Candida Bloodstream Infections Research Articles

1166. Evaluating the Impact of the 2016 Candidemia Guidelines on the Incidence of Ocular Complications of Candidemia

BackgroundThe incidence of Candida bloodstream infections has risen over the last several decades. Complications of candidemia include endogenous fungal endophthalmitis which can result in devastating outcomes including vision loss. In 2015, the IDSA guidelines were updated to recommend echinocandins as initial therapy for candidemia. Given the poor ocular penetration of echinocandins there has been some concern this change may portend an increased incidence of ocular complications in candidemic patients. We sought to examine whether patients who received empiric echinocandin therapy developed higher rates of ophthalmic complications of candidemia.MethodsWe identified patients in our healthcare system who had blood cultures positive for Candida species and a completed ophthalmology consult between January 1, 2014 and April 30, 2019. Chi-squared analysis was used to compare antifungal prescribing patterns before and after release of the updated IDSA guidelines. We assessed whether the switch to empiric echinocandin therapy as directed by the guidelines was associated with higher rates of abnormal eye exams.Results47 patients treated before the guideline change were compared to 57 patients treated after the guideline change. There was no significant difference in age, gender, or comorbid diabetes and hypertension between the groups. Before the guideline change, 24/47 (51%) of patients received eye-penetrating antifungals. This decreased to 21/57 after the updated guideline (37%, p=0.21). The percentage of patients with positive eye exams was nearly equal before and after the updated guidelines, 10/47 (21%) before vs 13/57 (22%) after (p=1). After the guideline change, 7/21 (33%) of the patients treated with penetrating antifungals had positive eye exams vs 6/36 (16%) who received echinocandins (p=0.19).ConclusionEchinocandins are known to have poor ocular penetration yet our data demonstrate no change in the incidence of ophthalmic complications of candidemia after the 2016 guideline endorsed echinocandins as empiric therapy. The prevalence of positive eye exams throughout our study period was 22%, suggesting ongoing utility for these exams. Ongoing investigation is necessary to confirm and further study these findings.Disclosures All Authors: No reported disclosures

A seven-year surveillance of Candida bloodstream infection at a university hospital in KSA

ObjectivesCandidemia incidence has increased in the past few years, with high mortality. Previous studies have reported a variable distribution of Candida spp. among different regions. This study aimed to identify the species found in Candida bloodstream infections, routine antifungal susceptibility testing, and mortality outcomes in an academic medical centre. MethodsBetween January 2012 and December 2018, the positive blood cultures for candidemia infection were retrieved and statistically analysed for species prevalence, susceptibility pattern, and crude mortality at 14, 30, 60 and 90 days. ResultsOf 156 candidemia cases, a majority (69.2%) was caused by non-albicans Candida spp. After Candida albicans (30.8%), Candida tropicalis and Candida parapsilosis were the second and third most frequeunt isolates spp, each counting for 23.7%. Acquired resistance was detected in 14.8% of candidemia strains. No other antifungal resistance was detected. The overall crude mortality rates of all species were 29.3%, 47.9%, 56.4%, and 58.0% at 14, 30, 60, and 90 days, respectively. A higher mortality rate was noted in cases of Candida krusei infection (crude mortality 71.4–100%, p = 0.002). ConclusionIn this study, a considerable shift to non-albicans Candida causing most bloodstream infections was observed. As such infections pose a serious threat to hospitalised patients, microbiology laboratories are urged to adopt rapid diagnostic and minimal inhibitory concentration-based testing for the detection of susceptible dose-dependent phenotypes. Prospective studies are essential to consider the prognosis of bloodstream infections by various Candida species in a multivariate model.

Wickerhamomyces anomalous: A Rare Cause of Fungemia Causing Febrile Neutropenia in Acute Lymphoblastic Leukemia

Candida bloodstream infection is the major cause of increased morbidity and mortality (20–49%) in hospitalized patients in both paediatric and adult age groups. Due to the increase in the number of immunocompromised patients, other important species such as Trichosporon asahii and Debaryomyces hansenii are emerging. One such organism, Wickerhamomyces anomalous, previously known as Pichia anomala (teleomorph stages of several Candida species), is increasingly being reported as a cause of fungemia in neonatal intensive care units and is now increasingly being reported in a lot of immunosuppressive conditions such as interstitial lung disease, endocarditis, enteritis, corticosteroids, and chemotherapy uptake. Though this yeast is ubiquitous in nature, systemic infections from isolated cases and sporadic outbreaks with high mortality have been reported in ICUs, which emphasize the importance to consider this fungus within the diagnostic possibilities. Here, we report a case of catheter-related bloodstream infection (CRBSI) caused by W. anomalus in a leukemic immunosuppressed patient who was successfully treated by early detection and treatment of this emerging fungus.

