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Purpose Risk factors for nosocomial candidemia, severity of sepsis, treatment, and outcome were compared between patients admitted to medicine wards and those to surgical and intensive care units (ICUs). Methods Data were retrospectively collected from patients belonging to six referral hospitals in Italy between January 2011 and December 2013. Risk factors for 30-day mortality were evaluated in the whole patient population. Results A total of 686 patients (mean age 70 ± 15 years) with candidemia were included. 367 (53.5 %) patients were in medicine wards, and 319 in surgery and ICUs. Host-related risk factors for candidemia were more common in medicine patients whereas healthcare-related factors in surgery/ICU patients. These patients showed severe sepsis and septic shock more commonly (71.7 %) than medicine patients (59.9 %) ( p 0.003). The latter underwent central venous catheter (CVC) removal and adequate antifungal therapy less frequently than surgery/ICU patients. 149 (40.6 %) patients died with candidemia in medicine wards and 69 (21.6 %) in other wards ( p  < 0.001). Overall, the 30-day mortality was 36.3 %. At multivariate analysis, independent risk factors for death were aging, higher Charlson score, severe sepsis and septic shock, and no antifungal therapy, while major surgery and CVC removal were associated with higher probability of survival. Conclusions The burden of risk factors for candidemia was different between medicine patients and those in other wards. Despite the lower severity of candidemia in medicine patients, their mortality turned out to be higher than in surgery or ICU patients. Awareness of the best management of candidemia should be pursued, especially in medicine wards.

Micafungin was shown to be as efficacious as caspofungin in treating patients with candidaemia and invasive candidiasis (IC). However, it remains unknown if micafungin or caspofungin is a cost-effective definitive therapy for candidaemia and IC in Turkey. The present study aimed to determine the economic impact of using micafungin versus caspofungin for treatment of candidaemia and IC in the Turkish setting. A decision analytic model was constructed and was populated with data (i.e. transition probabilities, duration of initial antifungal treatment, reasons for treatment failure, percentage of patients who stepped down to oral fluconazole, and duration on oral fluconazole) obtained from a published randomised clinical trial. Cost inputs were derived from the latest Turkish resources while data that were not readily available in the literature were estimated by expert panels. One-way sensitivity analyses, threshold analyses, scenario analyses and probabilistic sensitivity analyses were conducted. Caspofungin (€2693) incurred a lower total cost than micafungin (€4422), with a net cost saving of €1729 per treated patient. Drug acquisition cost was the main cost driver for both study arms. The model outcome was robust over wide variations (of ±100.0% from the base case value) for all input parameters except for micafungin drug cost and the duration of initial treatment with micafungin. Caspofungin appears to be a cost-saving option in treating candidaemia and IC from the Turkish hospital perspective.

The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes. In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines. 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04–1·11; p<0·0001] in patients with a central venous catheter and 1·09 [1·05–1·13; p<0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4–30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals. Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay. Scynexis.

Background. Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. Methods. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). Results. Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. Conclusions. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

Representatives of the Candida parapsilosis complex are important yeast species causing human infections, including candidaemia as one of the leading diseases. This complex comprises C. parapsilosis, Candida orthopsilosis and Candida metapsilosis, and causes a wide range of clinical presentations from colonization to superficial and disseminated infections with a high prevalence in preterm-born infants and the potential to cause outbreaks in hospital settings. Compared with other Candida species, the C. parapsilosis complex shows high minimal inhibitory concentrations for echinocandin drugs due to a naturally occurring FKS1 polymorphism. The emergence of clonal outbreaks of strains with resistance to commonly used antifungals, such as fluconazole, is causing concern. In this Review, we present the latest medical data covering epidemiology, diagnosis, resistance and current treatment approaches for the C. parapsilosis complex. We describe its main clinical manifestations in adults and children and highlight new treatment options. We compare the three sister species, examining key elements of microbiology and clinical characteristics, including the population at risk, disease manifestation and colonization status. Finally, we provide a comprehensive resource for clinicians and researchers focusing on Candida species infections and the C. parapsilosis complex, aiming to bridge the emerging translational knowledge and future therapeutic challenges associated with this human pathogen.In this Review, Lass-Flörl and Govrins explore the epidemiology, clinical manifestations and antifungal resistance of the Candida parapsilosis complex, and discuss diagnostics and new treatment approaches to tackle infections by these human pathogens.

