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Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Scedosporium and Lomentospora species are environmental moulds that are virulent in immunocompromised hosts and rarely cause bloodstream infection (BSI). Patients with Scedosporium and Lomentospora species BSI were identified by the state public laboratory service in Queensland, Australia, over a 20-year period. Twenty-two incident episodes occurred among 21 residents; one patient had a second episode 321 days following the first. Of these, 18 were Lomentospora prolificans, three were Scedosporium apiospermum complex and one was a nonspeciated Scedosporium species. Seventeen (81%) patients died during their index admission, and all-cause mortality at 30, 90 and 365 days was 73%, 82% and 91% respectively. All 20 patients with haematological malignancy died within 365 days of follow-up with a median time to death of 9 days (interquartile range, 6-20 days) following diagnoses of BSI., (© 2023 Royal Australasian College of Physicians.)

Introduction: Bacteremia is a major cause of morbidity and mortality in hospitalized patients. Predictors of mortality are critical for the management and survival of hospitalized patients. The objective of this study was to determine the factors related to blood culture positivity and the risk factors for mortality in patients whose blood cultures were collected., Methods: A prospective 2-cohort study (derivation with 784 patients and validation with 380 patients) based on the Pitt bacteremia score for all patients undergoing blood culture collection. The score was obtained from multivariate analysis. The Kaplan-Meier survival curve of the cohort derivation and the cohort validation groups was calculated, and the difference was assessed using a log-rank test. Mortality-related factors were older age, extended hospitalization, > 10% of immature cells in the leukogram, lower mean blood pressure, elevated heart rate, elevated WBC count, and elevated respiratory rate. These continuous variables were dichotomized according to their significance level, and a cut-off limit was created., Results: The area under the ROC curve (AUC) was 0.789. The score was validated in a group of 380 patients who were prospectively evaluated., Conclusion: Prolonged hospitalization, body temperature, and elevated heart rate were related to positive blood cultures. The Pitt score can be used to assess the risk of death; however it can be individualized according to the epidemiology of each hospital., (© 2021. Sociedade Brasileira de Microbiologia.)

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) ( P < 10 -4 ). For CAPA, the presence of several mycological criteria was associated with death ( P < 10 -4 ). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients ( P = 0.001). Antimold treatment did not alter prognosis ( P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.

Bloodstream fungal infections have a high mortality rate. There is little data about the long-term mortality rate of fungaemia.This study aimed to explore the mortality of fungaemia and the influencing factors associated with death. In total, 204 intensive care unit (ICU) patients with fungaemia from Multi-parameter Intelligent Monitoring in Intensive Care-III (MIMIC-III) Database were studied. Age, gender, major underlying diseases, data about vital signs and blood test results were analysed to identify the predictors of the mortality and prognosis of fungaemia in ICU patients. Cox regression models were constructed, together with Kaplan-Meier survival curves. The 30-day, 1-year, 2-year, 3-year and 4-year mortality rates were 41.2%, 62.3%, 68.1%, 72.5% and 75%, respectively. Age (P ＜ 0.001, OR = 1.530; P ＜ 0.001, OR = 1.485)，serum bilirubin (P = 0.016, OR = 2.125；P = 0.001, OR = 1.748) and international normalised ratio (INR) (P = 0.001, OR = 2.642; P ＜ 0.001 OR = 2.065) were predictors of both the 30-day and 4-year mortality rates. Renal failure (P = 0.009, OR = 1.643) performed good in prediction of the 4-year mortality. The mortality of fungaemia is high. Age，the serum bilirubin and INR are good predictors of the 30-day and 4-year mortality rates of fungaemia. Renal failure has good performance in predicting the long-term mortality.

Saccharomyces cerevisiae fungemia: risk factors, outcome and links with S. boulardii-containing probiotic administration., Objective: The aim of our study was to review cases of S. cerevisiae fungemia along with the corresponding risk factors (including S. boulardii probiotic intake), treatment and outcomes., Patients and Methods: Retrospective study (2005-2017) of S. cerevisiae fungemia. All the data were extracted from medical files., Results: We identified 10 patients with S. cerevisiae fungemia. Mean age was 59.4 years (range 21-88). Four fifths (80%) were on total parenteral or enteral nutrition, 70% had a central venous line, and 30% were admitted in an Intensive Care Unit (ICU). S. boulardii-containing probiotic prescription was identified in 6 subjects. Three patients with no risk factors such as ICU or central venous catheter were 80 years old or more. Mortality rate was 50%., Conclusion: S. cerevisiae fungemia is a rare but life-threatening infection, associated with intake of probiotics containing S. boulardii. Besides classical risk factors, older age should be a contraindication for these probiotics., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

We performed retrospective study to identify the characteristics of invasive Trichosporon asahii infection. A total of 102 patients with T. asahii were identified including 18 (18%) with invasive infection. Invasive infection was associated with indwelling central venous catheter (94% vs 54%, P = .001), prior antifungal agent use (50% vs 18%, P = .01), hematologic malignancy (33% vs 7%, P = .006), and end-stage renal disease (28% vs 7%, P = .02). Patients with invasive infections had higher in-hospital mortality than patients with noninvasive infections (61% vs 27%, P = .006). Those with the above risk factors should be monitored for the development of invasive T. asahii infection., Lay Summary: Patients with indwelling central venous catheter, prior antifungal agent use, hematologic malignancy, and end-stage renal disease were associated with invasive Trichosporon asahii infection. Patients with invasive infections had higher in-hospital mortality than patients without invasive infection., (© The Author 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown., Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites., Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants., Exposures: Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis., Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset., Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality., Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections ( P <0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.