Enhanced Molecular Diagnosis of Bloodstream Candida Infection with Size-Based Inertial Sorting at Submicron Resolution.

Inertial microfluidics has been proven to be a powerful tool for high-throughput, size-based cell sorting in diverse biomedical applications. In the case of Candida-related sepsis, Candida species and major blood cells (i.e., red blood cells and white blood cells) have a size distribution of 3-5 and 6-30 μm, respectively. To effectively retrieve a majority of Candida species and remove most of the interfering blood cells for accurate molecular analysis, inertial sorting of micron-sized biological particles with submicron size difference is highly desired, but far unexplored till now. In this work, we present a new channel design for an inertial microfluidic sorting device by embedding microsquares to construct periodic contractions along a series of repeating curved units. This unique channel design allows us to enhance inertial lift force at the microsquare zone and produce localized secondary Dean flow drag force in addition to global Dean flow drag force. This inertial sorting device has successfully separated 5.5 μm particles from 6.0 μm particles with a recovery ratio higher than 80% and a purity higher than 92%, demonstrating a size-based inertial sorting at submicron resolution (i.e., 0.5 μm). We further applied this inertial sorting device to purify Candida species from whole blood sample for enhanced molecular diagnosis of bloodstream Candida infection and especially compared it with the commonly used lysis-centrifugation-based purification method (STEM method) by recovering two species of Candida (Cornus glabrata and Candida albicans) from Candida-spiked blood samples. Through quantitative polymerase chain reaction (qPCR) analysis, we found that our inertial sorting approach has nearly 3-fold improvement on the pathogen recovery than the STEM method at pathogen abundances of 103 cfu/mL and 102 cfu/mL. The present inertial sorting at submicron resolution provides a simple, rapid, and efficient pathogen purification method for significantly improved molecular diagnosis of bloodstream Candida infection.

European confederation of medical mycology quality of clinical candidaemia management score: A review of the points based best practice recommendations.

Candidaemia is associated with high mortality. In the last few years, several guidelines have been published on the management of Candida bloodstream infection. However, adherence to the practice guidelines has been suboptimal. In order to facilitate and objectively measure the adherence to good practice recommendations, a scoring criterion was published by the European Confederation of Medical Mycology (ECMM). The ECMM Quality (EQUAL) of Clinical Candidaemia Management is an audit tool that comprises of 10 quality indicators. Each quality indicator is allotted between 1 and 3 points. The maximum achievable score is 22 or 19 in patients with or without a central venous catheter, respectively. This paper reviews each of the 10 quality indicators and provides the context for improving quality within the individual domains. The review also suggests areas that are in need of further clarity or areas which merit attention in the future updates of the EQUAL scoring system so that clinicians are able to derive maximum benefit from the audit tool. The EQUAL scoring tool is an important milestone in the quality improvement aspect of the management of candidaemia and contributes to the various components of clinical governance in the management of Candida infection of the bloodstream.

Epidemiology, clinical characteristics, and outcome of candidemia in critically ill patients in Germany: a single-center retrospective 10-year analysis

