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1.
BMC Infect Dis ; 20(1): 91, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000709

RESUMO

BACKGROUND: We compared the cryptococcal antigen detection and imaging findings between immunocompetent and immunocompromised patients in whom pulmonary cryptococcosis had been diagnosed. The aim of our study was to determine whether the patient's immune status and radiography affect the detection of cryptococcal antigen. METHODS: According to whether they took immunosuppressive drugs or not, seventy and eight adult patients with pulmonary cryptococcosis were divided into two groups: the immunocompetent group and the immunocompromised group. According to the detection of CrAg, each group was divided into the CrAg+ group and the CrAg- group. Then, clinical records, laboratory examinations and computed tomography findings were collected and analyzed. RESULTS: No difference was found in baseline characteristics, clinical symptoms, and laboratory investigations. By comparing CrAg detection in these two groups, it was found that the number of CrAg+ cases in the immunocompetent group was more than that in the immunocompromised group. And in the immunocompetent group, diffuse lesions were more common in CrAg+ group and limited lesions were more frequently observed in CrAg- group. CONCLUSIONS: The patient's immune status and radiography would affect the detection of cryptococcal antigen. And serum CrAg could be a useful tool for the diagnosis of pulmonary cryptococcosis in immunocompetent patients with extensive lung involvement.


Assuntos
Antígenos de Fungos/sangue , Criptococose/diagnóstico por imagem , Criptococose/imunologia , Cryptococcus neoformans/imunologia , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criptococose/tratamento farmacológico , Testes Diagnósticos de Rotina/métodos , Feminino , Seguimentos , Humanos , Testes Imunológicos , Imunossupressores/uso terapêutico , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
2.
BMC Infect Dis ; 20(1): 141, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059703

RESUMO

BACKGROUND: The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/µl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone. METHODS: A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher's exact test was used to compare categorical variables. RESULTS: A total of 170 patients, with median age of 36 (IQR 30-43) and median CD4 count of 45 cells/mm3 (IQR 23-63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4-9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks. CONCLUSION: A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.


Assuntos
Antígenos de Fungos/sangue , Criptococose/epidemiologia , Infecções por HIV/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , Antifúngicos/uso terapêutico , Estudos Transversais , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/mortalidade , Cryptococcus , Feminino , Fluconazol/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Prevalência , Estudos Prospectivos , Estudos Soroepidemiológicos , Serra Leoa/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos
3.
Artigo em Inglês | MEDLINE | ID: mdl-31967211

RESUMO

Cryptococcosis is an opportunistic fungal infection causes significant disease predominantly in immunocompromised patients. Here we present an excepcional case of disseminated cryptococcosis with pulmonary and cerebral involvement in an immunocompetent patient with no apparent predisposing factors at the time of hospital admission. We described a case of an apparently immunocompetent 66-years old man admitted to hospital with a one-month history of cough, fever and vertigo. During hospitalization, thorax imaging was suggestive of lung metastasis, therefore, he went through several investigations. During hospitalization, he developed neurological symptoms and subsequently underwent a lumbar puncture. Cerebrospinal fluid (CSF) culture was positive for Cryptococcus spp. isolated on Sabouraud's dextrose agar and bird seed agar. In addition, the direct microscopy examination was positive for the India ink test, as well as with the latex agglutination test for cryptococcal polysaccharide antigen (CrAg) in CSF, while serum CrAg was negative. Despite the absence of classic immunocompromising features, he was treated with amphotericin B and fluconazole due to suspected disseminated cryptococcal infection. Later, he was diagnosed with prostatic adenocarcinoma. Upon successful completion of treatment for disseminated cryptococcosis, the patient underwent radical prostate ablation surgery as a treatment forprostatic adenocarcinoma. This exceptional case emphasizes the high degree of suspicion of atypical infections, and in these cases, it is particularly important to consider fungal infections in hitherto healthy patients with no apparent predisposing factors. Although Cryptococcus spp. is predominantly reported in patients with hematological malignancies, cryptococcosis investigation should also be considered as part of the initial workup of patients with a new diagnosis of a solid tumour prior to chemotherapy or radiotherapy.


