Introdução/Objetivos: A epidemiologia de candidemia alterou-se durante a pandemia de COVID-19, mas comparações diretas de episódios ocorrendo em pacientes com e sem a doença ainda são limitadas. O objetivo deste trabalho foi comparar apresentação clínica, distribuição das espécies, manejo e os desfechos dos casos diagnosticados em pacientes com e sem COVID-19, internados em um hospital universitário de alta complexidade. Materiais e métodos: Foi realizado um estudo de coorte retrospectivo, que incluiu pacientes adultos, consecutivos, com episódios de candidemia diagnosticados no período de fevereiro de 2020 a fevereiro de 2023. Dados demográficos, clínicos, microbiológicos, de tratamento e de desfecho foram comparados de acordo com a coinfecção pelo SARS-CoV-2. Análise de regressão logística múltipla foi utilizada para identificar os fatores preditores de mortalidade em 30 dias, entre os pacientes que receberam tratamento antifúngico. Resultados: Entre 106 episódios documentados em 103 pacientes, 36 (34%) ocorreram em indivíduos com COVID-19. A incidência global foi de 4,41 episódios por 1000 internações. Os episódios associados à COVID-19 estiveram significativamente mais relacionados com internação em unidade de terapia intensiva, ventilação mecânica, exposição prévia a corticosteroides, maiores escores APACHE II, com hipotensão e uso de vasopressores. A sobrevida em 30 dias foi menor nos pacientes com COVID-19 (19,4% vs 48,6%; p = 0,003). Contudo, entre os episódios tratados, apenas o escore APACHE II e o uso de vasopressores mantiveram-se independentemente associados à mortalidade em 30 dias. Conclusões: Candidemia associada à COVID-19 ocorreu em um cenário de substancial maior gravidade de doença aguda. Marcadores de gravidade, e não a infecção por COVID-19, foram os principais fatores determinantes de mortalidade observado nestes pacientes. Conflito de interesse: Nenhum autor tem conflitos de interesse. Comitê de ética: Projeto aprovado pelo CEP HUCFF. Há Financiamento? Especifique: Bolsa PIBIC-UFRJ.

Vancomycin is still frequently started empirically in febrile neutropaenia, especially when patients are severely ill. Yet randomized evidence concerning anti-Gram-positive agents as a class shows no mortality benefit from routine empirical coverage, and contemporary cohort studies consistently link early shock and death to Gram-negative bacilli, inadequate Gram-negative coverage, pneumonia, septic shock and candidaemia rather than to Gram-positive bacteraemia or inadequate Gram-positive coverage. MRSA nasal screening further supports avoiding empirical anti-MRSA therapy in screen-negative patients. The default response to febrile neutropaenia should therefore be rapid, locally informed anti-pseudomonal beta-lactam therapy, with vancomycin reserved for documented infection or narrowly defined syndromes with a high pre-test probability of resistant Gram-positive disease.

Background:Data on clinical characteristics and prognosis of chronic pulmonary aspergillosis (CPA) in resource-limited, high tuberculosis (TB) burden settings, especially in Brazil, remain scarce. Methods:This multicenter retrospective study evaluated all CPA cases diagnosed between 2012 and 2018 across eight centers in Brazil, examining clinical presentation, diagnosis, treatment, mortality, and factors associated with death, including differences related to pulmonary TB. To identify independent predictors of mortality, we conducted multivariate Cox regression. One-year mortality was analyzed using Kaplan-Meier survival curves. Results:A total of 191 CPA cases were diagnosed, with a median age of 50 years (IQR 40-59) and 62% were male. TB was the most frequent predisposing condition (n = 138, 72%). Most patients (80%) received antifungal therapy, primarily itraconazole (n = 140, 73%). Surgery was performed in 34% of cases. According to Kaplan-Meier analysis, the cumulative mortality at 12 months was 6%. Compared to survivors, nonsurvivors had significantly lower rates of TB (52% vs 77%, P = .019) and higher rates of malignancies (13% vs 3%, P = .033). In multivariate analysis, only TB was independently associated with lower mortality (HR 0.413, 95% CI: .179-.954, P = .038). The TB group showed more hemoptysis (P = .008) and greater radiological involvement, suggesting delayed diagnosis. Conclusions:In Brazil, the mortality of CPA was lower compared with that reported in previous studies, particularly among patients with TB. In TB-endemic, resource-limited settings, overlapping clinical and radiological features may delay diagnosis and antifungal treatment.