BackgroundDespite advances in the management of bloodstream infections (BSI) caused by Candida spp., the mortality still remains high in critically ill patients. The worldwide epidemiology of yeast-related BSI is subject to changing species distribution and resistance patterns, challenging antifungal treatment strategies. The aim of this single-center study was to identify predictors of mortality after 28 and 180 days in a cohort of mixed surgical and medical critically ill patients with candidemia.MethodsPatients, who had been treated for laboratory-confirmed BSI caused by Candida spp. in one of 12 intensive care units (ICU) at a University hospital between 2008 and 2017, were retrospectively identified. We retrieved data including clinical characteristics, Candida species distribution, and antifungal management from electronic health records to identify risk factors for mortality at 28 and 180 days using a Cox regression model.ResultsA total of 391 patients had blood cultures positive for Candida spp. (incidence 4.8/1000 ICU admissions). The mortality rate after 28 days was 47% (n = 185) and increased to 60% (n = 234) after 180 days. Age (HR 1.02 [95% CI 1.01–1.03]), a history of liver cirrhosis (HR 1.54 [95% CI 1.07–2.20]), septic shock (HR 2.41 [95% CI 1.73–3.37]), the Sepsis-related Organ Failure Assessment score (HR 1.12 [95% CI 1.07–1.17]), Candida score (HR 1.25 [95% CI 1.11–1.40]), and the length of ICU stay at culture positivity (HR 1.01 [95% CI 1.00–1.01]) were significant risk factors for death at 180 days. Patients, who had abdominal surgery (HR 0.66 [95% CI 0.48–0.91]) and patients, who received adequate (HR 0.36 [95% CI 0.24–0.52]) or non-adequate (HR 0.31 [95% CI 0.16–0.62]) antifungal treatment, had a reduced mortality risk compared to medical admission and no antifungal treatment, respectively.ConclusionsThe mortality of critically ill patients with Candida BSI is high and is mainly determined by disease severity, multiorgan dysfunction, and antifungal management rather than species distribution and susceptibility. Our results underline the importance of timely treatment of candidemia. However, controversies remain on the optimal definition of adequate antifungal management.

A Statewide Assessment of Antifungal Stewardship Activities in Acute-Care Hospitals in Connecticut

Background: Morbidity and mortality associated with invasive fungal infections and concerns of emerging antifungal resistance have highlighted the importance of optimizing antifungal therapy among hospitalized patients. Little is known about antifungal stewardship (AFS) practices among acute-care hospitals. We sought to assess AFS activities within Connecticut and to identify opportunities for improvement. Methods: An electronic survey assessing AFS practices was distributed to infectious disease physicians or pharmacy antibiotic stewardship program leaders in Connecticut hospitals. Survey questions evaluated AFS activities based on antibiotic stewardship principles, including several CDC Core Elements. Questions assessed antifungal restriction, prospective audit and feedback practices, antifungal utilization measurements, and the perceived utility of a local or statewide antifungal antibiogram. Results: Responses were received from 15 respondents, which represented 20 of 31 hospitals (65%); these hospitals made up the majority of the acute-care hospitals in Connecticut. Furthermore, 18 of these hospitals (58%) include antifungals in their stewardship programs. Also, 16 hospitals (52%) conduct routine review of antifungal ordering and provide feedback to providers for some antifungals, most commonly for amphotericin B, voriconazole, micafungin, isavuconazole, and flucytosine. All hospitals include guidance on intravenous (IV) to oral (PO) conversions, when appropriate. Only 14 of hospitals (45%) require practitioners to document indication(s) for systemic antifungal use. Most hospitals (17, 55%) provide recommendations for de-escalation of therapy in candidemia, though only 4 (13%) have institutional guidelines for candidemia treatment, and only 11 hospital mandates an infectious diseases consultation for candidemia. Assessing outcomes pertaining to antifungal utilization is uncommon; only 8 hospitals (26%) monitor days of therapy and 5 (16%) monitor antifungal expenditures. Antifungal susceptibility testing on Candida bloodstream isolates is performed routinely at 6 of the hospitals (19%). Most respondents (19, 95%) support developing an antibiogram for Candida bloodstream isolates at the statewide level. Conclusions: Although AFS interventions occur in Connecticut hospitals, there are opportunities for enhancement, such as providing institutional guidelines for candidemia treatment and mandating infectious diseases consultation for candidemia. The Connecticut Department of Public Health implemented statewide Candida bloodstream isolate surveillance in 2019, which includes antifungal susceptibility testing. The creation of a statewide antibiogram for Candida bloodstream infections is underway to support empiric antifungal therapy.Funding: NoneDisclosures: None

Epidemiology, risk factors, treatment and outcome of Candida bloodstream infections because of Candida albicans and Candida non-albicans in two district general hospitals in the United Kingdom.