Background: While fungaemia caused by two or more different species of yeasts (mixed fungaemia, MF) is infrequent, it might be underestimated., Aims: This study aimed to determine the incidence of MF, clinical characteristics of the patients, and antifungal susceptibility profiles of the isolates with a systematic review of the literature., Sources: Data sources were PubMed and Scopus., Study Eligibility Criteria: Studies reporting ten or more mixed fungaemia episodes., Content: Study included MF episodes in adults between January 2000 and August 2018 in Hacettepe University Hospitals, Turkey. The isolation, identification and antifungal susceptibility testing (AFST) of the isolates were by standard mycological methods. Patient data were obtained retrospectively. Literature search was performed using relevant keywords according to PRISMA systematic review guidelines. A total of 32 patients with 33 MF episodes were identified. Among all fungaemia episodes, MF incidence was 3.7% (33/883). All patients had one or more underlying disorders among which solid-organ cancer (50.0%, 16/32) was the most common. Overall mortality was 51.5% (17/33). The most preferred antifungal agents for initial treatment were fluconazole (48.5%, 16/33) and echinocandins (39.4%, 13/33). Fluconazole susceptible-dose-dependent (S-DD) or -resistant Candida species were detected in 15 episodes, and an isolate of C. parapsilosis was classified as S-DD by AFST. All Candida isolates were susceptible to echinocandins. Non-candida yeasts with intrinsic resistance/reduced susceptibility to both echinocandins and fluconazole were detected in two episodes. Systematic review of the literature revealed 24 studies that reported more than ten MF episodes. Methodology was variable. Improvement of detection rates was reported when chromogenic agars were used. Most studies underlined detection of isolates with reduced susceptibility., Implications: Although rare, the MF rate is affected by the detection methods, which have improved in recent years. Fluconazole and echinocandins were used for initial treatment in accordance with the current guideline recommendations; however, isolates non-susceptible to both were detected. Detection of a mixed infection offers an opportunity for optimum treatment., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Cryptococcemia is a life-threatening fungal infection. Sometimes, it is hard to diagnose. The studies to describe the characteristics of cryptococcemia specifically were limited. We performed this retrospective analysis in a Chinese hospital during 2002-2015, including 85 cryptococcemia cases and 52 Cryptococcus spp. isolates. The species, mating type, antifungal susceptibility and multilocus sequence typing of Cryptococcus spp. were determined. C. neoformans var. grubii MATα of sequence type (ST) 5 is the representative strain of cryptococcemia, accounting for 51 isolates. The MIC50/90 values were 0.5/0.5, 1.0/1.0, 2.0/4.0, ≤0.06/0.25, and ≤0.06/≤0.06 μg/ml for amphotericin B, flucytosine, fluconazole, itraconazole, and voriconazole, respectively. Cryptococcemia was the first diagnostic proof of cryptococcosis in 37 patients (43.5%, 37/85). Compared with the patients initially diagnosed of cryptococcosis in other sites (mainly cerebrospinal fluid), the patients firstly diagnosed by blood culture had prolonged time from admission to diagnosis of cryptococcosis (9 days vs. 2 days, P < .001) and higher 30-day mortality (54.1% vs. 20.8%, P = .003), while fewer symptoms of meningitis (45.9% vs. 100%, P < .001). For the patients receiving lumbar puncture, the occurrence of meningitis was similar between the patients firstly diagnosed by blood culture and those firstly diagnosed in other sites (94.1% vs. 100%, P = .26). However, the patients first diagnosed by blood culture had lower baseline intracranial pressure (250 mm H2O vs. 342.5 mm H2O, P = .001). In conclusion, patients with cryptococcemia as the first diagnostic proof of cryptococcosis usually had neglected subtle symptoms of meningitis, which may result in delayed diagnosis and catastrophic outcome., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Fungaemia due to rare yeasts has been recognised as an emerging, clinically relevant, but less investigated condition. Intrinsic resistance or reduced susceptibility of these species to echinocandins or fluconazole remains as a challenge in empirical treatment., Objectives: To describe the clinical characteristics, administered antifungal agents, outcomes of patients with rare yeasts other than Candida (RY-OTC) fungaemia and determine the antifungal susceptibility profiles of the isolates., Patients and Methods: RY-OTC fungaemia between January-2001 and December-2018 were retrospectively evaluated. Antifungal susceptibility tests were performed according to CLSI M27-A3., Results: We identified 19 patients with fungaemia due to 20 RY-OTC (8 Trichosporon asahii, 4 Cryptococcus neoformans, 4 Saprochaete capitata, 3 Rhodotorula mucilaginosa, 1 Trichosporon mucoides) with an incidence of 2.2% among 859 fungaemia episodes. Haematological malignancy was the most common (42%) underlying disorder. In 6 patients, RY-OTC fungaemia developed as breakthrough infection while receiving echinocandins, amphotericin B or fluconazole. Amphotericin B, fluconazole or voriconazole were the drugs of choice for the initial treatment of breakthrough fungaemia. Among patients without previous exposure to antifungals, the most common empirical treatment was an echinocandin (50%), followed by fluconazole (42%) and amphotericin B (8%). Overall mortality was 47%. Worse outcome was most common among patients receiving echinocandins (83% vs 25%, P < .05). Voriconazole and posaconazole showed the highest in vitro activity against all the isolates tested. Amphotericin B MICs were relatively higher and the degree of activity of fluconazole and itraconazole was variable., Conclusions: Early recognition of RY-OTC and knowledge about their susceptibility patterns remain crucial in initial treatment pending susceptibility data of isolates., (© 2020 Blackwell Verlag GmbH.)

Introduction. Breakthrough bloodstream infections (BSIs) are rare among non-neutropenic patients. Aim. Our goal was to determine the risk factors associated with development of breakthrough BSIs among critically ill non-neutropenic patients and its role in mortality. Methodology. During a 24-month period (August 2016 to July 2018), all BSIs among non-neutropenic patients hospitalized at the University General Hospital of Patras, Greece, were included. Antimicrobial resistance of isolates was interpreted according to EUCAST guidelines. BSIs were considered as breakthrough when blood cultures yielded a pathogen in a patient who, for at least the previous 72 h, had been receiving at least one antibiotic to which the isolated microorganism was susceptible. Results. Among 217 episodes of BSI, 118 (54.4 %) developed a breakthrough infection. Primary BSIs predominated (101; 46.5 %), followed by catheter-related BSIs (56; 25.8 %). Gram-negative bacteria represented the most common pathogens isolated (157; 72.4 %), followed by Gram-positive bacteria (36; 16.6 %) and fungi (36; 16.6 %). Factors independently associated with the development of breakthrough BSIs were immunosuppressive therapy, obesity (body mass index ≥30 kg m - 2 ), infection by Gram-positive bacteria, noradrenaline dose during 24 h from BSI onset, prior use of colistin and antifungal treatment. Overall 14-day mortality was 23.0 % (50 patients). Multivariate analysis revealed noradrenaline dose during 24 h from BSI onset as an independent predictor of mortality, while appropriate empiric antimicrobial treatment and breakthrough BSI were identified as predictors of good prognosis. Conclusion. Breakthrough BSIs were common among critically ill non-neutropenic patients and these patients were associated with better survival because they were de facto receiving appropriate antibiotics.

