A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events.

BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.

Characteristics, mortality, associated variables with death, and therapeutic response among HIV-positive, solid organ transplant (SOT), and non-HIV-positive/non-transplant (NHNT) patients with cryptococcosis: First multicenter cohort study in Brazil.

Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. A total of 384 patients were included; the median age was 39 years and 283 (73.7%) were men. In all, 304 HIV-positive were hosts (79.2%), 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplant (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). A total of 271 (70.6%) patients were discharged and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional amphotericin B (AMB) mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Most patients who died belong to the CNS cryptococcosis category (83/113; 73.4%) when compared with the others (P = .017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .008 and OR, 1.84; 95% CI, 1.01-3.53; P = .048, respectively). Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.

This multicenter cohort study included 384 hospitalized individuals with cryptococcosis in Brazil. Most individuals were men (74%), HIV-positive (79%), had central nervous system involvement (82%), and received conventional amphotericin plus fluconazole (84%). In-hospital mortality was high (29%).

Combining urine antigen and blood polymerase chain reaction for the diagnosis of disseminated histoplasmosis in hospitalized patients with advanced HIV disease.

Disseminated histoplasmosis (DH) is endemic in Latin America and the Caribbean where diagnostic tools are restricted. We carried-out a 1-year prospective cohort study at a referral hospital in São Paulo, Brazil. Participants had > or =18 years old, were hospitalized due to any indication and had CD4+ < 200 cells/µl. A urine commercial monoclonal Histoplasma galactomannan enzyme-linked immunosorbent assay (IMMY, Norman, OK, USA) and 'in house' Histoplasma blood nested PCR were performed in all cases. Probable/proven DH cases were defined according to international guidelines. Conventional mycological methods were available in routine conditions to investigate suspected DH cases. Treatment of participants followed the institutional routine. One-hundred six participants were included. Median age (interquartile range [IQR]) was 39.5 years (30.0-47.3) and 80 individuals (75.5%) were males. Median (IQR) CD4 cell count was 26.5 (9.4-89.3) cells/mm3. DH was diagnosed in 8/106 patients (7.5%). Antigen assay and/or PCR were positive in 4.7% (5/106) of patients. The antigen assay and/or PCR identified 37.5% (3/8) of DH cases, which had not been diagnosed with conventional mycological methods, but had clinical manifestations compatible with HD. In conclusion, the use of Histoplasma urine antigen and Histoplasma blood PCR guided by CD4 status contributed to the diagnosis of DH in hospitalized individuals. These assays were complementary to conventional mycologic methods and are urgently needed in our setting. LAY SUMMARY: In this prospective cohort study carried-out in a referral center in São Paulo, Brazil, we found a high frequency of AIDS-related disseminated histoplasmosis (8/106, 7.5%). We used urine antigen test and blood PCR assay to improve the diagnosis of this opportunistic disease.

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study.

PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

Intensive care unit staff preparedness as an independent factor for death of patients during COVID-19 pandemic: An observational cohort study.

The pandemic of COVID-19 brought to the world an unprecedented challenge. This single center observational study aimed to evaluate the impact of staff preparedness by comparing the outcomes between two intensive care units (ICUs) from a hospital that had to expand ICU beds to deal with an incremented volume of critical patients. Patients consecutively admitted to these ICUs with suspected COVID-19, from March 1st until April 30th, 2020, were included. Both ICUs attended a similar population and had the same facilities, what differed was the staff: one previously well-established (ICU-1) and another recently assembled (ICU-2). 114 patients with severe respiratory syndrome were included. In-hospital mortality was 40%. Compared with patients in the well-established ICU-1, patients in the recently assembled ICU-2 were older (54 versus 61.5, p=0.045), received more antibiotics (93% versus 98%, p=0.001) and chloroquine/hydroxychloroquine 6% versus 30%, p=0.001), had a higher proportion of invasive mechanical ventilation (44% versus 52%, p=0.008) and had greater in-hospital mortality (30% versus 50%, p=0.017). The proportion of patients considered at high risk for death according to PSI was similar between the two ICU populations. Age ≥ 60 years (adjusted OR 2.33; 95% CI 1.02-5.31), need of invasive mechanical ventilation (adjusted OR 2.79; 95% CI 1.22-6.37), and ICU type (recently assembled) (adjusted OR 2.38; 95% CI 1.04-5.44) were independently associated with in-hospital mortality . This finding highlights the importance of developing support strategies to improve preparedness of staff recently assembled to deal with emergencies.