Assuntos
Adenocarcinoma/diagnóstico , Criptococose/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/imunologia , Adenocarcinoma/cirurgia , Idoso , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Criptococose/tratamento farmacológico , Criptococose/imunologia , Fluconazol/administração & dosagem , Humanos , Hospedeiro Imunocomprometido , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/cirurgia
4.
Braz J Infect Dis ; 24(1): 7-12, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31870760

RESUMO

BACKGROUND: This study aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis from 2013 to 2017 in a major teaching hospital in China. METHODS: Trends in antifungal drug susceptibility of 217 consecutive non-repetitive cryptococcal isolates collected from patients of an university hospital in China were analyzed between 2013 and 2017. Of those, 98 isolates were conserved for identification by internal transcribed spacer (ITS) sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Multilocus sequence typing (MLST) was used to designate molecular types. Clinical characteristics of the 98 patients with cryptococcosis during the period of 2013-2017 were retrospectively evaluated. RESULTS: There was a trend for gradual increase in the MIC range of fluconazole was from 2013 to 2017. The conserved 98 clinical cryptococcal isolates included 97 C. neoformans and one C. gattii, and 90 (91.8%) isolates belonged to ST5 genotype VNI. Out of the 98 patients with cryptococcosis, 28 (28.6%) were HIV-infected and 32 (32.7%) had no underlying diseases. HIV-infected patients had higher mortality than HIV-uninfected patients (28.6% vs 14.3%, p=0.147). CONCLUSIONS: Most of the patients with cryptococcosis were not HIV-infected in this study, while patients with HIV had a higher mortality. Reduced susceptibility to fluconazole was observed among C. neoformans isolates, most of them belonged to ST5 genotype VNI having an impact on the effective dose of fluconazole.


Assuntos
Criptococose/epidemiologia , Criptococose/microbiologia , Hospitais Universitários/estatística & dados numéricos , Adulto , Antifúngicos/uso terapêutico , China/epidemiologia , Estudos Transversais , Criptococose/tratamento farmacológico , Cryptococcus gattii/efeitos dos fármacos , Cryptococcus gattii/genética , Cryptococcus gattii/isolamento & purificação , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/genética , Cryptococcus neoformans/isolamento & purificação , Feminino , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo
5.
An Bras Dermatol ; 94(6): 744-746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31789256

RESUMO

This report describes a case of unusual deep skin ulcers with tortuous sinus tract formation in an immunocompetent woman. She was initially diagnosed with a Staphylococcus aureus skin infection and histopathologically diagnosed with pyoderma gangrenosum. However, culture from the deep end of ribbon gauze inserted into the subcutaneous sinus tract revealed shiny, light-yellow mucoid colonies, which were identified as Cryptococcus neoformans var. grubii. She was treated with fluconazole for nine months and completely healed. Cryptococcosis is an opportunistic infection caused by variants of C. neoformans species. Cutaneous manifestations of cryptococcosis are quite divergent, rarely occurring as deep skin ulcers with sinus formation.


Assuntos
Criptococose/patologia , Cryptococcus neoformans/isolamento & purificação , Dermatomicoses/patologia , Imunocompetência , Úlcera Cutânea/microbiologia , Úlcera Cutânea/patologia , Adulto , Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Feminino , Fluconazol/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Úlcera Cutânea/tratamento farmacológico
6.
BMC Infect Dis ; 19(1): 1051, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830905

RESUMO

BACKGROUND: Cryptococcal prostatitis is a rare clinical disease and has never been reported in China. CASE PRESENTATION: We report on a male HIV-infected patient with pulmonary and prostate cryptococcosis that was misdiagnosed (as tuberculosis) and delayed diagnosed. Although the patients accepted anti-fungal treatment and anti-retroviral treatment finally, the physician's mistakes reflect the rarity of this condition in China. CONCLUSION: Cryptococcal prostatitis is a rare disease that unusually presents in immunodeficient patients. Physicians should have a heightened awareness of this particular infection in the immunodeficient population.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Prostatite/diagnóstico , Retenção Urinária/diagnóstico , Retenção Urinária/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , China , Criptococose/complicações , Criptococose/tratamento farmacológico , Diagnóstico Tardio , Erros de Diagnóstico , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Flucitosina/administração & dosagem , Flucitosina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/microbiologia , Prostatite/tratamento farmacológico , Prostatite/microbiologia , Resultado do Tratamento , Voriconazol/administração & dosagem , Voriconazol/uso terapêutico
7.
BMC Infect Dis ; 19(1): 862, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623573

