Comparison of blood cultures versus T2 Candida Panel in management of candidemia at a large community hospital.

The T2 Candida Panel (T2CP) has high sensitivity and specificity to detect candidemia. Its role in the diagnosis and management of candidemia compared to blood cultures (BC) remains unclear. The purpose of this study was to evaluate the T2CP versus BC in detecting and treating candidemia. A retrospective, observational cohort study was conducted to compare clinical outcomes in patients with candidemia identified by BC versus T2CP. Patients with a positive BC or T2CP for Candida spp. from January 2012 to August 2020 were grouped by initial method of detection (BC vs T2CP). Co-primary endpoints assessed included time to detection of candidemia and time to antifungal therapy. Key secondary endpoints included length of stay (LOS), ICU LOS, and mortality. One hundred sixty-three patients with a positive BC and 89 patients with a positive T2CP were included in the evaluation. The average time to detection of candidemia was significantly shorter in the T2CP group compared to BC group (9 vs 41 h, p < 0.001). The time to antifungal was also significantly shorter in the T2CP group compared to the BC group (4 vs 37 h, p < 0.001). However, LOS was significantly shorter in the BC positive group than the T2CP group with no difference in ICU LOS. There was no difference in in-hospital or 30-day mortality between the two groups. Of patients diagnosed with candidemia at our large community hospital, identification by T2CP led to faster detection and initiation of antifungal compared to blood cultures without improvement in LOS or mortality.

CD8+ T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion.

Lethal fungal sepsis causes high morbidity and mortality in intensive care patients. Fungal infections have an immunological basis, and it has been shown in recent studies that decreased CD8+ T-cell count in fungal infections is related to prognosis, while the underlying mechanism is still unclear. Here, a lethal fungal sepsis model induced by candidemia was created and we found a decreased CD8+ T-cell count and exaggerated apoptosis. Simultaneously, expression of light chain (LC)3B in CD8+ T cells increased, along with increased autophagosomes and accumulation of p62 in infected mice. We regulated the activity of the mammalian target of rapamycin (mTOR) pathway using T-cell-specific mTOR/ TSC1 deletion mice. We observed increased number of autophagosomes and expression of LC3B in CD8+T cells after T-cell-specific mTOR knockout, while accumulation of p62 was not ameliorated, and there was no increase in the number of autolysosomes. Apoptosis rate and expression of BIM, a pro-apoptotic gene, decreased in CD8+ T cells in mTOR-deletion mice but increased in TSC1-deletion mice. Our results showed increased CD8+ T-cell death in spleen of lethal fungal sepsis mice, and decreased expression of mTOR ameliorated CD8+ T-cell survival. mTOR may be a possible target to reverse CD8+ T-cell immune dysfunction in lethal fungal sepsis.

T2Candida magnetic resonance in patients with invasive candidiasis: Strengths and limitations.

T2Candida enables detection of five Candida species in whole blood within approximately 5 hours. Routinely drawn EDTA blood samples were prospectively stored and tested with T2Candida in patients with invasive candidiasis identified by routine index blood or sterile site cultures. T2Candida was compared to diagnostic blood and sterile site cultures and also performed with samples obtained prior and after collection of index cultures. T2Candida was evaluated with 133 samples of 32 patients with candidemia and 22 patients with deep-seated invasive candidiasis. In the candidemic group 28/32 (87.5%) patients had at least one positive T2Candida result at any time point. A total of 17/25 (68%) candidemic patients had a positive T2Candida sample that was drawn concurrently to the index blood culture. In the per patient analysis 17/18 (94.4%) candidemic patients with matched T2Candida samples and peripheral blood cultures at any timepoint had a positive T2Candida test. T2Candida revealed discordant Candida species identification in two candidemic patients. Six of 22 (27.3%) deep-seated IC patients had a positive T2Candida result. Despite advanced time-to-results the clinical value of T2Candida in diagnosing candidemia seems to be limited by missing blood culture positive cases. Positivity rates of T2Candida increased when serial T2Candida samples were tested. In patients with suspected deep-seated invasive candidiasis T2Candida might act as a blood based adjunct to sterile site cultures.

