Understanding clinical outcomes and factors influencing mortality in intensive care unit patients with COVID-19-associated candidemia.

BACKGROUND: During the COVID pandemic, research has shown an increase in candidemia cases following severe COVID infection and the identification of risk factors associated with candidemia. However, there is a lack of studies that specifically explore clinical outcomes and mortality rates related to candidemia after COVID infection. OBJECTIVES: The aim of this international study was to evaluate the clinical outcomes and identify factors influencing mortality in patients who developed candidemia during their COVID infection. PATIENTS/METHODS: This study included adult patients (18 years of age or older) admitted to the intensive care unit (ICU) and diagnosed with COVID-associated candidemia (CAC). The research was conducted through ID-IRI network and in collaboration with 34 medical centres across 18 countries retrospectively, spanning from the beginning of the COVID pandemic until December 2021. RESULTS: A total of 293 patients diagnosed with CAC were included. The median age of the patients was 67, and 63% of them were male. The most common Candida species detected was C. albicans. The crude 30-day mortality rate was recorded at 62.4%. The logistic regression analysis identified several factors significantly impacting mortality, including age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07, p < .0005), SOFA score (OR 1.307, 95% CI 1.17-1.45, p < .0005), invasive mechanical ventilation (OR 7.95, 95% CI 1.44-43.83, p < .017) and duration of mechanical ventilation (OR 0.98, 95% CI 0.96-0.99, p < .020). CONCLUSIONS: By recognising these prognostic factors, medical professionals can customise their treatment approaches to offer more targeted care, leading to improved patient outcomes and higher survival rates for individuals with COVID-associated candidemia.

Candidemia in thoracic solid organ transplant recipients: Characteristics and outcomes relative to matched uninfected and bacteremic thoracic organ transplant recipients.

BACKGROUND: Little is understood about the risk factors and outcomes from candidemia in thoracic solid organ transplant recipients. METHODS: This is a single-center retrospective cohort study of patients undergoing heart or lung transplant between January 1, 2013 and December 31, 2022. We performed two comparisons among heart and lung transplant recipients: (1) recipients with candidemia versus matched, uninfected recipients, and (2) recipients with candidemia versus recipients with bacteremia. RESULTS: During the study 384 heart and 194 lung transplants were performed. Twenty-one (5.5%) heart and six (3.1%) lung recipients developed candidemia. Heart recipients with candidemia were more likely to have had delayed chest closure (38.1% vs. 0%, p < .0001), temporary mechanical circulatory support (57.1% vs. 11.9%, p = .0003), and repeat surgical chest exploration 76.2% vs. 16.7%, p < .0001) than uninfected controls. Heart and lung recipients who developed candidemia were more likely to have been on renal replacement therapy prior to infection relative to uninfected controls (57.1% vs. 11.9%, p = .0003 and 66.7% vs. 0%, p = .0041, respectively). Heart recipients with candidemia had significantly lower post-transplant survival and lower post-infection survival relative to matched uninfected controls and heart recipients with bacteremia, respectively (p < .0001 and p = .0002, respectively). CONCLUSIONS: Candidemia following heart and lung transplantation is associated with significant morbidity and mortality. Further research is needed to understand if heart recipients with delayed chest closure, temporary mechanical circulatory support, renal replacement therapy, and repeat surgical chest exploration may benefit from targeted antifungal prophylaxis.

Clinical and microbiological characteristics of and risk factors for bloodstream infections among patients with extracorporeal membrane oxygenation: a single-center retrospective cohort study.