The therapeutic landscape of acute leukaemia (AL) has evolved profoundly with the introduction of targeted and differentiation agents, altering the epidemiology of invasive fungal disease (IFD). While antifungal prophylaxis with triazoles remains standard for patients receiving intensive chemotherapy, this paradigm may no longer apply to those treated with novel regimens. Targeted agents such as tyrosine kinase inhibitors, blinatumomab, inotuzumab ozogamycin, ivosidenib, gilteritinib, and venetoclax are associated with higher remission rates, shorter or absent neutropenia, and minimal mucosal injury-key determinants of IFD risk. As a result, the incidence of IFD appears markedly lower in such populations. Redefining antifungal prophylactic strategies must account for this therapeutic heterogeneity to avoid overexposure to antifungal drugs and misdirected research priorities. Updated, risk-adapted strategies-integrating treatment intensity, myelotoxicity, and drug interactions-are essential to define which AL patients truly benefit from primary antifungal prophylaxis in the modern era.

INTRODUCTION:Invasive fusariosis is a rare but devastating mold infection in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT). Its clinical impact stems from delayed and challenging diagnosis, often made when fungal burden is already high; frequent dissemination with fungemia; and the limited availability of reliably effective antifungal agents. Together with the profound influence of host immune status on outcome, these factors drive persistently high mortality despite advances in antifungal therapy and supportive care, underscoring the urgent need for better diagnostic tools and novel therapeutic strategies. AREAS COVERED:We searched PubMed (1990-2025) for studies reporting the epidemiology, clinical presentation, diagnostic approaches, and management of fusariosis in transplant recipients. Key topics include the trimodal timing of fusariosis after HCT, species distribution across geographic regions, diagnostic challenges with culture and nonspecific biomarkers, and therapeutic outcomes with amphotericin B formulations and voriconazole. Emerging agents such as fosmanogepix and novel molecular platforms are also discussed. EXPERT OPINION:Despite its rarity, fusariosis poses a disproportionate threat to transplant recipients due to diagnostic delays, lack of randomized trials, and few effective antifungal options. Incorporating rapid molecular diagnostics, next-generation antifungals, and immune-directed strategies will be critical to improving real-world outcomes and survival.

Breakthrough invasive fungal infections (bIFIs) are a challenging serious complication in high-risk hematologic patients and allogeneic hematopoietic stem cell transplantation recipients that may negatively impact their outcome. Despite advances in antifungal prophylaxis, diagnostics, and supportive care, bIFI occurrence reflects a complex interaction between host immunosuppression, emergence of resistant pathogens and pharmacological variables, including subtherapeutic drug exposure. Candida spp. have shifted towards non-albicans yeasts, whereas breakthrough mold infections more frequently involve non-fumigatus Aspergillus, Mucorales, Fusarium spp., and Scedosporium/Lomentospora spp. Early clinical recognition, rapid therapy escalation, aggressive diagnostic investigation, a switch to liposomal amphotericin B-based regimens in patients on azole prophylaxis, and therapeutic drug monitoring are essential to improve outcomes. Reducing the growing global burden of bIFIs will also require improved access to high-quality diagnostics and strengthened educational and stewardship efforts that prioritize antifungal resistance as an urgent health concern.

The epidemiology of candidemia changed during the COVID-19 pandemic, but direct comparisons of episodes with and without coronavirus disease 2019 (COVID-19) remain limited. We performed a retrospective cohort study of consecutive adult patients with candidemia diagnosed from February 2020 through February 2023 at a Brazilian tertiary-care teaching hospital. Demographic, clinical, microbiological, treatment, and outcome variables were compared according to COVID-19 status, and predictors of 30-day mortality were evaluated among treated patients. Among 106 episodes in 103 patients, 36 (34.0%) occurred in patients with COVID-19. The overall incidence was 4.41 episodes per 1000 admissions (95% confidence interval [CI], 3.61-5.33), and the incidence among COVID-19 admissions was 20.97 per 1000 (95% CI, 14.69-29.03). Episodes with COVID-19 were associated with intensive care, mechanical ventilation, corticosteroid exposure, higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, hypotension, and vasopressor use. Thirty-day survival was lower with COVID-19 (19.4% vs. 48.6%; P = .003). Among treated episodes, APACHE II score and vasopressor use were independently associated with 30-day mortality. Candidemia associated with COVID-19 occurred in a setting of substantially greater acute illness severity, and severity markers rather than COVID-19 itself appeared to drive excess mortality.

