Cryptococcus laurentii fungemia in a patient with chronic kidney disease on hemodialysis / Fungemia por cryptococcus laurentii em paciente com doença renal crônica em hemodiálise

Introduction: Chronic Kidney Disease (CKD) is a relevant comorbidity from clinical and public health perspectives. Infections are an important cause of death in those patients. Although rare, fungal infections are increasing in incidence. Case report: a 45-year-old female patient with CKD due to systemic lupus erythematosus (SLE) was admitted to a tertiary hospital due to a bloodstream infection (BSI) caused by Cryptococcus laurentii. She received treatment with anidulafungin with good initial response but presented clinical and laboratory worsening after a few days, and the treatment was switched to amphotericin B. The hemodialysis access was changed. Chest tomography, echocardiogram, eye fundus examination, and cerebrospinal fluid study did not show changes. After 32 days of amphotericin B, the patient presented clinical improvement and was discharged to take oral fluconazole for three (3) months. Conclusion: BSI due to Cryptococcus laurentii is rare in patients on chronic hemodialysis with a high potential for complications. Physicians should have clinical suspicion for those infrequent infections infractions, and culture evaluation should always be performed. The diagnosis is still a challenge, as well as the therapeutic regimen.

Introdução: a doença renal crônica (DRC) é uma comorbidade relevante do ponto de vista clínico e de saúde pública. As infecções configuram importante causa de morte nesses pacientes. Embora raras, as infecções por fungos têm incidência crescente. Relato de caso: uma paciente do sexo feminino, 45 anos, com DRC por lúpus eritematoso sistêmico (LES) foi internada em hospital terciário devido à infecção de corrente sanguínea (ICS) por Cryptococcus laurentii. Recebeu tratamento com anidulafungina com boa resposta inicial, porém, devido à piora clínica e laboratorial, o tratamento foi modificado para anfotericina B, assim como foi realizada a troca do acesso para hemodiálise. A tomografia de tórax, o ecocardiograma, o exame de fundo de olho e o estudo do líquido cefalorraquidiano não evidenciaram alterações. Após 32 dias de anfotericina B, a paciente apresentou melhora clínica e recebeu alta hospitalar com fluconazol via oral por 3 meses. Conclusão: a ICS por Cryptococcus Laurentii é rara nos pacientes em hemodiálise crônica, porém com alto potencial de complicações. Há a necessidade de suspeição clínica e avaliação por culturas, sendo o diagnóstico ainda um desafio, bem como o esquema terapêutico.

Diversity of fungi obtained from bats captured in urban forest fragments in Sinop, Mato Grosso, Brazil / Diversidade de fungos em morcegos de fragmentos florestais urbanos de Sinop, Mato Grosso, Brasil

Bats are important for the homeostasis of ecosystems and serve as hosts of various microorganisms including bacteria, viruses, and fungi with pathogenic potential. This study aimed to isolate fungi from biological samples obtained from bats captured in the city of Sinop (state of Mato Grosso, Brazil), where large areas of deforestation exist due to urbanization and agriculture. On the basis of the flow of people and domestic animals, 48 bats were captured in eleven urban forest fragments. The samples were processed and submitted to microbiological cultures, to isolate and to identify the fungal genera. Thirty-four (70.83%) of the captured bats were positive for fungi; 18 (37.5%) and 16 (33.33%) of these bats were female and male, respectively. Penicillium sp., Scopulariopsis sp., Fusarium sp., Aspergillus sp., Alternaria sp., Cryptococcus sp., Trichosporon sp., and Candida sp., which may cause opportunistic infections, were isolated. The bat species with the highest number of fungal isolates was Molossus molossus: 21 isolates (43.8%). According to our results, bats captured in urban forest fragments in Sinop harbor pathogenic fungi, increasing the risk of opportunistic fungal infections in humans and domestic animals.