Bloodstream infections caused by Candida species, known as candidemia are on the rise because of increasing complexity of surgical procedures, patient's underlying co-morbidities and shift in patient's demographics. This study was conducted to evaluate the epidemiology, risk factors, co-morbidities, antifungal treatment and outcomes of candidemia in Candida albicans (C. albicans) and Candida non-albicans (C. non-albicans) in East Sussex Healthcare Trust (ESHT), England. This retrospective and prospective study was performed during January 2006 to June 2017. A total of 102 episodes of candidemia on 100 patients (55 males) were identified. C. non-albicans were predominant (55%). All isolates were sensitive to amphotericin B, caspofungin and voriconazole while one C. albicans and five C. non-albicans isolates were resistant to fluconazole. The risk factors in C. albicans and C. non-albicans groups were comparable which included intensive care unit (ICU) stay (15% vs 10%), the presence of intravascular line (35% vs 42%), previous antibiotic exposure (39% vs 49%), surgical intervention (19% vs 19%), mechanical ventilation (5% vs 8%), total parenteral nutrition (30% vs 27%) and urinary catheters (33 vs 38). The comorbidities in both groups (C. albicans and C. non-albicans) were solid organ cancer (15&14), haematology malignancy (1&3), steroid use (14&13), diabetes (9&7) and chemotherapy (2&4). Main sources of candidemia in C. albicans were line (12), respiratory (10) and urinary tracts (6) while line (26) and urinary tract (9) were predominant in C. non-albicans group. Only a small number of patients underwent echocardiography (30%) and ophthalmology reviews (20%). A total of 45 fatal cases were recorded (C. albicans 23). The highest mortality was seen in patients with C. albicans and among them the risk factors were elderly age group>65years (17/23), surgical intervention (9/23) and the history of ICU stay (7/23). C. albicans candidemia, >65years of age and surgical procedure is associated with significant mortality, however, the use of fluconazole has shown the increased survival rate. This study suggests the surveillance of candidemia, and antifungal susceptibility pattern in current practice and the treatment.

Candidaemia in the elderly: Epidemiology, management and adherence to the European Confederation of Medical Mycology quality indicators.

Candidaemia in the elderly has not been extensively investigated. We compared the management of candidaemia in the elderly patients (age ≥65years) and the very elderly subgroup of patients (age ≥75years) with those belonging to the younger group (age <65years) using the European Confederation of Medical Mycology (ECMM) Quality (EQUAL) standard. Over a 10-year period (April 2011-March 2020), patients with candida bloodstream infection were identified. Data pertaining to demographics, clinical risk factors, antifungal treatment, central venous catheter and investigations such as echocardiogram and fundoscopy were obtained from electronic sources and medical case notes. A total of 174 episodes of candidaemia were recorded, comprising of 74 episodes in younger patients and 100 in the elderly, of whom 56 were in the very elderly patients. Of the 177 Candida species recovered, 79 were Candida albicans. EQUAL scores were analysed for 148 patients. The mean score was significantly lower in the elderly (10.4) and the very elderly (9.7) patients compared to the patients in the younger age group (12.19) (P<.01). In particular, this was due to lower blood culture volume drawn (P<.01) and, in the very elderly group, significantly lower scores for the quality indicators pertaining to echocardiogram and fundoscopy (P=.03). The overall mean EQUAL score was 11.16 (median 11; interquartile range 8-14). The 30-day survival was 68% and was similar between all groups. Areas of improvement were identified in the management of candidaemia in the elderly patients.

Neonatal Candidemia: Clinical Presentation, Laboratory Profile, Risk Factors and Immediate Outcome in a Tertiary Hospital in Kerala- A Case-Control Study

Objective: To identify the clinical and laboratory profile and risk factors of bloodstream candida infection in newborns and to assess the immediate outcome of candidemia in newborns. Design: Case -control study. Setting: Tertiary care NICU of Govt. T.D. Medical College, Alappuzha, Kerala from 1st January 2010 to 31st December 2014. Methods: Through consecutive sampling, we got 94 cases and 188 controls. For comparison, chi-square test was used, and for strength association Odds ratio was used. Analysis was done using SPSS V18. Binary logistic regression has been used to identify independent risk factors.

