RESUMO

During the COVID-19 pandemic, an increase in the incidence of bloodstream infections caused by fungi of the Candida genus, also known as candidemia, was observed in patients with SARS-CoV-2 infection. This study aimed to assess the incidence of candidemia, the factors related to COVID-19-associated candidemia (CAC), and prognostic factors. A non-concurrent cohort of 87 cases of patients aged over 18 years with candidemia between March 2020 and February 2022 was evaluated. Incidence density (ID) was calculated by the number of patient-days during the period. All causes of mortality within 30 days of observation were considered. Logistic regression and Cox proportional hazards regression were used, respectively, to determine factors associated with CAC and prognostic factors. Values <0.05 were considered significant. The ID of CAC was eight times higher than candidemia in patients without COVID-19 [2.40 per 1000 person-days vs. 0.27 per 1000 person-days; P < .01]. The corticosteroid therapy was as an independent factor associated with CAC [OR = 15.98 (3.64-70.03), P < .01], while abdominal surgery was associated with candidemia in patients without COVID-19 [OR = 0.09 (0.01-0.88), P = .04]. Both patients with and without COVID-19 had a high 30 days-mortality rate (80.8% vs. 73.8%, respectively; P = .59). Liver disease [HR = 3.36 (1.22-9.27); P = .02] and the Charlson score [HR = 1.17 (1.01-1.34); P = .03] were independent factors of death, while the use of antifungals [HR = 0.15 (0.07-0.33); P < .01] and removal of the central venous catheter [HR = 0.26 (0.12-0.56); P < .01] independently reduced the risk of death. These findings highlight the high incidence of candidemia in COVID-19 patients and its elevated mortality.

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This study found that bloodstream infections by Candida spp. were significantly more common in patients with than without COVID-19, and Candida glabrata played a significant role in these infections. Liver disease and a higher number of comorbidities were associated with an increased risk of death.

Assuntos

COVID-19 , Candidemia , Hospitais de Ensino , Humanos , Candidemia/epidemiologia , Candidemia/mortalidade , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/complicações , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Hospitais de Ensino/estatística & dados numéricos , Incidência , Fatores de Risco , Estudos de Coortes , SARS-CoV-2 , Idoso de 80 Anos ou mais , Prognóstico , Adulto , Candida/isolamento & purificação , Candida/classificação , Estudos Retrospectivos

RESUMO

INTRODUCTION: Candidemia, a bloodstream infection predominantly affecting critically ill patients, poses a significant global health threat especially with the emergence of non-albicans Candida species, including drug-resistant strains. In Brazil, limited access to advanced diagnostic tools and trained microbiologists hampers accurate identification of Candida species and susceptibility to antifungals testing hindering surveillance efforts. METHODS: We conducted a systematic review spanning publications from 2017 to 2023 addressing Candida species distribution and antifungal susceptibility among Brazilian patients with candidemia. RESULTS: Despite initially identifying 7075 records, only 16 met inclusion criteria providing accurate information of 2305 episodes of candidemia. The predominant species were C. albicans, C. parapsilosis, and C. tropicalis, followed by notable proportions of Nakaseomyces glabratus. Limited access to diagnostic tests was evident as only 5 out of 16 studies on candidemia were able to report antifungal susceptibility testing results. In vitro resistance to echinocandins was rare (only 6/396 isolates, 1,5%). In counterpart, fluconazole exhibited resistance rates ranging from 0 to 43%, with great heterogeneity among different studies and species of Candida considered. CONCLUSION: Our review underscores the critical need for enhanced surveillance and research efforts to address the evolving landscape of candidemia and antifungal resistance in Brazil. Despite some limitations, available data suggest that while resistance to echinocandins and amphotericin B remains rare, there is a growing concern regarding resistance to fluconazole among Candida species.

Assuntos

Antifúngicos , Candida , Candidemia , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Candidemia/epidemiologia , Candidemia/microbiologia , Candidemia/diagnóstico , Candidemia/tratamento farmacológico , Brasil/epidemiologia , Humanos , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida/classificação

RESUMO

The incidence of candidemia in healthcare centers is associated with high morbidity and mortality. Frequency varies significantly among regions, with some species being more prevalent than others in Latin America. In this study, 191 clinical Candida isolates were collected from a major hospital in Ecuador from January 2019 to February 2020 aiming to assess their prevalence and distribution. After data processing, 168 isolates characterized by the VITEK 2 system were subsequently identified by ITS sequencing. Results showed diverse Candida species distributions, with C. albicans and C. tropicalis being the most prevalent across different clinical sources. In hospitalized individuals, C. tropicalis (38%) and C. albicans (37%) were the most prevalent, followed by, C. parapsilosis (16%), C. glabrata (5%), and other non-Candida albicans (NCA) species (6%). Conversely, C. parapsilosis (48%), C. albicans (20%), and C. glabrata (14%), associated with candidemia, were the most common in blood and CSF. Additionally, uncommon NCA species such as C. haemulonii, C. kefyr, and C. pelliculosa were identified in Ecuador for the first time. Discrepancies in species identification were observed between the VITEK 2 system and ITS sequencing, coinciding at 85%. This highlights the need for ongoing surveillance and identification efforts in Ecuador's clinical and epidemiological settings.