Os morcegos apresentam grande importância na homeostasia dos ecossistemas e são hospedeiros de uma rica diversidade de micro-organismos como bactérias, vírus e fungos com potencial patogênico. Portanto, este estudo visou isolar fungos presentes em amostras biológicas de morcegos na cidade de Sinop - MT, que possui grandes áreas de desmatamento devido à urbanização e agricultura. Foram capturados 48 morcegos de diferentes espécies, em onze fragmentos florestais urbanos definidos de acordo com fluxo de pessoas e animais domésticos, para obtenção de amostras biológicas. Essas amostras foram processadas e submetidas aos cultivos microbiológicos, para isolamento e identificação dos gêneros dos fungos. Dos 48 morcegos, 34 (70,83%) foram positivos para pelos menos um gênero de fungo, sendo 18 (37,5%) fêmeas e 16 (33,33%) machos, e os gêneros isolados a partir das amostras biológicas foram Penicillium sp., Scopulariopsis sp., Fusarium sp., Aspergillus sp., Alternaria sp., Cryptococcus sp., Trichosporon sp. e Candida sp., que podem ser causadores de infecções oportunistas. Desse total, a espécie que apresentou maior positividade para pelo menos um gênero de fungo foi Molossus molossus com 21 (43,8%). Nossos resultados demonstram que os morcegos capturados nos fragmentos florestais urbanos na cidade de Sinop - MT, podem atuar como agentes veiculadores de fungos com potencial patogênico, aumentando assim o risco de exposição e aquisição de infecções fúngicas oportunistas por pessoas e animais domésticos.

Meningeal cryptococcosis and SARS-CoV-2 infection in people living with HIV/AIDS / Criptococosis meníngea e infección por SARS-CoV-2 en personas con VIH/SIDA

Introduction. Fungal infections in patients with COVID-19 was one of the most debated topics during the pandemic. Objectives. To analyze the clinical characteristics and evolution of people living with HIV/ AIDS and coinfection with cryptococcus and COVID-19 (group A) or without it (group B). Materials and methods. This is an analytical and retrospective study. We reviewed medical records of patients with meningeal cryptococcosis between April 2020 and May 2021. Results. We studied 65 people living with HIV/AIDS and with cryptococcosis infection diagnosed from April 2020 to May 2021. Fifteen patients with HIV/AIDS suffered from cryptococcosis and COVID-19, and out of these, 14 presented meningitis (group A), while 28 suffered from meningeal cryptococcosis, but did not have COVID-19 (group B). Conclusions. No statistically significant differences were observed between the two groups (A and B) considering: intracranial hypertension, presence of Cryptococcus antigens in cerebrospinal fluid, sensorium deterioration or mortality. The detection of Cryptococcus antigens in serum by lateral flow assay was highly effective to rapidly diagnose cryptococcosis in patients with HIV/AIDS who also developed COVID-19. Patients of both groups consulted for cryptoccocosis sometime after, in comparison with the pre-pandemic cases related to this infection.

Introducción. Las infecciones fúngicas en pacientes con COVID-19 fue uno de los temas más debatidos durante la pandemia. Objetivo. Analizar las características clínicas y la evolución de personas con VIH/SIDA que presentaron la asociación de criptococosis meníngea y COVID-19 (grupo A), y compararlas con aquellas personas con VIH/SIDA que padecieron criptococosis meníngea, pero sin infección de COVID-19 (grupo B). Materiales y métodos. Se realizó un estudio analítico y retrospectivo en el que se revisaron las historias clínicas de pacientes que padecieron criptococosis meníngea entre abril de 2020 y mayo de 2021. Resultados. Se estudiaron 65 pacientes con HIV/SIDA y con criptococosis, diagnosticados entre abril de 2020 y mayo de 2021 (63 habían desarrollado sida y 2 eran negativos para VIH). De estos, 15 de los pacientes con sida padecían criptococosis y COVID-19, y 14 presentaban meningitis (grupo A), mientras que 28 pacientes padecieron criptococosis meníngea, pero no tuvieron COVID-19 (grupo B). Conclusiones. No se observaron diferencias estadísticamente significativas, entre los dos grupos, respecto a la hipertensión intracraneal, la presencia de antígenos de criptoccoco en líquido cefalorraquídeo, el deterioro del sensorio o la mortalidad. La detección de antígenos de Cryptococcus en suero por ensayo de flujo lateral fue efectiva para diagnosticar rápidamente criptococosis en personas con VIH/sida y con infección de COVID-19. Se observó que los pacientes de ambos grupos consultaron tarde por criptococosis en comparación con los casos prepandémicos de esta infección.

