Candida Albicans Bloodstream Infection Research Articles

The impact of the fluconazole trailing effect on the persistence of Candida albicans bloodstream infection when treated with fluconazole

ObjectivesThe trailing effect of Candida species is a phenomenon characterized by reduced but persistent growth at antifungal concentrations above the MIC. We assessed the impact of trailing growth on the persistence of Candida albicans candidemia in patients receiving fluconazole (FLC) therapy. MethodsWe retrospectively investigated candidemia isolates at three hospitals in southern Taiwan between 2013 and 2020. Patients treated with FLC for FLC-susceptible C. albicans candidemia were enrolled. The degree of trailing was determined as the average growth above the MIC divided by the measured growth at the lowest drug concentration using the EUCAST method and classified into four categories: residual (0.1–5%), slight (6–10%), moderate (11–15%), and heavy trailers (>15%). ResultsAmong isolates from 190 patients, the proportions of heavy trailers at 24 hours, 48 hours, and 72 hours were 63.7% (121/190), 63.2% (120/190), and 74.7% (142/190), respectively. Persistent candidemia was observed in 17 (8.9 %) patients. The proportion of persistent C. albicans candidemia in heavy trailing isolates at 48 hours was higher than in isolates without heavy trailing (13.3% [16/120] vs. 1.4% [1/70], p = 0.007). A multivariate analysis showed that immunosuppression (OR = 7.92; 95% CI: 2.38–26.39, p = 0.001), hospitalization days after the index date of C. albicans identification (OR = 1.03; 95% CI: 1.01–1.05, p = 0.011), and heavy trailing isolates at 48 hours (OR = 10.04; 95% CI: 1.27–79.88, p = 0.029) were independent factors for persistent candidemia. DiscussionThe current study revealed that heavy trailing in C. albicans isolates is associated with persistent candidemia in patients receiving FLC treatment.

Systematic Characterization of Epidemiology, Antifungal Susceptibility, Risk Factors and Outcomes of Candidaemia: A Six-Year Chinese Study

BackgroundCandida bloodstream infection (BSI), the fourth most common nosocomial BSI, is an urgent global health challenge with the tremendous growth in antifungal resistance rate and mortality rate.PurposeTo establish the epidemiology, species distribution, risk factors, and 30-day mortality of candidaemia among 115 patients in this 6-year surveillance study.Materials and MethodsWe retrospectively analyzed the clinical characteristics, epidemiology, antifungal susceptibility patterns, and risk factors for morbidity and mortality of 115 candidaemia cases diagnosed in one tertiary care hospital from January 2016 through December 2021.ResultsOf the 115 candidaemia cases, the most prevalent species were Candida tropicalis (33.0%), followed by Candida albicans (27.8%), Candida parapsilosis complex (19.1%), and others. The overall incidence was 0.21 cases/1000 admissions. The overall crude resistance rate of Candida spp. against azoles was 20.0% (23/115), while Candida tropicalis showed a significant increase in the resistance rate to azoles (from 1/6, 16.7% in 2017 to 6/10, 60.0% in 2021). Multivariate analyses demonstrated that hematological malignancy and neutropenia were significantly associated with Candida tropicalis BSI than Candida non-tropicalis BSI. Candida albicans BSI had a significantly higher rate of previous surgery than Candida non-albicans BSI. Candida parapsilosis BSI had a significantly higher rate of receiving total parenteral nutrition (TPN). The overall 30-day mortality rate was 27.0% (31/115). The presence of high age-adjusted Charlson comorbidity index (aCCI), neutropenia, and septic shock were factors independently associated with increased 30-day mortality.ConclusionCandida tropicalis are emerging as the predominant isolate in candidaemia. Of note, the unexpectedly increased resistance rate to azoles in Candida tropicalis BSI was observed. The aCCI scores, neutropenia, and septic shock were independently associated with 30-day mortality. Prompt, adequate antifungal treatment among high-risk patients may lead to a reduction in mortality.

Intestinal Flora-Derived Kynurenic Acid Protects Against Intestinal Damage Caused by Candida albicans Infection via Activation of Aryl Hydrocarbon Receptor.

