RESUMO
BACKGROUND: The clinical features of central nervous system (CNS) sporotrichosis are derived from case reports and a limited series of cases. Our objective was to carry out a systematic review and meta-analysis of CNS sporotrichosis. METHODS: We searched PubMed/MEDLINE, Embase, Scopus, and LILACS on 9 September 2023. Our inclusion criteria were documentation of Sporothrix and demonstrated CNS involvement. A metaproportion or metamean analysis was performed to estimate a summary proportion with 95% confidence intervals. RESULTS: We included 52 cases of CNS sporotrichosis published from 1966 to 2023. Forty-six patients were male (88%, 95% CI: 77-95), and the mean age was 39 years (95% CI: 36-43). Close contact with cats was reported in 55% of cases (95% CI: 37-72). Thirty-two (61.5%) patients were from Brazil, 18 patients from the United State of America (34.6%). Only two Sporothrix species were reported: S. schenckii (26/41, 63%), and S. brasiliensis (15/41, 37%). The most common neurological symptom was headache. Meningitis was chronic in approximately 80% of cases. A significant majority of the patients were immunocompromised. HIV infection was the primary cause of immunosuppression (85%, 95% CI: 61-95). Overall mortality was 56% (22/39). The comparison of Kaplan-Meier survival curve showed a higher mortality with a statistically significant difference in immunosuppressed patients (p = .019). CONCLUSION: CNS sporotrichosis represents a notable cause of chronic meningitis, especially in individuals living in the Americas with HIV infection and concurrent skin lesions.
Assuntos
Antifúngicos , Sporothrix , Esporotricose , Esporotricose/tratamento farmacológico , Esporotricose/diagnóstico , Humanos , Sporothrix/isolamento & purificação , Antifúngicos/uso terapêutico , Gatos , Masculino , Adulto , Feminino , Animais , Brasil/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. METHODS: All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. RESULTS: We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044). CONCLUSION: In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.
Assuntos
Criptococose , Imageamento por Ressonância Magnética , Neuroimagem , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neuroimagem/métodos , Criptococose/diagnóstico por imagem , Criptococose/mortalidade , Criptococose/microbiologia , Adulto , Idoso , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico por imagem , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Prognóstico , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/mortalidade , Hospitalização , Infecções por HIV/complicaçõesRESUMO
Though candidiasis is the most frequent invasive fungal infection, Candida spp. central nervous system (CNS) infections are rare but severe. To further describe clinico-patho-radiological presentations of this entity, we report a retrospective study from January 2005 to December 2018 including patients aged ≥ 28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included. Seventeen patients (70%) had CNS localization secondary to disseminated candidiasis (10 with hematologic malignancies [HM]; the seven other patients had infective endocarditis [IE]). Among patients with HM, seven previously had lumbar puncture for intrathecal chemotherapy, the three others had IE. Among patients with disseminated infection, magnetic resonance imaging (MRI) evidenced meningitis (17%), micro-abscesses (58%), or vascular complications (67%). Seven patients (30%) had isolated CNS involvement related to neurosurgery (n = 2), CARD9 deficiency (n = 2), intravenous drug use, diabetes mellitus, or no identified predisposing condition (n = 1 each). All evaluated patients with isolated CNS involvement had meningitis on cerebrospinal fluid (CSF) and intracranial hypertension. For the latter patients, MRI evidenced meningitis (71%) or abscesses (57%). Among all patients, cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. CSF ßDGlucan or mannan Ag were positive in respectively 86% and 80% of cases. Mortality attributed to CNS candidiasis was 42%: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection. CNS candidiasis are isolated or occur during disseminated infection in patients with HM and lumbar puncture for intrathecal chemotherapy or during IE. Clinical, radiological finding and outcome highly vary according to CNS localized versus disseminated candidiasis. LAY SUMMARY: Candida is a yeast and is the most common cause of fungal infections worldwide. Candida central nervous system (CNS) infections are rare, severe, and poorly described. We report a retrospective study from January 2005 to December 2018 including patients aged ≥ 28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included (14 men, median age 51 years). Seventeen patients had CNS localization secondary to disseminated candidiasis from blood to CNS (10 with hematologic malignancies [HM], the seven other patients had infective endocarditis [IE]). Seven patients had isolated CNS involvement related to neurosurgery (n = 2), CARD9 deficiency (n = 2), intravenous drug use (n = 1), diabetes mellitus (n = 1), or no identified risk factor (n = 1).During Candida CNS infections, brain lesions were meningitis abscesses or vascular complications. Cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. Forty-two percent of patients died from infection: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection.