Recomendaciones para el diagnóstico y tratamiento de la infección por Cryptococcus spp / Recommendations for the diagnosis and treatment of infection by Cryptococcus spp

Las infecciones por levaduras del género Cryptococcus pueden causar un abanico amplio de manifestaciones clínicas, dependiendo de si se trata de una infección invasora o no. Los pacientes susceptibles, especialmente de las formas invasoras, comparten el compromiso de la inmunidad celular, ya sea por afecciones primarias o secundarias. El grupo más estudiado es el de personas que viven con VIH. La mortalidad es alta, especialmente en entornos de recursos reducidos. El esquema de tratamiento es en fases, inicialmente combinado, para luego continuar con monoterapia por un periodo prolongado, dependiendo de la duración del factor de riesgo subyacente. Hacemos una revisión de la evidencia y recomendaciones actualizadas.

Infection by yeast of the Cryptococcus genus can cause a wide range of clinical manifestations, depending on whether it is an invasive infection or not. Susceptible patients, especially those with invasive forms, share the compromise of cellular immunity, either due to primary or secondary conditions. The most studied group is that of people living with HIV. Mortality is high, especially in resource-poor settings. The treatment scheme is in phases, initially combined, to then continue with monotherapy for a prolonged period, depending on the duration of the underlying risk factor. We review the evidence and update recommendations.

Antigenemia temprana de Cryptococcus en pacientes asintomáticos VIH positivos en Barranquilla, Colombia / Cryptococcus early antigenemia in HIV positive asymptomatic patients in Barranquilla, Colombia

Resumen La criptococosis meníngea presenta alta mortalidad mundial, especialmente en población VIH/sida. La OMS recomienda detectar el antígeno capsular de Crypto coccus como estrategia para un diagnóstico temprano y poder minimizar complicaciones. Objetivo: realizar antigenemia temprana de Cryptococcus mediante in munocromatografía/ensayo de flujo lateral en pacientes asintomáticos VIH+. Material y método: estudio descriptivo observacional; entre julio-2016 y mayo-2019 se procesaron mediante ensayo de flujo lateral, muestras de suero de 169 pacientes asintomáticos VIH+, con CD4 ≤120 cel/μL en Barranquilla, Colombia. Ante resultado positivo, se indicó profilaxis con fluconazol; se hizo seguimiento a todos los casos. Resultados: la antigenemia fue positiva en cinco pacientes (2,96%); uno falleció, cuatro recibieron profilaxis y la prueba se negativizó en dos. Los pacientes con resultado negativo inicial no desarrollaron durante el estudio sinto matología compatible con esta micosis. Discusión: el ensayo de flujo lateral de Cryptococcus está recomendado para el diagnóstico temprano de la criptococosis en población VIH/sida. Conclusión: detectar tempranamente el antígeno circulante de Cryptococcus mediante ensayo de flujo lateral en pacientes asintomáticos VIH+, permitió instaurar profilaxis oportuna, hacer seguimiento y control para reducir la mortalidad asociada con la criptococosis meníngea.

Abstract Meningeal cryptococcosis presents high levels of global mortality, especially in the HIV/AIDS population. The WHO recommends detecting the capsular antigen as an important strategy for early diagnosis and be able to minimize complications. Objective: Perform early cryptococcal antigenemia by immunochromatographic/ lateral flow assay in asymptomatic HIV+ patients. Material and method: descriptive observational study; between July-2016 and May-2019, serum samples from 169 asymptomatic HIV+ patients with CD4 ≤120 cells/μL were processed by lateral flow assay in Barranquilla, Colombia. Given a positive result, prophylaxis with fluconazole was indicated; all cases were followed up. Results: antigenemia was positive in five (2.96%) patients; one died; four received prophylaxis, and the test turned negative in two. The patients with an initial negative result, did not developed symptoms compatible with this mycosis during the study period. Discussion: lateral flow assay for Cryptococcus is recommended for the early diagnosis of cryptococcosis in the HIV/AIDS population. Conclusion: early detection of circulating Cryptococcus antigen by lateral flow assay in HIV+ patients allowed the establishment of timely prophylaxis, follow-up, and control to reduce mortality associated with meningeal cryptococcosis.

