of infected cysts should be pursued in such cases, particularly with PET-CT, and when technically possible followed by cyst aspiration and culture to guide treatment. Risk factors for this condition, such as Candida spp. colonization, previous antimicrobial therapy, hemodialysis, necrotizing pancreatitis, gastrointestinal/hepatobiliary surgical procedure, central venous catheter, total parenteral nutrition, diabetes mellitus and immunodeficiency (neutropenia < 500 neutrophils/mL, hematologic malignancy, chemotherapy, immunosuppressant drugs), should be also considered accepted criteria for empirical antifungal therapy.
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Candida albicans , Candidíase/diagnóstico por imagem , Candidíase/etiologia , Rim Policístico Autossômico Dominante/complicações , Adulto , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Cistos/diagnóstico por imagem , Cistos/microbiologia , Cistos/terapia , Drenagem , Evolução Fatal , Feminino , Fluconazol/uso terapêutico , Humanos , Masculino , Nefrectomia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Diálise Renal , Insuficiência Renal/terapia , Resultado do TratamentoRESUMO
Invasive Candidiasis (IC) and candidemia (as its most frequent manifestation) have become the main cause of opportunistic mycosis at hospital settings. This study, made by members of the Colombian Association of Infectious Diseases (ACIN), was aimed at providing a set of recommendations for the management, follow-up and prevention of IC / candidemia and mucous membrane candida infection in adult, pediatric and neonatal patients in a hospital setting, including the hemato-oncological and critical care units. All the data obtained through an exhaustive search were reviewed and analyzed in a comprehensive manner by all the members of the group, and the recommendations issued are being made after a careful review of the scientific literature available and the consensus of all specialists involved; the emergence of Candida Spp. problem is highlighted and a correct orientation to health professionals regarding the management of patients with candidiasis is provided in a rational and practical way, emphasizing patient evaluation, diagnostic strategies, prophylaxis, empirical treatment, directed treatment and preventative therapy.
La Candidiasis Invasora (CI) y la candidemia, como su manifestación más frecuente, se ha convertido en la principal causa de micosis oportunista a nivel hospitalario. Este manuscrito realizado por miembros de la Asociación Colombiana de Infectología (ACIN), tuvo como objetivo proporcionar un conjunto de recomendaciones para manejo, seguimiento y prevención de la CI/candidemia y de la infección candidiásica de mucosas, en población adulta, pediátrica y neonatal, en un entorno hospitalario, incluyendo las unidades hemato-oncológicas y unidades de cuidado crítico. Todos los datos obtenidos mediante una búsqueda exhaustiva, fueron revisados y analizados de manera amplia por todos los miembros del grupo, y las recomendaciones emitidas se elaboraron luego de la evaluación de la literatura científica disponible, y el consenso de todos los especialistas involucrados, reconociendo el problema de la emergencia de las infecciones por Candida Spp. y brindando una correcta orientación a los profesionales de la salud sobre el manejo de pacientes con enfermedad candidiásica, de una forma racional y práctica, enfatizando en la evaluación del paciente, estrategias de diagnóstico, profilaxis, tratamiento empírico, tratamiento dirigido y terapia preventiva.
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Recém-Nascido , Adulto , Candidemia , Candidíase Invasiva , Micoses , Administração dos Cuidados ao Paciente , Colômbia , Infecções Fúngicas Invasivas , Neutropenia/diagnósticoRESUMO
The Amazon region or regional Amazon complex includes nine states of Brazil with an area of around 5.1 million km, which is almost 60% of the country's territory. The sanitary conditions in this region are reflected by illness resulting from substandard living conditions and limited access to prevention measures and health care, in addition to the epidemiological profile of cryptococcosis. This article aims to provide a comprehensive review of the literature on cryptococcosis in the Amazon region and its future prospects. Thus, the present study searched the Scientific Electronic Library Online, Latin American and Caribbean Health Sciences Literature, Medical Literature Analysis and Retrieval System, Virtual Health Library, PubMed, and CAPES Periodical Portal for studies on cryptococcosis in the Amazon region, with an established search period of 1999 to 2018, using the search terms "Cryptococcus," "cryptococcosis," and "Amazon" with the Boolean operator AND. Out of 275 articles found, 29 were selected according to the inclusion criteria and were categorized into clinical and environmental studies. Analysis of these studies verified the increased occurrence of infection by Cryptococcus gattii at younger ages in the supposedly immunocompetent and the predominance of C. neoformans in HIV-positive patients. No occurrence of Cryptococcus laurentii infection has been identified in the literature. The regional endemic molecular types included VNI, VNII, and VGII. Similarly, the strain sequence type (ST) allelic profiles, including ST5, 7, 20, and 264-268, were identified in C. gattii isolated in Amazonas state. VNI isolates are a genetically monotypic group, with ST93 being highly important in HIV individuals. In urban environments, cryptococcosis agents were isolated in samples collected fromtrees, wooden houses, and dove excrement. Due to the absence of a control program and specific epidemiological surveillance for the primary disease, cryptococcal meningitis has become a failure parameter in the treatment of HIV/AIDS patients. The findings of the present study underscore the need for programs to track cryptococcal antigens and identify high-risk populations in order to reduce the morbimortality of this disease.
