Epidemiology of candidaemia in a tertiary care university hospital: 10‐year experience with 381 candidaemia episodes between 2001 and 2010

Defining the epidemiology of and risk factors for candidaemia is necessary to guide empirical treatment. The objectives of this study were to determine the ranking of Candida among positive blood cultures, to define the epidemiology of candidaemia and to investigate patient characteristics and their relationship with C. albicans vs. non‐albicans Candida (NAC) candidaemia. Candidaemia episodes between January 2001 and December 2010 were evaluated retrospectively. Patient characteristics were compared across Candida species. Candida ranked as the fifth most frequently isolated pathogen. Among 381 candidaemia episodes, 58.3% were due to C. albicans, followed by C. parapsilosis (15.2%), C. tropicalis (13.4%) and C. glabrata (6.8%). No statistically significant difference was observed in the distribution of C. albicans vs. NAC (P = 0.432). Patients with NAC had significantly higher rates of haematological disorders (P < 0.001) and neutropenia (P = 0.003), and were older (P = 0.024) than patients with C. albicans, whereas patients with urinary catheters had higher rates of C. albicans (P = 0.007). On species basis, C. tropicalis was more frequently isolated from patients with haematological disorders (P < 0.001) and neutropenia (P = 0.008). Patients with urinary catheters were less likely to have C. parapsilosis (P = 0.043). C. glabrata was most prevalent among patients with solid organ tumours (P = 0.038), but not evident in patients with haematological disorders. Local epidemiological features and risk factors may have important implications for the management of candidaemia.     

An outbreak due to Candida auris with prolonged colonisation and candidaemia in a tertiary care European hospital

Multidrug‐resistant Candida auris has emerged as a cause of insidious hospital outbreaks and complicated infections. We present the analysis of an ongoing C. auris outbreak including the largest published series of C. auris bloodstream infection. All C. auris‐positive patients from April‐2016 to January‐2017 were included. Environmental, clinical and microbiological data were recorded. Definitive isolate identification was performed by ITS‐rDNA sequencing, and typing by amplified fragment length polymorphism fingerprinting. One hundred and forty patients were colonised by C. auris during the studied period (68% from surgical intensive care). Although control measures were implemented, we were not able to control the outbreak. Forty‐one invasive bloodstream infections (87.8% from surgical intensive care) were included. Clinical management included prompt intravascular catheter removal and antifungal therapy with echinocandins. All isolates were fluconazole‐ and voriconazole‐resistant, but echinocandin‐ and amphotericin B‐susceptible. Thirty‐day mortality rate was 41.4%, and severe septic metastasis as spondylodiscitis and endocarditis were observed in 5 patients (12%). C. auris was also recovered from inanimate patient surroundings and medical equipment. Despite antifungal treatment, high mortality and late complication rates were recorded. Molecular typing suggested a clonal outbreak different from those previously published.     

The first cases of Candida auris candidaemia in Oman

Candida auris has been recognised as a problematic healthcare‐associated emerging yeast which is often misidentified as Candida haemulonii by commercial systems. Correct early identification of C. auris is important for appropriate antifungal treatment and implementing effective infection control measures. Here we report emergence of the first C. auris cases in Oman, initially misidentified as C. haemulonii.     

Risk factors,clinical presentation and prognosis of mixed candidaemia: a population‐based surveillance in Spain

The low incidence of mixed candidaemia (MC) may have precluded a better knowledge of its clinical presentation. The aim of the study was to analyse the risk factors, clinical presentation and prognosis of MC episodes. A comparison between MC and monomicrobial candidaemia within a prospective programme on candidaemia was performed in 29 hospitals between April 2010 and May 2011. In fifteen episodes of candidaemia corresponding to 15 patients, out of 752, two species of Candida (1.9%) were isolated. MC was more frequent in patients with HIV infection (12%, P = 0.038) and those admitted due to extensive burns (23%, P = 0.012). The Candida species most frequently identified in MC were C. albicans 12 patients (40%), C. glabrata seven patients (23.3%) and C. parapsilosis six patients (20%). Early mortality was higher (nine patients, 60%) in patients with MC than in patients with MMC (223 patients, 30.3%, P = 0.046). In conclusion, MC was was independently associated with increased mortality even after considering other prognostic factors. MC is an infrequent event that is more common in HIV infection and in patients suffering from burns, and is associated with increased mortality.     