Extracorporeal membrane oxygenation (ECMO) provides hemodynamic and oxygenation support to critically ill patients. Due to multiple catheter cannulations, patients on ECMO are vulnerable to bloodstream infections (BSIs). We aimed to investigate the incidence, clinical characteristics, risk factors, and microorganisms associated with BSIs during ECMO. This single-center retrospective cohort study was conducted between January 2015 and May 2021. Patients aged 18 years or older with an ECMO duration of > 48 h for cardiogenic or respiratory support were included in the study. Patients who developed bacteremia or candidemia from 12 h after ECMO cannulation to 7 days after de-cannulation were included. The clinical factors between non-BSI and BSI were compared, along with an analysis of the risk factors associated with BSI during ECMO. A total of 480 patients underwent ECMO for cardiogenic shock (n = 267, 55.6%) or respiratory failure (n = 213, 44.4%) during the study period. The incidence was 20.0 episodes per 1000 ECMO-days. Approximately 20.2% (97/480) and 5.4% (26/480) of the patients developed bacteremia and candidemia, respectively. The median numbers of days of BSI development were 8.00 days for bacteremia and 11.0 days for candidemia. The most common pathogens were methicillin-resistant coagulase-negative staphylococci (n = 24), followed by vancomycin-resistant Enterococcus (n = 21). Multivariable logistic analysis demonstrated that hemodialysis (odds ratio [OR] 2.647, p < 0.001), veno-arterial-venous mode (OR 1.911, p = 0.030), and total ECMO duration (OR 1.030, p = 0.007) were significant risk factors for bacteremia. The total ECMO duration was the only risk factor associated with candidemia (OR 1.035, p = 0.010). The mortality rate was significantly higher in the bacteremia (57.7%) and candidemia (69.2%) groups than that in the non-BSI group (43.6%). BSI is a common complication of patients receiving ECMO support and is associated with poor clinical outcomes. Determining the type of frequently isolated organisms and the median onset time of BSI would help in the selection of appropriate prophylactic antibiotics or antifungal agents.

Characteristics and Outcomes of Candidemia in Patients with Durable Left Ventricular Assist Device Support.

There are limited data on the characteristics and clinical course of fungal infections in patients on durable left ventricular assist device (LVAD) support. We sought to further characterize the epidemiology and outcomes of LVAD patients with fungemia. We performed a retrospective review of patients receiving LVAD support from January 2012 through June 2020 at a large academic institution. Among 336 patients on LVAD support, five (1.4%) were diagnosed with fungemia during the study period. Three patients had diabetes with mean hemoglobin A1c 7.1% (R 6.6, 7.4). Fever and leukocytosis (mean white blood count 17.0 thousand/µL [R 12.5, 29.9]) were the most common symptoms. Fungemia was diagnosed early after LVAD implantation (mean 14.4 support days [R 2, 19]). All patients were infected with Candida species, and four isolates were susceptible to fluconazole. Central nervous system outcomes included an ischemic stroke, subarachnoid hemorrhage, and malignant hemorrhagic stroke. Two patients were successfully transplanted, and two patients on destination therapy remain on suppressive fluconazole. In conclusion, fungemia is a rare and severe complication in LVAD patients occurring early postimplant.

The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches.

BACKGROUND: Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients remains poorly defined. METHODS: In order to better define the host response to Candida infection at the transcriptional level, we performed RNA sequencing on serial peripheral blood samples from 48 hospitalized patients with blood cultures positive for Candida species and compared them to patients with other acute viral, bacterial, and non-infectious illnesses. Regularized multinomial regression was utilized to develop pathogen class-specific gene expression classifiers. RESULTS: Candidemia triggers a unique, robust, and conserved transcriptomic response in human hosts with 1641 genes differentially upregulated compared to healthy controls. Many of these genes corresponded to components of the immune response to fungal infection, heavily weighted toward neutrophil activation, heme biosynthesis, and T cell signaling. We developed pathogen class-specific classifiers from these unique signals capable of identifying and differentiating candidemia, viral, or bacterial infection across a variety of hosts with a high degree of accuracy (auROC 0.98 for candidemia, 0.99 for viral and bacterial infection). This classifier was validated on two separate human cohorts (auROC 0.88 for viral infection and 0.87 for bacterial infection in one cohort; auROC 0.97 in another cohort) and an in vitro model (auROC 0.94 for fungal infection, 0.96 for bacterial, and 0.90 for viral infection). CONCLUSIONS: Transcriptional analysis of circulating leukocytes in patients with acute Candida infections defines novel aspects of the breadth of the human immune response during candidemia and suggests promising diagnostic approaches for simultaneously differentiating multiple types of clinical illnesses in at-risk, acutely ill patients.

