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Objectives To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients. Methods Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed. Results MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24–2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea. Conclusions DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.

Candidemia remains a major public health challenge due to its high mortality rates, especially in developing countries. Monitoring epidemiological trends may provide insights for better clinical outcomes. This study aimed to describe trends in the epidemiology, therapeutic practices, and mortality in candidemia through a retrospective comparative analysis between two surveillance cohorts of all candidemic adults at eleven tertiary hospitals in Brazil, from 2010–2011 (Period I) versus 2017–2018 (Period II). A total of 616 cases were diagnosed, with 247 being from Period II. These patients were more likely to have three or more coexisting comorbidities [72 (29.1%) vs. 60 (16.3%), p < 0.001], had a prior history of in-hospital admissions more often [102 (40.3%) vs. 79 (21.4%), p = 0.001], and presented with candidemia earlier after admission, within 15 days (0–328) vs. 19 (0–188), p = 0.01. Echinocandins were more frequently prescribed [102 (41.3%) vs. 50 (13.6%), p = 0.001], but time to antifungal initiation [2 days (0–14) vs. 2 (0–13), p = 0.369] and CVC removal within 48 h [90/185 (48.6%) vs. 148/319 (46.4%), p = 0.644] remained unchanged. Additionally, many patients went untreated in both periods I and II [87 (23.6%) vs. 43 (17.4%), p = 0.07], respectively. Unfortunately, no improvements in mortality rates at 14 days [123 (33.6%) vs. 93 (37.7%), p = 0.343] or at 30 days [188 (51.4%) vs. 120 (48.6%), p = 0.511] were observed. In conclusion, mortality rates remain exceedingly high despite therapeutic advances, probably associated with an increase in patients’ complexity and suboptimal therapeutic interventions. Management strategies should be tailored to suit epidemiological changes, expedite diagnosis to reduce the number of untreated eligible patients and guarantee early antifungal initiation and source control.

As neutropenic patients with haematological cancer are not typically included in randomized controlled trials (RCTs) of candidaemia, there is low quality of evidence regarding the management of this common opportunistic mycosis in this patient population, which is at high risk for poor outcomes. Herein we identify the gaps in knowledge that are not addressed by the modern RCTs and candidaemia guidelines, and outline some considerations for the future clinical research agenda in candidaemia/invasive candidiasis in haematological patients.

Background The clinical relevance and the potential prognostic role of persistently negative (1,3)-β-D-glucan (BDG) in adults with proven candidemia is unknown. Methods This retrospective study included all adults diagnosed with candidemia our tertiary university hospital from 2012–2017 who had at least 2 serum BDG determinations throughout the episode of fungemia (Fungitell Assay; positive cut-off ≥80pg/mL). Epidemiology and clinical outcomes were compared between patients with all negative versus any positive BDG tests. Poor clinical outcomes included complications due to candidemia or 30-day all-cause mortality. Results Overall, 26/148 (17.6%) candidemic adults had persistently negative BDG tests. These patients were less likely to present Candida growth in all 3 sets of blood cultures (15.4% vs 45.1%; P = .005) and had less severe clinical presentations (median Pitt score, 0 [interquartile range {IQR} 0–1] vs 1 [IQR 0–2] in patients with any positive BDG test; P = .039). Although adequate treatment was equally provided to both groups (96.2% in persistently negative group vs 93.4 in positive group; P = .599), the persistently negative group had a higher rate of microbiological clearance in the first follow-up blood cultures (92.3% vs 69.7% in positive group; P = .005), fewer complications due to candidemia (7.7% vs 33.6% in positive group; P = .008), a lower 30-day mortality rate (3.8% vs 23.8% in positive group; P = .004), and a shorter in-hospital stay (34 days [IQR 18–55] vs 51 days [IQR 35–91] in positive group; P = .003). In the multivariate analysis, persistently negative BDG tests were independently associated with better prognoses (odds ratio 0.12, 95% confidence interval 0.03–0.49; P = .003). Conclusions Candidemic patients with persistently negative BDG tests present a better prognosis than the comparative group, probably due to a lower systemic fungal burden. In this context, the appropriate use of persistently negative BDG results could be an aid to individualize therapeutic management in the near future.