Species distribution and antifungal susceptibility of blood Candida isolates at a tertiary hospital in southern Taiwan, 1999–2006

The aim of this study was to evaluate the incidence of candidaemia, consumption of fluconazole and susceptibility of blood Candida isolates at a tertiary hospital. From January 1999 to September 2006, all candidaemic episodes were identified and available strains were evaluated for the susceptibilities of antifungal agents. Annual defined daily doses of antifungal agents were collected. There had been 909 Candida isolates detected from the bloodstream of 843 patients during the study period. Among them, 740 isolates were available for the susceptibilities of antifungal agents. The incidence density of candidaemia was 28 episodes per 10 000 patient‐days. Species distribution of 909 isolates did not vary annually, but varied greatly in the units of the hospital. Candida parapsilosis was the more prominent (30.1%) isolate in the paediatric units, where C. tropicalis and C. glabrata were less common (12.3% and 1.4% respectively). Resistance rates for itraconazole, fluconazole and voriconazole were 6.9%, 3.8% and 3.8% respectively. There were 25 (3.4%) isolates resistant to amphotericin‐B. Although fluconazole usage increased over time (r² = 0.45; P = 0.07), fluconazole resistance did not increase accordingly (P = 0.33). In our institution in which the incidence of candidaemia was high, fluconazole resistance among blood Candida isolates remained rare.     

Detection of neonatal unit clusters of Candida parapsilosis fungaemia by microsatellite genotyping: Results from laboratory‐based sentinel surveillance,South Africa, 2009‐2010

Neonatal candidaemia is a common, deadly and costly hospital‐associated disease. To determine the genetic diversity of Candida parapsilosis causing fungaemia in South African neonatal intensive care units (NICUs). From February 2009 through to August 2010, cases of candidaemia were reported through laboratory‐based surveillance. C. parapsilosis isolates from neonatal cases were submitted for identification by internal transcribed spacer (ITS) region sequencing, antifungal susceptibility testing and microsatellite genotyping. Cluster analysis was performed using Unweighted Pair Group Method with Arithmetic Mean (UPGMA). Of 1671 cases with a viable Candida isolate, 393 (24%) occurred among neonates. Isolates from 143 neonatal cases were confirmed as C. parapsilosis sensu stricto. Many isolates were resistant to fluconazole (77/143; 54%) and voriconazole (20/143; 14%). Of 79 closely‐related genotypes, 18 were represented by ≥2 isolates; 61 genotypes had a single isolate each. Seven clusters, comprised of 82 isolates, were identified at five hospitals in three provinces. Isolates belonging to certain clusters were significantly more likely to be fluconazole resistant: all cluster 7 isolates and the majority of cluster 4 (78%), 5 (89%) and 6 (67%) isolates (P<.001). Candida parapsilosis‐associated candidaemia in public‐sector NICUs was caused by closely related genotypes and there was molecular evidence of undetected outbreaks as well as intra‐hospital transmission.     

Epidemiology,risk factors for and outcome of candidaemia among non‐neutropenic patients in a Greek intensive care unit

To determine the epidemiology, risk factors for and outcome of candidaemia in critically ill patients, a matched case–control study was performed in a 25‐bed intensive care unit (ICU) from August 2004 to January 2006. Candidaemia occurred in 33 patients; each patient was matched to four controls according to admission illness severity, diagnostic category and length of ICU stay. Candida non‐albicans species predominated (67.7%). The presence of acute respiratory distress syndrome (ARDS) was the only independent risk factor for candidaemia development (OR, 2.93; 95% CI 1.09–7.81, P = 0.032). Mortality was 60.6% among patients with candidaemia and 22% among controls (P < 0.001). The presence of candidaemia (OR, 9.37; 95% CI 3.48–25.26, P < 0.001) and the illness severity on admission (acute physiologic and chronic health evaluation II score, OR, 1.17; 95% CI 1.12–1.24, P < 0.001) were independently associated with mortality. Among candidaemic patients, risk factors for mortality were the severity of organ dysfunction (sequential organ failure assessment score, OR, 1.57; 95% CI 1.00–2.46, P = 0.05) and a low serum albumin level (OR, 0.74; 95% CI 0.59–0.94, P = 0.012) both of them occurred on candidaemia onset. We conclude that in critically ill patients matched for illness severity and length of ICU stay, the only independent risk factor for candidaemia was the presence of ARDS. Mortality was independently associated with acquisition of candidaemia and with the illness severity at candidaemia onset.     