Cryptococcal meningitis (CM) is a serious infectious disease of the central nervous system, and associated brain injuries can be found in the very early stage of disease. In this study, 92 adult CM patients (59 men, 33 women; median age 54.66 years, range 20-86 years) were enrolled, and their clinical, laboratory, neuroimaging features and therapeutic outcomes were analyzed. Two main clinical comparative analyses of the clinical characteristics and laboratory and neuroimaging features were made in this study. The first compared clinical differences between the survivors and non-survivors of all enrolled patients, and the second compared differences between the following three groups: Group I, the patients who died within 14 days of initiating treatment; Group II, the patients who died within 15 days to 1 year of initiating treatment, and Group III, the patients who survived for more than 1 year after initiating treatment. Prognostic factors including initial altered consciousness, increased cerebrospinal fluid (CSF) lactate level and the presence of cryptococcemia were significantly different between the different groups. The patients with early mortality had a higher CSF lactate level and higher rate of cryptococcemia. The presence of cryptococcemia was an important prognostic factor, and the patients with cryptococcemia had a higher incidence of positive CSF India ink stain. Further large-scale studies are needed to delineate the clinical and laboratory features of CM patients with early mortality., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Fungal infections are still a relevant challenge for clinicians involved in the cure of patients with cancer. We retrospectively reviewed charts of hospitalized patients with haematological malignancies (HMs), in which a documented fungaemia was diagnosed between January 2011 and December 2015 at 28 adult and 6 paediatric Italian Hematology Departments., Methods: During the study period, we recorded 215 fungal bloodstream infections (BSI). Microbiological analyses documented that BSI was due to moulds in 17 patients (8%) and yeasts in 198 patients (92%), being Candida spp identified in 174 patients (81%)., Results: Mortality rates were 70% and 39% for mould and yeast infections, respectively. Infection was the main cause of death in 53% of the mould and 18% of the yeast groups. At the multivariate analysis, ECOG ≥ 2 and septic shock were significantly associated with increased mortality, and removal of central venous catheter (CVC) survival was found to be protective. When considering patients with candidemia only, ECOG ≥ 2 and removal of CVC were statistically associated with overall mortality., Conclusions: Although candidemia represents a group of BSI with a good prognosis, its risk factors largely overlap with those identified for all fungaemias, even though the candidemia-related mortality is lower when compared to other fungal BSI. Management of fungal BSI is still a complex issue, in which both patients and disease characteristics should be focused to address a personalized approach., (© 2019 Stichting European Society for Clinical Investigation Journal Foundation.)

Candida tropicalis is the second most common Candida species causing fungaemia in Taiwan, and decreased susceptibility to fluconazole has been reported. This study analysed the clinical characteristics of adult patients with C. tropicalis fungaemia and the antifungal susceptibilities of isolates at five tertiary hospitals in Taiwan (1 July 2011 to 30 June 2014). A standardised case record form was used retrospectively to collect demographic, clinical and microbiological characteristics, antifungal treatment and outcomes. MICs of non-duplicate isolates were determined using Sensititre TM YeastOne TM and were interpreted using cut-off values recommended by the CLSI. A total 248 patients were diagnosed over the study period; 30-day crude mortality was 52.0%. Multivariate analysis showed that high Charlson comorbidity index ≥4 (OR = 2.09, 95% CI 1.22-3.59; P = 0.008), neutropenia (OR = 4.61, 95% CI 1.42-15.00; P = 0.011) and treatment with an azole-based regimen (OR = 0.39, 95% CI 0.17-0.90; P = 0.028) were significantly associated with 30-day mortality. A total of 33.9% of isolates were non-susceptible to fluconazole (MIC 50 , 2 mg/L; MIC 90 , 16 mg/L; MIC range, 0.25 to >256 mg/L), whilst 56.9% to voriconazole (MIC 50 , 0.25 mg/L; MIC 90 , 1 mg/L; MIC range, 0.015 to >8 mg/L) according to CLSI clinical breakpoints. There was no significant correlation between overall mortality and MICs of fluconazole or voriconazole. This study showed high mortality in patients with C. tropicalis fungaemia, and azole-based antifungal treatment could improve outcomes regardless of fluconazole MICs of infecting isolates compared with patients without any treatment within 48 h., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To investigate the risk factors and analyze the distribution of pathogens to provide a basis for the prevention of nosocomial blood stream infections (BSI) and reduce the incidence and mortality of nosocomial BSI in neurologic patients., Patients and Methods: A retrospective chart review of neurologic patients admitted to an adult intensive care unit from January 2012 to December 2017 was conducted. Every positive blood culture, clinical demographic, microbiologic and laboratory result, as well as 28-day outcome data, were compiled on a data collection sheet. The clinical significance of each isolate was determined; in addition, the antimicrobial susceptibilities of causative pathogens and the most likely source were recorded., Results: During the five-year study period, there were 121 nosocomial BSI yielding 151 isolates in 404 neurologic patients. Eighty-one percent of nosocomial BSI were monomicrobial. Gram-positive organisms caused 67.9% of these BSI, gram-negative organisms caused 32.1%, and fungi caused 0.8%. The crude incidence rate was approximately 29.9%, and the mortality of nosocomial BSI was as high as 29.8%. Intravascular lines were the most common source of nosocomial BSI (79.3%). The most common organisms causing BSI were coagulase-negative staphylococci (CoNS; 44.6% of isolates), Staphylococcus aureus (17.4%), Klebsiella species (11.5%), and Acinetobacter spp. (11.5%). Multivariable regression analysis revealed that the use of antibiotic agents in the 90 days prior (odds ratio [OR], 5.81; 95% confidence interval [CI], 3.18-10.62; p = 0.001), brain trauma (OR, 0.28; 95% CI, 0.15-0.51; p = 0.001), and transfusion (OR, 3.02; 95% CI, 1.45-6.29; p = 0.001) were significant predictors of nosocomial BSI., Conclusions: The incidence and mortality of nosocomial BSI were high in our neurologic patients. Strictly aseptic operations, hand hygiene, and reasonable use of transfusions and antibiotic agents are effective measures to prevent nosocomial BSI.

The efficiency of treatment of human infections with the unicellular eukaryotic pathogens such as fungi and protozoa remains deeply unsatisfactory. For example, the mortality rates from nosocomial fungemia in critically ill, immunosuppressed or post-cancer patients often exceed 50%. A set of six systemic clinical azoles [sterol 14α-demethylase (CYP51) inhibitors] represents the first-line antifungal treatment. All these drugs were discovered empirically, by monitoring their effects on fungal cell growth, though it had been proven that they kill fungal cells by blocking the biosynthesis of ergosterol in fungi at the stage of 14α-demethylation of the sterol nucleus. This review briefs the history of antifungal azoles, outlines the situation with the current clinical azole-based drugs, describes the attempts of their repurposing for treatment of human infections with the protozoan parasites that, similar to fungi, also produce endogenous sterols, and discusses the most recently acquired knowledge on the CYP51 structure/function and inhibition. It is our belief that this information should be helpful in shifting from the traditional phenotypic screening to the actual target-driven drug discovery paradigm, which will rationalize and substantially accelerate the development of new, more efficient and pathogen-oriented CYP51 inhibitors.

