Background The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. Methods A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). Results During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02–1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31–8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04–1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24–3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. Conclusions The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Candida spp. are an increasing cause of bloodstream infections, and are associated with high morbidity and mortality in both neutropenic and non-neutropenic critically ill patients. Risk factors associated with candidaemia are diverse and include exposure to broad spectrum antimicrobial agents, mucosal colonization by Candida spp., indwelling vascular catheters, prior surgery and cancer chemotherapy. During the last 20 years, there has been an increasing incidence worldwide in invasive candidiasis, but differences in geographical epidemiology are emerging, in particular regarding a shift towards non-albicans species. This shift has been correlated with routine fluconazole prophylaxis adopted in some patients, and the intrinsic/acquired azole resistance of Candida spp., which represents a very real problem, in terms of both selecting the appropriate empirical therapeutic approach and making prophylactic choices.

Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking.

Biomarkers to guide antibiotic treatment decisions have been proposed as an effective way to enhancing a more appropriate use of antibiotics. As a biomarker, procalcitonin (PCT) has been found to have good specificity to distinguish bacterial from non-bacterial inflammations. Decisions regarding antibiotic use in an individual patient are complex and should be based on the pre-test probability for bacterial infection, the severity of presentation and the results of PCT serum concentration. In the context of a high pre-test probability for bacterial infections and/or a high-risk patient with sepsis, monitoring of PCT over time helps to track the resolution of infection and decisions regarding early stop of antibiotic treatment. As outlined by the Evidence Based Laboratory Medicine (EBLM), not only the pre-test probability but also the positive likelihood ratio influence the performance of a test do be really diagnostic. This aspect should be taken into account in the interpretation of the results of clinical trials evaluating the performance of PCT in guiding antibiotic therapy.

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Introduction: New fungal species are increasingly reported in immunocompromised patients. Saprochaete clavata (S. clavata), an ascomycetous fungus formerly called Geotrichum clavatum, is intrinsically resistant to echinocandins and is often misidentified.Objective: We describe a cluster of seven S. clavata infections in hospitalized hematology patients who developed this rare fungemia within a span of 11 months. Three of the seven patients died. Identification of the isolates was determined only with the Saramis database of VitekMS system and sequencing of the internal transcribed spacer (ITS) region. Clonal relatedness of the isolates was determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) analysis; clonal correlation between the strains was investigated by means of phylogenetic analysis, based on single-nucleotide variants (SNPs). Clinical presentation, 1-3 β-Dglucan (BG) and galactomannan (GM) antigen results and analysis of possible sources of contamination are also described with a prospective case-control study of the outbreak.Results: MALDI-TOF MS-Vitek (bioMerieux, Marcy l'Etoile, France) failed to identify the six isolates, while SARAMIS (bioMerieux, Marcy l'Etoile, France) identified the isolates as S. clavata. Initially, Vitek 2 identified the strains as Geotrichum capitatum in two of the seven cases. Molecular identification gave 99% homology with S. clavata. BG was positive in three out of six patients (range 159 to >523 pg/ml), GM results were always negative. All the isolates were resistant to echinocandins (anidulafungin, micafungin, and caspofungin) and Fluconazole, but susceptible to Flucytosine and Voriconazole. One isolate showed acquired resistance to Flucytosine and Amphotericin Frontiers in Microbiology | www.frontiersin.org 1 January 2020 | Volume 11 | Article 84Lo Cascio et al.Saprochaete clavata Outbreak Investigation Strategy B during treatment. Both the correlation-based dendrograms obtained by MALDI-TOF MS (Bruker Daltonics) and MS-Vitek not only clustered six of the seven bloodstream infection (BSI) isolates in the same group, but also showed their strong relatedness. Phylogenetic analysis using SNPrelate showed that the seven samples recorded during the investigation period clustered together. We observed a split between one case and the remainder with a node supported by a z-score of 2.3 (p-value = 0.021) and 16 mutations unique to each branch.Conclusion: The use of proteomics for identification and evaluation of strain clonality in outbreaks of rare pathogens is a promising alternative to laborious and time-consuming molecular methods, even if molecular whole-genome sequencing (WGS) typing will still remain the reference method for rare emergent pathogens.

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Objectives To assess the association between country income status and national prevalence of invasive infections caused by the top-ranked bacteria on the WHO priority list: carbapenem-resistant (CR) Acinetobacter spp., Klebsiella spp. and Pseudomonas aeruginosa; third-generation cephalosporin-resistant (3GCR) Escherichia coli and Klebsiella spp.; and MRSA and vancomycin-resistant Enterococcus faecium (VR E. faecium). Methods Active surveillance systems providing yearly prevalence data from 2012 onwards for the selected bacteria were included. The gross national income (GNI) per capita was used as the indicator for income status of each country and was log transformed to account for non-linearity. The association between antibiotic prevalence data and GNI per capita was investigated individually for each bacterium through linear regression. Results Surveillance data were available from 67 countries: 38 (57%) were high income, 16 (24%) upper-middle income, 11 (16%) lower-middle income and two (3%) low income countries. The regression showed significant inverse association (P<0.0001) between resistance prevalence of invasive infections and GNI per capita. The highest rate of increase per unit decrease in log GNI per capita was observed in 3GCR Klebsiella spp. (22.5%, 95% CI 18.2%–26.7%), CR Acinetobacter spp. (19.2% 95% CI 11.3%–27.1%) and 3GCR E. coli (15.3%, 95% CI 11.6%–19.1%). The rate of increase per unit decrease in log GNI per capita was lower in MRSA (9.5%, 95% CI 5.2%–13.7%). Conclusions The prevalence of invasive infections caused by the WHO top-ranked antibiotic-resistant bacteria is inversely associated with GNI per capita at the global level. Public health interventions designed to limit the burden of antimicrobial resistance should also consider determinants of poverty and inequality, especially in lower-middle income and low income countries.