RESUMO

BACKGROUND: Idiopathic CD4 lymphocytopenia (ICL) is a rare clinical disease with relative CD4 deficiency in the absence of HIV infection. The pathogenicity of ICL is poorly understood with an unclear incidence rate in the general population. Sequelae of ICL includes AIDS-defining infections, which most commonly includes Cryptococcus neoformans. Typically, C. neoformans infections present with CNS involvement but rarely with extra-CNS manifestations. Here, we present a rare case of ICL with exclusively primary pulmonary cryptococcus and a review of the literature. CASE PRESENTATION: A 56-year-old female presented to our tertiary care hospital requiring a right hip open reduction intervention. The patient became febrile during admission, prompting a work-up that included a chest X-ray showing a peripheral pulmonary solitary nodule. Transthoracic biopsy revealed encapsulated yeast forms in keeping with C. neoformans. CD4 counts, repeated at least one month apart, were < 200 cells/mm3, with negative HIV testing. Flow cytometry and genetic testing were completed to elucidate the etiology of the immune deficiency, both of which were unremarkable. She was subsequently treated with 12 months of posaconazole with clinical resolution. CONCLUSIONS: Our patient highlights a rare clinical disease, which a review of literature revealed only five cases in the literature with exclusive pulmonary Cryptococcus in ICL/ This case demonstrates the strong clinical acumen required to properly diagnose and ultimately manage the patient.


Assuntos
Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Linfopenia/diagnóstico , Infecções Respiratórias/diagnóstico , Antifúngicos/uso terapêutico , Contagem de Linfócito CD4 , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Feminino , Humanos , Pulmão/microbiologia , Pulmão/patologia , Linfopenia/etiologia , Pessoa de Meia-Idade , Infecções Respiratórias/complicações , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Triazóis/uso terapêutico
8.
J Vet Diagn Invest ; 31(6): 828-835, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31551015

RESUMO

Cryptococcosis, caused by the Cryptococcus gattii and C. neoformans species complexes, is an environmentally acquired mycosis affecting a broad range of host species. Among 9 communally housed ferrets, a 5-y-old castrated male ferret domiciled in an outdoor enclosure in Sydney, Australia was diagnosed with sinonasal cryptococcosis. Clinical signs resolved during 18 mo of itraconazole therapy, but the ferret was eventually euthanized because of splenic hemangiosarcoma. At postmortem, microscopic foci of persistent cryptococcosis were detected. The diagnosis raised concerns that the owners and other ferrets were exposed to a common environmental source of infection, thus prompting an investigation. Soil samples, swabs of a hollow eucalypt log (used for behavioral enrichment), and nasal swabs from 8 asymptomatic ferrets were collected. Nasal exudate (obtained at diagnosis) and tissues (collected at postmortem) were available from the clinical case. Bird seed agar culture resulted in a heavy growth of Cryptococcus spp. from one environmental site (the log), one nasal swab, and nasal exudate and tissues from the clinical case. All other samples were culture-negative. Sub-cultured isolates from the log were a mixture of C. gattii molecular type VGI and C. neoformans molecular type VNI. Ferret isolates were a similar mixture of C. gattii VGI (all disease isolates) and C. neoformans VNI (nasal-colonizing isolate). Multilocus sequence typing further revealed the ferret isolates as identical to environmental isolates collected from the log, confirming the log as the source of clinical disease and nasal colonization. The log was removed to prevent further exposure to a high environmental load of Cryptococcus spp.


Assuntos
Antifúngicos/uso terapêutico , Criptococose/veterinária , Furões , Itraconazol/uso terapêutico , Doenças dos Seios Paranasais/veterinária , Animais , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus gattii/isolamento & purificação , Cryptococcus neoformans/isolamento & purificação , Masculino , New South Wales , Doenças dos Seios Paranasais/diagnóstico , Doenças dos Seios Paranasais/tratamento farmacológico
9.
Nat Commun ; 10(1): 4275, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537789

RESUMO

Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits complexed with FK506 and the FK506-binding protein (FKBP12) from human fungal pathogens (Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Coccidioides immitis). Fungal calcineurin complexes are similar to the mammalian complex, but comparison of fungal and human FKBP12 (hFKBP12) reveals conformational differences in the 40s and 80s loops. NMR analysis, molecular dynamic simulations, and mutations of the A. fumigatus CnA/CnB-FK506-FKBP12-complex identify a Phe88 residue, not conserved in hFKBP12, as critical for binding and inhibition of fungal calcineurin. These differences enable us to develop a less immunosuppressive FK506 analog, APX879, with an acetohydrazine substitution of the C22-carbonyl of FK506. APX879 exhibits reduced immunosuppressive activity and retains broad-spectrum antifungal activity and efficacy in a murine model of invasive fungal infection.


Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/metabolismo , Inibidores de Calcineurina/farmacologia , Calcineurina/metabolismo , Cryptococcus neoformans/metabolismo , Proteína 1A de Ligação a Tacrolimo/metabolismo , Tacrolimo/farmacologia , Animais , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus fumigatus/efeitos dos fármacos , Sítios de Ligação , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Células Cultivadas , Coccidioides/efeitos dos fármacos , Coccidioides/metabolismo , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Cristalografia por Raios X , Descoberta de Drogas/métodos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos A , Camundongos Endogâmicos C57BL , Simulação de Dinâmica Molecular , Tacrolimo/metabolismo
10.
BMC Infect Dis ; 19(1): 710, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405376

RESUMO

BACKGROUND: Pulmonary Cryptococcosis (PC) is diagnosed with increasing incidence in recent years, but it does not commonly involve the pleural space. Here, we report a HIV-negative case with advanced stage IIIB non-small cell lung cancer (NSCLC) treated with radiation therapy presented with dyspnea, a new PET-positive lung mass and bilateral pleural effusion suspecting progressive cancer. However, the patient has been diagnosed as pulmonary cryptococcal infection and successfully treated with oral fluconazole therapy. CASE PRESENTATION: A 77-year-old male with advanced stage non-small cell lung cancer treated with combined chemo-radiation therapy who presented with progressive dyspnea, a new PET-positive left lower lobe lung mass and bilateral pleural effusions. Initial diagnostic thoracentesis and bronchoscopy yielded no cancer, but instead found yeast forms consistent with cryptococcal organisms in the transbronchial biopsies of the left lower lobe lung mass. Subsequent to this, the previously collected pleural fluid culture showed growth of Cryptococcus neoformans. The same sample of pleural effusion was tested and was found to be positive for crytococcal antigen (CrAg) by a lateral flow assay (LFA). The patient has been treated with oral fluconazole therapy resulting in gradual resolution of the nodular infiltrates. CONCLUSION: PC should be considered in immunosuppressed cancer patients. Additionally, concomitant pleural involvement in pulmonary cryptococcal infections may occur. The incidence of false positive 18FDG-PET scans in granulomatous infections and the use of CrAg testing in pleural fluid to aid in diagnosis are reviewed.


Assuntos
Criptococose/diagnóstico por imagem , Criptococose/microbiologia , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/microbiologia , Derrame Pleural/microbiologia , Administração Oral , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Criptococose/tratamento farmacológico , Cryptococcus neoformans/patogenicidade , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/radioterapia , Masculino , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Tomografia por Emissão de Pósitrons
11.
Int J Nanomedicine ; 14: 5187-5199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371955

RESUMO

Introduction and objective: Previous studies indicate that miltefosine (MFS) may be an alternative as an antifungal agent; however, it presents several adverse effects. Thus, the aim of this study was to produce miltefosine-loaded alginate nanoparticles (MFS.Alg) for toxicity reduction to be used as an alternative for the treatment of cryptococcosis and candidiasis. Methods: Alginate nanoparticles were produced using the external emulsification/gelation method, and their physicochemical and morphological characteristics were analyzed. MFS encapsulation efficiency, release assay and toxicity on red blood cells and on Galleria mellonella larvae were assessed. The antifungal activity was evaluated using in vitro and in vivo larval models of G. mellonella infected with Candida albicans (SC5314 and IAL-40), Cryptococcus neoformans H99 and Cryptococcus gattii ATCC 56990. The treatment efficacy was evaluated by survival curve, colony forming unit (CFU) counting and histopathological analysis. Results: MFS.Alg nanoparticles presented a mean size of 279.1±56.7 nm, a polydispersity index of 0.42±0.15 and a zeta potential of -39.7±5.2 mV. The encapsulation efficiency of MFS was 81.70±6.64%, and its release from the nanoparticles occurred in a sustained manner. MFS in alginate nanoparticles presented no hemolytic effect and no toxicity in G. mellonella larvae. Treatment with MFS.Alg extended the survival time of larvae infected with C. albicans and C. gattii. In addition, the fungal burden reduction was confirmed by CFU and histopathological data for all groups treated with 200 mg/Kg of MFS.Alg. Conclusion: These results support the use of alginate-based drug delivery systems as carriers for MFS for drug toxicity reduction and control of the fungal infection in the in vivo model of G. mellonella.