Colonization of the intestinal tract by Candida albicans (C. albicans) can lead to invasive candidiasis. Therefore, a functional intestinal epithelial barrier is critical for protecting against invasive C. albicans infections. We collected fecal samples from patients with Candida albicans bloodstream infection and healthy people. Through intestinal flora 16sRNA sequencing and intestinal metabolomic analysis, we found that C. albicans infection resulted in a significant decrease in the expression of the metabolite kynurenic acid (KynA). We used a repeated C. albicans intestinal infection mouse model, established following intake of 3% dextran sulfate sodium salt (DSS) for 9 days, and found that KynA, a tryptophan metabolite, inhibited inflammation, promoted expression of intestinal tight junction proteins, and protected from intestinal barrier damage caused by invasive Candida infections. We also demonstrated that KynA activated aryl hydrocarbon receptor (AHR) repressor in vivo and in vitro. Using Caco-2 cells co-cultured with C. albicans, we showed that KynA activated AHR, inhibited the myosin light chain kinase-phospho-myosin light chain (MLCK-pMLC) signaling pathway, and promoted tristetraprolin (TTP) expression to alleviate intestinal inflammation. Our findings suggest that the metabolite KynA which is differently expressed in patients with C. albicans infection and has a protective effect on the intestinal epithelium, via activating AHR, could be explored to provide new potential therapeutic strategies for invasive C. albicans infections.

The impact of lemongrass, oregano, and thyme essential oils on Candida albicans’ virulence factors

Increased systemic infections and growing resistance of Candida species in immunosuppressed people have prompted research for additional treatment options. The purpose of this study was to investigate the potential of lemongrass, oregano, and thyme essential oils tested individually, combined, and combined with the antifungal agents fluconazole and caspofungin to kill Candida albicans isolates in a controlled laboratory setting. A quantitative design was used to analyze the experimental data collected and investigate risk factors related to age, gender, race, and co-morbidities. Kill rates of lemongrass, oregano, and thyme essential oils individually and combined, kill rates of fluconazole, caspofungin, and the kill rates when the antifungals were each combined with the three essential oils were compared using 117 isolates recovered from bloodstream infections between January 2009 through August 1, 2017. There were statistically significant increases in kill rates when the isolates were exposed to any of the combinations of essential oils tested. Data on the covariates age, gender, race, and co-morbidities were assessed for risk factors related to Candida albicans bloodstream infections. The age group 25-34, kidney failure, and solid organ tumor cancer, were all statistically significantly associated with an increased risk for Candida albicans bloodstream infections and multiple organ failure was negatively associated with the risk. Through the use of essential oils, the ability to reduce the number of patients becoming infected with life-threatening yeast infections could not only reduce mortality but also reduce the costs associated with serious infections.

Clinical characteristics, risk factors and outcomes of mixed Candida albicans/bacterial bloodstream infections

PurposeThe purpose of this study was to explore the clinical features, risk factors, and outcomes of mixed Candida albicans/bacterial bloodstream infections (mixed-CA/B-BSIs) compared with monomicrobial Candida albicans bloodstream infection (mono-CA-BSI) in adult patients in China.MethodsAll hospitalized adults with Candida albicans bloodstream infection (CA-BSI) were recruited for this retrospective observational study from January 1, 2013, to December 31, 2018.ResultsOf the 117 patients with CA-BSI, 24 patients (20.5%) had mixed-CA/B-BSIs. The most common copathogens were coagulase-negative Staphylococcus (CNS) (24.0%), followed by Klebsiella pneumoniae (20.0%) and Staphylococcus aureus (16.0%). In the multivariable analysis, a prior ICU stay > 2 days (adjusted odds ratio [OR], 7.445; 95% confidence interval [CI], 1.152–48.132) was an independent risk factor for mixed-CA/B-BSIs. Compared with patients with mono-CA-BSI, patients with mixed-CA/B-BSIs had a prolonged length of mechanical ventilation [17.5 (4.5, 34.8) vs. 3.0 (0.0, 24.5), p = 0.019] and prolonged length of ICU stay [22.0 (14.3, 42.2) vs. 8.0 (0.0, 31.5), p = 0.010]; however, mortality was not significantly different.ConclusionsThere was a high rate of mixed-CA/B-BSIs cases among CA-BSI cases, and CNS was the predominant coexisting species. A prior ICU stay > 2 days was an independent risk factor for mixed -CA/B-BSIs. Although there was no difference in mortality, the outcomes of patients with mixed -CA/B-BSIs, including prolonged length of mechanical ventilation and prolonged length of ICU stay, were worse than those with mono-CA-BSI; this deserves further attention from clinicians.

