•ABLC is effective and well-tolerated for the treatment of invasive fungal infections.•ABLC presented similar rates of safety outcomes when compared L-AMB.•Lipid formulations showed similar safety ...profiles, the same does not apply to D-AMB.•A minimum of 2 weeks of treatment with ABLC should be prioritized.•Standardization of clinical management is necessary to minimize harmful effects.
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.
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.
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%.
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.
Resistance to antimicrobial agents is increasing worldwide and imposes significant life-threatening risks to several different populations, especially those in intensive care units (ICUs). Bacteria ...can quickly develop or acquire resistance to antimicrobial drugs, and combined with their intrinsic potential to cause disease in humans, these bacteria can become deadly. Among Gram-negative bacteria, Acinetobacter baumannii is notorious as a frequent opportunistic pathogen associated with critically ill patients, and understanding the genetic basis of A. baumannii resistance to beta-lactams among patients in ICUs will result in better protocols to prevent the development of resistance as well as improved treatment regimens. In this study, we assessed 1333 patients in five ICUs, 56 of whom developed A. baumannii infections. Most of the A. baumannii isolates were resistant to beta-lactam antimicrobial drugs, specifically, 3rd- and 4th-generation cephalosporins and carbapenems, and 91.1% of the isolates were multi-drug resistant (MDR). The most frequent OXA gene present was OXA-23 (55.1%), which is significantly associated with MDR strains. Most of the A. baumannii isolates (76.8%) were capable of forming a biofilm. The antimicrobial drug classes that were effective against most of these isolates were polymyxins and tigecycline. The molecular profile of the isolates allowed detection of 12 different clusters comprising 2 to 8 isolates each. In conclusion, our data indicate a high incidence of resistance to carbapenems as well as MDR strains among the observed A. baumannii isolates, most of which exhibited a high prevalence of OXA-23 gene expression. Only a few selective drugs were effective, reinforcing the notion that bacterial resistance is an emerging problem that should be prioritized in every healthcare facility.
Abstract 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.
Oropharyngeal candidiasis (OPC) is the most common opportunistic fungal infection of the oral cavity and is a significant clinical problem, particularly in immunocompromised individuals, such as ...people living with HIV/AIDS (PLWHA). Although
Candida albicans
is the most frequent pathogen, at least 30 species capable of causing infection have been described. Identifying the infecting organism is necessary because the species respond differently to therapy, and antifungal susceptibility testing is important to determine the appropriate treatment. This study aimed to determine the epidemiological, clinical, and mycological profiles of OPC in hospitalized PLWHA. Clinical samples were collected from 103 PLWHA with suspected candidiasis admitted to the Hospital Estadual of Doenças Tropicais/Hospital Anuar Auad of Goiania, Goias, Brazil, for 14 months.
Candida
species were identified using phenotypic microbiological techniques and molecular analysis performed by PCR using species-specific primers. The antifungal susceptibility pattern of the isolates against the six antifungal agents was determined using the broth microdilution method. Here, female individuals were the most affected by OPC, presenting a higher risk of oral colonization by
Candida
spp. The main clinical manifestation was pseudomembranous candidiasis. The number of cases of candidiasis was 87.3% (90/103), with
C. albicans
being the most common species, followed by
C. tropicalis
and
C. glabrata
. In the susceptibility pattern, non-
albicans Candida
showed higher resistance to than
C. albicans
. The fast and accurate identification of
Candida
spp. is very important to identify therapeutic agents for the treatment of oral candidiasis in PLWHA.
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.
Abstract
Background
Histoplasmosis is highly endemic in the American continent. This condition is associated with a high mortality, particularly in people living with HIV/AIDS (PLWHA). Diagnosis of ...histoplasmosis is usually late in South America, as Histoplasma antigen detection is rarely available. Here we determined the prevalence, risk factors, and outcome of histoplasmosis in PLWHA in Brazilian hospitals.
Methods
This was a prospective cohort study (2016–2018) involving 14 tertiary medical centers in Brazil. We included hospitalized PLWHA presenting with fever and additional clinical findings. Patients were investigated at each participant center with classical mycology methods. Also, Histoplasma antigen detection was performed in urine samples (IMMY). Probable/proven histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria.
Results
From 616 eligible patients, 570 were included. Histoplasmosis was identified in 21.6% (123/570) of patients. Urine antigen testing increased the diagnostic yield in 53.8%, in comparison with standard mycology methods. Variables independently associated with histoplasmosis were CD4+ count <50 cells/mm3, use of an antiretroviral (protective effect), and sample collection in the Northeast region of Brazil. Dyspnea at presentation was independently associated with death. Histoplasmosis was more frequent than tuberculosis in patients with low CD4+ counts. Overall 30-day mortality was 22.1%, decreasing to 14.3% in patients with antigen-based diagnosis.
Conclusions
Histoplasmosis is a very frequent condition affecting PLWHA in Brazil, particularly when CD4+ counts are lower than 50 cells/mm3. Antigen detection may detect earlier disease, with a probable impact on outcomes. Access to this diagnostic tool is needed to improve clinical management of PLWHA in endemic countries.
Abstract
Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM
Objectives
To describe the characteristics, mortality, and therapeutic response among hospitalized patients with cryptococcosis in ...Brazil.