Mortality and risk factor analysis for Candida blood stream infection: A three-year retrospective study

BackgroundThe aim of this study was to evaluate the possible risk factors for mortality in adult patients with candidemia by investigating the causative agents, underlying conditions and predisposing factors. Material and methodsThe data including causative Candida species, predisposing factors, and underlying conditions of candidemia patients between the years 2015–2017 were collected and the impact of these factors on mortality was evaluated. Patients were divided into two groups as died (died patients within 30 days of the onset of candidemia) and survived and risk factors were evaluated for each group. ResultsWe found 163 adult candidemia cases during the study period. Overall 30-day mortality was 40.5%. Candida parapsilosis was the most frequent causative agent (49.1%). C. parapsilosis candidemia was more common in the survived group compared with the died group (n: 49 (61.3%) vs. n: 31 (38.8%), P=0.888). Mortality rates were significantly higher in patients with dialysis (n: 27 (69.2%) vs. n: 12 (30.8%), P<0.00) and concurrent bacteremia (n: 20 (57.1%) vs. n: 15 (42.9%), P=0.024). Survival rates were significantly higher in patients with follow-up blood cultures (n: 75 (65.8%) vs. n: 39 (34.2%), P=0.013). The most important source of candidemia was catheter (49.7%), and C. parapsilosis was the most common causative agent (58%). The catheter was removed in 96.3% of these patients and the mortality rate was 38.5%. All of the patients received antifungal therapy and there was no significant difference between the effects of antifungals on mortality (n: 65 (39.9%) vs. 98 (60.1%), P=0.607). ConclusionsDialysis and concurrent bacteremia are strong predictors of mortality in 30 days within patients with candidemia, whereas follow-up blood cultures have a protective role with lower mortality rates. In our study, the most important source of candidemia was catheter, and C. parapsilosis was the most common causative agent. The catheter was removed in almost all patients and the mortality rate was almost one third among these patients.

Candidemia: characteristics in elderly patients

Candidemia is a nosocomial bloodstream infection and an important cause of comorbidity and mortality. Elderly patients present the highest rates of candidemia but data about this population is scarce. To describe characteristics of candidemia in elderly patients, to identify risk factors associated with mortality and to evaluate the usefulness of a predictive score. A retrospective observational study of candidemia in elderly patients from a tertiary care hospital was carried out. We analyzed all Candida bloodstream infections during an eight-year period in patients older than 60 years. Fifty-nine episodes were included. Diabetes was the most frequent comorbidity. Most candidemia were catheter related infections (45%). Only 17% of patients had a Candida score > 2.5. Overall mortality at 48 hours was 20%, and at 15 days was 49%. Mortality-related factors were shock, assisted mechanical ventilation, thrombocytopenia, renal failure and leukocytosis (p range < 0.0001-0.006). On multivariate analysis septic shock was independently associated with mortality (HR 4.02 [CI 95% 1.18-13.72] p = 0.026). Nearly half of patients with candidemia died during the first fifteen days. Shock, assisted mechanical ventilation, thrombocytopenia, renal failure, and leukocytosis were factors associated with mortality. The predictive score was not useful in this population.

Integrating GWAS with bulk and single-cell RNA-sequencing reveals a role for LY86 in the anti-Candida host response.

Candida bloodstream infection, i.e. candidemia, is the most frequently encountered life-threatening fungal infection worldwide, with mortality rates up to almost 50%. In the majority of candidemia cases, Candida albicans is responsible. Worryingly, a global increase in the number of patients who are susceptible to infection (e.g. immunocompromised patients), has led to a rise in the incidence of candidemia in the last few decades. Therefore, a better understanding of the anti-Candida host response is essential to overcome this poor prognosis and to lower disease incidence. Here, we integrated genome-wide association studies with bulk and single-cell transcriptomic analyses of immune cells stimulated with Candida albicans to further our understanding of the anti-Candida host response. We show that differential expression analysis upon Candida stimulation in single-cell expression data can reveal the important cell types involved in the host response against Candida. This confirmed the known major role of monocytes, but more interestingly, also uncovered an important role for NK cells. Moreover, combining the power of bulk RNA-seq with the high resolution of single-cell RNA-seq data led to the identification of 27 Candida-response QTLs and revealed the cell types potentially involved herein. Integration of these response QTLs with a GWAS on candidemia susceptibility uncovered a potential new role for LY86 in candidemia susceptibility. Finally, experimental follow-up confirmed that LY86 knockdown results in reduced monocyte migration towards the chemokine MCP-1, thereby implying that this reduced migration may underlie the increased susceptibility to candidemia. Altogether, our integrative systems genetics approach identifies previously unknown mechanisms underlying the immune response to Candida infection.