Association between CAI microsatellite, multilocus sequence typing, and clinical significance within Candida albicans isolates.

Candida albicans bloodstream infection (BSI) is epidemiologically important because of its increasing frequency and serious outcome. Strain typing and delineation of the species are essential for understanding the phylogenetic relationship and clinical significance. Microsatellite CAI genotyping and multilocus sequence typing (MLST) were performed on 285 C. albicans bloodstream isolates from patients in Chang Gung Memorial Hospital at Linkou (CGMHL), Taiwan from 2003 to 2011. Data regarding demographics, comorbidities, risk factors, and clinical outcomes were recorded within adult patients with C. albicans BSI. Both CAI genotyping and MLST yielded comparable discriminatory power for C. albicans characterization. Besides, the distribution of CAI repetition showed a satisfactory phylogenetic association, which could be a good alternative method in the molecular phylogenetics of C. albicans and epidemiological studies. As for the clinical scenario, clade 17 isolates with CAI alleles either possessing 29 or more repetitions were related to higher 14-day and 30-day mortality, and shorter median survival days.

Impact of tolerance to fluconazole on treatment response in Candida albicans bloodstream infection.

Treatment of Candida albicans bloodstream infection with fluconazole is associated with significant mortality despite in vitro susceptibility to the drug. We sought to determine whether tolerance to fluconazole is predictive of treatment failure. We reviewed patients with monomicrobial C albicans bloodstream infection who received primary monotherapy with fluconazole. Tolerance to fluconazole, defined as the fraction of growth above the MIC, was quantified using the disc diffusion assay and digital image analyses. Survival analyses were performed with host and treatment factors as predictive variables. Among 44 patients included in the study, all-cause mortality was 29.5% at 30days and 43.1% at 12weeks. Forty-one isolates (93%) were susceptible to fluconazole (MIC50, 0.5mg/L). Fluconazole tolerance was strongly associated with death for patients treated with fluconazole within 24h of candidemia onset (33.3% vs 0%; p=.007), but not among patients whose treatment was started later. MIC did not correlate with survival, regardless of treatment delay. A Cox regression model including time to treatment, tolerance to fluconazole, fluconazole exposure and Pitt bacteraemia score provided good prediction of treatment outcome (area under the receiver-operator curve, 0.82). In patients with C albicans bloodstream infection, tolerance testing was predictive of fluconazole efficacy if the drug was started early. Further study is required to validate the utility of this metric to guide treatment choices.

Leukotriene B4-Mediated Neutrophil Recruitment Causes Pulmonary Capillaritis during Lethal Fungal Sepsis

Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflictedpatients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C.albicans yeast in a lethal septic mouse and human pulmonary circulation model. Live C.albicans sequester to the endothelium and are immediately captured by complement-dependent PMN chemotaxis, which is required for host survival. However, complement activation also leads to Leukotriene B4 (LTB4)-mediated intravascular PMN clustering and occlusion, resulting in capillaritis with pulmonary hemorrhage and hypoxemia. This clustering is unique to fungi and triggered by fungal cell wall components. PMN clustering is absent in mice lacking LTB4-receptor, and capillaritis is attenuatedupon pharmacological LTB4 blockade without affecting phagocytosis. Therefore, therapeutically disrupting infection-induced capillaritis may limit organ injury without impairing host defense during fungal sepsis.