Criptococosis y linfocitopenia T CD4 idiopática: Reporte de un caso / Cryptococcosis and idiopathic CD4 T lymphocytopenia: A case report

Resumen La linfocitopenia T CD4 idiopática (LCI) es un síndrome clínico inusual que se caracteriza por un déficit de células T CD4+ circulantes en ausencia de infección por VIH u otra condición de inmunosupresión. Los pacientes con dicha enfermedad pueden presentarse asintomáticos o con infecciones oportunistas, las más frecuentes son por criptococo, micobacterias o virales como herpes zoster. Presentamos el caso de un hombre de 32 años, sin antecedentes, en quien se descartó infección por retrovirus, con recuento de linfocitos T CD4+ menor a 300 células/m3; se diagnosticó LCI posterior al diagnóstico de criptococomas cerebrales mediante hallazgos imagenológicos los cuales fueron congruentes con estudios microbiológicos.

Summary Idiopathic CD4 T lymphocytopenia (ICL) is an unusual clinical syndrome characterized by a deficit of circulating CD4 + T cells in the absence of HIV infection or another immunosuppression condition. Patients with this disease may present asymptomatic or with opportunistic infections, the most frequent are cryptococcus, mycobacteria or viral such as herpes zoster. We present a case of a 32-year-old man with no prior disease, in whom retrovirus infection was discarded, with CD4 + T lymphocyte count less than 300 cells/m3; ICL was diagnosed after the diagnosis of brain cryptococomas by imaging findings which were consistent with microbiological studies.

Comparison of two commercial tests (Immy vs. Dynamiker) for cryptococcal capsular antigen

Abstract INTRODUCTION Lateral flow assay is an advanced method useful in the early diagnosis of cryptococcal meningitis. We aimed to compare two commercial tests for cryptococcal capsular antigen in the sera of asymptomatic patients with human immunodeficiency virus in Barranquilla, Colombia. METHODS Thawed (n=162) previously collected serums (2016-2019) were processed using IMMY and Dynamiker cryptococcal antigen lateral flow assay. RESULTS Compared to IMMY's results, Dynamiker's sensitivity, specificity, positive predictive value, negative predictive value, and kappa index were 100%, 89.9%, 48.3%, 100.0%, and 0.61, respectively. CONCLUSIONS The Dynamiker test had excellent sensitivity, acceptable specificity, and a low detection threshold for cryptococcal antigen in the tested samples.

Asymptomatic cryptococcal antigenemia in HIV-infected patients: a review of recent studies / 中华医学杂志(英文版)

The prevalence of asymptomatic cryptococcal antigenemia (ACA) in human immunodeficiency virus (HIV) infected individuals has been observed to be elevated. The prevalence of ACA ranges from 1.3% to 13%, with different rates of prevalence in various regions of the world. We reviewed studies conducted internationally, and also referred to two established expert consensus guideline documents published in China, and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4 T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines, although it is likely that this recommendation may change in the future. Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis, and is lifesaving. Further studies are warranted to explore issues related to the optimal management of ACA.

Rastreio de leveduras patogênicas isoladas de fezes de pombos no Distrito Federal-Pombos: propagadores de fungos patogênicos? / Screening for pathogenic yeasts isolated from pigeon droppings in the Federal District-Pigeons: propagators of pathogenic fungi? / Detección de levaduras patógenas aisladas de excrementos de paloma en el Distrito Federal-Palomas: ¿propagadores de hongos patógenos?

Objetivo: Investigar a presença de fungos patogênicos isolados a partir de amostras de fezes de pombos, em locais de atenção a pacientes imunocomprometidos no DF. Método: As amostras foram coletadas em hospitais onde se oferta atendimento a pacientes HIV/AIDS e que tenha uma presença massiva de pombos. Colônias de leveduras foram previamente selecionados em meio Ágar Sabouraud Dextrose acrescido de cloranfenicol, seguindo-se com análise microscópica das estruturas leveduriformes. Colônias de leveduras com suspeita de pertencerem ao gênero Candida spp. ou Cryptococcus sp., foram inoculadas no meio Ágar Cromogênico para identificação das espécies de Candida e em meio Ágar quimicamente definido para indução dos fenótipos de virulência característicos de Cryptococcus sp. Resultados: 100% das amostras analisadas apresentaram crescimento de leveduras do gênero Candida spp. e Rhodotorula sp. No meio Ágar Cromogênico foram identificadas nas amostras C. krusei em 75%; C. tropicalis em 50% e C. glabrata em 15%. Em 15% das amostras foi identificado leveduras do gênero Cryptococcus sp. Conclusão: Dados deste estudo sugerem que fezes de pombo podem estar dispersando leveduras patogênicas e contribuindo com a incidência de infecções fúngicas no DF.