Characteristics, Risk Factors and Predictors for Candidemia in the Pediatric Intensive Care Unit at the University Hospital Centre Zagreb in Croatia: A 9-Year Retrospective Study.

BACKGROUND: Candidemia is one of the leading causes of bloodstream infections in the pediatric intensive care unit (PICU). The aim of this study was to define characteristics and risk factors for candidemia in the PICU setting and propose a predictive model to identify the patients at risk. METHODS: This was a retrospective matched case-control study in the PICU during a 9-year period. Patients with candidemia were studied and matched with control patients without candidemia. Univariate analysis was performed for potential risk factors and multivariate analysis was conducted to determine the prediction score for candidemia. RESULTS: Forty-two cases of candidemia were matched with 84 control patients. Candida parapsilosis was the most common (71.4%) species. Risk factors independently associated with candidemia were: the use of >2 antibiotics in a maximum period of 4 weeks before the candidemia (odds ratio [OR]: 10.59; 95% confidence interval [CI]: 2.05-54.83), a previous bacterial infection in a maximum period of 4 weeks before the candidemia (OR: 5.56; 95% CI: 1.44-21.5) and the duration of PICU stay of >10 days (OR: 4.22; 95% CI: 1.02-17.41). The proposed predictive scoring system has a sensitivity of 95.24%, specificity of 76.12%, OR 64.0, 95% CI 14.2-288.6, the positive predictive value of 66.67% and the negative predictive value of 96.97%. CONCLUSIONS: Previously reported risk factors for candidemia have been confirmed and some new have been detected. The presented scoring system can help identify patients who would benefit from prophylactic antifungal therapy.

Lack of relationship between genotype and virulence in Candida species / Ausencia de relación entre el genotipo y la virulencia en especies de Candida

BACKGROUND: The virulence of isolates among different Candida species causing candidemia may play a role in the prognosis of the patients. Furthermore, the potential relationship between genotype and virulence is still unclear and need to be further studied. AIMS: We aim to assess the relationship between genotype and virulence in Candida species using a Galleria mellonella larvae infection model. METHODS: One hundred and ninety-four isolates from 68 clusters (Candida albicans, 114/41; Candida parapsilosis, 74/24; Candida tropicalis, 6/3) were compared against the same number of each species singleton genotypes in terms of survival of G. mellonella larvae. RESULTS: The median of survival and the IQR ranges of clusters and singleton were as follows: C. albicans (2 days, IQR 1.5-2 vs. 2 days, IQR 1-2.25), C. parapsilosis (2 days, IQR 1.5-2.6 vs. 2 days, IQR 2-3.3), and C. tropicalis (1 day, IQR 1-3.5 vs. 2 days, IQR 2-3.5; p < 0.05). High intra-cluster variability in terms of median of survival was found regardless the species. CONCLUSIONS: No relationship between genotype and virulence in Candida was observed with the G. mellonella model