Assuntos
Candidíase/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Candidíase/líquido cefalorraquidiano , Candidíase/complicações , Candidíase/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico por imagem , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Criança , Monitoramento Epidemiológico , Feminino , França/epidemiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Fungal infections of the central nervous system (CNS) are uncommon. Despite several advancements in diagnosis and treatment of these infections, the mortality rates remain high. The current retrospective study was planned to define the demographic and clinical features of patients with CNS fungal infections. Conducted at Aga Khan University Hospital, Karachi, and comprising CNS fungal infections operated between January 2000 and December 2015. The study analysed whether a short course of pre-operative anti-fungal therapy may improve outcomes in these patients. There were 47 cases confirmed on histopathology and/or microbiology. Outcome measures used were Glasgow coma score (GCS), Glasgow outcome score (GOS) and Karnofsky performance score (KPS). The overall 30-day mortality was 20(42.5%). Fungal infections of the CNS can occur in both immune-compromised and immune-competent patients. Early diagnosis, radical surgery, pre-operative anti-fungal therapy for at least 2 weeks, pre- and postoperative Voriconazole therapy results in more favourable outcomes.
Assuntos
Infecções Fúngicas do Sistema Nervoso Central , Craniotomia , Cuidados Pré-Operatórios/métodos , Voriconazol/administração & dosagem , Antifúngicos/administração & dosagem , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Infecções Fúngicas do Sistema Nervoso Central/cirurgia , Craniotomia/efeitos adversos , Craniotomia/métodos , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Paquistão/epidemiologia , Fatores de Risco , Fatores de TempoRESUMO
Paracoccidioidomycosis (PCM) is a systemic mycosis prevalent among immunocompetent patients in Latin America. This study aimed to describe the frequency, demographics and clinical characteristics of central nervous system PCM (NPCM) and PCM in an endemic region, and the impact of human immunosuppression virus (HIV) co-infection. This was a retrospective study of autopsy and biopsy reports from the Medical Pathology Section of the Hospital de Clinicas, UFPR, Curitiba, Southern Brazil, between 1951 and 2014. PCM was present in 0.1% of 378,323 cases examined, with 5.7% being NPCM. Infection was prevalent in working-age men, agricultural workers and rural residents. Numbers of HIV autopsy cases increased over time, while those of PCM cases decreased. Prevalence of co-infection of HIV/PCM and HIV/NPCM was 1.6%, and 0.4%, respectively. Adrenals were affected more frequently in the NPCM group compared with the PCM group. Mortality was higher on NPCM group. The clinical course of PCM in HIV patients resembles an acute/sub-acute infection. Association of NPCM and HIV is rare, while diagnosis of NPCM is difficult, it should be considered a differential diagnosis in HIV patients who live in, or have visited, endemic areas and present with neurological symptoms.