The increased role of non‐albicans species in candidaemia: results from a 3‐year surveillance study

Various studies have documented a shift in species distribution in Candida bloodstream infections (BSI), but there are little data from Southeast Asia. This study was performed to determine the species epidemiology and antifungal susceptibilities of Candida species BSI in Singapore. Candida spp. from BSI were collected from a tertiary and secondary referral hospital, and an obstetrics/paediatric hospital over a 3‐year period. The most common isolates were Candida albicans (36%), Candida tropicalis (27%), Candida glabrata (16%) and Candida parapsilosis (16%). Candida parapsilosis and C. albicans were predominant in the paediatric hospital, and C. albicans and C. tropicalis predominant in the other two institutions. Candida tropicalis temporarily replaced C. albicans as the predominant strain from BSI in 2006. Overall, 87.3% of Candida isolates were susceptible to fluconazole, and 10.4% classified as susceptible‐dose‐dependent. Fluconazole resistance was detected in C. tropicalis (3.6%), C. parapsilosis (2.1%) and C. glabrata (4.0%). Candida albicans is the predominant species isolated from BSI in Singapore. However, non‐albicans species accounted for nearly two‐thirds of all cases of candidaemia and the relative increase in C. tropicalis infections deserves further investigation. Resistance to fluconazole was uncommon.     

Current trends in candidemia and species distribution among adults: Candida glabrata surpasses C. albicans in diabetic patients and abdominal sources

Candidemia rate and species distribution vary according to the type of patients, country of origin and antifungal prophylaxis use. To present current candidemia epidemiological trends. A retrospective examination of candidemia in adults (≥18 years‐old) hospitalised from 2007 to 2015. Cases were identified through the microbiology laboratory. Candida species were distinguished based on colony morphology and VITEK‐2 YBC cards, (bioMerieux, Durham, NC, USA). Patient characteristics, species distribution, source and outcome were assessed. We encountered 275 patients (294 episodes) with candidemia. The rate of candidemia dropped in 2010 (P = 0.003) without further decline. Nearly all cases (97.5%) were healthcare‐associated. C. albicans (n = 118) and C. glabrata (n = 77) proportions varied without a discernable trend. C. glabrata was more common in diabetics [52.9% vs. 32.0% (non‐diabetics); P = 0.004] and abdominal sources [53.3% vs. 35.5% (other sources); P = 0.03], especially gastric/duodenal foci [88.9% vs. 44.1% (other abdominal foci); P = 0.02]. All‐cause 30‐day mortality rate was 43.3% without changes over time or differences between C. albicans and C. glabrata. In conclusion, the candidemia rate remains stable after a decline in 2010. C. albicans remains the most common species but C. glabrata predominates in diabetics and abdominal sources. These findings suggest possible species‐related differences in colonisation dynamics or pathogenicity.     

Comparative sensitivity of 1,3 beta‐D‐glucan for common causes of candidaemia in South Africa

Culture‐based diagnosis of candidaemia suffers poor sensitivity and prolonged turnaround time. The 1,3‐beta‐D‐glucan (BDG) assay is a non‐culture‐based broad fungal antigen with rapid turnaround time. To assess overall, species‐specific and population‐specific sensitivity of the BDG assay for candidaemia, to determine if the BDG assay is able to detect candidaemia prior to blood culture collection, and to evaluate the performance of the assay for the detection of Candida auris candidaemia. A retrospective review of all blood cultures (BC) with C albicans, C parapsilosis, C glabrata, C krusei and C auris was performed. A corresponding BDG result (Fungitell^®) within 10 days of the BC was sought on the laboratory information system. Overall sensitivity of the assay was 79% (95% CI 73‐85; 173/218). Per species sensitivity was 81% (95% CI 72‐90; 66/81) for C albicans, 72% (61‐83; 60/83) for C parapsilosis, 90% (95% CI 79‐100; 27/30) for C glabrata, 71% (95% CI 43‐99; 10/14) C auris and 100% (10/10) for C krusei. No statistically significant difference in sensitivity between species was noted (P = .093). The assay demonstrated 92% (59/64) sensitivity in neonatal ICU (P = .047) compared to 94% (15/16) in surgery, 81% (59/73) in adult ICUs and 71% (15/21) in Oncology. BDG results were positive up to 10 days prior to blood culture collection with no significant difference in detection rate (P = .563). BDG results were positive up to 10 days prior to blood culture collection. BDG when collected a mean of 2.5 days (range 1‐10 days) prior to blood culture collection were positive.     