This chapter outlines recommendations for the control and management of infections following hematopoietic cell transplantation. Given the complexity and scope of the subject, the authors chose a format that considers the various interventions available to prevent, minimize, or when appropriate treat infections relevant to the hematopoietic cell transplantation setting. We consider the active and collaborative involvement of the transplant infectious disease specialist in transplantation centers to be essential in ensuring the best possible care for this vulnerable population.

Aspergillosis is a disease caused by the filamentous fungus Aspergillus spp. with a spectrum of clinical presentation that includes invasive and noninvasive forms. The invasive clinical presentation of aspergillosis most frequently affects people with compromised immune systems. In patients with oncohematologic pathology, invasive lung aspergillosis is a significant opportunistic mycosis, because it occurs frequently and has a major impact on morbidity, mortality, and high costs. The global problem of antimicrobial resistance, to which improper use of antifungals contributes, has put Aspergilus spp. in the spotlight, so it is important to generate guidelines for guidance in the proper use of antifungals in the management of invasive lung aspergillosis, to obtain better clinical outcomes and promote rational use of antifungals. This guideline contains recommendations for diagnosing and treating invasive lung aspergillosis in patients with oncohematologic disease, based on evidence and defined through a participatory process of expert consensus, for the Latin American context.

(1) Background: Invasive aspergillosis is a life-threatening fungal infection, particularly in patients with hematologic malignancies. Isavuconazole, a broad-spectrum triazole, has emerged as a key treatment option, but real-world data in high-risk populations from middle-income countries remain limited. (2) Methods: We conducted a multicenter, retrospective study to evaluate the clinical response rate and tolerability of isavuconazole in patients with hematologic malignancies and probable or proven invasive aspergillosis across four medical centers in Brazil. (3) Results: We enrolled 50 patients aged 18 to 82 years (64% male) with proven or probable invasive aspergillosis, diagnosed in the context of complex hematologic conditions. Among them, 60% had active or refractory malignancies, and 22% had a prior COVID-19 infection. Isavuconazole was used as a first-line therapy in 64% of cases. No patients discontinued treatment due to toxicity. The 6-week overall survival was 60%. Prior COVID-19 infection was associated with a lower survival rate (44% vs. 69% in patients without COVID-19, p = 0.04). (4) Conclusions: This study provides real-world evidence supporting the efficacy and tolerability of isavuconazole in a high-risk population. The findings reinforce its role as a key antifungal therapy, particularly in patients with complex underlying conditions.

Candidemia is the predominant form of invasive candidiasis and the most frequently occurring serious fungal infection in critically ill patients in Intensive Care Units (ICU). Studies carried out in Latin America reveal a higher incidence of candidemia and higher mortality rates when compared to North America or Europe. This highlights the need to develop guidelines for correctly diagnosing and treating candidemia in critically ill patients in the ICU. These guidelines are part of the efforts to implement antifungal optimization programs in the region to obtain better clinical outcomes and promote rational antifungal use. This evidence-based clinical standard, established through expert consensus for the Latin American context, contains recommendations and algorithms for diagnosing and treating candidemia in critically ill ICU patients.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 x 109/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