Assuntos
Infecções Fúngicas do Sistema Nervoso Central/patologia , Coinfecção/patologia , Infecções por HIV/complicações , Paracoccidioidomicose/patologia , Adulto , Autopsia , Biópsia , Brasil/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Coinfecção/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Paracoccidioidomicose/epidemiologia , Paracoccidioidomicose/mortalidade , Prevalência , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon yet potentially lethal fungal infection. Although most cases originate from developing countries, an ageing population and increased prevalence of chronic illness may mean some clinicians practicing in developed countries will encounter ROCM cases in their careers. Yohai et al published a systematic review of 145 case reports from 1970 to 1993 assessing prognostic factors for patients presenting with ROCM. We present an updated review of the literature and assess whether survival outcomes have changed in the two decades since that seminal paper. SEARCH STRATEGY: An extensive Medline literature search was performed for case reports published between 1994 and 2015. RESULTS: In total, 210 published cases were identified from the literature review, of which 175 patients from 140 papers were included in this review. Fifty-five were female, with an overall mean age of 43 years. Overall survival rate was 59.5%, which was not significantly better than the previous series reported (60%) reported by Yohai et al. Survival rates in patients with chronic renal disease had improved, from 19% to 52%, and in patients with leukaemia (from 13% to 50%). Facial necrosis and hemiplegia remained poor prognostic indicators (33% and 39% survival rates, respectively). Early commencement of medical treatment related to better survival outcomes (61% if commenced within first 12 days of presentation, compared to 33% if after 13 days). Timing of surgery had less of an effect on overall survival. However, in 28 cases that did not receive any surgical treatment, survival was only 21%. CONCLUSIONS: Although overall survival rates have not improved, survival in patients with renal disease were better, potentially due to the introduction of liposomal amphotericin B which is less nephrotoxic. Prompt recognition of ROCM, reversal of predisposing co-morbidities and aggressive medical treatment remain the cornerstone of managing this highly aggressive disease.
Assuntos
Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Previsões , Mucormicose/mortalidade , Doenças Nasais/mortalidade , Doenças Orbitárias/mortalidade , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Saúde Global , Humanos , Doenças Nasais/microbiologia , Doenças Orbitárias/microbiologia , Prognóstico , Taxa de Sobrevida/tendênciasRESUMO
Cladophialophora bantiana is a phaeoid fungus that only rarely has been isolated from sources other than the human brain. It has a particular tropism for the central nervous system (CNS). We have integrated and updated large-scale data related to several aspects of C. Bantiana and reviewed all the available reports on its cerebral infections, focusing on their geographical distribution, infection routes, immune status of infected individuals, type and location of infections, clinical manifestations and treatment and outcome, briefly looking over the spectrum of other disease entities associated with C. bantiana, that is, extra-cerebral and animal infections and on the environmental sources of this fungus. Among the agents of phaeohyphomycosis, a term used to describe an infection caused by a dark pigmented fungus, C. bantiana has some significant specific features. A total of 120 case reports were identified with a significantly higher percentage of healthy subjects than immune-debilitated patients (58.3% vs. 41.7%). Infections due to C. bantiana occur worldwide. The main clinical manifestations are brain abscess (97.5%), coinfection of brain tissue and meninges (14.2%) and meningitis alone (2.5%). Among immunocompetent patients, cerebral infection occurred in the absence of pulmonary lesions. The mortality rate is 65.0% regardless of the patient's immune status. The therapeutic options used include surgery or antifungals alone, and the combination of both, in most cases the fatal outcome being rapid after admission. Since the fungus is a true pathogen, laboratory workers should be made aware that BioSafety Level-3 precautions might be necessary.
Assuntos
Antifúngicos/uso terapêutico , Ascomicetos/fisiologia , Infecções Fúngicas do Sistema Nervoso Central , Feoifomicose/microbiologia , Animais , Infecções Fúngicas do Sistema Nervoso Central/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Infecções Fúngicas do Sistema Nervoso Central/patologia , Infecções Fúngicas do Sistema Nervoso Central/terapia , Terapia Combinada , Humanos , Resultado do TratamentoAssuntos
Anfotericina B/administração & dosagem , Infecções Fúngicas do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Voriconazol/administração & dosagem , Adolescente , Adulto , Aloenxertos , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Infecções Fúngicas do Sistema Nervoso Central/etiologia , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Criança , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
With increased use of expanded-spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer-Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post-IFI mortality. All patients received antifungal prophylaxis. Fifty-three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n = 31; 50%) and candidaemia (n = 15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n = 6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp., Cladosporium sp., Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR) = 6.0], graft-versus-host disease (OR = 5.3), central venous catheter use (OR = 5.2) and hypoalbuminaemia (OR = 0.3 g(-1) dl(-1) increase in albumin). The 90-day mortality rate after IFI was 57%. Non-cytomegalovirus systemic viral co-infection (OR = 3.5) and stay in an ICU (OR = 2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging.
Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas do Sistema Nervoso Central/epidemiologia , Quimioprevenção/métodos , Fungemia/epidemiologia , Fungos/classificação , Transplante de Células-Tronco Hematopoéticas , Hospedeiro Imunocomprometido , Adulto , Estudos de Casos e Controles , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Feminino , Fungemia/microbiologia , Fungemia/mortalidade , Fungos/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
BACKGROUND: Late-onset sepsis (LOS) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants. AIM: To determine the incidence, risk factors and etiology of LOS. METHODS: LOS was investigated in a multicenter prospective cohort of infants at eight public university neonatal intensive care units (NICUs). Inclusion criteria included inborn, 23-33 weeks of gestational age, 400-1499 g birth weight, who survived >3 days. RESULTS: Of 1507 infants, 357 (24%) had proven LOS and 345 (23%) had clinical LOS. Infants with LOS were more likely to die. The majority of infections (76%) were caused by Gram-positive organisms. Independent risk factors for proven LOS were use of central venous catheter and mechanical ventilation, age at the first feeding and number of days on parenteral nutrition and on mechanical ventilation. CONCLUSION: LOS incidence and mortality are high in Brazilian VLBW infants. Most risk factors are associated with routine practices at NICU.
Assuntos
Doenças do Prematuro/microbiologia , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Sepse/mortalidade , Idade de Início , Brasil/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/sangue , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Criança , Feminino , Idade Gestacional , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/mortalidade , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Modelos Logísticos , Masculino , Vigilância da População , Estudos Prospectivos , Fatores de Risco , Sepse/sangue , Sepse/microbiologiaRESUMO
Mucormycosis is a fungus that exhibits angiocentric growth and can cause a thrombotic arteritis. Infection with this organism is uncommon and cerebral involvement is most often secondary to direct invasion through the paranasal sinuses. Here, we present a case of mucormycosis with cerebral involvement without sinus disease, which resulted in ischemic stroke with rapid progression resulting in death.
Assuntos
Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Mucormicose/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Vasculite do Sistema Nervoso Central/microbiologia , Idoso , Causas de Morte , Infecções Fúngicas do Sistema Nervoso Central/complicações , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Humanos , Masculino , Mucormicose/diagnóstico , Mucormicose/mortalidade , Vasculite do Sistema Nervoso Central/complicações , Vasculite do Sistema Nervoso Central/mortalidadeRESUMO
Six cases of Rhinocladiella mackenziei cerebral phaeohyphomycosis are being reported for the first time in Pakistan. Identification was confirmed by DNA sequencing (isolates and fixed tissue). Diabetes, head trauma, immunosuppressive treatment, and postpartum state were present in 4 cases. Two survivals and 3 fatalities occurred, with 1 patient lost to follow-up.
Assuntos
Ascomicetos/isolamento & purificação , Infecções Fúngicas do Sistema Nervoso Central/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Adulto , Idoso , Ascomicetos/genética , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Doenças Transmissíveis Emergentes/mortalidade , DNA Fúngico/química , DNA Fúngico/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Análise de Sequência de DNARESUMO
AIM: To investigate mortality risk factors in patients with zygomycosis. PATIENTS AND METHODS: Retrospective case history review of patients diagnosed with proven zygomicosis in 17 centres in Spain. We compared demographics and risk factors in patients who survived, and in those who died. RESULTS: We identified twenty-five patients with proven zygomycosis. The primary site of infection was rhino-orbito-cerebral (28%) and disseminated (20%) or cutaneous/soft infections (20%) of the patients. Eleven patients (44%) received preemptive or empirical antifungal treatment; of these patients, 4 received liposomal amphotericin B, 1 received amphotericin B lipid complex, and 6 received other antifungals. The overall mortality rate was 72%. In the univariate analysis factors associated with an increased risk of death were the presence of a haematological malignancy (P=.03), neutropenia (P=.03) and monocytopenia (P=.008). CONCLUSION: Our study supports previous research that has documented a high mortality rate among patients with invasive zygomycosis, especially among those with an underlying haematological malignancy, and the need for a rapid initiation of an effective antifungal treatment.