Candidaemia in polish hospitals – a multicentre survey

Significant changes in the frequency of candidaemia and the distribution of causative species have been noted worldwide in the last two decades. In this study, we present the results of the first multicentre survey of fungaemia in Polish hospitals. A total of 302 candidaemia episodes in 294 patients were identified in 20 hospitals during a 2‐year period. The highest number of infections was found in intensive care (30.8%) and surgical (29.5%) units, followed by haematological (15.9%), ‘others’ (19.2%) and neonatological (4.6%) units. Candida albicans was isolated from 50.96% of episodes; its prevalence was higher in intensive care unit and neonatology (61.22% and 73.33%, respectively), and significantly lower in haematology (22%; P < 0.001). The frequency of C. krusei and C. tropicalis was significantly higher (24% and 18%) in haematology (P < 0.02); whereas, the distribution of C. glabrata (14.1%) and C. parapsilosis (13.1%) did not possess statistically significant differences between compared departments. Obtained data indicates that species distribution of Candida blood isolates in Polish hospitals reflects worldwide trends, particularly a decrease in the prevalence of infections due to C. albicans.     

Five‐year profile of candidaemia at an Indian trauma centre: High rates of Candida auris blood stream infections

Candidaemia is a potentially fatal infection with varied distribution of Candida species and their antifungal susceptibility profiles. The recent emergence of Candida auris in invasive candidiasis is a cause for concern. This study describes the profile of candidaemia at an Indian tertiary care hospital and reports the emergence of C. auris. All patients diagnosed with candidaemia between 2012 and 2017 were studied. The isolates were identified using conventional methods, VITEK 2 and MALDI‐TOF MS. The isolates not identified by MALDI‐TOF were sequenced. Antifungal susceptibility testing was done by the CLSI broth microdilution method and VITEK 2. A total of 114 isolates of Candida species were analysed. Candida tropicalis (39.4%) was the most common species, followed by C. auris (17.5%), C. albicans (14%) and C. parapsilosis (11.4%). Notably, Diutina mesorugosa isolates (n = 10) were not identified by MALDI‐TOF and were confirmed by sequencing. Furthermore, 45% (n = 9) C. auris strains exhibited low MICs of FLU (0.05‐4 μg/mL) and the remaining 55% (n = 11) isolates had high MICs ≥ 64 μg/mL. Also, D. mesorugosa exhibited high MICs of FLU (32 μg/mL) in 2 isolates. A high rate of errors in antifungal susceptibility was noted with the VITEK 2 as compared to the CLSI method. Candida auris was the second most prevalent species causing candidaemia warranting infection control practices to be strengthened to prevent its spread.     

Prevalence of biofilm formation in clinical isolates of Candida species causing bloodstream infection

Candida species are the fourth most common cause of nosocomial invasive infections. Biofilm formation is recognised as one virulence factor of Candida species. A total of 243 Candida albicans, 81 C. glabrata, 33 C. parapsilosis, 14 C. dubliniensis, 8 C. tropicalis, 8 C. lusitaniae, 5 C. krusei and 1 C. pelliculosa isolates causing bloodstream infections were evaluated for biofilm formation. The biofilm formed on silicone elastomer preincubated with human serum was quantified by estimation of the metabolic activity through XTT assay and visualised by light and scanning electron microscopy. Forty per cent of the C. albicans isolates formed biofilm compared to 88.7% of the non‐albicans Candida isolates (P < 0.0001). Among non‐albicans Candida spp., biofilm formation was most commonly observed in C. tropicalis and C. lusitaniae (100%), followed by C. glabrata (95%), C. dubliniensis (85.7%) and C. parapsilosis (66.7%). A quantitative correlation was observed between the amount of biofilm observed microscopically, and that determined by metabolic activity measurements. The biofilms of all Candida species were composed of basal yeast cells with the exception of C. parapsilosis which produced biofilms consisting of pseudohyphae and aggregated yeast cells. These results suggest that biofilm formation as a virulence factor might have a higher significance for non‐albicans Candida species than for C. albicans.     