Objective: To investigate the presence of pathogenic fungi isolated from pigeon stool samples, in places of care for immunocompromised patients in the Federal District. Method: The samples were collected in hospitals where care is offered to HIV / AIDS patients and which has a massive presence of pigeons. Yeast colonies were previously selected on Sabouraud Dextrose Agar plus chloramphenicol, followed by microscopic analysis of the yeast structures. Yeast colonies suspected of belonging to the genus Candida spp. or Cryptococcus sp., were inoculated in the Chromogenic Agar medium to identify Candida species and in chemically defined Agar medium to induce the virulence phenotypes characteristic of Cryptococcus sp. Results: 100% of the analyzed samples showed growth of yeasts of the genus Candida spp. and Rhodotorula sp. In the chromogenic agar medium, 75% were identified in C. krusei samples; C. tropicalis in 50% and C. glabrata in 15%. In 15% of the samples, yeasts of the genus Cryptococcus sp. Conclusion: Data from this study suggest that pigeon feces may be dispersing pathogenic yeasts and contributing to the incidence of fungal infections in DF

Objetivo: Investigar la presencia de hongos patógenos aislados de muestras de heces de palomas, en los lugares de atención a pacientes inmunodeprimidos del Distrito Federal. Método: Las muestras se recolectaron en hospitales donde se brinda atención a pacientes con VIH / SIDA y que tiene una presencia masiva de palomas. Las colonias de levadura se seleccionaron previamente en Sabouraud Dextrose Agar más cloranfenicol, seguido de un análisis microscópico de las estructuras de la levadura. Las colonias de levaduras sospechosas de pertenecer al género Candida spp. o Cryptococcus sp., se inocularon en medio de agar cromogénico para identificar especies de Candida y en medio de agar químicamente definido para inducir los fenotipos de virulencia característicos de Cryptococcus sp. Resultados: el 100% de las muestras analizadas presentó crecimiento de levaduras del género Candida spp. y Rhodotorula sp. En el medio agar cromogénico, el 75% se identificó en muestras de C. krusei; C. tropicalis en 50% y C. glabrata en 15%. En el 15% de las muestras, levaduras del género Cryptococcus sp. Conclusión: Los datos de este estudio sugieren que las heces de las palomas pueden estar dispersando levaduras patógenas y contribuyendo a la incidencia de infecciones fúngicas en el DF.

Catheter-related infection due to Papiliotrema laurentii in an oncologic patient: Case report and systematic review

ABSTRACT Background: Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte and thought to be non-pathogenic to humans. Nevertheless, increasing number of reports of human infection have emerged in recent years, mostly in oncologic patients. Aim: To report a case of a female patient with pyloric obstructive cancer with a catheter-related Papiliotrema laurentii blood stream infection and systematically review the available evidence on P. laurentii infection in humans. Methods: Retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Library for Systematic Reviews and Opengray.eu. There was no language or date of publication restrictions. The reference lists of the studies retrieved were searched manually. Results: The search strategy retrieved 1703 references. In the final analysis, 31 references were included, with the description of 35 cases. Every patient but one had a previous co-morbidity - 48.4 % of patients had a neoplasm. Amphotericin B was the most used treatment and only a single case of resistance to it was reported. Most patients were cured of the infection. Conclusion: P. laurentii infection in humans is usually associated to neoplasia and multiple co-morbidities, and amphotericin B seems to be a reliable agent for treatment.

Criptococosis vertebral: comunicación de un caso y revisión bibliográfica / Vertebral cryptococosis: case report and literature review

Resumen La criptococosis es una micosis sistémica producida por un hongo levaduriforme encapsulado denominado Cryptococcus neoformans. Es una enfermedad universal, que ocurre con mayor frecuencia en pacientes inmunocomprometidos, manifestándose principalmente como una enfermedad diseminada con compromiso meníngeo o pulmonar. Sin embargo, la osteomielitis ocurre solo en 5-10% de los casos, siendo el compromiso vertebral el más frecuente. Presentamos un caso de criptococosis vertebral aislada y una búsqueda bibliográfica sobre el tema. Se recomienda realizar una terapia antifúngica de inducción intravenosa y continuar con una fase de consolidación, vía oral, de duración variable. La indicación quirúrgica se considera en lesiones que comprometen la estabilidad vertebral y aquellas que presentan un compromiso neurológico, producen deformidad y para reducir el inóculo infeccioso.