Assuntos
Zigomicose/mortalidade , Adulto , Idoso , Antifúngicos/uso terapêutico , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Terapia Combinada , Complicações do Diabetes/mortalidade , Feminino , Fungemia/tratamento farmacológico , Fungemia/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Leucopenia/complicações , Leucopenia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Neutropenia/epidemiologia , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Infecções Oportunistas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/mortalidade , Espanha/epidemiologia , Adulto Jovem , Zigomicose/tratamento farmacológico , Zigomicose/cirurgiaRESUMO
BACKGROUND: Central nervous system (CNS) involvement with Blastomyces dermatitidis is an uncommon and potentially fatal complication of blastomycosis. METHODS: We retrospectively reviewed 22 patients with CNS blastomycosis at our institutions from 1990 through 2008 (13 proven, 5 probable, and 4 possible cases). RESULTS: Magnetic resonance imaging was used in most patients, alone or in addition to computed tomography. CNS blastomycosis manifested as epidural abscess (1 of 22), meningitis (7 of 22), intracranial mass lesions (10 of 22), and concomitant intracranial mass lesions and meningitis (4 of 22). All patients received amphotericin B deoxycholate or a lipid formulation of amphotericin B as part of their treatment regimens. Most patients received amphotericin B followed by a prolonged course of oral azole therapy (voriconazole, fluconazole, or itraconazole). Four (18%) of 22 patients died during follow-up. CONCLUSIONS: On the basis of these data, we recommend initial treatment with a lipid formulation of amphotericin B followed by a prolonged course of oral azole therapy, preferably voriconazole.
Assuntos
Antifúngicos/uso terapêutico , Blastomyces/isolamento & purificação , Blastomicose/diagnóstico , Blastomicose/tratamento farmacológico , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Adolescente , Adulto , Blastomicose/mortalidade , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Feminino , Cabeça/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Tomografia , Resultado do Tratamento , Adulto JovemRESUMO
Clinical manifestations, treatment, and outcomes of cutaneous cryptococcosis in solid organ transplant (SOT) recipients are not fully defined. In a prospective cohort comprising 146 SOT recipients with cryptococcosis, we describe the presentation, antifungal therapy, and outcome of cutaneous cryptococcal disease. Cutaneous cryptococcosis was documented in 26/146 (17.8%) of the patients and manifested as nodular/mass (34.8%), maculopapule (30.4%), ulcer/pustule/abscess (30.4%), and cellulitis (30.4%) with 65.2% of the skin lesions occurred in the lower extremities. Localized disease developed in 30.8% (8/26), and disseminated disease in 69.2% (18/26) with involvement of the central nervous system (88.9%, 16/18), lung (33.3%, 6/18), or fungemia (55.6%, 10/18). Fluconazole (37.5%) was employed most often for localized and lipid formulations of amphotericin B (61.1%) for disseminated disease. Overall mortality at 90 days was 15.4% (4/26) with 16.7% in disseminated and 12.5% in localized disease (P = 0.78). SOT recipients who died were more likely to have renal failure (75.0% vs. 13.6%, P = 0.028), longer time to onset of disease after transplantation (87.5 vs. 22.6 months, P = 0.023), and abnormal mental status (75% vs. 13.6%, P = 0.028) than those who survived. Cutaneous cryptococcosis represents disseminated disease in most SOT recipients and preferentially involves the extremities. Outcomes with appropriate management were comparable between SOT recipients with localized and disseminated cryptococcosis.