RESUMO

Introduction: Invasive candidiasis is a global public health problem as it poses a significant threat in hospital-settings. The aim of this study was to evaluate C14R, an analog derived from peptide BP100, as a potential antimicrobial peptide against the prevalent opportunistic yeast Candida albicans and the emergent multidrug-resistant yeast Candida auris. Methods: Antifungal susceptibility testing of C14R against 99 C. albicans and 105 C. auris clinical isolates from Colombia, was determined by broth microdilution. Fluconazole was used as a control antifungal. The synergy between C14R and fluconazole was assessed in resistant isolates. Assays against fungal biofilm and growth curves were also carried out. Morphological alterations of yeast cell surface were evaluated by scanning electron microscopy. A permeability assay verified the pore-forming ability of C14R. Results: C. albicans and C. auris isolates had a geometric mean MIC against C14R of 4.42 µg/ml and 5.34 µg/ml, respectively. Notably, none of the isolates of any species exhibited growth at the highest evaluated peptide concentration (200 µg/ml). Synergistic effects were observed when combining the peptide and fluconazole. C14R affects biofilm and growth of C. albicans and C. auris. Cell membrane disruptions were observed in both species after treatment with the peptide. It was confirmed that C14R form pores in C. albicans' membrane. Discussion: C14R has a potent antifungal activity against a large set of clinical isolates of both C. albicans and C. auris, showing its capacity to disrupt Candida membranes. This antifungal activity remains consistent across isolates regardless of their clinical source. Furthermore, the absence of correlation between MICs to C14R and resistance to fluconazole indicates the peptide's potential effectiveness against fluconazole-resistant strains. Our results suggest the potential of C14R, a pore-forming peptide, as a treatment option for fungal infections, such as invasive candidiasis, including fluconazole and amphotericin B -resistant strains.

Assuntos

Antifúngicos , Candidíase Invasiva , Candidíase , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Candida auris , Peptídeos/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica

RESUMO

Candida bloodstream infections in children are of special concern in neonatal and pediatric intensive care and patients with comorbidities. This study aimed to estimate the incidence and risk factors associated with mortality in candidemia cases occurring in a public children's hospital in Ribeirao Preto, Brazil. It is a retrospective transversal study. Every patient under the age of 18 admitted to the study facility from January 1, 2013, to December 31, 2019, was considered potentially eligible to be included if they had candidemia. We collected clinical data from medical records. We included 113 blood cultures yielding positive results for Candida. The incidence rate was 2.12 per 1000 admissions. The most common Candida species was Candida parapsilosis. Septic shock during the candidemia episode was the only clinical outcome associated with a relative risk-adjusted (RRa) of 2.77 with an interval >1 (1.12-6.85). Our findings show that the incidence rate and mortality rates of candidemia are in line with those in other children's services in Brazil. We found a global mortality rate of 28.31% (32/113) from candidemia episodes. We highlight the predominance of non-albicans Candida species including C. parapsilosis. Septic shock was the most important factor showing a significant risk of mortality.

Assuntos

Candidemia , Hospitais Pediátricos , Hospitais Públicos , Humanos , Candidemia/epidemiologia , Candidemia/mortalidade , Candidemia/microbiologia , Brasil/epidemiologia , Fatores de Risco , Estudos Retrospectivos , Pré-Escolar , Lactente , Criança , Masculino , Feminino , Incidência , Hospitais Públicos/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Estudos Transversais , Adolescente , Recém-Nascido , Choque Séptico/mortalidade , Choque Séptico/epidemiologia , Choque Séptico/microbiologia , Candida/isolamento & purificação