Background: Few published data are available on the morbidity and mortality of bloodstream infections (BSIs) in Japan. We sought to investigate the epidemiology of BSIs, the involvement of antimicrobial resistance, and the factors that influence patient prognosis., Methods: This single-center study retrospectively evaluated patients who were found to have positive blood cultures at a tertiary teaching hospital between January 2012 and December 2016., Results: A total of 2,105 patients with BSIs were included; 1,786 survived and 319 died, and the 30-day mortality rate was 15.2% over the 5-year study period. BSIs caused by yeasts were independently associated with 30-day mortality. The 30-day mortality rate of BSIs caused by extended-spectrum beta lactamase-producing gram-negative bacteria was significantly higher than that of BSIs caused by nonproducing bacteria., Discussion: The differences in mortality may be caused by differences in the distribution of pathogens and in the delivery of health care., Conclusions: This study reported epidemiology and antimicrobial resistance data of BSIs in Japan and identified several risk factors associated with 30-day mortality. National surveillance of BSIs is required in Japan for comparison with other countries., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Neonatal fungemia is associated with adverse neonatal outcomes and higher overall healthcare expenditure. Our objective is to review the epidemiology of invasive fungal infections (IFIs) in neonates in Canada., Methods: A retrospective cohort study using data collected by the Canadian Neonatal Network (CNN) was conducted. Using a nested matched cohort study design, risk factors and outcomes of neonates born <33 weeks gestation (n = 39,305) during 2003-2013 were compared between neonates diagnosed with an IFI during their stay to infection-free controls., Results: Overall incidence of IFI among all admitted neonates was 0.22% (n = 286), while the incidence of IFI in the group of neonates born <33 weeks gestation was 0.64%. Of the isolates, 170 (59%) had Candida albicans and 59 (21%) had Candida parapsilosis. Risk factors for IFI were lower gestation, male sex, Apgar score <7 at 5 minutes, higher severity of illness score, maternal diabetes and vaginal birth. Neonates with IFI had higher odds of mortality [adjusted odds ratio (aOR): 1.60; 95% confidence interval (CI): 1.06-2.43], necrotizing enterocolitis (aOR: 2.97; 95% CI: 1.76-5.01) and severe retinopathy of prematurity (aOR: 2.15; 95% CI: 1.26-3.67)., Conclusions: The overall incidence of IFI in neonates was low in Canada in comparison to other large population cohort studies; however, the mortality and morbidity remained high.

Objectives: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens., Methods: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray., Results: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001)., Conclusions: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Objectives: Bacterial infections are associated with negative outcomes in cirrhosis but fungal infections are being increasingly recognized. The objective of this study is to define risk factors for fungal infection development and impact on 30-day survival., Methods: In a large, multi-center cirrhotic inpatient cohort, demographics, cirrhosis details, intensive care unit (ICU), organ failures/acute-on-chronic liver failure (ACLF), and 30-day survival were compared between patients without infections and with bacterial infections alone, with those with fungal infections. Variables associated with fungal infection development were determined using multi-variable regression. Ordinal variables (0=no infection, 1=community-acquired bacterial infection, 2=nosocomial bacterial, and 3=fungal infection) were input into a 30-day survival model., Results: A total of 2,743 patients (1,691 no infection, 918 bacterial, and 134 fungal infections) were included. Patients with fungal infection, all of which were nosocomial, were more likely to be admitted with bacterial infections, on spontaneous bacterial peritonitis prophylaxis, and have diabetes and advanced cirrhosis. Bacterial infection types did not predict risk for fungal infections. Multi-variable analysis showed male gender to be protective, whereas diabetes, longer stay, ICU admission, acute kidney injury (AKI), and admission bacterial infection were associated with fungal infection development (area under the curve (AUC)=0.82). Fungal infections were associated with significantly higher ACLF, inpatient stay, ICU admission, and worse 30-day survival. The case fatality rate was 30% with most fungal infections but >50% for fungemia and fungal peritonitis. On a multi-variable analysis, age, AKI, model for end-stage liver disease, ICU admission, and ordinal infection variables impaired survival (P<0.0001, AUC=0.83)., Conclusions: Fungal infections are associated with a poor 30-day survival in hospitalized cirrhotic patients compared with uninfected patients, and those with bacterial infections. Patients with diabetes, AKI, and those with an admission bacterial infection form a high-risk subgroup.

We report the presentation and management of 17 cases of Exophiala dermatitidis and Rhodotorula mucilaginosa bloodstream infections caused by a compounded parenteral medication at an oncology clinic. Twelve patients were asymptomatic. All central venous catheters were removed and antifungal therapy, primarily voriconazole, was administered to patients. Three patients died.

Objectives: Using registry data to compare fungaemia caused by uncommon yeast species (UYS; i.e. other than Candida albicans , Candida glabrata , Candida parapsilosis , Candida tropicalis and Candida krusei ) and C. albicans -related fungaemia can reveal specific predisposing factors of UYS with potential impact on treatment strategies., Methods: We analysed 338 episodes of UYS fungaemia prospectively collected from 27 hospitals (Paris, France; 1 October 2002-31 December 2014) and compared these with 1998 single episodes of C. albicans fungaemia using univariate and multivariate analyses., Results: The proportion of UYS fungaemia was stable over time. Thirty-five different species were identified (27 ascomycetes, 8 basidiomycetes), 11 had caspofungin MIC 50  >0.25 mg/L and 15 fluconazole MIC 50  >4 mg/L. Haematological malignancies [OR=2.39 (95% CI 1.79-3.18)] and prior exposure to antifungal drugs [OR=1.87 (1.30-2.69)] were independent predisposing factors for UYS infections upon multivariate analysis. However, when considering the genus/species complex level, only infections due to Candida kefyr -related species [OR=4.01 (2.42-6.64)] and to Trichosporon spp. [OR=5.38 (1.72-16.81)] remained associated with haematological malignancies, those due to the GEOTRICHUM group with acute leukaemia [OR=61.29 (19.23-195.36)], and infections with Trichosporon spp. or the GEOTRICHUM group with prior exposure to caspofungin [OR=15.67 (3.62-67.80) and OR=13.17 (3.33-52.03), respectively] but not to fluconazole. The global mortality at day 30 for UYS was similar to that for C. albicans (35.4%, and 39.9%, respectively), but very divergent results were observed according to the specific UYS., Conclusions: UYS encompass a high diversity of species, each with its own behaviour and predisposing factors for human infections. This variety makes it important to rapidly identify an isolate to the species level in order to optimize antifungal treatment., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Intra-abdominal infections are the second most frequent cause of sepsis. In a recent cohort, fungal specimens were found in 51.9% of all patients with sepsis and peritonitis. Current systematic reviews comparing untargeted antifungal treatment with placebo or no treatment in patients who are critically ill have provided conflicting results, and clinical equipoise exists. Accordingly, we aim to assess patient-important benefits and harms of untargeted antifungal therapy versus placebo or no treatment in adult patients with complicated intra-abdominal infection., Methods and Analysis: We will conduct a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials assessing any untargeted antifungal therapy compared with placebo or no treatment in adult patients with complicated intra-abdominal infections. The primary outcome is all-cause mortality, and secondary outcomes include adverse events, duration of mechanical ventilation and inotropic support, need for renal replacement therapy, emergence of antibiotic resistance and intensive care unit and hospital length-of-stay. Conventional meta-analysis, including sensitivity and subgroup analyses, and assessment of the risk of systematic (bias) and random errors will be conducted. The review will be prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, the Cochrane methodology and the Grading of Recommendations, Assessment, Development and Evaluation., Ethics and Dissemination: Ethical approval is not required as this systematic review only includes previously published data. We aim to publish the review in an international peer-reviewed journal., Trial Registration Number: International Prospective Register of Systematic Reviews registration number: CRD42016053508., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Bacterial infections are common complications in kidney transplant recipients (KTRs). Little is known about incidence rates of bacteremia and fungemia (BAF) in KTRs., Methods: In this population-based cohort study, we used medical and administrative registries to identify episodes of BAF among KTRs in the Central Denmark and North Denmark Regions during 1995-2010. KTRs were followed from the date of their first transplantation to the earliest of BAF, graft loss, death, emigration or 31 December 2010. We calculated incidence rates of first BAF episode overall and stratified by time from transplantation. Potential risk factors were assessed using Cox regression analysis. The Kaplan-Meier analysis was used to estimate 30- and 90-day mortality., Results: Among 612 KTRs, we identified 138 first episodes of bacteremia during 2397 person-years of follow-up (PYFU). The overall incidence rate (IR) was 5.8 BAF episodes per 100 PYFU (95% confidence interval [CI]: 4.9-6.8). The incidence rate declined from 84.0 per 100 PYFU (95% CI: 61.6-114.5) during post-transplant day 0-30 to 2.3 per 100 PYFU (95% CI: 1.7-3.0) from post-transplant day 365 and onwards. Hospital-onset BAF comprised 39% of the episodes of BAF. The most frequently isolated microorganisms were Escherichia coli and Klebsiella species causing 49 (35.5%) and 29 (21.0%) episodes of BAF, respectively. The 30-day mortality was 2.1% (95% CI: 0.7-6.6)., Conclusions: While the risk of BAF in KTRs was high, thirty-day mortality was low. After the first post-transplant year, the IR of bacteremia was substantially lower than in the immediate post-transplant period.

