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There is worldwide concern with the increasing rates of infections due to multiresistant Candida isolates reported in tertiary medical centers. We checked for historical trends in terms of prevalence rates and antifungal susceptibility of the Candida haemulonii species complex in our yeast stock culture collected during the last 11 years. The isolates were identified by sequencing the rDNA internal transcribed spacer (ITS) region, and antifungal susceptibility tests for amphotericin B, voriconazole, fluconazole, anidulafungin, and 5-fluorocytosine were performed by the Clinical and Laboratory Standards Institute (CLSI) microbroth method. A total of 49 isolates were identified as Candida haemulonii sensu stricto (n = 21), followed by C. haemulonii var. vulnera (n = 15) and C. duobushaemulonii (n = 13), including 38 isolates cultured from patients with deep-seated Candida infections. The prevalence of the C. haemulonii species complex increased from 0.9% (18 isolates among 1931) in the first period (December 2008 to June 2013) to 1.7% (31 isolates among 1868) in the second period (July 2014 to December 2019) of analysis (p = 0.047). All isolates tested exhibited high minimum inhibition concentrations for amphotericin B and fluconazole, but they remained susceptible to 5-fluorocytosine and anidulafungin. We were able to demonstrate the increased isolation of the multiresistant Candida haemulonii species complex in our culture collection, where most isolates were cultured from patients with deep-seated infections.

We describe the rate of incidence of Clostridium difficile-associated diarrhea (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC-FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and 1,000 days of neutropenia and the risk factors associated with the severe form of the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the detections of toxins A/B was used to identify C. difficile. A multivariate analysis was performed to evaluate potential factors associated with severe CDAD and death within 14 days after the diagnosis of CDAD, using multiple logistic regression. Sixty-six episodes were identified in 64 patients among 439 patients with diarrhea during the study period. CDA rate of incidence varied from 0.78 to 5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days. The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64 (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64 (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of the patients (89%) received treatment with oral metronidazole and 19/64 (26%) died. The independent risk factors associated with death were the severe form of CDAD, and use of linezolid. Descrevemos a taxa de incidência de diarreia associada a Clostridium difficile (CDAD) em pacientes hematológicos e submetidos a transplante de células-tronco hematopoiéticas (TCTH) internados no HC-FMUSP no período de janeiro de 2007 a junho de 2011 usando dois denominadores 1.000 paciente e 1.000 dias de neutropenia e os fatores de risco associados à forma grave da doença e morte. O método de ELISA (Ridascreen-Biopharm, Germany) de detecção de toxinas A/B foi utilizado para o diagnóstico de C. difficile. Análise multivariada usando regressão logística múltipla foi conduzida para avaliar os potenciais fatores de risco associados com forma grave de CDAD e morte em até 14 dias do diagnóstico. Sessenta e seis episódios foram identificados em 64 pacientes entre 439 pacientes que apresentaram diarreia durante o período do estudo. A taxa de incidência de CDAD variou de 0,78 a 5,45 por 1.000 dias de neutropenia e de 0,65 para 5,45 por 1.000 pacientes-dias. A doença de base mais comum foi leucemia mielóide aguda 30/64(44%), 32/64 (46%) pacientes estavam neutropênicos, 31/64 (45%) foram submetidos à TCTH alogênico, 61/64 (88%) usaram antibióticos previamente e 9/64 (13%) apresentaram forma grave da doença. A maioria dos pacientes (89%) utilizou metronidazol oral no tratamento da CDAD e 19/64 (26%) evoluiram para óbito. Os fatores de risco independentes associados à morte foram forma grave da doença e uso de linezolida.

Candida parapsilosis produces biofilm, which colonizes catheters and other invasive medical devices that are manipulated by health care workers. In previous studies, C. parapsilosis in vitro biofilms have exhibited high resistance rates against conventional antifungals, but susceptibility to both echinocandins and lipid formulations of amphotericin B (lipid complex and liposomal). However, a recent study showed good activity of amphotericin B deoxycholate on the biomass of C. parapsilosis biofilms. Although moderate activity of echinocandins has been demonstrated against low metabolic activity biofilms of C. parapsilosis, few studies have analyzed the action of these drugs on high metabolic activity biofilms. Moreover, high biofilm-forming isolates have been associated with central venous catheter-related fungemia outbreaks and higher mortality rates. Therefore, it is relevant to verify the activity of the main antifungal drugs against high metabolic activity biofilms of C. parapsilosis. Our study aimed to evaluate the in vitro activity of amphotericin B deoxycholate, anidulafungin, caspofungin, and micafungin against high biofilm-forming and high metabolic activity clinical isolates of C. parapsilosis. Our results showed good activity of amphotericin B against C. parapsilosis biofilms, but none of the echinocandin drugs was effective. This suggests that amphotericin B deoxycholate may be a better choice than echinocandins for the treatment of biofilm-associated infections by C. parapsilosis, mainly in countries with insufficient health care resources to purchase lipid formulations of amphotericin B. These results warn of the possibility of persistent catheter-related candidemia caused by high biofilm-forming C. parapsilosis strains when treated with echinocandin drugs.