Candida bloodstream infection in patients with systemic autoimmune diseases

ObjectivesTo describe the epidemiological, clinical and microbiological characteristics and mortality of patients with Candida bloodstream infection and systemic autoimmune diseases. MethodsWe performed a retrospective multicenter study of candidemia in adults with systemic autoimmune diseases between 2010 and 2016. ResultsAmong 1040 patients with candidemia, 36 (3.5%) had a systemic autoimmune disease. The most common systemic autoimmune disease was rheumatoid arthritis (27.8%). The most common species was Candida albicans (66.7%). Twenty-two (61.1%) patients received a corticosteroid therapy and nine (25%) received an immunosuppressive therapy at the time of candidemia. The mortality rate was 27.8%. ConclusionsSystemic autoimmune diseases are not common in patients with candidemia. The unadjusted mortality rate was comparable to other candidemia studies in the general population.

Impact of Obesity in Patients with Candida Bloodstream Infections: A Retrospective Cohort Study.

BackgroundCandida species are responsible for 15% of bloodstream infections, leading to prolonged hospitalizations and increased mortality. With the rise in obesity, antifungal dosing is unclear. The purpose of this study was to determine differences in clinical outcomes between obese versus non-obese patients with Candida bloodstream infections.MethodsThis retrospective cohort included adult patient’s first episode of Candida bloodstream infection treated with ≥ 48 h of antifungal therapy between 1 June 2013 and 31 August 2019. Patients were excluded for: dual systemic antifungal therapy, polymicrobial infections, or chronic candidiasis. The primary outcome was infection-related length of stay. Secondary outcomes included: time to candidemia resolution, 30-day readmission rates, and in-hospital mortality.ResultsEighty patients were included (28 obese; 52 non-obese). Most were male (55%); median age was 54 years. Median BMI and weight were 36.3 kg/m2 and 103 kg versus 20.4 kg/m2 and 61 kg, respectively (p < 0.01). Baseline characteristics were comparable. C. albicans was isolated in 37.5% of cultures and C. glabrata in 30%. Micafungin was utilized empirically in 72.5% of patients; obese patients received definitive micafungin more frequently (57.1% vs. 21.2%; p < 0.01) and were treated longer (13 versus 10 days; p = 0.04). Infection-related length of stay was 19 days in the obese patients and 13 days in the non-obese patients (p = 0.05). Non-obese patients had a shorter duration of candidemia (5 versus 6 days; p = 0.02). In-hospital mortality was numerically higher in obese patients (21.4% versus 13.5%; p = 0.36). There were no differences in 30-day readmissions between groups.ConclusionsWorse clinical outcomes were observed for obese versus non-obese patients. Further clinical research is warranted.

Trouble brewing in the gut

Infection Invasive infections with fungi like Candida albicans can be a serious complication of organ transplantation and chemotherapy. One possible explanation is that these procedures alter the intestinal microbiota, which may provide an opening for opportunistic fungi. For better insight into this relationship, Zhai et al. investigated patients receiving allogeneic hematopoietic stem cell transplants. They used high-resolution mycobiota and microbiota sequencing of recipients' blood and feces to track the dynamics of infection. A pronounced loss of bacterial microbiota and diversity (especially of anaerobes) was accompanied by expansion of pathogenic Candida species in the intestine. This overgrowth in the gut preceded bloodstream Candida infections. In the future, similar monitoring approaches may be used to better target patients at risk for invasive fungal infections. Nat. Med. 26 , 59 (2020).

Efficacy of a "Checklist" Intervention Bundle on the Clinical Outcome of Patients with Candida Bloodstream Infections: A Quasi-Experimental Pre-Post Study.

IntroductionTo evaluate the clinical impact of a comprehensive care bundle for the management of candidemia.MethodsA quasi-experimental pre-post study was implemented. During the pre-intervention period (May 2014–September 2015), a non-mandatory antifungal stewardship program (ASP) was implemented, and patients with candidemia were visited by an infectious disease specialist who provided diagnostic and therapeutic advice according to standard of care as soon as possible. During the post-intervention period (October 2015–May 2017), patients were managed according to a candidemia care bundle with clear and structured recommendations written in their medical history.ResultsOverall, 109 patients were included, 56 in the pre-intervention and 53 in the post-intervention period. Overall, compliance with the Candida bundle significantly improved between the pre- [27/56 (48.2%)] and post-intervention [43/53 (81.1%); p = 0.01] period. Individual bundle components that significantly improved in the post-intervention period were early adequate antifungal therapy [47/56 (83.9%) vs. 51/53 (96.2%), p = 0.05], early adequate source control of the infection [37/56 (82.2%) vs. 41/53 (97.6%), p = 0.03] and appropriate duration of therapy [27/56 (48.2%) vs. 43/53 (81.1%), p = 0.01]. Adherence to follow-up blood cultures, ophthalmologic examination and echocardiography improved in the post-intervention period, but the difference was not statistically significant. Multivariate analysis revealed that being managed according to candidemia bundle had a favorable impact on 14-day mortality (HR 0.08, 95% CI 0.01–0.45, p = 0.02) and 30-day mortality (HR 0.40, 95% CI 0.18–0.89, p = 0.02).ConclusionsA simple bundle focused on increasing adherence to a few evidence-based interventions contributed to a significant reduction in 14- and 30-day mortality in patients with candidemia.