Phenotypic and genotypic characteristics of Candida albicans isolates from bloodstream and mucosal infections

The interaction of Candida albicans with the host is of a complex nature involving fungal factors and host's response. In this study, we concentrated on the phenotypic expression of virulence attributes and genotypic characteristics of C. albicans isolates from two distinct clinical entities of candidiasis—blood stream and vaginal infections, and the possible role of these factors. Hence, we conducted a comparative in vitro assessment of virulence characteristics, including adhesion to epithelial cells and HaCat cell line, biofilm formation, aspartic proteinases and phospholipase activity of 20 C. albicans isolates from patients with C. albicans bloodstream infection and 22 isolates from patients with C. albicans vaginitis. Further, we studied the epigenetic phenotypic switching of the strains and their ploidy, by flow cytometry and CHEF techniques. These studies indicated that although no overall differentiation between the isolates of the two groups (bloodstream infection and vaginitis) could be demonstrated, several characteristics were more specific to one of the groups than the other. While the strains from vaginal infection had higher capacity to adhere, the strains from patients with bloodstream infection had higher activity of phospholipase. Differences were also noted in phenotypic switching, with the strains from bloodstream infection revealing primarily the “white” type colonies, known to be more virulent, and had higher DNA content. This study is unique considering the concurrent comparison of isolates from different clinical entities, at the phenotypic and genotypic level.     

Neonatal candidaemia in Kuwait: a 12-year study of risk factors, species spectrum and antifungal susceptibility

A study of candidaemia in neonatal intensive care unit (NICU) over a 12-year period (1995–2006) taking into consideration demographic variables, risk factors, aetiological Candida species and therapeutic outcomes is presented. The yeast isolates were identified by VITEK2 yeast identification system and antifungal susceptibility was determined by E-test. Of 4815 neonates admitted in NICU, 182 cases of candidaemia were detected with an overall prevalence of 4.0% and crude mortality of 27.7%. The annual rate of candidaemia per 1000 admissions was the highest in 1997 (84 cases) and the lowest in 2004 (10 cases). Of the 112 assessable candidaemia cases, 78 (70%) occurred in very low birth weight neonates (≤1500 g), 65 (58%) were born with gestational age of ≤30 weeks. The main identifiable risk factors were use of ≥2 antibiotics (87%), total parenteral nutrition for >5 days (82%), placement of central venous catheter (78%) and prior colonisation with Candida species (54%). Candida albicans and non- albicans Candida species accounted for 43% and 57% of candidaemia cases, respectively, and C. parapsilosis emerged as a predominant species. No fluconazole resistance was observed in C. albicans and C. parapsilosis isolates. This is the first comprehensive study on the epidemiology of neonatal candidiasis in Kuwait.     

Efficacy of micafungin in invasive candidiasis caused by common Candida species with special emphasis on non‐albicans Candida species

The incidence of invasive candidiasis caused by non‐albicans Candida (NAC) spp. is increasing. The aim of this analysis was to evaluate the efficacy of micafungin, caspofungin and liposomal amphotericin B in patients with invasive candidiasis and candidaemia caused by different Candida spp. This post hoc analysis used data obtained from two randomised phase III trials was conducted to evaluate the efficacy and safety of micafungin vs. caspofungin and micafungin vs. liposomal amphotericin B. Treatment success, clinical response, mycological response and mortality were evaluated in patients infected with C. albicans and NAC spp. Treatment success rates in patients with either C. albicans or NAC infections were similar. Outcomes were similar for micafungin, caspofungin and liposomal amphotericin B. Candida albicans was the most prevalent pathogen recovered (41.0%), followed by C. tropicalis (17.9%), C. parapsilosis (14.4%), C. glabrata (10.4%), multiple Candida spp. (7.3%) and C. krusei (3.2%). Age, primary diagnosis (i.e. candidaemia or invasive candidiasis), previous corticosteroid therapy and Acute Physiology and Chronic Health Evaluation II score were identified as potential predictors of treatment success and mortality. Micafungin, caspofungin and liposomal amphotericin B exhibit favourable treatment response rates that are comparable for patients infected with different Candida spp.     