Assuntos
Alginatos/química , Candidíase/tratamento farmacológico , Criptococose/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Fosforilcolina/análogos & derivados , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candidíase/microbiologia , Criptococose/microbiologia , Liberação Controlada de Fármacos , Larva/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Fosforilcolina/farmacologia , Fosforilcolina/uso terapêutico , Fosforilcolina/toxicidade , Ovinos
13.
BMJ Case Rep ; 12(8)2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401574

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory syndrome characterised by unregulated macrophage and T-lymphocyte activation, resulting in cytokine overproduction and subsequent histiocytic phagocytosis. Here we report a case of pulmonary cryptococcosis, in a 59-year-old diabetic patient, with no other risk factors whose clinical course was complicated by secondary hemophagocytosis. Even after addressing the primary underlying illness (pulmonary cryptococcosis), his clinical condition continued to worsen. After excluding the other causes of HLH and possible reasons of his clinical worsening, glucocorticoids were added following which the patient experienced a remarkable improvement in his clinical and laboratory parameters. To our knowledge, this is the first case report of HLH being caused by pulmonary cryptococcosis and only second case report of cryptococcosis being complicated with HLH (previous report being associated with meningoencephalitic cryptococcosis).


Assuntos
Criptococose/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Antifúngicos/administração & dosagem , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Cryptococcus neoformans/isolamento & purificação , Dexametasona/administração & dosagem , Fluconazol/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
14.
BMJ Case Rep ; 12(8)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451456

RESUMO

We report a case of primary pulmonary cryptococcosis in a 59-year-old female patient with a history of systemic lupus erythematosus, interstitial lung disease and glaucoma. She presented with a cough, severe fatigue, unintentional weight loss, shortness of breath (increase in home oxygen use from baseline) and pleuritic chest pain of 2 months duration. During these 2 months, her symptoms had worsened despite multiple hospital visits, empirical antibiotics and empirical increase of her steroid dosage. Cytopathology of the bronchoalveolar lavage fluid showed yeast cells with narrow-based budding and grew Cryptococcus neoformans on fungal culture. She was treated with oral fluconazole 400 mg/day for 6 months with an improvement in cough, decrease in shortness of breath (return to baseline oxygen use) and resolution of pleuritic chest pain.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Criptococose , Cryptococcus neoformans/isolamento & purificação , Fluconazol/administração & dosagem , Doenças Pulmonares Intersticiais , Pulmão , Lúpus Eritematoso Sistêmico , Antifúngicos/administração & dosagem , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/microbiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Medicine (Baltimore) ; 98(28): e16354, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305427

RESUMO

RATIONALE: Cryptococcosis is a significant life-threatening fungal infection in worldwide, mainly reported in immunocompromised patients. Pleural effusion presentation of cryptococcal infection as the only clinical presentation is rarely seen in pulmonary cryptococcosis, which may lead to be misdiagnosed, and the study on this subject will provide further insights. PATIENT CONCERNS: A 64-year-old man was hospitalized in our department and diagnosed as hepatic B cirrhosis. A computed tomography (CT) of the thorax showed a massive right pleural effusion without pulmonary parenchymal abnormalities. He was started on empirical treatment for pleural tuberculosis (TB). However, during his hospitalization, a right pleural effusion developed and fever was not controlled. DIAGNOSES: On day 14 admission, pleural fluid cultured positive for Cryptococcus neoformans. The C neoformans isolate belonged to ST5 and molecular type VNI (var. grubii). INTERVENTIONS: The patient was diagnosed with cryptococcal pleuritis, then amphotericin B and fluconazole were administrated. OUTCOMES: Finally, the patient was improved and discharged from our hospital. LESSONS: Similar cases in cryptococcal pleuritis patients with pleural effusion as the only clinical presentation in the literature are also reviewed. Through literature review, we recommend that pleural effusion cryptococcal antigen test should be used to diagnose cryptococcal pleuritis to reduce misdiagnosis. The early administration of antifungal drug with activity to Cryptococcus seemed beneficial in preventing dissemination of cryptococcosis.