Cryptococcosis is an infectious disease caused by a ubiquitous encapsulated yeast called Cryptococcus neoformans, it is usually associated with immunosuppressed patients. Osteomyelitis occurs in 5-10%, the spine involvement is one of the most reported. The purpose of this work is to present a case of isolated vertebral cryptococcosis and detail the results of a literature review. The treatment protocol is not yet established but it is recommended to start with aggressive intravenous therapy and continue with a suppressive treatment orally during a variable time. Surgical indication is considered in lesions that affect the spinal stability, deformity or neurological compromise and for local infectious control.

Antifungal Mechanism of Action of Lauryl Betaine Against Skin-Associated Fungus Malassezia restricta

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.

A review of the management and outcome of patients admitted with cryptococcal meningitis at a regional hospital in KwaZulu-Natal province

Background: South Africa has 7.06 million people who are HIV-positive, with those having a low CD4 count being susceptible to cryptococcal meningitis (CCM), which has an estimated mortality of 30­50%. This study aimed to establish the outcome of patients admitted with CCM to a regional hospital in Durban between June 2015 and May 2016, and the extent to which the National Department of Health (NDoH) protocol was adhered to in managing their condition. Method: This retrospective observational descriptive study reviewed the records of patients ≥ 12 years old admitted with CCM between June 2015 and May 2016, from which their demographic and medical data were extracted.Results: Seventy-six complete records were found of which 49 were men and 27 were women. The average CD4 count was 55.9 cells/mm3, 85.5% were treated with intravenous amphotericin B and high-dose oral fluconazole, 6.7% received only amphotericin B and 5.2% received only fluconazole. There was an in-hospital mortality of 31.6%, and the NDoH protocol was adhered to in 72.4% (55/76) of patients. There was, however, no significant difference in outcome between those who were and were not managed as per the protocol (p = 0.177).Discussion and conclusion: In-hospital mortality for CCM continues to be significant despite high rates of adherence to the NDoH protocol in the majority of patients. For this to be addressed, early diagnosis of HIV and initiation of ART to prevent the profound immunosuppression is essential

Cryptococcal Meningitis Complicated by a Brain Abscess and an Abdominal Pseudocyst Following Ventriculoperitoneal Shunting / 대한내과학회지

Ventriculoperitoneal (VP) shunt insertion is the standard treatment for hydrocephalus; shunt-associated infection is the most common complication after surgery. However, fungal infections are unusual. We present a case of cryptococcal meningitis complicated by a brain abscess and an infected intra-abdominal pseudocyst that developed 14 weeks after VP shunt insertion to treat hydrocephalus in a 74-year-old patient. Cryptococcal central nervous system (CNS) infection has a high mortality rate; however, diagnosis is challenging. Therefore, prompt diagnosis and treatment are required when a cryptococcal CNS infection is suspected in patients with VP shunts.

Drug development for cryptococcosis treatment: what can patents tell us?

BACKGROUND Cryptococcosis is one of the most devastating fungal infections in humans. Despite the disease's clinical importance, current therapy is based on limited antifungals that are either toxic, inefficient, unavailable worldwide, or that quickly lead to resistance. OBJECTIVES The goal of this study was to provide insight into the future of cryptococcosis treatment by describing the patent scenario in this field. METHODS We identified and analysed patent documents revealing compounds with anti-cryptococcal activity supported by experimental evidence. FINDINGS Patenting in this field has been historically low, with an overall tendency of increase since 2012. Most applications are single filings, suggesting that they do not encompass strategic inventions requiring broad protection. Research and development essentially took place in China and the United States, which also represent the main countries of protection. Both academic and corporate institutions contributed to patenting in this field. Universities are the leading actors, with the highest patent family counts. CONCLUSION The low number of patents in this field indicates that efforts to mitigate the unmet needs for cryptococcosis treatment remain insufficient. Without investment to drive research and innovation, patients will likely continue to face inadequate assistance. Given the current scenario characterised by poor funding and low interest for technological development, drug repurposing may be the best alternative for cryptococcosis treatment.