To describe the epidemiology of invasive Candida infection in a tertiary care paediatric hospital. Prospective single-centre survey on all Candida strains isolated from normally sterile fluids and urines in the period 2005-2015 . A total of 299 ICI were documented in 262 patients. Urinary tract infection represented the most frequent diagnosis (62%), followed by fungaemia (34%) and peritonitis (4%). Fungaemia was most frequent in children with cancer (59%) or in low birth weight neonates (61%), while urinary tract infections were more frequent in patients with urinary tract malformation. C.albicans was the most frequently isolated species (60%) compared with C. non-albicans, but differences were present according to the site of isolation and underlying conditions. Overall 90-day mortality was 7%, 13% in fungaemias, 8% in peritonitis and 2% in urinary tract infections. The rates of invasive Candida infection increased during the study period. Invasive Candida infection is diagnosed with increasing frequency in children. Site of isolation and aetiology are frequently related with the presence of underlying, favouring conditions. Mortality was not negligible, especially in the presence of more invasive infections and specific underlying conditions., (© 2016 Blackwell Verlag GmbH.)

Background:  Previous reports on molecular rapid diagnostic testing (mRDT) do not consistently demonstrate improved clinical outcomes in bloodstream infections (BSIs). This meta-analysis seeks to evaluate the impact of mRDT in improving clinical outcomes in BSIs., Methods:  We searched PubMed, CINAHL, Web of Science, and EMBASE through May 2016 for BSI studies comparing clinical outcomes between mRDT and conventional microbiology methods., Results:  Thirty-one studies were included with 5920 patients. The mortality risk was significantly lower with mRDT than with conventional microbiology methods (odds ratio [OR], 0.66; 95% confidence interval [CI], .54-.80), yielding a number needed to treat of 20. The mortality risk was slightly lower with mRDT in studies with antimicrobial stewardship programs (ASPs) (OR, 0.64; 95% CI, .51-.79), and non-ASP studies failed to demonstrate a significant decrease in mortality risk (0.72; .46-1.12). Significant decreases in mortality risk were observed with both gram-positive (OR, 0.73; 95% CI, .55-.97) and gram-negative organisms (0.51; .33-.78) but not yeast (0.90; .49-1.67). Time to effective therapy decreased by a weighted mean difference of -5.03 hours (95% CI, -8.60 to -1.45 hours), and length of stay decreased by -2.48 days (-3.90 to -1.06 days)., Conclusions:  For BSIs, mRDT was associated with significant decreases in mortality risk in the presence of a ASP, but not in its absence. mRDT also decreased the time to effective therapy and the length of stay. mRDT should be considered as part of the standard of care in patients with BSIs., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: we assessed the incidence, risk factors and outcome of BSI over a 14-year period (2000-2013) in a Swedish county., Methods: retrospective cohort study on culture confirmed BSI among patients in the county of Östergötland, Sweden, with approximately 440,000 inhabitants. A BSI was defined as either community-onset BSI (CO-BSI) or hospital-acquired BSI (HA-BSI)., Results: of a total of 11,480 BSIs, 67% were CO-BSI and 33% HA-BSI. The incidence of BSI increased by 64% from 945 to 1,546 per 100,000 hospital admissions per year during the study period. The most prominent increase, 83% was observed within the CO-BSI cohort whilst HA-BSI increased by 32%. Prescriptions of antibiotics in outpatient care decreased with 24% from 422 to 322 prescriptions dispensed/1,000 inhabitants/year, whereas antibiotics prescribed in hospital increased by 67% (from 424 to 709 DDD per 1,000 days of care). The overall 30-day mortality for HA-BSIs was 17.2%, compared to 10.6% for CO-BSIs, with an average yearly increase per 100,000 hospital admissions of 2 and 5% respectively. The proportion of patients with one or more comorbidities, increased from 20.8 to 55.3%. In multivariate analyses, risk factors for mortality within 30 days were: HA-BSI (2.22); two or more comorbidities (1.89); single comorbidity (1.56); CO-BSI (1.21); male (1.05); and high age (1.04)., Conclusion: this survey revealed an alarming increase in the incidence of BSI over the 14-year study period. Interventions to decrease BSI in general should be considered together with robust antibiotic stewardship programmes to avoid both over- and underuse of antibiotics., Competing Interests: Competing Interests: LEN has shares in Mylan. ÅÖB has received lecture fees from Valneva, Abbvie and Ferring Pharmaceuticals. CGG has received lecture honoraria from AstraZeneca, Meda, Cepheid and Pfizer, and has had research collaboration with bioMérieux, ThermoFisher and Rosco Diagnostics.