Time to and differential time to blood culture positivity for assessing catheter-related yeast fungaemia: A longitudinal, 7-year study in a single university hospital.

BACKGROUND: Time to positivity (TTP) and differential time to positivity (DTTP) between central and peripheral blood cultures are commonly used for bacteraemia to evaluate the likelihood of central venous catheter (CVC)-related bloodstream infection. Few studies have addressed these approaches to yeast fungaemia. OBJECTIVES: This study aimed to evaluate TTP and DTTP to assess CVC-related yeast fungaemia (CVC-RYF). PATIENTS/METHODS: We retrospectively analysed the results from 105 adult patients with incident fungaemia, with CVC removed and cultured, collected from 2010 to 2017. The bottles were incubated in a BioMérieux BacT/ALERT 3D and kept for at least 5 days. RESULTS: Of the 105 patients included, most were oncology patients (85.7%) and had of long-term CVC (79.6%); 32 (30.5%) had a culture-positive CVC (defined as CVC-RYF) with the same species as in blood culture, and 69.5% had culture-negative CVC (defined as non-CVC-RYF, NCVC-RYF). Candida albicans represented 46% of the episodes. The median TTP was statistically different between CVC-RYF and NCVC-RYF (16.8 hours interquartile range (IQR) [9.7-28.6] vs 29.4 hours [IQR 20.7-41.3]; P = .001). A TTP <10 hours had the best positive likelihood ratio (21.5) for CVC-RYF, although the sensitivity was only 28%. DTTP was available for 52 patients. A DTTP >5 hours had a sensitivity of 100% and a specificity of 71% for CVC-RYF. CONCLUSIONS: Since the median TTP was 17 hours and the most performing DTTP >5 hours, these delays are too long to take a decision in the same operational day. More rapid methods for detecting infected catheters should be tested to avoid unnecessary CVC withdrawal.

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.

Candida auris in various hospitals across Kuwait and their susceptibility and molecular basis of resistance to antifungal drugs.

BACKGROUND: Candida auris, a multidrug-resistant species, has the propensity of nosocomial transmission despite normal decontamination procedures. Here, we describe the isolation of C auris from patients in various hospitals in Kuwait during 2014-2018. Susceptibility to antifungal drugs and molecular basis of resistance to fluconazole, voriconazole and micafungin were also studied. METHODS: Candida auris (n = 314) obtained from 126 patients in eight hospitals were studied. All isolates were identified by PCR amplification and/or PCR-sequencing of ribosomal DNA (rDNA). Antifungal susceptibility was determined by Etest. Molecular basis of resistance to fluconazole and micafungin was studied by PCR-sequencing of ERG11 and FKS1 genes, respectively. FINDINGS: Bloodstream (n = 58), urine (n = 124), respiratory (n = 98) and other (n = 34) specimens yielded 314 C auris isolates. The proportion of bloodstream C auris among all yeast isolates was higher (42 of 307, 13.7%) in 2018 as compared to 2014-2017 (16 of 964, 1.7%) (P = .001). More bloodstream isolates (42 of 139) were cultured in 2018 than during 2014-2017 (16 of 175) (P = .001). Resistance to amphotericin B, fluconazole, voriconazole and micafungin was detected in 27.1%, 100%, 41.1% and 1.7% isolates, respectively. Fluconazole-resistant isolates contained either Y132F or K143R mutation in ERG11. Isolates with K143R mutation were additionally resistant to voriconazole. Micafungin-resistant isolates contained S639F mutation in hot spot 1 of FKS1. CONCLUSIONS: Our study highlights spreading of C auris in major hospitals across Kuwait and its increasing role as a bloodstream pathogen in 2018. Cross-resistance to voriconazole was also seen in isolates with K143R mutation in ERG11, while micafungin-resistant isolates harboured S639F mutation in hot spot 1 of FKS1.