First case report of cryptococcosis due to Cryptococcus decagattii in a pediatric patient in Argentina

Abstract We report the first case of cryptococcosis due to Cryptococcus decagattii in an immunocompetent pediatric patient from an indigenous community in Argentina with a successful outcome. Two isolates (blood, cerebrospinal fluid) were genotyped by restriction fragment length polymorphism of the orotidine monophosphate pyrophosphorylase (URA5) gene as VGIV and identified by multi-locus sequence typing as C. decagattii. Matrix-assisted laser desorption/ionization time of flight mass spectrometry identification indicated genotype VGIII. The minimum inhibitory concentration of amphotericin B, fluconazole, itraconazole, and voriconazole was determined (cerebrospinal fluid: 0.25, 16, 0.12, and 0.12, blood: 0.25, 4, 0.12, and 0.06, respectively, all in mg/L).

Fatores microbiológicos da criptococose e sua importância na carga da doença em pacientes atendidos em um hospital de referência do Estado de São Paulo / Not available

Introdução: A meningite criptocócica causa elevada mortalidade, sobretudo em pacientes acometidos de alguma condição imunossupressora. O objetivo deste estudo foi identificar fenômenos de baixa suscetibilidade a antifúngicos e outros preditores clínicos que possam explicar falha terapêutica e recidiva da neurocriptococose Metodologia: Foram avaliados 96 casos com coleta de dados clínicos epidemiológicos e laboratoriais. Os isolados foram identificados quanto a genótipo molecular, suscetibilidade de anfotericina B (AMB) e fluconazol (FCZ) pela determinação da concentração inibitória mínima (Minimal Inhibitory Concentration, MIC), nível de heteroresistência ao FCZ (NHF) e determinação do tempo de morte frente AMB (Time-Kill, TK). Foram selecionados isolados heterorresistentes para análise quantitativa de DNA por PCR em tempo Real, expressão de bombas de efluxo por citometria de fluxo e isolados tolerantes a AMB para estudo de resistência ao estresse oxidativo. Foi realizada análise univariável e múltipla usando regressão logística para identificar preditores de óbito hospitalar e de um desfecho composto definido pelo óbito, encaminhamento para unidade de terapia intensiva ou recidiva 6 meses após alta hospitalar. Resultados: A maioria dos pacientes eram imunodeprimidos, com CD4 de 2 a 722 cel./mm3 e 96,7% eram portadores do HIV. Foram identificados 93 isolados de C. neoformans, sendo 76 do genótipo VNI e 17 VNII e 3 C. gattii, todos VGII. MIC de AMB variou de 0,012 a 0,94 mg/L e MIC de FCZ estiverem entre 0,12 e 64 mg/L. Resistência a FCZ (MIC>16mg/L) foi maior em VNI do que em VNII (p=0,03). Dentre os isolados VNI, 64,5% sofreu atividade fungicida até as 24h (TK24) de exposição à AMB e 6 cepas VNI não sofreram ação fungicida (TK>72). A maioria dos isolados VNII (64,7%) apresentou TK24. Os 3 isolados VGII sofreram atividade fungicida a partir de TK24. A maioria dos isolados VNI, VNII e todos os isolados VGII apresentaram alto NHF (>32mg/L). Diferença no NHF de acordo com os genótipos foi observada (p=0,005). No modelo múltiplo, as variáveis associadas significativamente ao óbito foram: idade em anos (OR=1,08;IC95%=1,02-1,15), contagem de leveduras no líquido cefalorraquidiano em logaritmo (LCR) (OR=1,66;IC95%=1,21-2,28) e uma variável composta por hipertensão arterial sistêmica ou diagnóstico de edema cerebral ou dilatação ventricular por tomografia (OR=35,68;IC95%=4,97-256,31). Para o desfecho composto, as variáveis associadas foram: contagem de leveduras do 1D em logaritmo (OR=1,50; IC95%=;1,20-1,86; p=<0,001), cultura de sangue positiva para Cryptococcus spp. (OR=3,30; IC95%=0,86-12,59; p=0,08) e descrição de neurotoxoplasmose (OR=18,62; IC95%=1,85-187,5; p=0,01). As associações foram consistentes em modelos de sobrevida. Conclusão: Foi possível descrever genótipos mais frequentes e identificar fatores genéticos, como aumento da expressão de genes e bombas de efluxo, relacionados à resistência aos fármacos. Nenhum dos testes de suscetibilidade esteve associado com os desfechos. Variáveis obtidas nos primeiros dias de internação mostraram utilidade para predizer o prognóstico em pacientes com meningite criptocóccica. Estes preditores podem ajudar a identificar os casos com maior potencial de óbito e que necessitam da otimização dos recursos terapêuticos.