The epidemiology of Candida species infection has changed over recent decades, influenced by local hospital-related factors, patient predisposing conditions and type of antifungal agents administered. A shift from Candida albicans as the predominant pathogen towards an increasing prevalence of the species Candida glabrata and Candida parapsilosis amongst critically ill patients has been documented. Changes in Candida species distribution may impact treatment recommendations due to differences in susceptibility to antifungal agents among species. Previous exposure to antifungal agents has likely contributed to this shift in species distribution. Another evolving epidemiological factor to consider is the global increase in antifungal resistance to certain antifungal drug types, which has been contributed to by the inappropriate use of these agents. Proposed management strategies to optimize treatment of patients with Candida infection include starting prompt 'early' antifungal therapy, early cessation of inappropriate therapy, using an adequate dose and duration of therapy and de-escalating treatment whenever possible. The implementation of institutional antifungal stewardship programmes has the potential to promote appropriate utilization of antifungal agents and to significantly improve the care of patients with Candida infection. However, a cultural change among healthcare providers and authorities is currently needed to improve antifungal use worldwide., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate the etiology, clinical features and outcome of hospitalized patients with bloodstream infections (BSIs) in a tertiary hospital., Methods: Positive blood cultures were obtained from the microbiological laboratory in Fuxing Hospital, Capital Medical University from January 1, 2012 to December 31, 2012. BSIS events were identified and the epidemiology data were collected., Results: A total of 149 patients and 154 BSIs events were confirmed by pathogenic and clinical evidence. The in-patients' BSIs rate was 0.8% in our hospital in 2012. According to the disease entities of the first BSIs onset, 15 patients (10.1%) were from surgical departments, 83 patients (55.7%) from the medical departments, and 51 patients (34.2%) from ICU. Thirty-three patients (22.1%) were diagnosed as septic shock. Sixty-eight patients died during hospital stay. The in-hospital mortality rate was 45.6%. Among the 154 BSIs events, 125 (81.2%) were nosocomial and 29 (18.8%) were community-acquired. A total of 188 strains were isolated from all BSIs, including 106 strains of (56.4%) gram-negative bacilli, 67 (35.6%) strains of gram-positive bacteria, and 15 (8.0%) strains of fungi. One hundred and fifty-nine strains of bacteria (84.6%)were isolated from 125 events of hospital-acquired BSIs. Twenty-six strains of bacteria were from catheter related bloodstream infections (CRBSIs). In gram-negative BSIs, there were more enterobacteriaceae in community-acquired BSIs. More non-fermentative bacteria were found in hospital-acquired BSIs than in community-acquired ones. The distribution of gram-negative bacilli was quite different between surgical departments, non-surgical departments and ICU (P=0.049)., Conclusions: Pathogens of BSIs are quite different according to disease entities and where the patients are from. Local epidemiology of BSIs and distribution of related pathogens are helpful to physicians searching the optimal empirical antibiotics and improving the outcome.

Hospital mortality rates are elevated in critically ill patients with bloodstream infections. Given that mortality may be even higher if appropriate treatment is delayed, we sought to determine the effect of inadequate initial empiric treatment on mortality in these patients. A retrospective cohort study was conducted across 13 intensive care units in Canada. We defined inadequate initial empiric treatment as not receiving at least one dose of an antimicrobial to which the causative pathogen(s) was susceptible within one day of initial blood culture. We evaluated the association between inadequate initial treatment and hospital mortality using a random effects multivariable logistic regression model. Among 1,190 patients (1,097 had bacteremia and 93 had candidemia), 476 (40%) died and 266 (22%) received inadequate initial treatment. Candidemic patients more often had inadequate initial empiric therapy (64.5% versus 18.8%), as well as longer delays to final culture results (4 vs 3 days) and appropriate therapy (2 vs 0 days). After adjustment, there was no detectable association between inadequate initial treatment and mortality among bacteremic patients (Odds Ratio (OR): 1.02, 95% Confidence Interval (CI) 0.70-1.48); however, candidemic patients receiving inadequate treatment had nearly three times the odds of death (OR: 2.89, 95% CI: 1.05-7.99). Inadequate initial empiric antimicrobial treatment was not associated with increased mortality in bacteremic patients, but was an important risk factor in the subgroup of candidemic patients. Further research is warranted to improve early diagnostic and risk prediction methods in candidemic patients.

Fusarium species are ubiquitously present in environment and are well known as human pathogens with high mortality rate in immunocompromised patients. We report here two cases where immunocompromised patients developed fatal bloodstream infections by this organism. Isolates were further identified by ITS1 region sequencing which confirmed them as Fusarium solani. Antifungal susceptibility testing was done following CLSI M38-A2 guidelines to amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and micafungin. Both patients had a fatal outcome and expired of septic shock. Therefore, identification up to species level is of utmost importance as that helps in directing the management of the patient thereby leading to a favourable outcome.

Background: To characterize and identify prognostic factors for 28-day mortality among patients with hospital-acquired fungemia (HAF) in the Intensive Care Unit (ICU)., Methods: A sub-analysis of a prospective, multicenter non-representative cohort study conducted in 162 ICUs in 24 countries., Results: Of the 1156 patients with hospital-acquired bloodstream infections (HA-BSI) included in the EUROBACT study, 96 patients had a HAF. Median time to its diagnosis was 20 days (IQR 10.5-30.5) and 9 days (IQR 3-15.5) after hospital and ICU admission, respectively. Median time to positivity of blood culture was longer in fungemia than in bacteremia (48.7 h vs. 38.1 h; p = 0.0004). Candida albicans was the most frequent fungus isolated (57.1%), followed by Candida glabrata (15.3%) and Candida parapsilosis (10.2%). No clear source of HAF was detected in 33.3% of the episodes and it was catheter-related in 21.9% of them. Compared to patients with bacteremia, HAF patients had a higher rate of septic shock (39.6% vs. 21.6%; p = 0.0003) and renal dysfunction (25% vs. 12.4%; p = 0.0023) on admission and a higher rate of renal failure (26% vs. 16.2%; p = 0.0273) at diagnosis. Adequate treatment started within 24 h after blood culture collection was less frequent in HAF patients (22.9% vs. 55.3%; p < 0.001). The 28-day all cause fatality was 40.6%. According to multivariate analysis, only liver failure (OR 14.35; 95% CI 1.17-175.6; p = 0.037), need for mechanical ventilation (OR 8.86; 95% CI 1.2-65.24; p = 0.032) and ICU admission for medical reason (OR 3.87; 95% CI 1.25-11.99; p = 0.020) were independent predictors of 28-day mortality in HAF patients., Conclusions: Fungi are an important cause of hospital-acquired BSI in the ICU. Patients with HAF present more frequently with septic shock and renal dysfunction on ICU admission and have a higher rate of renal failure at diagnosis. HAF are associated with a significant 28-day mortality rate (40%), but delayed adequate antifungal therapy was not an independent risk factor for death. Liver failure, need for mechanical ventilation and ICU admission for medical reason were the only independent predictors of 28-day mortality.