Candidemia is one of the healthcare-associated infections that has high mortality. The risk factors that predispose a patient to develop this infection are mostly found in patients of greater severity and COVID-19 contributes to the risk of death. The aim of this study is to evaluate epidemiological characteristics and risk factors for mortality in patients with candidemia before and during the COVID-19 pandemic era. This is a retrospective study conducted at Instituto Central from 2016 to 2020 of patients with candidemia that were evaluated for demographic data, medical history, risk factors, microbiological data, therapeutic measures, complementary exams, device management, and outcome defined by 30-day mortality. A total of 170 episodes were included (58.2% males; mean age of 56 years). The overall incidence density of candidemia per 1000 admissions and per 1000 patient-days was 1.17 and 0.17, respectively, with an increase of 38% in the year 2020. The use of a central venous catheter was the most prevalent (93.5%) condition, followed by the previous use of antibiotics (91.1%). Corticosteroid use ranked seventh (56.4%). C. albicans was responsible for 71 (41.7%) of the isolates, followed by C. tropicalis and C. glabrata, with 34 (20%) isolates each. Echinocandin was prescribed in 60.1% of cases and fluconazole in 37%. Echocardiography resulted in six (5.08%) cases of endocarditis and fundoscopy resulting in two (2.4%) endophthalmitis. The 30-day mortality was 93/170 (54.7%). The risk factors associated with mortality were age (OR 1.03, CI 95% 1.01–1.06), heart disease (OR 7.51, CI 95% 1.48–37.9), hemodialysis (OR 3.68, CI 95% 1.28–10.57), and use of corticosteroids (OR 2.83, CI 95% 1.01–7.92). The COVID-19 pandemic had an impact on the increase incidence of candidemia. The persistently high mortality highlights the need for better management strategies, control of risk factors, and guarantee of adequate treatment.

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.

Background Acute post-cataract endophthalmitis (APE) is a rare complication potentially causing irreversible visual loss. A 10-year study of APE was conducted to determine its incidence, microbiological spectra and antibiotic resistance profile of APE-related pathogens at a major tertiary referral center in Brazil. Methods APE cases reported between January 2010 and December 2019 were included. Phacoemulsification and extracapsular cataract techniques were eligible; combined procedures, traumatic and congenital cataract were excluded. Vitreous samples were cultured and antimicrobial resistance was compared for the periods of 2010–2014 and 2015–2019. The results were analyzed with Fisher’s exact test. Results Our sample consisted of 40,491 cataract surgeries and 51 (0.126%) APE cases. Culture was positive in 35 cases (71.4%), of which 31 (88.6%) Gram-positive, 3 (8.6%) Gram-negative, and 1 (2.9%) fungal. The most frequently isolated organism was Staphylococcus epidermidis (n = 17/35, 48.6%), followed by Staphylococcus aureus (n = 4/35, 11.4%). From 2010–2014 to 2015–2019, antimicrobial resistance increased against moxifloxacin (11.1–54.5%, p  = 0.07), ciprofloxacin (54.5–72.7%, p  = 0.659) and oxacillin (66.7–93.3%, p  = 0.13). Conclusions The observed incidence and microbial spectra were compatible with previous studies. A trend towards growing moxifloxacin and ciprofloxacin resistance was observed. Surveillance remains crucial to prevent treatment failure from antimicrobial resistance.

ABSTRACT Invasive fusariosis (IF) is an exceptionally severe disease, particularly affecting patients with prolonged neutropenia. Even with antifungal therapy, mortality rates remain high, emphasizing the need for stringent control over hospital environment and further research to enhance patient outcomes. This study aims to assess the antifungal susceptibility of clinical and environmental Fusarium isolates and their clinical relevance in a cancer hospital. Sixteen environmental and 21 clinical isolates were identified, with the Fusarium solani species complex being the most common. Amphotericin B demonstrated in vitro activity, but most isolates exhibited elevated minimum inhibitory concentrations (MICs) for azoles. A total of 80% of patients had IF, primarily those with hematological malignancies, and the 30-day mortality rate was 43.8%. Isolates with elevated MICs were often managed with combination therapy. In conclusion, elevated azole MICs may lead to increased use of combination therapy in real-world clinical settings. Our findings emphasize the importance of careful interpretation of antifungal susceptibility testing results in IF management.