Invasive candidiasis is an important fungal disease caused by Candida albicans and, increasingly, non- albicans Candida pathogens. Invasive Candida infections originate most frequently from endogenous human reservoirs and are triggered by impaired host defences. Signs and symptoms of invasive candidiasis are non-specific; candidaemia is the most diagnosed manifestation, with disseminated candidiasis affecting single or multiple organs. Diagnosis poses many challenges, and conventional culture techniques are frequently supplemented by non-culture-based assays. The attributable mortality from candidaemia and disseminated infections is ~30%. Fluconazole resistance is a concern for Nakaseomyces glabratus , Candida parapsilosis , and Candida auris and less so in Candida tropicalis infection; acquired echinocandin resistance remains uncommon. The epidemiology of invasive candidiasis varies in different geographical areas and within various patient populations. Risk factors include intensive care unit stay, central venous catheter use, broad-spectrum antibiotics use, abdominal surgery and immune suppression. Early antifungal treatment and central venous catheter removal form the cornerstones to decrease mortality. The landscape of novel therapeutics is growing; however, the application of new drugs requires careful selection of eligible patients as the spectrum of activity is limited to a few fungal species. Unanswered questions and knowledge gaps define future research priorities and a personalized approach to diagnosis and treatment of invasive candidiasis is of paramount importance. Invasive candidiasis is a fungal disease caused by Candida pathogens. In this Primer, Lass-Flörl et al. summarize current knowledge of epidemiology and mechanisms and discuss the diagnosis, treatment and quality of life of patients with invasive candidiasis. They also highlight outstanding research questions.

Candidemia is a growing problem in hospitals all over the world. Despite advances in the medical support of critically ill patients, candidiasis leads to prolonged hospitalization, and has a crude mortality rate around 50%. We conducted a multicenter surveillance study in 16 hospitals distributed across five regions of Brazil to assess the incidence, species distribution, antifungal susceptibility, and risk factors for bloodstream infections due to Candida species. From June 2007 to March 2010, we studied a total of 2,563 nosocomial bloodstream infection (nBSI) episodes. Candida spp. was the 7th most prevalent agent. Most of the patients were male, with a median age of 56 years. A total of 64 patients (46.7%) were in the ICU when candidemia occurred. Malignancies were the most common underlying condition (32%). The crude mortality rate of candidemia during the hospital admission was 72.2%. Non-albicans species of Candida accounted for 65.7% of the 137 yeast isolates. C. albicans (34.3%), Candida parapsilosis (24.1%), Candida tropicalis (15.3%) and Candida glabrata (10.2%) were the most prevalent species. Only 47 out of 137 Candida isolates were sent to the reference laboratory for antifungal susceptibility testing. All C. albicans, C. tropicalis and C. parapsilosis isolates were susceptible to the 5 antifungal drugs tested. Among 11 C. glabrata isolates, 36% were resistant to fluconazole, and 64% SDD. All of them were susceptible to anidulafungin and amphotericin B. We observed that C. glabrata is emerging as a major player among non-albicans Candida spp. and fluconazole resistance was primarily confined to C. glabrata and C. krusei strains. Candida resistance to echinocandins and amphotericin B remains rare in Brazil. Mortality rates remain increasingly higher than that observed in the Northern Hemisphere countries, emphasizing the need for improving local practices of clinical management of candidemia, including early diagnosis, source control and precise antifungal therapy.