♦ BACKGROUND: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). ♦ OBJECTIVE: The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. ♦ METHODS: Design: Observational cohort study., Setting: Central and North Denmark regions., Participants: patients who initiated PD during 1995 - 2010. For each patient we sampled up to 10 controls from the general population matched on age, sex, and municipality. ♦ MAIN OUTCOME: Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. ♦ RESULTS: Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 - 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 - 0.5) per 100 PYFU in population controls (IRR = 10.4; 95% CI, 8.1 - 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 - 31.0) and 20.7% (95% CI, 16.3 - 25.9) among PD patients and population controls, respectively. ♦ CONCLUSIONS: Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Coccidioidomycosis, or valley fever, is a growing health concern endemic to the southwestern United States. Safer, more effective, and more easily administered drugs are needed especially for severe, chronic, or unresponsive infections. The novel fungal CYP51 inhibitor VT-1161 demonstrated in vitro antifungal activity, with MIC50 and MIC90 values of 1 and 2 μg/ml, respectively, against 52 Coccidioides clinical isolates. In the initial animal study, oral doses of 10 and 50 mg/kg VT-1161 significantly reduced fungal burdens and increased survival time in a lethal respiratory model in comparison with treatment with a placebo (P < 0.001). Oral doses of 25 and 50 mg/kg VT-1161 were similarly efficacious in the murine central nervous system (CNS) model compared to placebo treatment (P < 0.001). All comparisons with the positive-control drug, fluconazole at 50 mg/kg per day, demonstrated either statistical equivalence or superiority of VT-1161. VT-1161 treatment also prevented dissemination of infection from the original inoculation site to a greater extent than fluconazole. Many of these in vivo results can be explained by the long half-life of VT-1161 leading to sustained high plasma levels. Thus, the efficacy and pharmacokinetics of VT-1161 are attractive characteristics for long-term treatment of this serious fungal infection., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: There is a lack of outcome data on hospitalized patients with bacteraemia or fungaemia caused by medical devices or procedures., Aim: To determine the association between death and bacteraemia or fungaemia caused by medical devices and procedures., Methods: From December 2012 to November 2013, demographic, clinical, and microbiological data were collected on consecutive inpatients with bacteraemia or fungaemia. Multivariate analysis, using generalized estimating equations, was used to define the association., Findings: A total of 594 bacteraemic or fungaemic episodes occurred in 500 patients. Among patients with episodes caused by medical devices or procedures, 7-day and 30-day mortality were 7/167 [4.2%; 95% confidence interval (CI): 1.7-8.4] and 12/167 (7.2%; CI: 3.8-12.2) respectively. After adjustment, the association between death and bacteraemic or fungaemic episodes related to medical devices and procedures was non-significant as 7- and 30-day mortality odds ratios (OR) were 2.86 (95% CI: 0.80-10.12) and 1.72 (95% CI: 0.71-4.16) respectively. The difference between 30-day mortality associated with Escherichia coli and Staphylococcus aureus bacteraemia demonstrated a trend towards significance [6/47 (12.8%; CI: 4.8-25.7) vs 0/24; P = 0.067]. Thirty-day mortality associated with bacteraemia or fungaemia in patients with urinary catheter infections (often E. coli-associated) was significantly higher than intravascular device-associated infections (often S. aureus-associated) [4/51 (7.8%; 95% CI: 2.2-18.8) vs 1/62 (1.6%; 95% CI: 0.0-8.7); P = 0.028]., Conclusion: Special attention is required to prevent medical device- or procedure-related bacteraemia caused by E. coli. Greater attention should be placed on preventing infections caused by urinary catheters., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies., Methods: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed., Results: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective., Conclusions: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Saprochaete capitata is a very rare pathogen that causes invasive disease particularly in patients with haematological malignancies. We recognised a clustering of S. capitata fungaemia in recent years. So, we report our 6-year surveillance study of fungaemia among patients with haematological malignancies and haematopoietic stem cell transplant. We performed a retrospective and observational study. Hospitalised patients aged >18 years with haematological malignancies were included in the study. A total of 51 fungaemia episodes of 47 patients were analysed. The characteristics of fungaemia in patients with S. capitata compared to patients with candidemia. Median duration of neutropenia was 21.5 days in patients with S. capitata fungaemia, whereas this duration was significantly shorter in patients with candidemia (8 days). Interval between first and last positive culture was significantly longer in patients with S. capitata fungaemia (P < 0.05). Previous use of caspofungin was significantly more common in patients with S. capitata fungaemia. Thirty-day mortality was found 40% for patients with candidemia, whereas it was 39% for patients with S. capitata. In conclusion, despite its limitations this study showed that a novel and more resistant yeast-like pathogen become prevalent due to use of caspofungin in patients with long-lasting neutropenia which was the most noteworthy finding of this 6-year surveillance study., (© 2015 Blackwell Verlag GmbH.)

With increased use of expanded-spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer-Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post-IFI mortality. All patients received antifungal prophylaxis. Fifty-three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n = 31; 50%) and candidaemia (n = 15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n = 6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp., Cladosporium sp., Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR) = 6.0], graft-versus-host disease (OR = 5.3), central venous catheter use (OR = 5.2) and hypoalbuminaemia (OR = 0.3 g(-1)  dl(-1) increase in albumin). The 90-day mortality rate after IFI was 57%. Non-cytomegalovirus systemic viral co-infection (OR = 3.5) and stay in an ICU (OR = 2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging., (© 2015 Blackwell Verlag GmbH.)

We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The epidemiology of paediatric bloodstream infection (BSI) in Sub-Saharan Africa is poorly documented with limited data on hospital-acquired sepsis, impact of HIV infection, BSI trends and antimicrobial resistance., Methods: We retrospectively reviewed paediatric BSI (0-14 years) at Tygerberg Children's Hospital between 1 January 2008 and 31 December 2013 (excluding neonatal wards). Laboratory and hospital data were used to determine BSI rates, blood culture contamination, pathogen profile, patient demographics, antimicrobial resistance and factors associated with mortality. Fluconazole resistant Candida species, methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Acinetobacter baumannii and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae were classified as antimicrobial resistant pathogens., Results: Of 17001 blood cultures over 6 years, 935 cultures isolated 979 pathogens (5.5% yield; 95% CI 5.3-5.7%). Contamination rates were high (6.6%, 95% CI 6.4-6.8%), increasing over time (p = 0.003). Discrete BSI episodes were identified (n = 864) with median patient age of 7.5 months, male predominance (57%) and 13% HIV prevalence. BSI rates declined significantly over time (4.6-3.1, overall rate 3.5 per 1000 patient days; 95% CI 3.3-3.7; Chi square for trend p = 0.02). Gram negative pathogens predominated (60% vs 33% Gram positives and 7% fungal); Klebsiella pneumoniae (154; 17%), Staphylococcus aureus (131; 14%) and Escherichia coli (97; 11%) were most prevalent. Crude BSI mortality was 20% (176/864); HIV infection, fungal, Gram negative and hospital-acquired sepsis were significantly associated with mortality on multivariate analysis. Hospital-acquired BSI was common (404/864; 47%). Overall antimicrobial resistance rates were high (70% in hospital vs 25% in community-acquired infections; p < 0.0001); hospital-acquired infection, infancy, HIV-infection and Gram negative sepsis were associated with resistance. S. pneumoniae BSI declined significantly over time (58/465 [12.5%] to 33/399 [8.3%]; p =0.04)., Conclusion: Although BSI rates declined over time, children with BSI had high mortality and pathogens exhibited substantial antimicrobial resistance in both community and hospital-acquired infections. Blood culture sampling technique and local options for empiric antimicrobial therapy require re-evaluation.