ANTECEDENTES: La virulencia de cepas de diferentes especies de Candida causantes de candidemia puede jugar un papel en el pronóstico de los pacientes, y su estudio en el modelo de infección en Galleria mellonella puede ser útil para entender su contribución general a la infección. Además, la potencial relación entre genotipo y virulencia requiere de más estudios. OBJETIVOS: Se evaluó la relación entre genotipo y virulencia en especies de Candida mediante el modelo de infección de larvas de G. mellonella. MÉTODOS: Se estudió la supervivencia de las larvas infectadas con 194 aislados incluidos en 68 clusters (Candida albicans, 114/41; Candida parapsilosis, 74/24; Candida tropicalis, 6/3) y con el mismo número de aislados con genotipos únicos por especie. RESULTADOS: La mediana de supervivencia y los rangos intercuartílicos (IQR) de clusters y genotipos únicos se muestra a continuación: C. albicans (2 días, IQR: 1,5-2 vs. 2 días, IQR: 1-2,25), C. parapsilosis (2 días, IQR: 1,5-2,6 vs. 2 días, IQR: 2-3,3), y C. tropicalis (un día, IQR: 1-3,5 vs. 2 días, IQR: 2-3,5; p < 0,05). Encontramos una importante variabilidad en la mediana de supervivencia entre cepas del mismo cluster, independientemente de la especie analizada. CONCLUSIONES: No se encontró relación entre el genotipo y la virulencia entre los aislados de Candida evaluados mediante el modelo de infección de G. mellonella

Impact of early candidemia on the long-term outcome of allogeneic hematopoietic stem cell transplant in non-leukemic patients: an outcome analysis on behalf of IDWP-EBMT.

We assessed the incidence and outcome of early candidemia after hematopoietic stem cell transplant (HSCT). The analysis included all first HSCTs performed from 2000 to 2015 in adult and pediatric patients with a non-leukemic disease and recorded in the EBMT registry. Overall survival (OS), non-relapse mortality (NRM), and relapse mortality (RM) were evaluated. Candidemia was diagnosed in 420 of 49,852 patients at a median time of 17 days post HSCT (range 0-100), the cumulative incidence being 0.85%. In 65.5% of episodes, candidemia occurred by day 30 after HSCT. The mortality rate by day 7 was 6.2%, whereas 100-day NRM was higher (HR 3.47, p < 0.0001), and 100-day OS was lower (HR 3.22, p < 0.0001) than that of patients without candidemia. After a median follow-up of 4.3 years, 5-year OS, NRM, and RM for patients with and without candidemia were 50.5% vs. 60.8%, p < 0.0001, 28.2% vs.18.8%, p < 0.0001, and 25.3% vs. 27.2%, p = 0.4, respectively. In conclusion, in non-leukemic transplant patients, the occurrence of an early episode of candidemia is rare but it is still associated with a negative effect on the outcome.

Characteristics of late recurrent candidemia in adult patients.

BACKGROUND AND OBJECTIVES: Candida species are one of the most common causes of health care-associated bloodstream infections. However, recurrent candidemia is rare, and the characteristics of late recurrent (LR) candidemia are partly unclear. Our aim was to evaluate the characteristics of LR candidemia in adult patients. PATIENTS AND METHODS: A retrospective cohort study was performed in the hospital district of Helsinki and Uusimaa in Finland (2007-2016). All candidemia cases were searched in an electronic database during the study period. Patients with LR candidemia were compared with patients with a single candidemia episode to evaluate the characteristics of LR candidemia. LR candidemia was defined as having at least two episodes of candidemia more than 30 days apart. RESULTS: We identified 24 episodes of LR candidemia in 20 patients. Patients with LR candidemia represented 6% of all patients with candidemia during the study period, and most of these cases were nosocomial. The median time between the first and the recurrent episode was 5.1 months. One-year mortality in LR candidemia was 45%. Underlying gastrointestinal disease (OR 7.21, 95% CI 2.52-20.61) and history of intra-venous drug use (IVDU) (OR 3.62, 95% CI 1.03-12.69) were independent risk factors for LR candidemia in the multivariable analysis. CONCLUSION: Our study indicates that the gastrointestinal tract may be a continuous source of infection in patients with chronic gastrointestinal diseases. Gastrointestinal diseases and IVDU should be regarded as risk factors for LR candidemia.

Risk factors for candidaemia: A prospective multi-centre case-control study.