Candida biofilm production is associated with higher mortality in patients with candidaemia.

BACKGROUND: Candidaemia is a common life-threatening disease among hospitalised patients, but the effect of the Candida biofilm-forming ability on the clinical outcome remains controversial. OBJECTIVE: The aim was to determine the impact of biofilms, specifically focusing on biofilm mass and metabolic activity, on the mortality in candidaemia. PATIENTS/METHODS: The clinical data of patients (n = 127) treated at the University of Debrecen, Clinical Centre, between January 2013 and December 2018, were investigated retrospectively. Biofilm formation was assessed using the crystal violet and XTT assays, measuring the biofilm mass and metabolic activity, respectively. Isolates were classified as low, intermediate and high biofilm producers both regarding biofilm mass and metabolic activity. The susceptibility of one-day-old biofilms to fluconazole, amphotericin B, anidulafungin, caspofungin and micafungin was evaluated and compared to planktonic susceptibility. RESULTS: Intermediate/high biofilm mass was associated with significantly higher mortality (61%). All Candida tropicalis, Candida parapsilosis and Candida glabrata isolates originating from fatal infections were intermediate/high biofilm producers, whereas this ratio was 85% for Candida albicans. Solid malignancy was associated with intermediate/high biofilm producers (P = .043). The mortality was significantly higher in infections caused by Candida strains producing biofilms with intermediate/high metabolic activity (62% vs. 33%, P = .010). The ratio of concomitant bacteraemia was higher for isolates forming biofilms with low metabolic activity (53% vs 28%, P = .015). CONCLUSIONS: This study provides evidence that the Candida biofilms especially with intermediate/high metabolic activity are related to higher mortality in candidaemia.

Prolonged Outbreak of Candida krusei Candidemia in Paediatric Ward of Tertiary Care Hospital.

BACKGROUND: A sudden rise of Candida krusei candidemia cases was noticed in our hospital within 1 year with maximum cases from paediatric unit. The present study reports the results of epidemiological investigation of possible outbreak of candidemia by C. krusei in paediatric unit at our tertiary care centre. METHODS: Clinical characteristics and risk factors associated with C. krusei candidemia were evaluated. Yeast identification and antifungal susceptibility testing was performed according to standard protocol. To find the potential source of C. krusei in hospital environment and hand colonization, swabs were collected from different fomites (n = 40) and hand washings from 24 health care workers (HCW), respectively. Infection control and prevention practices were intensified following the recognition of outbreak. Genetic typing was done by fluorescent amplified fragment length polymorphism (FAFLP) technique. Case-control comparison was performed with C. tropicalis and C. pelliculosa cases. RESULTS: Candida krusei fungaemia significantly affected paediatric group (82/186, 44%) as compared to adults (14/130, 10.8%; p < 0.001). Among paediatric group, maximum isolation was reported from neonatal unit of paediatric emergency (NUPE). C. krusei was isolated from hands of one HCW and washbasin in NUPE. FAFLP revealed clonality between blood and environmental isolates indicating cross-transmission of C. krusei. Gastrointestinal disease (p = 0.018), previous antibiotics (p = 0.021) especially to carbapenems (p = 0.039), was significant among C. krusei candidemia cases compared to C. pelliculosa cases. CONCLUSION: We report the largest outbreak of C. krusei candidemia in paediatric unit within 1 year with isolation of related strains from environment and hands of HCW. Routine screening of hand hygiene practices revealed non-compliance to standard practices leading to the increase in C. krusei candidemia cases.

Serological biomarkers of candidemia: a retrospective evaluation of three assays.