Assuntos
Criptococose/patologia , Cryptococcus neoformans/isolamento & purificação , Dermatomicoses/patologia , Transplantes/efeitos adversos , Antifúngicos/uso terapêutico , Infecções Fúngicas do Sistema Nervoso Central/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Estudos de Coortes , Criptococose/complicações , Criptococose/tratamento farmacológico , Criptococose/mortalidade , Dermatomicoses/complicações , Dermatomicoses/tratamento farmacológico , Dermatomicoses/mortalidade , Feminino , Fluconazol/uso terapêutico , Fungemia/epidemiologia , Fungemia/mortalidade , Humanos , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , TransplanteRESUMO
BACKGROUND: Cryptococcus neoformans is an important pathogen of immunocompromised hosts. Manifestations of cryptococcal infection have not been compared between populations based on the nature of the underlying immune deficiencies. METHODS: The Prospective Antifungal Therapy Alliance (PATH) is a registry that collects clinical data from patients with invasive fungal infections from medical centers in North America. Univariate analyses and group comparisons were conducted from the PATH registry for cases of infection due to Cryptococcus species occurring between March 2004 and April 2008. RESULTS: A total 235 cases of proven infection due to Cryptococcus species were documented, all of which were due to C. neoformans (52 in solid organ transplant [SOT] recipients, 107 in patients infected with the human immunodeficiency virus [HIV], and 76 with neither HIV nor organ transplantation). A total of 140 cases manifested as meningitis (25 in SOT recipients, 88 in HIV-positive patients, and 27 in those with neither risk factor). Of individuals with cryptococcal infection, 44.2% of SOT recipients had central nervous system (CNS) disease, while 84.1% of those with HIV infection presented with CNS involvement (P=0.0265). SOT recipients receiving calcineurin inhibitors (CNIs) were less likely to have CNS involvement in cryptococcal infection (40.1% versus 66.7%). Overall, 12-week mortality for patients with cryptococcal infection in the PATH Alliance registry was 22.6% (21.2% for SOT, 15.9% for HIV-infected patients, and 32.9% for patients with risk factors other than HIV infection or organ transplantation). CONCLUSIONS: In a prospectively assembled cohort of individuals with proven infection due to C. neoformans, CNS involvement was more common in individuals with HIV infection than in SOT recipients. The role of CNIs in the reduction of risk for CNS cryptococcosis remains to be defined. Overall survival of patients with cryptococcal infection in immunocompromised hosts has improved over time. Observed differences in the context of various host immune deficits provide a basis for further investigation of cryptococcosis and other opportunistic infections.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Criptococose , Cryptococcus neoformans , Infecções por HIV/complicações , Transplante de Órgãos/efeitos adversos , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus neoformans/isolamento & purificação , Cryptococcus neoformans/patogenicidade , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Meningite Criptocócica/microbiologia , Meningite Criptocócica/mortalidade , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
INTRODUCTION: Mortality from invasive fungal disease involving the central nervous system (CNS) is excessive. Achieving therapeutic drug concentrations at the site of infection within the CNS is always difficult and its evaluation is complex due to anatomical barriers and variable pathophysiological lesions. Areas covered: This review provides an updated summary of the CNS PK of antifungal therapies. It considers factors that influence the success of antifungal regimens for CNS infection as well as preclinical and clinical data that quantify antifungal pharmacokinetics (PK) in the CNS. Furthermore, it presents state-of-the-art technologies to enhance the clinical use of existing antifungal drugs, and introduces novel antifungal drugs in development. Expert opinion: The antifungal drugs currently available are either suboptimal, or are being used suboptimally, for CNS disease. Therapeutic drug monitoring is mandatory to enhance their effectiveness. Novel drugs in development may offer more efficacious options. In all cases, contemporary technologies to assess CNS PK offer the opportunity to enhance our understanding and use of antifungal drugs for CNS fungal disease.
Assuntos
Antifúngicos/administração & dosagem , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Sistema Nervoso Central/metabolismo , Animais , Antifúngicos/farmacocinética , Sistema Nervoso Central/microbiologia , Sistema Nervoso Central/fisiopatologia , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Desenho de Fármacos , Monitoramento de Medicamentos/métodos , Humanos , Distribuição Tecidual , Resultado do TratamentoRESUMO
Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.