Summary: Background: Mortality rates among adults with candidemia vary widely in different geographical settings. Studies directly comparing epidemiology and clinical practices between countries are scarce and could bring insights into improving clinical outcomes. Methods: Retrospective cohort including adults with candidemia diagnosed in five tertiary hospitals from Brazil and Spain between 2010-2018. Adequate therapeutic management included appropriate antifungal therapy and central-venous-catheter (CVC) removal within 48 h of fungemia. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors associated with 30-day mortality. Findings: Overall, 720 patients were included, being 323 from Spain. Spanish patients received echinocandins more often (52·5% vs. 39·3%, p = 0.001), initiated antifungals earlier [2 (0-7) vs. 2 days (0-16), p1 [OR 2·56, 95%CI (1·776-3·690), p

Objectives The role of biofilm production in the outcome of candidaemia remains under discussion. Current evidence relies on variable biofilm detection methods while evaluating distinct clinical end points. We aimed to determine the impact of biofilm production measured by metabolic activity (MA) and biomass (BM) on the prognosis of adults with candidaemia. Methods Retrospective cohort including 280 adults with candidaemia admitted from 2010 to 2016. BM was assessed using crystal violet binding stain and the XTT reduction assay was used to detect MA. Strains were classified as high and moderate-low biofilm producers according to published cut-offs. The primary outcome was overall mortality within 7 and 30 days. The secondary outcome was unfavourable prognosis defined as metastatic infection, admission to an intensive care unit due to the severity of candidaemia, or death within 30 days. Results High BM and high MA were detected in 90 (32.1%) and 114 (40.7%) of the 280 isolates, respectively. Comparison of high and moderate-low biofilm forming isolates revealed no correlation between biofilm production and 7-day mortality (BM high 15/90 (16.7%) versus moderate-low 24/190 (12.6%); MA high 12/114 (10.5%) versus moderate-low 27/166 (16.3%)), 30-day mortality (BM high 34/90 (37.8%) versus moderate-low 61/190 (32.1%); MA high 33/114 (28.9%) versus moderate-low 62/166 (37.3%)), or unfavourable prognosis (BM high 45/90 (50.0%) versus moderate-low 73/190 (38.4%); MA high 41/114 (36.0%) versus moderate-low 77/166 (46.4%)). Conclusions Biofilm production was not a predictor of mortality or of unfavourable prognosis in adults with candidaemia.

We report the first case of disseminated infection by Gymnascella hyalinospora in a solid organ transplant recipient. This case highlights the role of low-virulence environmental molds as an emerging cause of breakthrough invasive fungal infection in immunocompromised hosts. Nosocomial strategies of infection control including antimicrobial stewardship and advances on fast diagnostic methods are strongly encouraged to improve patient prognosis.

The high rates of antifungal resistance in Candida glabrata may be facilitated by the presence of alterations in the MSH2 gene. We aimed to study the sequence of the MSH2 gene in 124 invasive C. glabrata isolates causing incident episodes of candidemia (n = 81), subsequent candidemia episodes (n = 9), endocarditis (n = 2), and in vitro-generated echinocandin-resistant isolates (n = 32) and assessed its relationship with genotypes, acquisition of antifungal resistance in vivo and in vitro, and patient prognosis. The MSH2 gene was sequenced, and isolates were genotyped using six microsatellite markers and multilocus sequence typing (MLST) based on six housekeeping genes. According to EUCAST, isolates causing candidemia (n = 90) were echinocandin susceptible, and four of them were fluconazole resistant (MIC ≥64 mg/liter). One isolate obtained from a heart valve was resistant to micafungin and anidulafungin (MICs, 2 mg/liter and 1 mg/liter, respectively). MSH2 gene mutations were present in 44.4% of the incident isolates, the most common being V239L. The presence of MSH2 mutations was not correlated with in vitro or in vivo antifungal resistance. Microsatellite and MLST revealed 27 genotypes and 17 sequence types, respectively. Fluconazole-resistant isolates were unrelated. Most MSH2 mutations were found in cluster isolates; conversely, some mutations were found in more than one genotype. No clinical differences, including previous antifungal use, were found between patients infected by wild-type MSH2 gene isolates and isolates with any point mutation. The presence of MSH2 gene mutations in C. glabrata isolates causing candidemia is not correlated with specific genotypes, the promotion of antifungal resistance, or the clinical outcome.

To evaluate the secular trend of menarche according to body mass index (BMI).Six hundred and eighty five girls (7-18 years) assessed in 2001 were compared with 750 evaluated in 2010. They were grouped by BMI Z-score: (thin + normal) and (overweight + obese). Menarche was reported by status quo and age at menarche estimated by a logit model. We used the Qui-square test, Mann-Whitney test, and Logistic Regression, at a 5% significance level.Menarche advanced 3.24 months. There was an increase in obesity, and a decrease of the prevalence of normal girls. Menarche was anticipated by 1.44 month in the thin + normal group and by 5.76 months in the overweight + obese group. There was no interaction between the effects determined by the evaluated period and nutritional diagnosis.Although both the period and BMI influence the menarche, one cannot attribute this advance only to changes in the nutritional profile of the sample. Other factors that were not tested may also contribute to this finding.