PURPOSE: Serologic testing allows for rapid detection of candidemia. More data are needed for the Virion\Serion ELISA antigen test (Ag), Hemkit Candida IHA antibody test (Ab), and Wako ß-1,3-D-glucan assay (BDG). METHODS: Tests were performed on serum samples from 120 cases of culture-confirmed candidemia and 44 Candida-negative controls. Sensitivities and specificities of individual tests as well as combinations were assessed. RESULTS: The overall sensitivity of Ag, Ab, and Ag/Ab testing was 30, 40, and 54%, respectively, while in transplant patients it significantly dropped to 16, 26, and 40% (p = 0.02). For BDG testing it was 67%, both overall and in transplant patients. Especially Ag testing performed poorly among women ≤ 65 years with a significantly reduced sensitivity of 9% (p < 0.002). While the sensitivity of Ag/Ab testing was somewhat higher at 67% for C. albicans, it was significantly lower for non-albicans species at 42% (p = 0.006). The sensitivity of BDG testing for C. albicans and non-albicans species was not significantly different at 64 and 69%, respectively. Both Ag/Ab and BDG testing had a high specificity of 93%, for Ag testing it was 100%. Similar sensitivities were calculated for sera sampled on the day of and 4-6 days before sampling of positive blood cultures. CONCLUSIONS: Serological markers are valuable tools for the early diagnosis of candidemia. Ab, Ag, and BDG testing are all characterized by high specificity. The Wako BDG test is significantly more sensitive compared to combined Candida-Ag/Ab testing, particularly in the setting of non-albicans species and specific host factors.

The diagnostic value of (1,3)-ß-D-glucan alone or combined with traditional inflammatory markers in neonatal invasive candidiasis.

BACKGROUND: Asymptom of invasive candidiasis (IC) and low positive rate of blood culture lead to delay diagnose of neonatal infection. Serum (1,3)-ß-D-glucan (BDG) performs well in adult IC, but its use in neonatal IC is unclear. We evaluated the use of BDG, procalcitonin (PCT), high-sensitive C-reactive protein (hsCRP) or platelet count (PC) in neonatal IC. METHODS: We collected the data of neonates admitted to our institute. Eighty neonates were enrolled, and divided into IC group, bacterial infection (BI) group and control (CTRL) group. We analyzed the difference of these indicators between groups, and generated Receiver operator characteristic (ROC) curve. The value of BDG in antifungal therapy efficacy assessment was also investigated. RESULTS: The BDG level was higher in IC group compared with BI and CTRL group. C. albicans lead to significant increase of BDG compared with C. parapsilosis. IC group had highest hsCRP level and lowest PC. PCT level was similar between groups. ROC showed that BDG or hsCRP performs well in neonatal IC, the optimal cut-off for BDG was 13.69 mg/ml. Combined BDG with hsCRP, PCT and PC increased diagnostic value. Serum BDG level was decreased during antifungal treatment. CONCLUSION: Serum BDG performs well in identification of neonatal IC and in monitoring the antifungal therapy efficacy.

Procalcitonin levels in candidemia versus bacteremia: a systematic review.

BACKGROUND: Procalcitonin (PCT) is a biomarker used to assess systemic inflammation, infection, and sepsis and to optimize antimicrobial therapies. Its role in the in the differential diagnosis between candidemia and bacteremia is unclear. The aim of this systematic review was to summarize the current evidence about PCT values for differentiating candidemia from bacteremia. METHODS: PubMed and EMBASE were searched for studies reporting data on the diagnostic performance of serum PCT levels in intensive care unit (ICU) or non-ICU adult patients with candidemia, in comparison to patients with bacteremia. RESULTS: We included 16 studies for a total of 45.079 patients and 785 cases of candidemia. Most studies claimed to report data relating to the use of PCT values for differentiating between candidemia and bacteremia in septic patients in the intensive care unit. However, the studies identified were all retrospective, except for one secondary analysis of a prospective dataset, and clinically very heterogeneous and involved different assessment methods. Most studies did show lower PCT values in patients with candidemia compared to bacteremia. However, the evidence supporting this observation is of low quality and the difference seems insufficiently discriminative to guide therapeutic decisions. None of the studies retrieved actually studied guidance of antifungal treatment by PCT. PCT may improve diagnostic performance regarding candidemia when combined with other biomarkers of infection (e.g., beta-D-glucan) but more data is needed. CONCLUSIONS: PCT should not be used as a standalone tool for the differential diagnosis between candidemia and bacteremia due to limited supporting evidence.