Assuntos
Anfotericina B/uso terapêutico , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Fatores Etários , Anticorpos Antifúngicos/líquido cefalorraquidiano , Antígenos de Fungos/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Infecções Fúngicas do Sistema Nervoso Central/complicações , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Feminino , Histoplasmose/complicações , Histoplasmose/mortalidade , Humanos , Hospedeiro Imunocomprometido , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medula Espinal/efeitos dos fármacosRESUMO
BACKGROUND: Historically considered to have very poor outcome, there is paucity of recent data regarding invasive mold infections (IMIs) of the central nervous system (CNS) in patients with hematologic cancer (HC) or stem cell transplantation (SCT). METHODS: We reviewed the records of HC patients and/or SCT recipients who were diagnosed with CNS IMIs (EORTC/MSG criteria) at MD Anderson Cancer Center (1/1/2000-6/31/2016). Risk factors for survival at day (d) 42 post diagnosis were assessed. RESULTS: We identified 40 such patients (16 with proven infection). The incidence density was 3.8 cases/100000 patient days and mortality remained stable throughout the study period. Most patients had active HC and neutropenia at diagnosis (95% and 53% respectively). Of the 25 patients with a microbiological diagnosis, Aspergillus spp and Mucorales accounted for 85% of cases. CNS IMIs were deemed to be secondary to hematogenous spread in 31 (77%), mostly (90%) fungal pneumonia. CNS lesions typically presented as solitary ring-enhancing abscesses in MRI (26; 65%). Most patients (34; 85%) received lipid AMB and were treated with combination therapy (33; 83%); Mortality 42d was 48%. In univariate analysis, lack of surgical drainage (p = 0.01), absence of giant cells (p = 0.01) and granulomas (p = 0.03) were associated with increased 42d mortality. In multivariate analysis, co-infection was associated with increased (p = 0.005), while steroid tapering was associated with decreased mortality (p = 0.01). CONCLUSIONS: Although less lethal, improved outcome in these uncommon infections was related only to immune response in histopathology, steroid tapering and possibly surgical drainage. In a contemporary 16-year cohort of 40 patients with hematologic cancer and mold infections of Central Nervous System, 42-day mortality was 48%. Improved survival was related to immune response in histopathology, absence of co-infections, corticosteroid tapering and possibly surgical drainage.
Assuntos
Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco/efeitos adversos , Infecções Fúngicas do Sistema Nervoso Central/epidemiologia , Estudos de Coortes , Feminino , Neoplasias Hematológicas/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neutropenia/epidemiologia , Pneumonia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Centros de Atenção Terciária , Fatores de TempoRESUMO
BACKGROUND: Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis. The involvement of the central nervous system (CNS) in paracoccidioidomycosis is higher than previously thought and 2 clinical presentations have been reported, meningitis and pseudotumoral. METHODS: Twenty medical records of patients with CNS paracoccidioidomycosis treated from 1986 to 2003 were analyzed. The follow-up ranged from 1 to 18 years (mean = 8.9 +/- 4.2). RESULTS: Besides CNS paracoccidioidomycosis, all patients but one had the chronic systemic form and the pseudotumoral clinical presentation was the most frequent. Based on computed tomography scan findings, 4 image patterns were identified: low-density lesion with ring enhancement, lesion with calcification and ring enhancement, multiloculated low-density lesion with ring enhancement, and diffuse subarachnoid enhancement. The magnetic resonance imaging was performed in 3 patients and showed subarachnoid enhancement in 1 patient and heterogeneous lesion with ring enhancement in 2 patients. Eleven patients were submitted to medical treatment and 9 needed neurosurgical treatment; ventriculoperitoneal shunts in 4 patients, brain lesions resection in 3 patients, and partial resection of spinal cord lesions in 2 patients. Eleven patients had excellent outcome, 4 patients died, 3 are in good clinical condition with residual pulmonary dysfunction, and 1 patient was lost to follow-up. CONCLUSIONS: The diagnosis of paracoccidioidomycosis with involvement of the CNS is difficult and clinical suspicion is a key point to achieve the correct diagnosis. Patients with early diagnosis have a favorable outcome with clinical or surgical treatment.