Fungal endocarditis with right ventricular candidal mycetoma in a premature neonate

Fungal mycetoma or endocarditis is rare in premature neonates and it is often associated with high mortality. In the majority of the cases diagnosis is made postmortem. Here we report a 30-week-old preterm neonate who developed Candida albicans blood stream infection complicated by endocarditis and subsequent mycetoma. Initially, this neonate had Klebsiella sepsis requiring multiple antibiotic courses. A peripherally inserted central venous catheter was used to give total parenteral nutrition. On day 24 of life, he developed candidemia, treated with 14 day course of fluconazole and shown improvement. Further, on day 60 of life he developed cholestasis, deranged liver function tests and persistent thrombocytopenia along with apnea, bradycardia and desaturations. Blood culture again grew again C. albicans. Echocardiography showed large fungal vegetation on tricuspid valve with a mycetoma filling the right ventricle. He was treated with intravenous amphotericin B, fluconazole and supportive measures, but he deteriorated and succumbed after two weeks. J Microbiol Infect Dis 2015;5(3): 142-145 Key words: Prematureneonate, candida sepsis, endocarditis, mycetoma

Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection—Scotland, 2012–2013

Bloodstream infections caused by Candida species remain a significant cause of morbidity and mortality in hospitalized patients. Biofilm formation by Candida species is an important virulence factor for disease pathogenesis. A prospective analysis of patients with Candida bloodstream infection (n = 217) in Scotland (2012–2013) was performed to assess the risk factors associated with patient mortality, in particular the impact of biofilm formation. Candida bloodstream isolates (n = 280) and clinical records for 157 patients were collected through 11 different health boards across Scotland. Biofilm formation by clinical isolates was assessed in vitro with standard biomass assays. The role of biofilm phenotype on treatment efficacy was also evaluated in vitro by treating preformed biofilms with fixed concentrations of different classes of antifungal. Available mortality data for 134 patients showed that the 30-day candidaemia case mortality rate was 41%, with predisposing factors including patient age and catheter removal. Multivariate Cox regression survival analysis for 42 patients showed a significantly higher mortality rate for Candida albicans infection than for Candida glabrata infection. Biofilm-forming ability was significantly associated with C. albicans mortality (34 patients). Finally, in vitro antifungal sensitivity testing showed that low biofilm formers and high biofilm formers were differentially affected by azoles and echinocandins, but not by polyenes. This study provides further evidence that the biofilm phenotype represents a significant clinical entity, and that isolates with this phenotype differentially respond to antifungal therapy in vitro. Collectively, these findings show that greater clinical understanding is required with respect to Candida biofilm infections, and the implications of isolate heterogeneity.

Clinical and molecular characteristics of bloodstream infections caused by Candida albicans in children from 2003 to 2011

We investigated the clinical and molecular characteristics of Candida albicans bloodstream infection (BSI) in children from a tertiary-level medical centre in Taiwan over a 9-year period from January 2003 to December 2011. We performed multilocus sequence typing (MLST) to investigate the genetic relatedness of these C. albicans BSI isolates. A total of 79 episodes of C. albicans BSI in 76 paediatric patients were identified, including 41 (51.9%) from the paediatric intensive care unit, 24 (30.4%) from the neonatal intensive care unit and 14 (17.7%) from general wards. More than half (59.5%) of these patients had underlying chronic co-morbidities, and the majority (94.9%) had a catheter or some other artificial device. All the isolates were susceptible to the antifungal agents tested. Only 32.9% (26/79) received effective antifungal agents within 24 h of onset of candidaemia. Twenty-five (31.6%) patients had persistent candidaemia (>3 days after the start of antifungal treatment) and candidaemia-attributable mortality rate was 22.8% (18/79). The 72 isolates available for MLST yielded 53 unique diploid sequence types (DSTs). Forty-five DSTs were singletons and eight DSTs were shared by 27 (37.5%) isolates. Seventy-one (98.6%) isolates were clustered within previously known clades. Based on the definition of two or more strains with shared DST occurring within a period of 90 days, 10.1% of the infections were categorized as nosocomial clusters, most commonly identified in the intensive care units. Although cluster-associated candidaemia was not associated with a higher mortality rate, none of the clusters were identified by the hospital infection control team.