Objetivos O objetivo foi avaliar a toxicidade do protocolo LACE e sua aplicação como protocolo alternativo em nosso meio. Materiais e métodos Realizamos uma análise retrospectiva de 29 pacientes submetidos a transplante autólogo de medula óssea com o protocolo LACE (lomustina, citarabina, ciclofosfamida e etoposídeo) no Hospital Universitário Clementino Fraga Filho (UFRJ) entre 2018 e 2022. Foram coletados dados de variáveis demográficas, tratamentos prévios e parâmetros para avaliação de toxicidade, como neutropenia febril, mucosite, disfunção orgânica, necessidade de terapia intensiva e mortalidade. Resultados Foram identificados 29 pacientes, com idade mediana de 36 anos (variando de 23 a 62 anos), com diagnóstico de linfoma (17 Hodgkin e 12 não Hodgkin. A mediana de linhas de tratamentos anteriores foi de 2 (variando de 1 a 4 linhas) e o GDP (gencitabina, dexametasona e cisplatina) foi utilizado em 41% dos casos de resgate anterior ao TAMO (n = 12). A maioria dos pacientes – 82,8% - apresentava doença sensível à quimioterapia (n = 22) e apenas 6,9% dos pacientes foram considerados resistentes ao tratamento de resgate (n = 2). Nenhum paciente apresentou mucosite grau 3 ou 4 e 1 paciente necessitou de nutrição parenteral total devido a enterocolite neutropenica (3%). Toxicidades não hematológicas (hepáticas, renais ou cardíacas) grau 3 ou 4 ocorreram em 4 casos (13,7%), destes, 2 casos foram de elevações assintomáticas de enzimas hepáticas. A mortalidade associada ao transplante foi de 3% (n = 1). A sobrevida mediana no total de pacientes foi de 45 meses, sendo que na população de linfoma de Hodgkin não foi atingida e na população de linfoma não Hodgkin foi de 28 meses (p = 0,169). Discussão O transplante autólogo de células tronco hematopoiéticas é uma modalidade de tratamento frequentemente empregada nos linfomas recaídos ou refratários à primeira linha de tratamento. O BEAM (carmustina, etoposideo, citarabina e melfalano) está entre os protocolos tradicionalmente utilizados como condicionamento, entretanto, faltam dados comparativos na literatura em relação ao regime com maior eficácia e segurança. No período do estudo, houve desabastecimento de carmustina, medicação utilizada no protocolo BEAM. O cenário de desabastecimento de quimioterápicos a nível nacional não é infrequente e salienta a importância da investigação de regimes alternativos, principalmente no âmbito do Sistema Único de Saúde, onde a importação de fármacos não é uma realidade para a maioria das instituições. Os resultados encontrados sugerem um baixo perfil de toxicidade, tanto do ponto de vista hematológico quanto de outros sistemas. A sobrevida mediana sugere que pacientes com Linfoma de Hodgkin possam contar com benefício adicional em termos de resposta, o que precisa ser confirmado em análises posteriores. Conclusão O condicionamento com o protocolo LACE apresentou perfil de toxicidade baixo, colocando-o como alternativa aos protocolos convencionais. Os resultados obtidos não diferem dos reportados na literatura com o mesmo protocolo.

Introduction Infection is a major complication in patients with AML receiving intensive induction chemotherapeutic regimens, and antibacterial and antifungal prophylaxis are common practices. However, for patients receiving VEN-HMA regimens, antimicrobial prophylaxis is not the standard of care due to potentially lower infection rates. Furthermore, the use of azoles and quinolones requires dose adjustments for venetoclax because they inhibit its main metabolic pathway. In this study, we evaluated antimicrobial prophylaxis practices and documented infection rates in patients with AML or MDS treated with VEN-HMA. Methods This is a multicenter retrospective study conducted in 12 Brazilian centers. We included patients (pts) with AML or MDS who were treated with VEN-HMA either as first-line or salvage therapy. We collected data on antibacterial and antifungal prophylaxis practices, documentation of infection during neutropenia, and outcomes. Results A total of 92 patients were analyzed; 66% were male, and the median age was 69 years (range 19-89). Most patients had AML (91%) with high-risk disease (64%), and azacytidine was given to all but 4 patients. VEN-HMA was given as first-line therapy to 60 pts and as salvage therapy to 32 pts (of whom 19 received it as second-line therapy). The first cycle of VEN-HMA was given on an outpatient basis in 34.5% of patients. Quinolone prophylaxis was given to 12 pts (13%) and anti-Aspergillus azole to 6 pts (6.5%). Twenty patients (21.7%) received an echinocandin as antifungal prophylaxis. Febrile neutropenia occurred in 54.7% of patients, with 43.5% classified as fever of unknown origin, 23.9% as clinically documented, 21.7% as microbiologically documented infection, and 10.9% as bacteremia (Gram-negative bacilii in 3 and coagulase-negative staphylococci in 2). Proven or probable invasive fungal disease (IFD) was diagnosed in 7.6% (aspergillosis in 4, and candidiasis, fusariosis, and trichosporonosis in 1 case each). There were no differences in antimicrobial prophylaxis practices or infection documentation between patients receiving VEN-HMA as first-line therapy and those receiving it as salvage therapy. The death rate after cycle 1 was 7.6% and the rate of complete remission (CR) + CR with incomplete hematologic recovery was 51% (58% in first-line therapy). In cycles 2 and 3, febrile neutropenia occurred in 19.7%, and 17.3%, respectively, with 1 case of bacteremia (cycle 3) and no case of IFD. Conclusions In the present study, we observed a low rate of bacteremia and IFD despite a low frequency of antibacterial (13%) and anti-mold prophylaxis (6.5% with azoles, 21.7% with echinocandins). The rates of febrile neutropenia and documented infection after the second and third cycles were also very low. These data suggest that antimicrobial prophylaxis should not be routinely given to AML/MDS patients receiving the first cycle of VEN-HMA. Additionally, antimicrobial prophylaxis should be discouraged in subsequent cycles.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Abstract Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.