OBJECTIVES: Candidaemia carries a mortality of up to 40% and may be related to increasing complexity of medical care. Here, we determined risk factors for the development of candidaemia. METHODS: We conducted a prospective, multi-centre, case-control study over 12 months. Cases were aged ≥18 years with at least one blood culture positive for Candida spp. Each case was matched with two controls, by age within 10 years, admission within 6 months, admitting unit, and admission duration at least as long as the time between admission and onset of candidaemia. RESULTS: A total of 118 incident cases and 236 matched controls were compared. By multivariate analysis, risk factors for candidaemia included neutropenia, solid organ transplant, significant liver, respiratory or cardiovascular disease, recent gastrointestinal, biliary or urological surgery, central venous access device, intravenous drug use, urinary catheter and carbapenem receipt. CONCLUSIONS: Risk factors for candidaemia derive from the infection source, carbapenem use, host immune function and organ-based co-morbidities. Preventive strategies should target iatrogenic disruption of mucocutaneous barriers and intravenous drug use.

Increased incidence of candidemia in a tertiary care hospital with the COVID-19 pandemic.

BACKGROUND: The incidence of candidemia in our hospital has been stable over an 18-year period (1.3 episodes per 1000 admissions). Since March 2020, we have observed an increase in cases of candidemia. METHODS: In March 2020, the hospital was prepared to receive patients with COVID-19, with cancellation of elective procedures, discharge of less sick patients and the activation of beds for COVID-19. We compared the incidence of candidemia in 2 periods: from January 2019 to February 2020 (period 1) and from March to September 2020 (period 2). RESULTS: We diagnosed 41 episodes of candidemia, 16 in period 1 and 25 in period 2 (9 COVID-19 patients). Compared with non-COVID-19 patients, COVID-19 patients with candidemia were more likely to be under mechanical ventilation (100% vs. 34.4%, P < .001). The median number of monthly admissions in period 1 and 2 was 723 (interquartile range 655-836) and 523 (interquartile range 389-574), respectively. The incidence of candidemia (per 1000 admissions) was 1.54 in period 1 and 7.44 in period 2 (P < .001). In period 2, the incidence of candidemia (per 1000 admissions) was 4.76 if we consider only cases of candidemia in non-COVID-19 patients, 2.68 if we consider only cases of candidemia in COVID-19 patients and 14.80 considering only admissions of patients with COVID-19. CONCLUSIONS: The increase in the incidence of candidemia in our hospital may be attributed to 2 factors: a reduction in the number of admissions (denominator) and the occurrence of candidemia in COVID-19 patients.

Candida nivariensis: Identification strategy in mycological laboratories.

Candida nivariensis is a cryptic fungal species classified within the Candida glabrata complex. It was described for the first time in 2005 by the means of DNA sequencing. We report a rare case of C. nivariensis deep-seated infection occurring in a 77-year-old man hospitalized for cysto-prostatectomy. Phenotypic testing based on the direct examination and the macroscopic features of the in vitro culture initially suggested C. glabrata species, while MALDI-TOF mass spectrometry enables correct identification. The isolate was found resistant to fluconazole, like in almost 20% of the reported cases. Herein, we present our practical strategy to reliably characterize this rare cryptic species. To date, MALDI-TOF mass spectrometry-based analysis showed very good results for such a purpose.

[Candida hellenica Candidemia Occurred After Esophagus Surgery]. / Özofagus Cerrahisi Sonrasi Gelisen Candida hellenica Kandidemisi.