The primary objective of this study was to determine the incidence and types of microbiologically documented fungal infections in 56 children with acute myeloid leukemia admitted to Wolfson Children's Hospital. The secondary objective was to determine the factors that may affect the treatment and outcome of these infections, such as antifungal prophylaxis, absolute neutrophil count, age, and phase of therapy. Medical records were reviewed from January 1, 2000 to July 31, 2012. Over the 12.5-year study period, there were 11 patients with 25 episodes of fungal infections. Adolescents with acute myeloid leukemia (13 to 18 y old) represented 48% of the population. Children less than 3 years of age and between 3 and 12 years of age represented one quarter each. None of the patients less than 3 years of age developed fungal infections, whereas 64% of the adolescents did (P=0.01). Blood-borne infections were the most common site of infection (44%). Eighty-four percent of infections occurred in neutropenic patients. The mortality rate in the overall cohort was 28%. Patients with fungal infections had increased mortality rate of 55%. Overall candidiasis and aspergillosis were the major pathogens (28% each), although there have been no occurrences of Aspergillus sp. since 2005. On the basis of the results of our study, it would be prudent to provide antifungal coverage for both these pathogens, such as with voriconazole or echinocandins over fluconazole.

Purpose: Bloodstream infections (BSIs) are serious complications with high mortality and morbidity in patients with critical illness. This study was conducted to analyze the clinical and microbiological characteristics as well as outcomes in patients with intensive care unit (ICU)-acquired BSIs., Methods: Data from 1,545 patients admitted to the ICU were retrospectively collected from January 2005 to December 2010. ICU-acquired BSI was defined as a positive blood culture for a clinically significant bacterial or fungal pathogen obtained >72 h after admission to the ICU. Data on clinical and demographic characteristics, comorbid illness, causes of infections, causative pathogens, and clinical outcomes were analyzed., Results: Among the 1,545 ICU patients analyzed, 129 ICU-acquired BSIs occurred in 124 patients. Catheter-related BSIs (CR-BSIs) and ventilator-associated pneumonia (VAP) were the most common causes (29.4 and 20.9%, respectively). The most common isolates were Staphylococcus aureus in 35 (25.7%) and Candida species in 32 (24.8%) cases. Ninety-eight patients died (overall hospital mortality rate, 75.9%). ICU-acquired BSI-related mortality occurred in 23 (63.8%) and 7 (19.4%) of the VAP and CR-BSIs cases, respectively. The most commonly isolated microorganisms from these fatalities were S. aureus (12, 25.7%) and Acinetobacter species (12, 25.7%). In 99 ICU-acquired BSI cases, patients did not receive adequate empirical antimicrobial treatment at the onset of BSIs, whereas the patients in 30 cases did., Conclusion: ICU-acquired BSIs may be associated with high mortality in patients with critical illness. Meticulous infection control and adequate treatment may reduce ICU-acquired BSI-related mortality.

Eleven uncommon yeast species that are associated with high mortality rates irrespective of antifungal therapy were isolated from 17/187 (201 episodes) pediatric and elderly patients with fungemia from Qatar. The samples were taken over a 6-year period (January 2004-December 2010). Isolated species included Kluyveromyces marxianus, Lodderomyces elongisporus, Lindnera fabianii, Candida dubliniensis, Meyerozyma guilliermondii, Candida intermedia, Pichia kudriavzevii, Yarrowia lipolytica, Clavispora lusitaniae, Candida pararugosa, and Wickerhamomyces anomalus. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry provided correct identifications compared with molecular analysis testing of the same isolates. Low minimal inhibitory concentrations were found when isavuconazole and voriconazole were used for all uncommon yeast species evaluated in this study. Resistance to antifungal drugs was low and remained restricted to a few species., (© The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Previous work has suggested that central-line-associated bloodstream infection (CLABSI) is associated with increased costs and risk of mortality; however, no studies have looked at both total and variable costs, and information on outcomes outside of the intensive-care unit (ICU) is sparse. The aim of this study was to determine the excess in-hospital mortality and costs attributable to CLABSI in ICU and non-ICU patients. We conducted a retrospective cohort and cost-of-illness study from the hospital perspective of 398 patients at a tertiary-care academic medical centre from 1 January 2008 to 31 December 2010. All CLABSI patients and a simple random sample drawn from a list of all central lines inserted during the study period were included. Generalized linear models with log link and gamma distribution were used to model costs as a function of CLABSI and important covariates. Costs were adjusted to 2010 US dollars by use of the personal consumption expenditures for medical care index. We used multivariable logistic regression to identify independent predictors of in-hospital mortality. Among both ICU and non-ICU patients, adjusted variable costs for patients with CLABSI were c. $32 000 (2010 US dollars) higher on average than for patients without CLABSI. After we controlled for severity of illness and other healthcare-associated infections, CLABSI was associated with a 2.27-fold (95% CI 1.15-4.46) increased risk of mortality. Other healthcare-associated infections were also significantly associated with greater costs and mortality. Overall, CLABSI was associated with significantly higher adjusted in-hospital mortality and total and variable costs than those for patients without CLABSI., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Bloodstream infections remain a leading cause of morbidity and mortality in neonatal intensive care units (NICU) worldwide. Commonly isolated NICU pathogens are increasingly resistant to standard antimicrobial treatment regimes., Objectives: The primary aim of this study was to determine the burden of bloodstream infections (BSI) in an NICU in a low-to-middle-income country and to describe the spectrum of pathogens isolated together with their drug susceptibility patterns., Methods: This retrospective, descriptive study included NICU patients admitted to the Tygerberg Children's Hospital, Cape Town, between 1 January and 31 December 2008. All blood culture samples submitted to the reference laboratory were extracted and clinical data on patients were obtained by hospital record review., Results: There were 78 culture-confirmed episodes of BSI in 54/503 (11%) patients admitted; median gestational age was 31 weeks (IQR 29-37) and birth weight 1370 g (IQR 1040-2320). Common isolates included coagulase-negative Staphylococcus (22/78, 28%), Klebsiella spp. (17/78, 22%), Acinetobacter spp. (14/78, 18%), Candida spp. (9/78, 11·5%) and methicillin-resistant Staphylococcus aureus (5/78, 6%). There was a predominance of gram-negative organisms (38/78, 48·7%). All Staphylococcus aureus isolates were methicillin-resistant and 59% of Klebsiella pneumoniae isolates were extended spectrum β-lactamase (ESBL) producers. Acinetobacter baumanii isolates showed low susceptibility to the aminoglycosides, carbapenems and cephalosporins. Of 54 infants admitted to the NICU with BSI, 25 (46%) died; 9/25 deaths (36%) were attributable solely to infection., Conclusion: Compared with overall mortality in the NICU, that attributable solely or partly to BSI was high. Many bacterial BSI isolates were resistant to current empiric antibiotic regimens. Regular microbiological and clinical surveillance of BSI in NICUs is required to inform appropriate antibiotic protocols and monitor the impact of infection prevention strategies.