Antifungal susceptibility trend and analysis of resistance mechanism for Candida species isolated from bloodstream at a Japanese university hospital.

We compared the susceptibility of six commercially available antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin, micafungin, and amphotericin B) against 133 Candida bloodstream isolates between 2008 and 2013 at Aichi Medical University Hospital. C. albicans was the most common isolate, followed by C. parapsilosis, C. glabrata, and C. tropicalis. MIC90s of voriconazole against C. albicans, C. parapsilosis, and C. tropicalis were the lowest and that of micafungin against C. glabrata was the lowest among the agents tested. Of the 133 isolates, two strains were identified as drug-resistant. One was a fluconazole-resistant C. glabrata strain, in which the ATP-binding cassette (ABC) transporter gene expression was upregulated. The other was a micafungin-resistant C. glabrata strain, that had 13 amino acid substitutions in FKS1 and FKS2, including a novel substitution V1342I in FKS1 hotspot 2. We also evaluated the susceptibility of T-2307, a novel class of antifungal agents used in clinical trials, against the fluconazole- and micafungin-resistant C. glabrata strain; the MICs of T-2307 were 0.0039 and 0.0078 µg/mL, respectively. In conclusion, the incidence of bloodstream infection caused by drug-resistant Candida spp. was rare from 2008 to 2013 at our hospital. Of 133 isolates, only two strains of C. glabrata were resistant to azoles or echinocandins, that upregulated the ABC transporter genes or had novel FKS mutations, respectively.

Detecting Infections Rapidly and Easily for Candidemia Trial, Part 2 (DIRECT2): A Prospective, Multicenter Study of the T2Candida Panel.

Background: Blood cultures are approximately 50% sensitive for diagnosing invasive candidiasis. The T2Candida nanodiagnostic panel uses T2 magnetic resonance and a dedicated instrument to detect Candida directly within whole blood samples. Methods: Patients with Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, or Candida krusei candidemia were identified at 14 centers using diagnostic blood cultures (dBCs). Follow-up blood samples were collected concurrently for testing by T2Candida and companion cultures (cBCs). T2Candida results are reported qualitatively for C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis. T2Candida and cBCs were positive if they detected a species present in the dBC. Results: Median time between collection of dBC and T2Candida/cBC samples in 152 patients was 55.5 hours (range, 16.4-148.4). T2Candida and cBCs were positive in 45% (69/152) and 24% (36/152) of patients, respectively (P < .0001). T2Candida clinical sensitivity was 89%, as positive results were obtained in 32/36 patients with positive cBCs. Combined test results were both positive (T2+/cBC+), 21% (32/152); T2+/cBC-, 24% (37/152); T2-/cBC+, 3% (4/152); and T2-/cBC-, 52% (79/152). Prior antifungal therapy, neutropenia, and C. albicans candidemia were independently associated with T2Candida positivity and T2+/cBC- results (P values < .05). Conclusions: T2Candida was sensitive for diagnosing candidemia at the time of positive blood cultures. In patients receiving antifungal therapy, T2Candida identified bloodstream infections that were missed by cBCs. T2Candida may improve care by shortening times to Candida detection and species identification compared to blood cultures, retaining sensitivity during antifungal therapy and rendering active candidemia unlikely if results are negative. Clinical Trials Registration: NCT01525095.

Rapid Detection and Differentiation of Clinically Relevant Candida Species Simultaneously from Blood Culture by Use of a Novel Signal Amplification Approach.