Recent reports have demonstrated a decline in bacterial bloodstream infections (BSIs) following adherence to central line insertion practices; however, declines have been less evident for BSIs due to Candida species. We conducted active, population-based laboratory surveillance for candidemia in metropolitan Atlanta, GA and Baltimore, MD over a 5-year period. We calculated annual candidemia incidence and antifungal drug resistance rates. We identified 3,848 candidemia cases from 2008-2013. Compared with 2008, candidemia incidence per 100,000 person-years decreased significantly by 2013 in both locations (GA: 14.1 to 9.5, p<0.001; MD: 30.9 to 14.4, p<0.001). A total of 3,255 cases (85%) had a central venous catheter (CVC) in place within 2 days before the BSI culture date. In both locations, the number of CVC-associated cases declined (GA: 473 to 294; MD: 384 to 151). Candida albicans (CA, 36%) and Candida glabrata (CG, 27%) were the most common species recovered. In both locations, the proportion of cases with fluconazole resistance decreased (GA: 8.0% to 7.1%, -10%; MD: 6.6% to 4.9%, -25%), while the proportion of cases with an isolate resistant to an echinocandin increased (GA: 1.2% to 2.9%, +147%; MD: 2.0% to 3.5%, +77%). Most (74%) echinocandin-resistant isolates were CG; 17 (<1%) isolates were resistant to both drug categories (multidrug resistant [MDR], 16/17 were CG). The proportion of CG cases with MDR Candida increased from 1.8% to 2.6%. We observed a significant decline in the incidence of candidemia over a five-year period, and increases in echinocandin-resistant and MDR Candida. Efforts to strengthen infection control practices may be preventing candidemia among high-risk patients. Further surveillance for resistant Candida is warranted.

Background. Candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported. Methods, We conducted active, population-based surveillance in metropolitan Atlanta, Georgia, and Baltimore City/County, Maryland (combined population 5.2 million), during 2008–2011. We calculated candidemia incidence and antifungal drug resistance compared with prior surveillance (Atlanta, 1992–1993; Baltimore, 1998–2000). Results. We identified 2675 cases of candidemia with 2329 isolates during 3 years of surveillance. Mean annual crude incidence per 100 000 person-years was 13.3 in Atlanta and 26.2 in Baltimore. Rates were highest among adults aged ≥65 years (Atlanta, 59.1; Baltimore, 72.4) and infants (aged <1 year; Atlanta, 34.3; Baltimore, 46.2). In both locations compared with prior surveillance, adjusted incidence significantly declined for infants of both black and white race (Atlanta: black risk ratio [RR], 0.26 [95% confidence interval {CI}, .17–.38]; white RR: 0.19 [95% CI, .12–.29]; Baltimore: black RR, 0.38 [95% CI, .22–.64]; white RR: 0.51 [95% CI: .29–.90]). Prevalence of fluconazole resistance (7%) was unchanged compared with prior surveillance; 32 (1%) isolates were echinocandin-resistant, and 9 (8 Candida glabrata) were multidrug resistant to both fluconazole and an echinocandin. Conclusions. We describe marked shifts in candidemia epidemiology over the past 2 decades. Adults aged ≥65 years replaced infants as the highest incidence group; adjusted incidence has declined significantly in infants. Use of antifungal prophylaxis, improvements in infection control, or changes in catheter insertion practices may be contributing to these declines. Further surveillance for antifungal resistance and efforts to determine effective prevention strategies are needed.

Purpose A systematic epidemiological study on intensive care unit (ICU)-acquired candidemia across India. Method A prospective, nationwide, multicentric, observational study was conducted at 27 Indian ICUs. Consecutive patients who acquired candidemia after ICU admission were enrolled during April 2011 through September 2012. Clinical and laboratory variables of these patients were recorded. The present study is an analysis of data specific for adult patients. Results Among 1,400 ICU-acquired candidemia cases (overall incidence of 6.51 cases/1,000 ICU admission), 65.2 % were adult. Though the study confirmed the already known risk factors for candidemia, the acquisition occurred early after admission to ICU (median 8 days; interquartile range 4–15 days), even infecting patients with lower APACHE II score at admission (median 17.0; mean ± SD 17.2 ± 5.9; interquartile range 14–20). The important finding of the study was the vast spectrum of agents (31 Candida species) causing candidemia and a high rate of isolation of Candida tropicalis (41.6 %). Azole and multidrug resistance were seen in 11.8 and 1.9 % of isolates. Public sector hospitals reported a significantly higher presence of the relatively resistant C. auris (8.2 vs. 3.9 %; p  = 0.008) and C. rugosa (5.6 vs. 1.5 %; p  = 0.001). The 30-day crude and attributable mortality rates of candidemia patients were 44.7 and 19.6 %, respectively. Logistic regression analysis revealed significant independent predictors of mortality including admission to public sector hospital, APACHE II score at admission, underlying renal failure, central venous catheterization and steroid therapy. Conclusion The study highlighted a high burden of candidemia in Indian ICUs, early onset after ICU admission, higher risk despite less severe physiology score at admission and a vast spectrum of agents causing the disease with predominance of C. tropicalis.