Interactions between Candida albicans and Candida glabrata in biofilms: Influence of the strain type,culture medium and glucose supplementation

The relationship among Candida species may be influenced by several factors. Thus, this study evaluated the interactions between Candida albicans and Candida glabrata in biofilms, varying the strain type, culture medium and glucose supplementation. Biofilms were formed for 48 hours in Sabouraud dextrose broth (SDB) or RPMI 1640, supplemented with 0%, 1% or 5% glucose. Each strain of C. albicans was combined with two strains of C. glabrata, generating four biofilm associations, which were quantified by colony‐forming units (CFUs), total biomass and metabolic activity. Data were analysed by ANOVA and Tukey's HSD test (α = 0.05). For CFUs, all associations were classified as indifferent for biofilms formed in RPMI 1640, while for SDB the interactions were antagonistic for C. albicans and indifferent for C. glabrata. The association of reference strains resulted in a dual‐species biofilm with biomass significantly higher than that observed for each single biofilm developed in SDB. The metabolic activity of dual‐species biofilms did not significantly differ from that found for single ones, except for co‐culture of the reference strains. Glucose supplementation and culture media had a significant influence on all parameters. In conclusion, the strain type, culture medium and glucose supplementation influenced the interactions between C. albicans and C. glabrata.     

Vulvovaginal candidiasis: species distribution,fluconazole resistance and drug efflux pump gene overexpression

The increasing incidence of vulvovaginal candidiasis (VVC) and the emergence of fluconazole resistance are an indisputable fact. However, little information is available regarding the correlation between fluconazole resistance in vaginal Candida albicans and the expression of drug efflux pump genes. In this study, we investigated the species distribution, fluconazole susceptibility profiles and the mechanisms of fluconazole resistance in Candida strains. In total, 785 clinical Candida isolates were collected from patients with VVC. C. albicans was the most frequently isolated species (n = 529) followed by C. glabrata (n = 164) and C. krusei (n = 57). Of all Candida isolates, 4.7% were resistant to fluconazole. We randomly selected 18 fluconazole‐resistant isolates of C. albicans to evaluate the expression of CDR1, CDR2, MDR1 and FLU1 genes. Compared with fluconazole‐susceptible C. albicans isolates, CDR1 gene expression displayed 3.16‐fold relative increase, which was statistically significant. CDR2, MDR1 and FLU1 overexpression was observed in several fluconazole‐resistant C. albicans isolates, but statistical significance was not achieved. These results demonstrate a high frequency of non‐albicans species (32.6%); however, C. albicans is the most common Candida species implicated in vaginitis, and this strain displays considerable fluconazole resistance. Meanwhile, our study further indicates that fluconazole resistance in C. albicans may correlate with CDR1 gene overexpression.     

Enzymatic activity profile of a Brazilian culture collection of Candida albicans isolated from diabetics and non‐diabetics with oral candidiasis

The secretion of hydrolytic enzymes is a fundamental virulence factor of Candida albicans to develop disease. The objective of this study was to characterise the virulence of 148 clinical isolates of C. albicans from oral candidiasis by assessing the expression of phospholipase (PL) and secreted aspartyl proteinase (SAP). Isolates were obtained from healthy subjects (HS) and diabetics (DOC) and non‐diabetics with oral candidiasis (NDOC). An aliquot (5 μl) of each cell suspension was inoculated on PL and SAP agar plates and incubated. Enzymes secretion was detected by the formation of an opaque halo around the colonies and enzymatic activity (PZ) was determined by the ratio between colony diameter and colony diameter plus the halo zone. Statistical comparisons were made by a one‐way anova followed by Tukey's post hoc test (α = 0.05). The clinical sources of C. albicans had significant effect (P < 0.001) on the PZ values of both enzymes. For PL, clinical isolates from NDOC and DOC had highest enzymatic activity than those from HS (P < 0.05), with no significant differences between them (P = 0.506). For SAP, C. albicans from NDOC showed the lower enzymatic activity (P < 0.001). There were no significant differences between isolates from HS and DOC (P = 0.7051). C. albicans isolates from NDOC and DOC patients showed an increased production of PL.