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Criptococose/epidemiologia , Cryptococcus gattii , Cryptococcus neoformans , Adulto , Alelos , Animais , Doenças das Aves/microbiologia , Doenças das Aves/transmissão , Brasil/epidemiologia , Columbidae/microbiologia , Criptococose/transmissão , Cryptococcus gattii/classificação , Cryptococcus gattii/genética , Cryptococcus neoformans/classificação , Cryptococcus neoformans/genética , Fezes/microbiologia , Genótipo , Humanos , Fatores de RiscoRESUMO
Lasiodiplodia theobromae is a rare ocular pathogen. We report a patient with fungal keratitis caused by L. theobromae. The patient was a 75-year-old male, a farmer with diabetes type II, and no previous history of ocular trauma. Histopathology analysis revealed the presence fungi invading Descemet's membrane of the cornea. The fungus was characterized by septate, highly bulged fungal filaments involving full corneal thickness in the corresponding histopathology specimens. A dematiaceous mold was isolated and initally identified as L. theobromae by microscopic and macroscopic morphology, and further confirmed by PCR-based determination of internal transcribed spacer (ITS) regions of ribosomal DNA. Antifungal susceptibility tests showed sensitivity to amphotericin B (AMB) and voriconazole ( VRC), and resistance to other azoles, including itraconazole (ITC) and fluconazole (FLC). Corneal transplant was performed. Despite in vitro itraconazole resistance, the patient was successfully treated with oral itraconazole, topical voriconazole and natamycin, combined with ocular injections of amphotericin B and voriconazole.
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Ascomicetos/citologia , Ascomicetos/isolamento & purificação , Infecções Oculares Fúngicas/microbiologia , Ceratite/microbiologia , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Ascomicetos/genética , Córnea/patologia , Transplante de Córnea , DNA Fúngico/química , DNA Fúngico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Diabetes Mellitus Tipo 2/complicações , Farmacorresistência Fúngica , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/cirurgia , Histocitoquímica , Humanos , Ceratite/tratamento farmacológico , Ceratite/cirurgia , Masculino , Testes de Sensibilidade Microbiana , Técnicas Microbiológicas , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Resultado do TratamentoRESUMO
We present a fatal case of persistent neonatal candidemia by Candida parapsilosis following omphalocele, without other anomalies. Despite an encouraging initial prognosis, after surgical correction and closure of the abdominal wall the case became difficult to treat, as in addition to the exposure of the patient to multiple risk factors for candidemia, antifungal therapy apparently was not adequate.
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BACKGROUND: Cryptococcosis is still a life-threatening mycosis that continues to be of serious concern in Latin American countries, especially among HIV+positive population. However, there is not any reliable information about the prevalence of this disease in this region. AIMS: The aim of this study is to report data of 2041 patients with cryptococcosis that were attended at the Infectious Diseases Hospital F. J. Muñiz over a 30 year-period. METHODS: Information about demographic and clinical data, survival time and the applied treatment, was taken from the Mycology Unit database. Mycological exams from different clinical samples were performed. Cryptococcal capsular antigen in serum and cerebrospinal fluid was detected through the latex agglutination technique. Cryptococcus isolates were phenotypically identified and the genotype was determined in some of them. Susceptibility tests were carried out following M27-A3 document. RESULTS: Seventy five percent of HIV+positive patients and 50% of the HIV-negative population were males. Mean ages were 34.1 in HIV+positive patients and 44.8 in the HIV-negative. Cryptococcosis was associated with AIDS in 98% of the cases. Meningeal compromise was seen in 90% of the patients. Although cerebrospinal fluid rendered more positive results, blood culture was the first diagnostic finding in some cases. Cryptococcal antigen showed positive results in 96.2% of the sera samples and in the 93.1% of the cerebrospinal fluid samples. Most of the isolates were Cryptococcus neoformans and belonged to genotype VNI. Minimal inhibitory concentration values were mostly below the epidemiological cutoff values. CONCLUSIONS: We observed that thanks to a high level of clinical suspicion, early diagnosis, combined therapy and intracranial pressure control by daily lumbar punctures, the global mortality rate has markedly decreased through the years in the analyzed period.