PO-0559 Candida Bloodstream Infections In A Nicu (2001–2012)

<h3>Background and aims</h3> Recent reports indicate that the incidence of Candida ssp. bloodstream infection (BSI) is decreasing among NICU patients, and is associated with antifungal prophylaxis and the dwell time of peripherally inserted central catheters (PICCs). This study describes the epidemiology of invasive fungal infections in a single NICU. <h3>Methods</h3> We conducted a retrospective study of invasive candidiasis occurring in 6730 infants admitted to our NICU. Positive fungal blood cultures were identified through searching our microbiology database. <h3>Results</h3> From a total of 2637 blood cultures performed during the study period, there were 6 (&lt;0.1%) Candida spp. (Candida albicans n = 5, Candida lusitaniae n = 1) BSIs reported. In 3 cases premature rupture of membranes was observed, and in 2 cases maternal vaginal smears were positive for Candida ssp. All Patients with Candida albicans BSI (Gestational age 24.3 to 27.0 weeks) had PICCs, while blood cultures became positive between day 1 to 10. 1 patient died on day 13. Treatment consisted in Fluconazole (67%), Amphotericin B (33%), and Caspofungin (17%), partially combined. Persistent positive Candida BSIs were not reported. Systemic antifungal prophylaxis is not implemented at our NICU. During the same period 402 positive fungal cultures in 198 patients were documented from other sources. <h3>Conclusions</h3> Even without prophylactic systemic antifungal therapy at our NICU the observed rate of Candida BSIs is low but in line with other studies. Prenatal vaginal smears might help to detect ELBW infants being at high risk for candidemia.

A Virtual Infection Model Quantifies Innate Effector Mechanisms and Candida albicans Immune Escape in Human Blood

Candida albicans bloodstream infection is increasingly frequent and can result in disseminated candidiasis associated with high mortality rates. To analyze the innate immune response against C. albicans, fungal cells were added to human whole-blood samples. After inoculation, C. albicans started to filament and predominantly associate with neutrophils, whereas only a minority of fungal cells became attached to monocytes. While many parameters of host-pathogen interaction were accessible to direct experimental quantification in the whole-blood infection assay, others were not. To overcome these limitations, we generated a virtual infection model that allowed detailed and quantitative predictions on the dynamics of host-pathogen interaction. Experimental time-resolved data were simulated using a state-based modeling approach combined with the Monte Carlo method of simulated annealing to obtain quantitative predictions on a priori unknown transition rates and to identify the main axis of antifungal immunity. Results clearly demonstrated a predominant role of neutrophils, mediated by phagocytosis and intracellular killing as well as the release of antifungal effector molecules upon activation, resulting in extracellular fungicidal activity. Both mechanisms together account for almost of C. albicans killing, clearly proving that beside being present in larger numbers than other leukocytes, neutrophils functionally dominate the immune response against C. albicans in human blood. A fraction of C. albicans cells escaped phagocytosis and remained extracellular and viable for up to four hours. This immune escape was independent of filamentation and fungal activity and not linked to exhaustion or inactivation of innate immune cells. The occurrence of C. albicans cells being resistant against phagocytosis may account for the high proportion of dissemination in C. albicans bloodstream infection. Taken together, iterative experiment–model–experiment cycles allowed quantitative analyses of the interplay between host and pathogen in a complex environment like human blood.

Time to blood culture positivity as a predictor of clinical outcome in patients with Candida albicansbloodstream infection

BackgroundFew studies have assessed the time to blood culture positivity as a predictor of clinical outcome in fungal bloodstream infections (BSIs). The purpose of this study was to evaluate the time to positivity (TTP) of blood cultures in patients with Candida albicans BSIs and to assess its impact on clinical outcome.MethodsA historical cohort study with 89 adults patients with C. albicans BSIs. TTP was defined as the time between the start of incubation and the time that the automated alert signal indicating growth in the culture bottle sounded.ResultsPatients with BSIs and TTPs of culture of ≤36 h (n=39) and >36 h (n=50) were compared. Septic shock occurred in 46.2% of patients with TTPs of ≤36 h and in 40.0% of patients with TTP of >36 h (p=0.56). A central venous catheter source was more common with a BSI TTP of ≤36 h (p=0.04). Univariate analyis revealed that APACHE II score≥20 at BSI onset, the development of at least one organ system failure (respiratory, cardiovascular, renal, hematologic, or hepatic), SOFA at BSI onset, SAPS II at BSI onset, and time to positivity were associated with death. By using logistic regression analysis, the only independent predictor of death was time to positivity (1.04; 95% CI, 1.0-1.1, p=0.035), with the chance of the patient with C. albicans BSI dying increasing 4.0% every hour prior to culture positivity.ConclusionA longer time to positivity was associated with a higher mortality for Candida albicans BSIs; therefore, initiating empiric treatment with antifungals may improve outcomes.