Gravidade do déficit neurológico e incidência de infecções hospitalares em pacientes idosos com acidente vascular cerebral agudo / Severity of neurological deficit and incidence of nosocomial infections in elderly patients with acute stroke

OBJETIVOS: Avaliar a associação entre gravidade do déficit neurológico/grau de incapacidade funcional e incidência de infecções hospitalares, tempo de permanência hospitalar e mortalidade, em pacientes idosos com acidente vascular cerebral agudo. MÉTODOS: Um estudo de coorte prospectivo avaliou pacientes idosos com diagnóstico de acidente vascular cerebral agudo, internados no Hospital de Clínicas da Faculdade de Medicina de Marília, em Marília, SP. Os critérios de inclusão foram idade igual ou superior a 60 anos e diagnóstico de acidente vascular cerebral agudo. Os pacientes foram agrupados de acordo com a gravidade do acidente vascular cerebral pela National Institute of Health Stroke Scale e o grau de dependência pela escala modificada de Rankin. Todos os pacientes foram acompanhados desde o momento da internação até a alta hospitalar ou óbito. RESULTADOS: Foram estudados 113 pacientes com média de idade de 70,8 anos, sendo 63 (55,7%) homens. As principais doenças de base relacionadas foram hipertensão arterial (77,9%) e diabetes mellitus tipo 2 (30,1%). Setenta e oito (69%) pacientes foram acometidos pela primeira vez e 86 (76,1%) apresentaram acidente vascular cerebral isquêmico. Tiveram infecção hospitalar 24 pacientes (21,2%) sendo pneumonia a mais frequente (13,5%). O tempo médio de permanência hospitalar dos pacientes com infecção hospitalar foi maior, quando comparados àqueles sem infecção hospitalar (16,2±16,2 dias e 33,2±22,9 dias, p<0,001). Observou-se relação entre escore de 16 a 42 pontos, na National Institute of Health Stroke Scale, e a ocorrência de infecção hospitalar (rico relativo 4,4; intervalo de confiança 95% 1,8 a 11,0). A mortalidade intra-hospitalar foi de 15,9%, sendo maior entre pacientes considerados muito graves à admissão, quando comparados com aqueles com gravidade moderada a leve pela National Institute of Health Stroke Scale, (34,6% e 1,6% respectivamente, p<0,001) e também entre aqueles que desenvolveram infecção hospitalar quando comparados aos que não apresentaram esta complicação (37,5% e 10,1% respectivamente, p=0,003). CONCLUSÕES: As infecções hospitalares foram complicações importantes entre os pacientes idosos com acidente vascular cerebral agudo e estiveram associadas com maior gravidade do déficit neurológico, maior grau de dependência, tempo de hospitalização mais prolongado e taxa de mortalidade mais alta.

AIMS: To evaluate the association between severity of neurological deficit/degree of functional disability and incidence of nosocomial infections, length of hospital stay, and mortality, in elderly patients with acute stroke. METHODS: A prospective cohort study evaluated elderly patients with acute stroke, hospitalized at the Hospital of the Marilia Medical School, in Marilia, SP, Brazil. Inclusion criteria were patients aged 60 years or more and diagnosed with acute stroke. Patients were stratified according to the severity of the stroke by the National Institutes of Health Stroke Scale and the degree of dependence by the modified Rankin scale. All patients were followed from the time of admission to discharge or death. RESULTS: We studied 113 patients with a mean age of 70.8 years, 63 (55.7%) men. The main underlying diseases were hypertension (77.9%) and type 2 diabetes mellitus (30.1%). Seventy-eight (69%) patients were affected for the first time and 86 (76.1%) had ischemic stroke. Nosocomial infection occurred in 24 patients (21.2%) and pneumonia was the most frequent (13.5%). The average length of hospital stay among patients with nosocomial infection was higher when compared to those without nosocomial infection (16.2±16.2 days and 33.2±22.9 days, p<0.001). There was association between score 16-42 points on the National Institute of Health Stroke Scale and the occurrence of nosocomial infection (risk ratio 4.4; 95% confidence interval 1.8 to 11.0). In-hospital mortality was 15.9%, higher among patients considered severe at admission compared to those with moderate to mild severity by the National Institute of Health Stroke Scale (34.6% and 1.6% respectively, p<0.001) and also among those who developed nosocomial infection when compared to those without this complication (37.5% and 10.1% respectively, p=0.003). CONCLUSIONS: Nosocomial infections were major complications among elderly patients with acute stroke and were associated with severity of neurological deficit, higher degree of dependence, longer hospital stay and higher mortality rate.