RESUMO

Candidemia is a significant cause of mortality among hospitalized patients, both worldwide and in Brazil. Prompt and appropriate treatment are essential to mitigate mortality, and clinical practice guidelines aim to optimize patient care based on the best scientific evidence. This study aims to examine the management of candidemia, assessing adherence to the guidelines of the Brazilian Society of Infectious Diseases in a single center located at São Paulo, Brazil. All adult patients hospitalized from 2016 to 2018 who presented one positive blood culture for Candida spp. were included. Electronic medical records were retrospectively reviewed to collect information relevant to the treatment for candidemia, in order to assess the adherence to the Brazilian guideline for the management of candidemia in relation to nine defined outcomes, and we correlated those findings with 30-day mortality by using uni- and multivariate analyses. A total of 115 patients were included; 68 patients (59.1%) were male, with a mean age of 55 years. C. albicans, C. tropicalis and C. glabrata were the most prevalent species. In total, 80 patients (69.5%) received antifungal treatment. The adherence to Brazilian guideline recommendations was determined as described in the following: initial treatment with echinocandin in 48 (60%); step-down to fluconazole in 21 (26.2%); collection of first control blood culture in 43 (58.9%); collection of second control blood culture, if the first one had been positive, in 14 (73.6%); treatment for 14 days after the first negative blood culture in 53 (65.4%); central venous catheter (CVC) removal in 66 (82.5%); CVC removal if the first control blood culture had been positive in 17 (89.4%); performance of a transthoracic echocardiogram in 51 (63.7%) and performance of a fundoscopy in 59 (73.7%). Univariate analysis showed that CVC removal and initial echinocandin therapy were more prevalent in the surviving group, but with no statistically significant difference. On the other hand, step-down to fluconazole demonstrated higher survival rate in the multivariate analysis OR 0.15 (95% CI 0.03-0.8); p = 0.02. The analysis of these nine recommendations demonstrates that it is necessary to improve adherence to specific recommendations and also disseminate strategies of the initial use of echinocandin as the drug of choice and addressing length of treatment and follow-up and complementary exams. Our study provides reassurance that the step-down to fluconazole is safe and may be recommended, if the preexisting conditions are present.

RESUMO

Introducción: La tasa de mortalidad de la candidemia es variable, pero puede estar influenciada por la patología de base, en especial aquella que condiciona la presencia de neutropenia. En niños con patología oncohematológica, son pocos los trabajos que han abordado la mortalidad relacionada a candidemias y sus factores asociados. Las preguntas que promueven esta revisión sistemática, son: ¿Cuáles son las características epidemiológicas, clínicas y de evolución de los pacientes pediátricos oncohematológicos con candidemia? ¿Cuál es la mortalidad relacionada con esta entidad? Materiales y métodos: Revisión sistemática de la literatura. Se utilizaron los siguientes términos de búsqueda: candidemia por Candida spp. y los siguientes filtros humanos, niños y adolescentes y patología oncohematológica. Se revisaron los artículos publicados en inglés, español o francés hasta el 21 de septiembre de 2023. Las referencias bibliográficas de los artículos incluidos se revisaron manualmente para identificar estudios relevantes adicionales. Resultados: Se encontraron 66 artículos. Del análisis cualitativo realizado en sus textos completos, quedaron finalmente 4 estudios que se consideró que cumplían con los criterios de inclusión. Todos los artículos seleccionados sumaron 191 pacientes con diversas patologías oncohematológicas. La presencia de accesos vasculares fue frecuente en esta serie y la no extracción del catéter venoso central fue el factor más prevalente entre los que fallecieron. El agente infectante predominante fue Candida no albicans y la mortalidad osciló entre el 11,3 y el 31% con una mediana de 25%. No fue posible establecer si la especie de Candida influía en la letalidad

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Introduction: The mortality rate of candidemia is variable, but may be influenced by underlying diseases, especially those causing neutropenia. In children with cancer and blood disorders, few studies have addressed mortality related to candidemia and its associated factors. The questions that motivated this systematic review were: What are the epidemiological, clinical and outcome characteristics of pediatric cancer patients with candidemia? What is the mortality related to this condition? Materials and methods: Systematic review of the literature. The following search terms were used: Candida spp., candidemia, with the following filters: human, children and adolescents, and cancer and blood disorders. Articles published in English, Spanish, or French up to September 21, 2023 were reviewed. References of included articles were manually reviewed to identify additional relevant studies. Results: 66 articles were identified. From the qualitative analysis carried out on their full texts, 4 studies that were considered to meet the inclusion criteria were finally selected. The selected articles included a total of 191 patients with various types of cancer and blood disorders. The presence of vascular access was common in this series and failure to remove the central venous catheter was the most prevalent factor among those who died. The predominant infectious agent was non-albicans Candida and mortality ranged from 11.3% to 31% with a median of 25%. It was not possible to establish whether Candida species influenced mortality.