Risk factors for candidemia with non-albicans Candida spp. in intensive care unit patients with end-stage renal disease on chronic hemodialysis

The objective of this study was to describe factors associated with bloodstream infections (BSIs) with non-albicans Candida species (NAC), compared with Candida albicans BSIs, and antifungal susceptibility patterns in adult intensive care unit (ICU) patients with chronic renal failure undergoing hemodialysis. To the best of our knowledge, this is the first study to report the potential factors for NAC candidemia in ICU patients with end-stage renal disease on chronic hemodialysis. This prospective, observational, multicenter study was conducted in the two centers of Baskent University between January 2007 and July 2010. All adult patients excluding patients with neutropenia, malignancy, glucocorticoid treatment or AIDS, were included. Sixty cases (58.8%) of candidemia were due to C. albicans and 42 (41.2%) to NAC. Multivariate regression analysis revealed that the presence of a central venous catheter was the only risk factor independently associated with BSI due to NAC (p=0.046, odds ratio: 5.90, 95% confidence interval: 1.032-33.717). Mortality was more frequent in those with NAC than C. albicans BSIs (64.3% vs. 55%), but the difference was not significant (p=0.067). Except for two Candida glabrata strains, which were dose-dependently fluconazole susceptible, all Candida species were susceptible to fluconazole, caspofungin, voriconazole and amphotericin B. Central venous catheterization was the only factor significantly associated with BSI due to NAC in ICU patients with end-stage renal disease.

Fructose-1,6-Bisphosphate Reduces the Mortality in Candida albicans Bloodstream Infection and Prevents the Septic-Induced Platelet Decrease

Due to the fact that an increased number of patients have experienced bloodstream infections caused by Candida species and the high mortality of this infection, there is a need for a strategy to reduce this scenery. One possible strategy is the use of new drugs, such as fructose-1,6-bisphosphate (FBP), which is a high-energy glycolytic metabolite and has shown to have therapeutic effects in several pathological conditions such as ischemia, shock, toxic injuries, and bacterial sepsis. The aim of this manuscript was to determine the role of FBP in experimental Candida albicans bloodstream infection. We used mice that were divided into three experimental groups: sham (not induced), bloodstream infection (induced with intratracheal instillation of C. albicans) and FBP (bloodstream infection plus FBP 500 mg/kg i.p.). Blood was taken for assessment of complete hematological profile and cytokine assay (IL-6 and MCP-1). Results of the study demonstrated that mortality decreased significantly in groups that received FBP. All cytokine and hematological indexes of FBP group were similar to bloodstream infection group with exception of platelets count. FBP significantly prevented the decrease in platelets. Taken together, our results demonstrate that FBP prevented the mortality in C. albicans bloodstream infection.

Comparison of costs, length of stay, and mortality associated with Candida glabrata and Candida albicans bloodstream infections

We compared costs, length of stay, and mortality between adults with Candida albicans and Candida glabrata bloodstream infections. Early evidence of C glabrata, as defined by a positive culture within 2 days of admission, was associated with higher costs ($56,026 vs $32,810; P = .04) and longer hospital stays (19.7 vs 14.5 days; P = .05) compared with early evidence of C albicans. Mortality was similar between the groups.

Risk factors for albicans and non-albicans candidemia in the intensive care unit*