Assuntos
Criptococose/diagnóstico , Cirrose Hepática/diagnóstico , Derrame Pleural/diagnóstico , Pleurisia/diagnóstico , Criptococose/complicações , Criptococose/tratamento farmacológico , Diagnóstico Diferencial , Hepatite B/complicações , Hepatite B/diagnóstico , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Derrame Pleural/complicações , Derrame Pleural/tratamento farmacológico , Pleurisia/complicações , Pleurisia/tratamento farmacológico
17.
Int J Antimicrob Agents ; 54(3): 301-308, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279153

RESUMO

Approximately 180,000 people worldwide die from cryptococcosis each year, probably due to the ineffectiveness and toxicity of drugs currently available to treat the disease. Amphotericin B (AMB) is effective for killing the fungus, but has serious adverse effects linked to excessive production of reactive oxygen species which compromise renal function. Pioglitazone (PIO) is a peroxisome proliferator-activated receptor-γ agonist widely repositioned as an adjuvant of various drugs that have toxic effects due to its antioxidant and anti-inflammatory effects. This study evaluated PIO in combination with AMB for the treatment of cryptococcosis. PIO was found to reduce serum creatinine and glutamic-oxalacetic transaminase levels in mice treated with PIO+AMB. In vitro, PIO was able to control harmful oxidative bursts induced by AMB without compromising the antifungal effect. In vivo, PIO+AMB increased the survival rate compared with AMB alone, and improved the morbidity of the animals. PIO+AMB was more efficient than AMB alone for inhibiting fungal transmigration from the lungs to the brain, and killing yeasts that reached the central nervous system, avoiding the establishment of meningoencephalitis. In a phagocytosis assay, PIO did not influence the engulfment and fungicidal activity of macrophages induced by AMB, but reduced the oxidative bursts after the reduction of fungal burden, pointing to control of the pathogen without leading to excessive stress which can be damaging to the host. In conclusion, PIO+AMB was found to ameliorate cryptococcosis in a murine model, indicating that it is a promising therapeutic adjuvant for combating and controlling this fungal infection.


Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Antioxidantes/administração & dosagem , Criptococose/tratamento farmacológico , Pioglitazona/administração & dosagem , Anfotericina B/farmacologia , Animais , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Criptococose/patologia , Cryptococcus gattii/efeitos dos fármacos , Modelos Animais de Doenças , Reposicionamento de Medicamentos , Quimioterapia Combinada/métodos , Camundongos Endogâmicos C57BL , Pioglitazona/farmacologia , Análise de Sobrevida , Resultado do Tratamento
18.
Transpl Infect Dis ; 21(5): e13137, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31267603

RESUMO

A 68-year-old man presented for outpatient evaluation of dyspnea and new-onset atrial fibrillation 9 months after undergoing bilateral lung transplantation. Echocardiography prior to cardioversion raised concern for tamponade. Therapeutic pericardiocentesis returned fluid containing 1875 wbc/mcl (68% pmn) and yielded Cryptococcus neoformans in culture. Cryptococcal antigen was detected in serum at a titer of 1:20. Cerebrospinal (CSF) fluid was without evidence of inflammation and without detectable cryptococcal antigen. There was no radiographic evidence of pulmonary cryptococcosis. Cultures of blood and CSF were without growth. Liposomal amphotericin B (3 mg/kg/day) was administered for 15 days. Oral fluconazole was added on day seven of amphotericin, and the patient was discharged to home 3 days later. Daily dosages of prednisone (10 mg), mycophenolate (500 mg), and tacrolimus (3 mg) at discharge were the same as at hospital admission. He was readmitted 12 days later with dyspnea and with re-accumulation and loculation of pericardial fluid. A pericardial window was created. Pericardial fluid contained 722 wbc/mcl (35% pmn); Cryptococcus was not identified on direct examinations or cultures of pericardial fluid or tissue. Cryptococcus antigen was present in serum at 1:160. Liposomal amphotericin B was resumed and continued for 2 weeks followed by resumption of fluconazole. Mycophenolate was stopped. Prednisone and tacrolimus were continued. Restrictive pericarditis was evident 3 weeks after window creation. Colchicine was initiated, prednisone increased to 15 mg daily and pericardiectomy planned. We aim to raise awareness to Cryptococcus as a potential etiology for pericarditis in solid organ transplant recipients.