Fungal bloodstream infections are a significant problem in the United States, with an attributable mortality rate of up to 40%. An early diagnosis to direct appropriate therapy has been shown to be critical to reduce mortality rates. Conventional phenotypic methods for fungal detection take several days, which is often too late to impact outcomes. Herein, we describe a cost-effective multiplex assay platform for the rapid detection and differentiation of major clinically relevant Candida species directly from blood culture. This approach utilizes a novel biotin-labeled polymer-mediated signal amplification process combined with targeting rRNA to exploit phylogenetic differences for sensitive and unambiguous species identification; this assay detects seven pathogenic Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. lusitaniae, and C. guilliermondii) simultaneously with very high specificity to the species level in less than 80 min with the limits of detection at 1 × 103 to 10 × 103 CFU/ml or as few as 50 CFU per assay. The performance of the described assay was verified with 67 clinical samples (including mixed multiple-species infections as well), with an overall 100% agreement with matrix-assisted laser desorption ionization (MALDI) mass spectrometry-based reference results. By providing a species identity rapidly, the clinician is aided with information that may direct appropriate therapy sooner and more accurately than current approaches, including PCR-based tests.

Blood Cultures Drawn From Arterial Catheters Are Reliable for the Detection of Bloodstream Infection in Critically Ill Children.

OBJECTIVES: Arterial catheters may serve as an additional source for blood cultures in children when peripheral venipuncture is challenging. The aim of the study was to evaluate the accuracy of cultures obtained through indwelling arterial catheters for the diagnosis of bloodstream infections in critically ill pediatric patients. DESIGN: Observational and comparative. SETTING: General and cardiac ICUs of a tertiary, university-affiliated pediatric medical center. PATIENTS: The study group consisted of 138 patients admitted to the general or cardiac PICU in 2014-2015 who met the following criteria: presence of an indwelling arterial catheter and indication for blood culture. INTERVENTIONS: Blood was drawn by peripheral venipuncture and through the arterial catheter for each patient and sent for culture (total 276 culture pairs). MEASUREMENTS AND MAIN RESULTS: Two specialists blinded to the blood source evaluated each positive culture to determine if the result represented true bloodstream infection or contamination. The sensitivity, specificity, and positive and negative predictive values of the arterial catheter and peripheral cultures for the diagnosis of bloodstream infection were calculated. Of the 56 positive cultures, 41 (15% of total samples) were considered diagnostic of true bloodstream infection. In the other 15 (5%), the results were attributed to contamination. The rate of false-positive results was higher for arterial catheter than for peripheral venipuncture cultures (4% vs 1.5%) but did not lead to prolonged unnecessary antibiotic treatment. On statistical analysis, arterial catheter blood cultures had high sensitivity (85%) and specificity (95%) for the diagnosis of true bloodstream infection, with comparable performance to peripheral blood cultures. CONCLUSION: Cultures of arterial catheter-drawn blood are reliable for the detection of bloodstream infection in PICUs.

Three cases of Candida fermentati fungemia following hematopoietic stem cell transplantation.

Bloodstream infection with non-Candida albicans Candida species is one of the serious complications among patients with hematological malignancies who receive long-term prophylactic antifungal agents. Here we describe three cases of Candida fermentati (C. fermentati) candidemia after allogeneic stem cell transplantation for hematological malignancies. Case 1 is fluconazole-breakthrough C. fermentati fungemia, which was well controlled with liposomal amphotericin B. Case 2 and 3 were caspofungin-breakthrough C. fermentati fungemia. In case 2, blood culture turned negative for Candida responding to liposomal amphotericin B. Although in vitro susceptibility data for the isolated pathogen suggested the efficacy of both caspofungin and liposomal amphotericin B in all three cases, clinically liposomal amphotericin B seemed to have been more effective for eradication of the pathogen from blood stream. C. fermentati needs to be considered as a possible cause for breakthrough candidemia among post-transplant patients with prolonged antifungal prophylaxis. Discrepancy between in vitro and in vivo susceptibility to antifungals, especially to echinocandins, might provide a clue for the optimal choice of antifungals for C. fermentati infections.

Role of Early Onset Neutropenia in Development of Candidemia in Premature Infants.