To determine risk factors for bloodstream infections (BSI) with Candida non-albicans (C-NA) species and Candida albicans (CA) among critically ill patients. Case-control study. Adult medical and surgical intensive care units (ICUs) at two university hospitals. Consecutive patients with C-NA and CA BSIs from 1995-2005 formed the two case groups. Controls were patients without candidemia who were randomly selected in a ratio of 5:1 and matched by study hospital, ICU type (medical vs. surgical) and by ICU admission date within a 3-month period. Data collected included demographics, comorbidities, exposure to antibiotics and antifungals, and ICU factors such as total parenteral nutrition (TPN), blood product transfusions, invasive procedures, central venous catheters, hemodialysis, and mechanical ventilation. We built multivariable logistic regression models, which identified risk factors for C-NA or CA BSIs compared with controls. Variables were adjusted for time-at-risk. There were 67 patients with C-NA BSIs, 79 patients with CA BSIs, and 780 controls. In multivariable models, factors associated with an increased risk of C-NA compared with controls included major pre-ICU operations [odds ratio; (95% confidence interval)] [2.12; (1.14-3.97)], gastrointestinal procedures [2.24; (1.49-3.38)], enteric bacteremia [3.43; (1.39-8.48)], number of hemodialysis days [6.20; (2.67-14.4)], TPN duration [2.87; (1.40-5.90)], and mean number of red blood cell transfusions [2.72; (1.33-5.58)]. Factors associated with an increased risk of CA BSIs compared to controls were very similar and included major ICU operations [1.26; (1.14-3.97)], enteric bacteremia [3.45; (1.38-8.63)], number of hemodialysis days [3.84; (1.75-8.40)], TPN duration [11.0; (5.52-21.7)] and mean number of red blood cell transfusions [1.97; (0.98-3.99)]. We found multiple common risk factors for both non-C. albicans and C. albicans BSIs, however we could not differentiate between these two groups based on clinical characteristics alone.

Therapy and outcome of Candida glabrata versus Candida albicans bloodstream infection

Candida glabrata is a common cause of bloodstream infection (BSI) and exhibits reduced susceptibility to antifungal agents. Those with C. glabrata BSI may therefore be at increased risk for a delay in receiving appropriate therapy and poor treatment outcome. We compared treatment and outcome of patients with C. glabrata to controls with Candida albicans BSI. Each patient with C. glabrata BSI from July 1997 through December 2004 was matched with a control patient infected with C. albicans. Appropriateness of therapy was defined using current guidelines, and the mortality end point was 30 days following the initial positive blood culture. Overall, 78% of patients received appropriate therapy (39/54 [72%] for C. glabrata versus 45/54 [83%] for C. albicans, P = 0.2). Crude 30-day mortality was high for both groups (41% for C. glabrata versus 44% for C. albicans, P = 0.7). There was no trend in mortality according to time of therapy initiation, but mortality was lower for those who received appropriate therapy (35% versus 71% for inappropriate therapy, P = 0.002). Twelve percent of patients received no antifungal therapy and contributed disproportionately to overall crude mortality. Strategies to decrease the incidence of untreated candidemia may favorably impact outcome.

Changing Incidence ofCandidaBloodstream Infections Among NICU Patients in the United States: 1995–2004

Recent reports suggest that candidemia caused by fluconazole-resistant strains is increasing in certain adult populations. We evaluated the annual incidence of neonatal candidemia and the frequency of disease caused by different species of Candida among neonates in the United States. The study included neonates admitted to 128 NICUs participating in the National Nosocomial Infections Surveillance system from January 1, 1995, to December 31, 2004 (study period). Reports of bloodstream infection (BSI) with Candida spp.; Candida BSIs, patient admissions, patient-days, and central venous catheter days were pooled by birth weight category. The number of Candida BSIs per 100 patients (attack rate) and per 1000 patient-days (incidence density) was determined. Both overall and species-specific rates were calculated; data were pooled over time to determine the differences by birth weight category and by year to determine trends over time. From the 130,523 patients admitted to NICUs during the study period, there were 1997 Candida spp. BSIs reported. Overall, 1472 occurred in the <1000-g birth weight group. Candida albicans BSIs were most common, followed by Candida parapsilosis, Candida tropicalis, Candida lusitaniae, Candida glabrata, and only 3 Candida krusei. Among neonates <1000 g, incidence per 1000 patient-days decreased from 3.51 during 1995-1999 to 2.68 during 2000-2004 but remained stable among heavier neonates. No increase in infections by species that tend to demonstrate resistance to fluconazole (C glabrata or C krusei) was observed. Although Candida BSI is a serous problem among neonates <1000 g, incidence has declined over the past decade, and disease with species commonly resistant to azoles was extremely rare.