Assuntos

Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Leucemia/complicações , Fatores de Risco , Mortalidade Hospitalar , Candidemia/microbiologia , Candidemia/mortalidade , Neoplasias/complicações , Hospedeiro Imunocomprometido , Antifúngicos/uso terapêutico

RESUMO

BACKGROUND: The natural history of candidemia in kidney transplant recipients (KTR) remains poorly understood. This study aimed to evaluate mortality, prognostic factors and overall graft loss after candidemia in KTRs. METHODS: This is a retrospective multicentre study enrolling all KTRs ≥15 years old with candidemia diagnosed at hospitals in Brazil, Spain and Italy from 2010 to 2020. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors of 14-day mortality and overall graft loss. RESULTS: We enrolled 93 KTRs of which 75 were from Brazil. The mean time interval from transplantation to the onset of candidemia was 45.2 ± 61.5 months. 42% of all patients were on haemodialysis, 31.3% had an episode of sepsis and 39% underwent surgery within 30 days before fungemia. European patients were more likely to receive echinocandin (32 vs. 72%, p < .001). 22.7% of Brazilian patients did not receive any antifungal before death. All-cause mortality at 14 days was higher in Brazil (41.3 vs. 11.1%, p = .016). Candida colonisation (OR 6.91 [95% CI: 1.08-44.3], p = .042) and hypotension (OR 4.87 [95% CI: 1.62-14.66], p = .005) were associated with 14-day mortality. Echinocandin treatment had a protective effect (OR 0.19 [95% CI: 0.05-0.73], p = .015). Graft loss at 90 days occurred in 48% of patients (70.7 in Brazil vs. 22.2% in Europe, p < .01). CONCLUSIONS: Candidemia in KTR is usually documented late after engraftment in patients requiring HD, surgical procedures and dysbiosis secondary to antibiotic use. Mortality was higher in Brazil. Echinocandin therapy was associated with improved survival.

Assuntos

Candidemia , Transplante de Rim , Adolescente , Humanos , Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Equinocandinas/uso terapêutico , Transplante de Rim/efeitos adversos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto

RESUMO

BACKGROUND: Infections are a major cause of morbidity and mortality in patients with pemphigus vulgaris (PV). One of the most common infections in these patients is candidiasis. This is probably due to the use of systemic immunosuppressants, including oral and intravenous corticosteroids, mainly in megadoses (pulse therapy), although it is unknown if there are other associated factors, in addition to immunosuppressive treatment. We determine the factors associated with candidiasis in PV patients in two second-care level hospitals in Mexico. METHODS: We reviewed 100 cases with PV. Cases were randomly selected from the databases of two second-care level hospitals between January 2010 and December 2019 (10 years). The primary endpoint was the incidence of candidiasis in patients with PV. RESULTS: One hundred patients with PV were enrolled in this retrospective study. Candidiasis was observed in 79 patients (79%). A maximum corticosteroid dose of 55 mg/day during the last year (p = 0.001) and a higher neutrophil/lymphocyte ratio were associated with candidiasis in patients with PV (p = 0.001). CONCLUSION: Risk factors favoring candidiasis in patients with PV are not only related to the use of corticosteroids, but also to demographic factors, the activity of the disease, and the systemic inflammation associated with autoimmunity.

RESUMO

Candida albicans, a ubiquitous opportunistic fungal pathogen, plays a pivotal role in human health and disease. As a commensal organism, it normally resides harmlessly within the human microbiota. However, under certain conditions, C. albicans can transition into a pathogenic state, leading to various infections collectively known as candidiasis. With the increasing prevalence of immunocompromised individuals and the widespread use of invasive medical procedures, candidiasis has become a significant public health concern. The emergence of drug-resistant strains further complicates treatment options, highlighting the urgent need for alternative therapeutic strategies. Antifungal peptides (AFPs) have gained considerable attention as potential candidates for combating Candida spp. infections. These naturally occurring peptides possess broad-spectrum antimicrobial activity, including specific efficacy against C. albicans. AFPs exhibit several advantageous properties, such as rapid killing kinetics, low propensity for resistance development, and diverse mechanisms of action, making them promising alternatives to conventional antifungal agents. In recent years, extensive research has focused on discovering and developing novel AFPs with improved efficacy and selectivity against Candida species. Advances in biotechnology and synthetic peptide design have enabled the modification and optimization of natural peptides, enhancing their stability, bioavailability, and therapeutic potential. Nevertheless, several challenges must be addressed before AFPs can be widely implemented in clinical practice. These include optimizing peptide stability, enhancing delivery methods, overcoming potential toxicity concerns, and conducting comprehensive preclinical and clinical studies. This commentary presents a short overview of candidemia and AFP; articles and reviews published in the last 10 years were searched on The National Library of Medicine (National Center for Biotechnology Information-NIH-PubMed). The terms used were C. albicans infections, antimicrobial peptides, antifungal peptides, antifungal peptides mechanisms of action, candidemia treatments and guidelines, synthetic peptides and their challenges, and antimicrobial peptides in clinical trials as the main ones. Older publications were cited if they brought some relevant concept or helped to bring a perspective into our narrative. Articles older than 20 years and those that appeared in PubMed but did not match our goal to bring updated information about using antifungal peptides as an alternative to C. albicans infections were not considered.