Background: The aim of the study was to assess the effect of early-onset neutropenia (EON) on the development of candidemia in premature infants and evaluate other risk factors. Materials and Methods: This prospective study was carried out in a neonatal intensive care unit of Cairo University Hospital. Fifty neutropenic premature infants were matched to 50 non-neutropenics. Subjects were then regrouped into candidemics and non-candidemics to study other risk factors such as central venous catheters, mechanical ventilation, parenteral nutrition, drugs as corticosteroids and others. Candidemia was assessed by Bactec and then seminested polymerase chain reaction for culture negatives. Results: Candidemia developed in 28 neutropenic preterms and in 8 non-neutropenics (odds ratio = 6.68, 95% confidence interval = 2.61-17.1, p <0.001). Risk factors for invasive fungal infection in univariate analysis included bacterial septicemia, mechanical ventilation, parenteral nutrition and steroid therapy. Independent predictors of candidemia in multivariate regression analysis included EON, mechanical ventilation and steroid therapy. Conclusion: EON is an independent risk factor for candidemia in premature infants.

Direct Detection of Candida albicans with a Membrane Based Electrochemical Impedance Spectroscopy Sensor.

Candidemia and invasive candidiasis is a cause of high mortality and morbidity rates among hospitalized patients worldwide. The occurrence of the infections increases due to the complexity of the patients and overuse of the antifungal therapy. The current Candida detection method includes blood culturing which is a lengthy procedure and thus delays the administration of the antifungal therapy. Even though the results are available after 48 h it is still the gold standard in pathogen detection in a hospital setting. In this work we present an electrochemical impedance sensor that is capable of detecting Candida albicans yeast. The yeast cells are captured on electrodes specifically functionalized with anti-Candida antibodies and detection is achieved by electrochemical impedance spectroscopy. The sensor allows for detection of the yeast cells at clinically relevant concentrations in less than 1 h.

Long-Term Impact of an Educational Antimicrobial Stewardship Program on Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections: A Quasi-Experimental Study of Interrupted Time-Series Analysis.

BACKGROUND: The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. METHODS: We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). RESULTS: A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, -216.8 defined daily doses per 1000 OBDs; 95% confidence interval, -347.5 to -86.1), and was sustained during subsequent years (average reduction, -19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, -.003 to .039) reverted toward a decreasing trend of -0.130 per quarter (change in slope, -0.029; -.051 to -.008), and so did the mortality rate (change in slope, -0.015; -.021 to -.008). CONCLUSIONS: This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.

Risk factors and predictors of mortality of candidaemia among critically ill patients: role of antifungal prophylaxis in its development and in selection of non-albicans species.

PURPOSE: The aim of the present study is to identify risk factors for development and predictors of mortality of candidaemia among critically ill patients. METHODS: A 1:7 case-control study was conducted during a 4-year period (2012-2015) in a Greek Intensive Care Unit (ICU). Candidaemia was confirmed by positive blood cultures. All yeasts were identified using API 20C AUX System or Vitek 2 Advanced Expert System. Epidemiologic data were collected from the ICU computerized database and patients' chart reviews. RESULTS: Fifty-three patients developed candidaemia with non-albicans species being the predominant ones (33 patients, 62.3%). Multivariate analysis found that prior emergency surgery, malignancy, hospitalization during summer months, prior septic shock by KPC-producing Klebsiella pneumoniae and number of antibiotics administered were independently associated with candidaemia, while, prior administration of azole was a protective factor. Non-albicans candidaemia was associated with number of antibiotics administered and prior administration of echinocandin. Mortality of 14 days was 28.3% (15 patients) and was associated with SOFA score upon infection onset and septic shock, while, appropriate empirical antifungal treatment was associated with better survival. CONCLUSIONS: Prophylactic azole administration prevents development of candidaemia, while, echinocandin administration predisposes to non-albicans candidaemia. Empirical administration of an appropriate antifungal agent is associated with better survival.