Methods
This is a multicenter retrospective cohort study of seven Brazilian public tertiary hospitals (Figure 1). Medical records of patients admitted from January 2014 to December 2019 were evaluated. Confirmed cases of the first episode of cryptococcosis were included. Hosts were classified as HIV-positive, solid organ transplant (SOT), and non-HIV-positive/non-transplant (NHNT). Mortality was defined as the time of patient admission to in-hospital death from any cause. Statistical analysis was performed using the software R and JAMOVI.
Results
A total of 384 patients were included; the median (25th-75th) age was 39 (31-48) years and 283 (73.7%) were men. Hosts were 304 (79.2%) HIV-positive, 16 (4.2%) SOT, and 64 (16.7%) NHNT. More frequent diagnosis tools were culture, direct microscopic examination of infected body fluids using India ink, histological examination of tissue samples, and detection of cryptococcal polysaccharide antigen in body fluids (CrAg) using latex. Central nervous system (CNS) cryptococcosis had a significantly higher counting level across disease categories, with 313 cases or 81.5%. NHNT were more likely to have CNS cryptococcosis than people HIV-positive (84.4% vs. 81.9%, respectively). SOT patients had more pulmonary form infections (31.2%) as compared with HIV-positive (3.3%) and NHNT (1.6%). Other extrapulmonary sites category had HIV-positive and NHNT basically the same percentage of disease involvement (14%) compared with SOT (6.2%) (P < .001, Figure 2). Among cases with identification of specie, 56% were Cryptococcus neoformans and 4.4% were C. gattii. A total of 271 (70.6%) patients were discharged home with total or partial improvement and 113 (29.4%) patients died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT patients was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with AMB had the conventional deoxycholate mainly in combination with fluconazole (234, 84.2%). Only 80 (22.3%) patients received an AMB lipid formulation (liposomal AMB, n = 35 and AMB lipid complex, n = 45). The median (25th-75th) length of AMB therapy was 20 (14–32) days. Death patients had more age when compared with discharged-to-home cases (43 vs. 38 years, P < .002). Patients with CNS cryptococcosis had lower mortality (83/313, 26.5%) when compared with the other categories pulmonary, 5/16 (31.2%) and other extrapulmonary sites, 25/55 (45.4%) (P = .017). Survival benefits were seen for patients who received monotherapy or combination therapy. However, D-AMB alone showed a higher mortality rate, although not statistically significant (P = .537).
Conclusion
HIV infection is the most important condition among patients with cryptococcosis in Brazil and CNS involvement is the commonest manifestation in all hosts, mainly HIV-positive and NHNT. The proportion of pulmonary cryptococcosis is relevant in SOT patients. Mortality was high in all categories of hosts. Understanding the epidemiology and characteristic of patients admitted to our hospitals will help to understand the burden and causes of mortality and identify strategies to improve this scenario. Optimized diagnosis (i.e., lateral flow assay) and treatment (i.e., AMB lipid formulation plus flucytosine) are urgently necessary for our setting.
A paracoccidioidomicose (PCM) possui elevada incidência na América Latina, com amplo espectro clínico e imagiológico. A forma crônica é a mais prevalente, com o clássico acometimento pulmonar. Há ...ainda formas menos convencionais, destacando-se o acometimento do Sistema Nervoso Central (SNC). O padrão ouro para o diagnóstico é a visualização do fungo e seu crescimento em cultura de espécimes clínicos. Métodos sorológicos são complementares, com sensibilidade/especificidade variando de 80-95% e 85-100%, respectivamente, a depender dos antígenos utilizados. Homem, 60 anos, procedente do Tocantins, transportador de grãos, tabagista, queixava-se de vertigem há um ano, cefaleia há 5 meses, alteração progressiva da fala, da marcha e paresia em braço E. Tomografia computadorizada (TC) e Ressonância Magnética (RM) de crânio demostravam lesões nodulares volumosas (maior 4 x 3,8 cm), heterogêneas e com edema adjacente em cerebelo D, lobos frontal D e parietal E, sugestivas de neoplasia. TC de tórax com múltiplos nódulos, espessamento e adenomegalias mediastinais. Submetido a biópsia cerebral em hospital oncológico, tendo diagnóstico de COVID-19 na internação. Transferido ao Hospital das Clínicas. Avaliação da infectologia descreveu raio X de tórax com padrão em asa de borboleta e lesão granulomatosa em palato. Raspado da lesão e aspirado traqueal demonstraram leveduras multibrotantes. Histopatológico (AP) da biópsia de SNC foi resgatado e descrevia estruturas leveduriformes, birrefringentes, com brotamentos em roda denteada, compatíveis com PCM. Imunodifusão dupla reagente e cultura positiva para Paracoccidioides spp. Recebeu Anfotericina B desoxicolato por 7 dias e complexo lipídico por mais 20 dias. Obteve alta com melhora da cognição, da fala e da marcha, ainda necessitando auxilio para atividades. Em acompanhamento ambulatorial, paciente sem déficits, comunicativo e sem novas queixas. RM de controle mantém lesões nodulares, com redução significativa do tamanho, do edema e da captação de contraste. Programado Sulfametoxazol Trimetoprima 3cp 12h/12h por 18-24 meses, pela melhor penetração em SNC. A forma neurológica da PCM é de difícil diagnóstico, muitas vezes confundida com neoplasias devido ao seu efeito de massa. A pesquisa direta, AP, cultura e sorologias são métodos diagnósticos disponíveis, que facilitam a definição etiológica. A busca por outros locais de comprometimento, como pulmonar, mucosas e linfonodos podem agilizar o diagnóstico e o tratamento da PCM.
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