Assuntos
Criptococose/diagnóstico , Transplante de Pulmão/efeitos adversos , Pericardite/microbiologia , Transplantados , Idoso , Antifúngicos/uso terapêutico , Antígenos de Fungos/líquido cefalorraquidiano , Criptococose/tratamento farmacológico , Cryptococcus neoformans/isolamento & purificação , Ecocardiografia , Humanos , Masculino , Pericardite/diagnóstico , Resultado do Tratamento
19.
J Infect Chemother ; 25(11): 901-905, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31182330

RESUMO

INTRODUCTION: Cryptococcus neoformans is known to be a cause of meningitis. However, as cryptococcal endocarditis is rare, it is not well understood. Here, we describe a case with Implantable Cardioverter Defibrillator associated endocarditis and meningitis caused by Cryptococcus neoformans and we review the literature associated cryptococcal endocarditis. CASE PRESENTATION: A 72 years old Japanese male presented in emergency department with non-productive cough and respiratory discomfort. His past medical history was ischemic heart disease four years ago and ICD was implanted. Physical examination was unremarkable. Chest computer tomography revealed ground glass opacity in the right lung. He received a diagnosis of amiodarone-induced interstitial pneumonitis and high dose steroid pulse therapy. Septic shock and acute respiratory failure occurred after steroid therapy. Cryptococcus neoformans was identified by blood culture and cerebral spinal fluid. Intravenous liposomal Amphotericin B and oral flucytosine were initiated. Transesophageal echocardiography revealed vegetation on the lead of the ICD. Diagnosis of cryptococcal endocarditis was made. The patient died despite antifungal therapy was continued. DISCUSSION: We analyzed our case and 8 cases of cryptococcal endocarditis in the literature for 40 years. Almost all of the patients had previous valve replacement surgery or immunocompromised state. Three cases had meningitis. Surgery performed in 3 cases. The overall mortality rate were 44.4%. CONCLUSIONS: Cryptococcal endocarditis is rare and carries a high mortality. Almost all of the patients had underlying diseases. Diagnosis needs repeating blood culture and echocardiogram, sometimes. Cryptococcal endocarditis needs lumber puncture for rule out meningitis.


Assuntos
Criptococose/diagnóstico , Cryptococcus neoformans/patogenicidade , Idoso , Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus neoformans/efeitos dos fármacos , Humanos , Masculino , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/microbiologia , Meningite Criptocócica/mortalidade
20.
Medicine (Baltimore) ; 98(19): e15544, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083210

RESUMO

Concomitant influenza and cryptococcal infections are rare. Herein, we describe an unusual case of an avian influenza A (H7N9) infection with several severe mixed bacterial infections and systemic super-infection with Cryptococcus neoformans presenting as ventilator-associated pneumonia (VAP) and bloodstream infection in a previously immunocompetent man during hospitalization.A 58-year-old man was admitted to our hospital complaining of hyperpyrexia, dyspnoea, cough, and phlegm with blood. A chest computed tomography scan revealed multiple ground-glass opacities and consolidation in both lungs with right pleural effusion. An initial sputum test was positive for influenza A (H7N9) virus. After antiviral treatment and other supportive measures, the patient's condition improved. However, the patient's condition deteriorated again approximately 2 weeks after admission, and bronchoalveolar lavage fluid (BALF) and blood cultures were positive for C. neoformans. Therapy with intravenous liposomal amphotericin B and fluconazole was started. After a 2-week antifungal treatment, BALF and blood cultures were negative for C. neoformans. However, the patient had persistent lung infiltrates with severe pulmonary fibrosis with a prolonged course of disease. On hospital day 40, BALF and blood cultures were both positive for multidrug-resistant Stenotrophomonas maltophilia. Finally, the patient developed septic shock, disseminated intravascular coagulation and multi-organ failure and succumbed to treatment failure.Cryptococcal infection can occur in patients with severe influenza during hospitalization with a more severe condition, and the clinician should be aware of this infection.


Assuntos
Coinfecção , Criptococose/complicações , Cryptococcus neoformans , Influenza Humana/complicações , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Criptococose/sangue , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Diagnóstico Diferencial , Evolução Fatal , Humanos , Influenza Humana/sangue , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
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