Background: Cryptococcal meningitis causes high mortality in immunocompromised patients. The objective of this study was to identify the phenomena of low susceptibility to antifungal and other clinical predictors that may explain therapeutic failure and relapse of neurocryptococcosis Methodology: It was analyzed 96 cases with clinical and epidemiological data. The respective isolates were identified for genotype, susceptibility profile by Minimal Inhibitory Concentration (MIC), FCZ heteroresistance level (NHF), and time to death determination against 1 mg / L BMA (Time-Kill, TK). We isolated heteroresistant DNA expression analysis by real-time PCR, expression of efflux pumps by flow cytometry and, some isolates tolerant to AMB were selected to study resistance to oxidative stress. Univariable and multiple analyses using logistic regression were performed to identify predictors of in-hospital mortality and a composed outcome defined by death, referral to the intensive care unit and relapse 6 months after hospital discharge. Results: Most of the patients were immunocompromised, with CD4 range from 2 to 722 cells/mm3 and 96.7% patients HIV-positive. It was analyzed 93 strains of Cryptococcus neoformans of which 76 were genotype VNI and 17 were VNII and 3 were C. gattii, all were VGII. AMB MIC ranged from 0.012 to 0.94 mg/L and FCZ MIC were between 0.12 and 64 mg/L. Resistance to FCZ (MIC>16mg/L) was higher to VNI than VNII (p=0.03). Among the VNI strains, 64.5% had fungicidal activity up to 24h (TK24) of exposure to AMB and 6 VNI did not present this activity until 72h (TK> 72). Most VNII strains (64.7%) had TK24. The 3 VGII strains presented fungicidal activity from TK24. According to the MIC, all strains were susceptible to AMB. The majority of VNI strains (93.4%) and VNII (76.5%) and 3 VGII strains showed high NHF (>32mg/L) and it was observed statistical difference according to the genotypes VNI and VNII (p=0.005). At the multiple analysis, the variables significantly associated with the death were the age in years (OR=1.08,95%CI=1.02-1.15), the cerebrospinal fluid (CSF) yeasts count-log (OR=1.66,95%CI=1.21-2.28), and a variable composed of systemic arterial hypertension or diagnosis of cerebral edema or ventricular dilatation by tomography (OR=35.68,95%CI=4.97-256.31). At the composed outcome, the variables associated were: CSF yeasts count-log (OR=1,50; IC95%=;1,20-1,86; p=<0,001), positive blood culture for Cryptococcus spp. (OR=3,30; IC95%=0,86-12,59; p=0,08) and neurotoxoplasmosis (OR=18,62; IC95%=1,85-187,5; p=0,01). The associations were consistent at survival models. Conclusion: It was possible to describe more frequent genotypes and to identify genetic factors, such as increased gene expression and efflux pumps, related to drug resistance. The antifungal susceptibilities were not associated with the outcomes. were not associated with outcomes. Variables available in the first days of hospitalization showed utility to predict the prognosis in patients with cryptococcal meningitis. These predictors can help to identify the cases with higher potential of death and that require the optimization of the therapeutic resources.

Pesquisa de Cryptococcus spp. em fezes de pombos recém-emitidas coletadas em espaços públicos de Goiânia-GO / Research for Cryptococcus spp. in pigeon's feces newly issued collected in public spaces of Goiânia-GO

Objetivo: Este estudo objetivou a pesquisa de Cryptococcus spp. em locais públicos de Goiânia-GO onde há grande fluxo de pessoas. Métodos: Sessenta amostras foram coletadas com swabs umedecidos em NaCl 0,85%, inoculadas em tubos com ágar Sabouraud e incubadas à temperatura ambiente, sendo as leituras das culturas realizadas com 24 horas, 48 horas e 72 horas. Após análise macroscópica, as colônias de leveduras foram submetidas à coloração de Gram e à coloração com tinta nanquim, para análise microscópica. Resultados: Cryptococcus spp. foi identificado em seis (10,0%) das sessenta amostras analisadas, sendo encontrado em 100,0% dos espaços públicos pesquisados. Conclusão: Os pombos representam importantes reservatórios deste fungo na natureza, atuando como disseminadores. Assim, ressalta-se a necessidade do controle dessas aves, bem como a conscientização da população sobre os riscos da proliferação desses animais nos centros urbanos.

Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

ABSTRACT Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800 mg.