The epidemiology and clinical characteristics of candida blood stream infection: 6 years experience in a tertiary care center

The epidemiology and clinical characteristics of candida blood stream infection: 6 years experience in a tertiary care center

Antifungal resistance in patients with Candidaemia: a retrospective cohort study

BackgroundCandidaemia is the most common form of invasive candidiasis. Resistant Candida blood stream infection (BSI) is rising, with limitations on the development of broader-spectrum antifungal agents worldwide. Our study aimed to identify the occurrence of antifungal-resistant candidaemia and the distribution of these species, determine the risk factors associated with antifungal resistance and evaluate the association of antifungal-resistant candidaemia with the length of intensive care unit (ICU) and hospital stay and with 30-day mortality.MethodsA retrospective cohort study was conducted at King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia. Adult patients diagnosed with candidaemia from January 2006 to December 2017 were included.ResultsA total of 196 BSIs were identified in 94 males (49.74%) and 95 females (50.26%). C. glabrata was the most commonly isolated Candida species, with 59 (30%), followed by C. albicans with 46 (23%). Susceptibility data were available for 122/189 patients, of whom 26/122 (21%) were resistant to one or more antifungals. C. parapsilosis with available sensitivity data were found in 30/122 isolates, of which 10/30 (33%) were resistant to fluconazole. Risk factors significantly associated with antifungal-resistant candidaemia included previous echinocandin exposure (odds ratio (OR) =1.38; 95% confidence interval (CI) (1.02–1.85); P = 0.006) and invasive ventilation (OR = 1.3; 95% CI (1.08–1.57); P = 0.005). The median length of ICU stay was 29 days [range 12–49 days] in the antifungal-resistant group and 18 days [range 6.7–37.5 days] in the antifungal-sensitive group (P = 0.28). The median length of hospital stay was 51 days [range 21–138 days] in the antifungal-resistant group and 35 days [range 17–77 days] in the antifungal-sensitive group (P = 0.09). Thirty-day mortality was 15 (57.7%) and 54 (56.25%) among the antifungal-resistant and antifungal-sensitive groups, respectively (OR = 1.01; 95% CI (0.84–1.21); P = 0.89).ConclusionsOur results indicate a high frequancy of non- C. albicans candidaemia. The rise in C. parapsilosis resistance to fluconazole is alarming. Further studies are required to confirm this finding.

High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis.

The intestinal microbiota is a complex community of bacteria, archaea, viruses, protists and fungi1,2. While the composition of bacterial constituents has been linked to immune homeostasis and to infectious susceptibility3–7, the role of non-bacterial constituents and of cross-kingdom microbial interactions in these processes is poorly understood2,8. Fungi represent a major cause of infectious morbidity and mortality in immune-compromised individuals, though the relationship of intestinal fungi (i.e., the mycobiota) with fungal bloodstream infections (BSI) remains undefined9. We integrated an optimized bioinformatics pipeline with high-resolution mycobiota sequencing and comparative genomic analyses of fecal and blood specimens from recipients of allogeneic hematopoietic cell transplant (allo-HCT). Patients with Candida BSI experienced a prior marked intestinal expansion of pathogenic Candida species; this expansion consisted of a complex dynamic between multiple species and subspecies with a stochastic translocation pattern into the bloodstream. The intestinal expansion of pathogenic Candida species was associated with a significant loss in bacterial burden and diversity, particularly in the anaerobes. Thus, simultaneous analysis of intestinal fungi and bacteria identifies dysbiosis states across kingdoms that may promote fungal translocation and facilitate invasive disease. These findings support microbiota-driven approaches to identify patients at risk for fungal BSI for pre-emptive therapeutic intervention.