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Criptococose/epidemiologia , Adulto , Antifúngicos/uso terapêutico , Argentina/epidemiologia , Comorbidade , Criptococose/complicações , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus gattii/efeitos dos fármacos , Cryptococcus gattii/isolamento & purificação , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/isolamento & purificação , Farmacorresistência Fúngica , Diagnóstico Precoce , Feminino , Infecções por HIV/epidemiologia , Hospitais Especializados/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Humanos , Infectologia , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/terapia , Masculino , Pessoa de Meia-Idade , Micologia/métodos , Punção EspinalRESUMO
BACKGROUND: Candidemia is an increasing problem in tertiary care hospitals worldwide. Here, we report the first outbreak of candidemia caused by fluconazole-resistant C. parapsilosis (FRCP) strains in Brazil. METHODS: This was a cross-sectional study of clinical and microbiological data of all candidemic episodes diagnosed from July 2011 to February 2012 in a 200-bed tertiary care hospital. Initial yeast identification and susceptibility testing were performed using the VITEK 2 - System. Isolates of Candida spp. resistant to fluconazole were sent to a reference laboratory (LEMI-UNIFESP) for further molecular identification and confirmation of resistance by CLSI microdilution test. A multivariate analysis was conducted to identify factors associated with FRCP infection. RESULTS: We identified a total of 40 critically ill patients with candidemia (15 women) with a median age of 70 years. The incidence of candidemia was 6 cases/1,000 patients admissions, including 28 cases (70 %) of infection with C. parapsilosis, 21 of which (75 %) were resistant to fluconazole. In only 19 % of FRCP candidemia cases had fluconazole been used previously. The results of our study indicated that diabetes is a risk factor for FRCP candidemia (p = 0.002). Overall, mortality from candidemia was 45 %, and mortality from episodes of FRCP infections was 42.9 %. CONCLUSIONS: The clustering of incident cases in the ICU and molecular typing of strains suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is required.
Assuntos
Antifúngicos , Candidemia/microbiologia , Surtos de Doenças , Farmacorresistência Fúngica , Fluconazol , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Candida , Candidemia/epidemiologia , Infecção Hospitalar/microbiologia , Estudos Transversais , Feminino , Hospitais , Humanos , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Fatores de Risco , Adulto JovemRESUMO
Introducción: La laringitis fúngica es una patología poco planteada en pacientes inmunocompetentes, sin embargo se debería tener en consideración en el diagnóstico diferencial de leucoplaquias en estos pacientes, más aún con factores predisponentes como reflujo faringolaríngeo, tabaquismo crónico y/o uso de corticoides. Objetivo: Presentar una serie de casos de pacientes inmunocompetentes con diagnóstico clínico de laringitis fúngica y tratamiento antimicótico empírico. Describir la asociación con factores predisponentes claves. Material y método: Estudio retrospectivo que incluyó a 11 pacientes con diagnóstico clínico de laringitis fúngica por correlación de la clínica, factores predisponentes y hallazgos en la videoestroboscopía laríngea (leucoplaquias múltiples en los pliegues vocales) sumado a la respuesta a tratamiento empírico con fluconazol oral. Se realizó además una revisión de la literatura disponible hasta el año 2015. Resultados: Todos los diagnósticos fueron clínicos correlacionando síntomas con hallazgo de leucoplaquias características en la laringe. El principal factor asociado fue el reflujo faringolaríngeo (91%) seguido por uso de corticoides (55%). Todos los pacientes fueron tratados con un esquema empírico de fluconazol oral por 14-21 días. El 100% de los pacientes respondió de forma exitosa al uso de este fármaco con remisión de los síntomas y de las lesiones laríngeas. Conclusión: El diagnóstico clínico y tratamiento con fluconazol oral como tratamiento de primera línea generarían buena tasa de respuesta, siempre que se correlacionen los síntomas y signos del paciente con los hallazgos encontrados en la laringe.
Introduction: The fungal laryngitis is an unusual disease in immunocompetent patients, however should take into consideration in the differential diagnosis of leukoplakias, especially in patients with predisposing factors such as pharyngolaryngeal reflux, use of inhaled, oral or intravenous corticosteroids. Aim: Describe a series of cases of fungal laryngitis in immunocompetent patients with clinical diagnosis and empirical antifungal treatment. In addition, finding the association with predisposing factors keys. Material and method: Retrospective study of 11 patients with diagnosis of fungal laryngitis according to clinical presentation, predisposing factors and findings in the laryngeal videostroboscopy (vocal folds leukoplakias) joined the response to empirical treatment with oral fluconazole. Also an extensive literature review was conducted until 2015. Results: The main predisposing factor was the pharyngolaryngeal reflux (91%) followed by use of corticosteroids (55%). All patients were treated empirically with fluconazole for 14-21 days. 100% of patients responded successfully, with remission of symptoms and laryngeal lesions. Conclusion: Clinical diagnosis and treatment with fluconazole as first-line treatment generate good response rate, provided that the patient's symptoms and signs with the findings in the larynx are correlated.