In this study, a case of candidemia caused by Candida hellenica as the first report in our country was presented. Fluconazole and liposomal amphotericin B treatment was initiated in a 20-year-old male patient in October 2018 due to the diagnosis of candidemia following esophageal surgery. The patient had a history of multiple esophageal operations. The patient was discharged during the last 24 hours due to the lack of fever, improvement in general condition and lack of growth in blood cultures. Germination tube test of the Candida isolate grown in blood culture was negative and the colony morphology in corn meal tween 80 agar was not defining. It was identified as C.hellenica according to the profile obtained from the ID32C® (bioMérieux, France) method based on carbohydrate assimilation. The target ITS regions of the rRNA genes were amplified by polymerase chain reaction and sequenced using suitable primers for the confirmation of the identification on species level. The DNA sequences obtained were searched by using the "National Center for Biotechnology Information (BLAST)" (http://www.ncbi.nlm.nih.gov/ BLAST/) database and the isolate was identified as C.hellenica with a 99% homology with GenBank sequences. MALDI-TOF (Vitek MS, bioMerieux) could not identify the yeast isolate. The reference microdilution method was performed according to the recommendations of the Clinical and Laboratory Standards Institute in order to test the antifungal susceptibility. The minimal inhibitory concentrations for the isolate, determined after 24-hour incubation were 0.25 µg/ml for amphotericin B, 8 µg/ml for fluconazole, 0.25 µg/ml for voriconazole, and 0.25 µg/ml for itraconazole. As our case had a previous history of gastrointestinal tract surgery it was thought that gastrointestinal tract was the endogenous source of candidemia by leading to mucosal disruption and this mucosal disruption might facilitate the translocation of Candida. The carbohydrate assimilation test ID32C®, was able identify the causative agent of candidaemia at the species level in this case. However, uncommon or previously unrecognized organisms may be misidentified by commercial systems. While the phenotypic definition is sufficient in routine laboratories, it is mandatory to confirm the microorganism species definition by DNA sequence analysis, as done in this case. We have presented a correctly identifed and successfully treated candidemia case. Although the candidemia was not mortal in our patient, the mortality rate of candidemia which is 50%, should be remembered. A total of two C.hellenica infections have been reported in the literature, including one candidaemia and one respiratory tract colonization. Our successfully treated case was presented to draw attention to this rare infectious agent.

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

BACKGROUND: The 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 METHODS: The 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. RESULTS: We 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). CONCLUSIONS: Dialysis 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.

Fungal arthritis with adjacent osteomyelitis caused by Candida pelliculosa: a case report.

BACKGROUND: Candida sp. osteoarticular infection is rare and most often due to hematogenous seeding during an episode of candidemia in immunocompromised patients. However, the diagnosis can be delayed in patients with subtle symptoms and signs of joint infection without a concurrent episode of candidemia. CASE PRESENTATION: A 75-year-old woman presented with a three-year history of pain and swelling of the left knee. Candida pelliculosa was detected from the intraoperative tissue when the patient had undergone left total knee arthroplasty 32 months ago, but no antifungal treatment was performed. One year after the total knee arthroplasty, C. pelliculosa was repeatedly isolated from the left knee synovial fluid and antifungal treatment comprising amphotericin B deoxycholate and fluconazole was administered. However, joint infection had extended to the adjacent bone and led to progressive joint destruction. The patient underwent surgery for prosthesis removal and received prolonged antifungal treatment with micafungin and fluconazole. CONCLUSIONS: This case shows that C. pelliculosa, an extremely rare non-Candida albicans sp., can cause fungal arthritis and lead to irreversible joint destruction owing to delayed diagnosis and treatment.

Candida bloodstream infection in patients with systemic autoimmune diseases.

OBJECTIVES: To describe the epidemiological, clinical and microbiological characteristics and mortality of patients with Candida bloodstream infection and systemic autoimmune diseases. METHODS: We performed a retrospective multicenter study of candidemia in adults with systemic autoimmune diseases between 2010 and 2016. RESULTS: Among 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%. CONCLUSIONS: Systemic autoimmune diseases are not common in patients with candidemia. The unadjusted mortality rate was comparable to other candidemia studies in the general population.

Epidemiological features of nosocomial candidaemia in neonates, infants and children: A multicentre study in Iran.