Purpose Rare yeasts species are increasingly reported as causative agents of invasive human infection. Proper identification and antifungal therapy are essential to manage these infections. Candida blankii is one of these emerging pathogens and is known for its reduced susceptibility to multiple antifungals. Methods To obtain more insight into the characteristics of this species, 26 isolates reported as C. blankii were investigated using genetic and phenotypical approaches. Results Among the 26 isolates, seven recovered either from blood, sputum, urine, or the oral cavity, displayed substantial genetic and some phenotypical differences compared to the other isolates, which were confirmed as C. blankii . We consider these seven strains to represent a novel species, Tardiomyces depauwii . Phylogenomics assigned C. blankii, C. digboiensis, and the novel species in a distinct branch within the order Dipodascales , for which the novel genus Tardiomyces is erected. The new combinations Tardiomyces blankii and Tardiomyces digboiensis are introduced. Differences with related, strictly environmental genera Sugiyamaella, Crinitomyces, and Diddensiella are enumerated. All three Tardiomyces species share the rare ability to grow up to 42 °C, display slower growth in nutrient-poor media, and show a reduced susceptibility to azoles and echinocandins. Characteristics of T. depauwii include high MIC values with voriconazole and a unique protein pattern. Conclusion We propose the novel yeast species Tardiomyces depauwii and the transfer of C. blankii and C. digboiensis to the novel Tardiomyces genus.

Candidemia infection remains a critical challenge in intensive care units (ICUs), with high morbidity and mortality rates despite advances in therapeutic practices. This multicenter prospective surveillance study assessed the epidemiology, clinical management, and mortality predictors of candidemia in critically ill patients across two periods (2010–2012 and 2017–2018) in 11 tertiary hospitals in Brazil. Among 314 ICU patients with candidemia, the overall mortality rate was 60.2%, with no significant reduction over time (58.8% vs. 62.6%, p = 0.721). Candida albicans was the predominant pathogen (43.6%), followed by C. tropicalis (20%) and C. glabrata (13.7%). The use of echinocandins increased significantly in the second period (21.1% to 41.7%, p < 0.001); however, 70% of patients still did not receive these agents as first-line therapy. Catheter removal due to candidemia was performed in only 52.1% of cases but was associated with improved 30-day survival (p < 0.001). Multivariate analysis identified cancer, inadequate treatment, and vasoactive drug use as independent predictors of mortality. Our findings underscore persistent gaps in adherence to guidelines, particularly regarding timely echinocandin initiation and catheter removal. Strengthening therapeutic strategies focused on these key interventions is essential to improving outcomes for ICU patients with candidemia.

Invasive fusariosis (IF) is a life-threatening opportunistic infection that affects vulnerable hosts. We conducted a multicenter and multinational retrospective study to characterize the natural history and clinical management of IF in pediatric cancer patients. We selected patients <18 years old who were sequentially hospitalized in 10 Latin American medical centers with a diagnosis of IF between 2002 and 2021. Data were collected using an electronic case report form complemented by a dictionary of terms. We assessed mortality rates at 30, 60, and 90 days. We collected data from 60 episodes of IF (median age, 9.8 years) that were mostly documented in patients with hematologic cancer (70%). Other risk conditions found were lymphopenia (80%), neutropenia (76.7%), and corticosteroid exposure (63.3%). IF was disseminated in 55.6% of patients. Skin lesions was present in 58.3% of our patients, followed by pulmonary involvement in 55%, sinusitis in 21.7%, bone/joint involvement in 6.7% and 1 case each of endocarditis and brain abscess. Positive blood and skin biopsy cultures were detected in 60% and 48.3% of cases, respectively. Fusarium solani complex was the most commonly identified agent (66.6%). The majority of patients received monotherapy within the first 72 hours (71.6%), either with voriconazole or amphotericin B formulation. The mortality rates at 30, 60, and 90 days were 35%, 41.6%, and 45%, respectively. An important factor affecting mortality rates appears to be disseminated disease. The high percentage of patients with fungal involvement in multiple organs and systems highlights the need for extensive workup for additional sites of infection in severely immunocompromised children.