Nosocomial bloodstream candidaemia is a life-threatening fungal infection with high morbidity and mortality, especially among paediatric patients undergoing intensive immunosuppressive therapy. Limited data on the epidemiology of candidaemia and susceptibility profiles are available for Iran. To characterise candidaemia epidemiology, comorbidity risk factors, species distribution, and antifungal susceptibility profiles among paediatric patients in Iran. This observational cross-sectional study enrolled 26 189 patients <18 years old at three reference paediatric hospitals in Mazandaran and Tehran over 2 years. Blood samples from patients with suspected fungal bloodstream infection were analysed using the BACTEC culture system. Fungal isolates were identified using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF) and DNA sequencing. Antifungal susceptibility testing was performed using the Clinical and Laboratory Standards Institute broth microdilution guideline. We observed 109 episodes of nosocomial candidaemia in paediatric patients with or without immunosuppressive therapy. The most common healthcare-associated factor was central vascular catheter use (97%). The all-cause mortality rate was 40%, of which 48% was attributable to candidaemia. While Candida albicans was the most frequent causative agent (49%), emerging and uncommon Candida species were also isolated. Candidaemia mortality by non-albicans Candida species was significantly higher than that by C. albicans (P < .05). All fluconazole-resistant species were non-albicans Candida species. Uncommon Candida species with reduced susceptibility to antifungals are emerging as major agents of nosocomial candidaemia in high-risk paediatric patients in Iran. Appropriate source control, antifungal regimens and improved antifungal stewardship are warranted for managing and decreasing the burden of nosocomial candidaemia.

Contribution of Genetic and Clinical Risk Factors to Development of Candidemia in Patients Receiving Home Parenteral Nutrition.

BACKGROUND: Patients receiving home parenteral nutrition (HPN) have an increased risk for central line-associated bloodstream infections (CLABSIs), including candidemia. Recently, 7 single-nucleotide polymorphisms (SNPs) in TLR1, CD58, LCE4A-Clorf68, and TAGAP have been associated with the development of candidemia. Identification of host-genetic as well as clinical risk factors may help to identify patients who have an increased susceptibility to such infections. The aim of this study was to investigate the relevance of the reported SNPs in patients receiving HPN, and to explore clinical risk factors associated with candidemia. METHODS: We analyzed blood samples of adult patients who started HPN between 1976 and 2017 at our referral center for intestinal failure. Primary outcome was the association between TLR1, CD58, LCE4A-Clorf68, or TAGAP SNPs and candidemia. Secondary outcomes included the relation between severity of infection and these SNPs, and clinical risk factors for candidemia. RESULTS: Of 341 included patients, 42 (12%) experienced a candidemia (range 1-6). None of the 7 SNPs were associated with candidemia or the severity of infection. The rate of non-Candida-related CLABSIs was significantly associated with candidemia (rate ratio, 1.29; 95% CI, 1.14-1.46; P < 0.001). CONCLUSIONS: None of 7 known SNPs in TLR1, CD58, LCE4A-Clorf68, or TAGAP were associated with candidemia or severity of infection in patients receiving HPN. The rate of non-Candida-related CLABSIs was significantly associated with the development of candidemia. The latter supports the key role of aseptic catheter handling with respect to Candida susceptibility in patients receiving HPN.

Diagnostic usefulness of differential time to positivity in neutropenic cancer patients with suspected catheter-related candidemia.

Methods for distinguishing catheter-related candidemia (CRC) from non-CRC before catheter removal remain limited. We thus evaluated the diagnostic performance of differential time to positivity (DTP) to diagnose CRC in neutropenic cancer patients with suspected CRC. Of the 35 patients enrolled, 15 (43%) with CRC (six definite and nine probable) and 17 (49%) with non-CRC were finally analyzed. Based on the receiver operating characteristic curve, the optimal cutoff value of DTP for diagnosing CRC was ≥1.45 hours with the sensitivity 80% (95% confidence interval [CI], 51-95) and specificity 100% (95% CI, 80-100), respectively.

Etiology and Outcome of Candidemia in Neonates and Children in Europe: An 11-year Multinational Retrospective Study.

BACKGROUND: Data on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia. MATERIAL AND METHODS: All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients' demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality. RESULTS: One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8-2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed. CONCLUSIONS: This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.